Messenger RNA (mRNA) SARS Coronavirus ‘Vaccines’ and their Potential Autoimmunity Part 2

Messenger RNA (mRNA) SARS Coronavirus ‘Vaccines’ and their Potential Autoimmunity Part 2

Febuary 24, 2021

Messenger RNA (mRNA) SARS Coronavirus ‘Vaccines’ and their Potential Autoimmunity Part 2

James Odell, OMD, ND, L.Ac.

Reference Commentary – The material published in this commentary is intended to foster scholarly inquiry and a rich discussion of the controversial topic of bioethics and health policy. The views expressed in this article are solely the authors and do not represent the policy or position of the Bioregulatory Medicine Institute (BRMI), nor any of its Board Advisors or contributors. The views expressed are not intended to malign any religious or ethnic group, organization, company, individual, or any other. Every effort has been made to attribute the sources of this article to the rightful authors listed in references.The content of this article is presented in summary form, is general, and is provided for informational purposes only: it is not advice, nor should it be treated as such. If you have any healthcare-related concerns, please call, or see your physician or other qualified healthcare providers. Never disregard medical advice or delay seeking it because of something you have read in this article.

 

In my last article entitled COVID 19 mRNA Vaccines, published in the 24th BRMI E-Journal, I reviewed many of the safety concerns about the experimental messenger RNA SARS coronavirus ‘vaccines’ not being discussed in the medical media. Because no long-term safety studies have had time to be performed to ensure that any of these products do not cause cancer, seizures, paralysis, heart disease, or autoimmune diseases, it is of paramount importance for the public to become informed as to any potential risk. Unfortunately, the medical media and pharmaceutical manufacturers have not provided adequate or complete information on the potential adverse effects these experimental mRNA ‘vaccines’ may cause. Partly, because much of this research is being gathered in real-time. In short, there is a gross lack of informed consent as much is still not known about their efficacy and safety. This commentary is an attempt to disclose pertinent information that potential recipients should know to make a truly informed decision as to whether to receive the injection.

 

After the last article, I received many inquiries about details of vaccine immunity in relation to this new mRNA platform. Many readers requested that information be simplified on vaccine immunology, whereas others asked that for more details about the technical aspects of vaccine immunity and their potential for autoimmunity. So, this part-two reference commentary is an attempt to compromise and further evaluate both how vaccines affect immunity and their potential for causing autoimmunity.

 

Emergency Use Authorization

 

The Pfizer-BioNTech and Moderna COVID-19 ‘vaccines’ have not been approved or licensed by the U.S. Food and Drug Administration (FDA), but instead have received authorized for emergency use by the FDA under an Emergency Use Authorization (EUA) for use in individuals 16 years of age and older. Thus, both products are experimental in that they have not been approved by the FDA for a biological license and were approved under EUA without long term safety data. The FDA has not fully evaluated the data and still has not decided if the potential risks outweigh the benefits of receiving it. Human trial data is not complete and published yet, and this is partly why it is considered ‘experimental’ and still unlicensed by the FDA as a biological drug.

 

According to the FDA website, medical products that may be considered for a EUA are those that “may be effective” to prevent, diagnose, or treat serious or life-threatening diseases or conditions that can be caused by a CBRN agent(s) (chemical, biological, radiological, and nuclear) identified in the HHS Secretary’s declaration of emergency or threat of emergency under section 564(b). The “maybe effective” standard for EUAs provides for a lower level of evidence than the “effectiveness” standard that the FDA uses for product approvals.

 

The World Health Organization announced on January 8th that Pfizer’s COVID-19 vaccine was not recommended for pregnant women unless they are at particularly high risk for the virus or a health care worker. They followed that recommendation with another on February 2nd advising against pregnant women taking the Moderna coronavirus vaccine unless they are health care workers or have preexisting conditions. Pregnant and lactating women were excluded from Pfizer/BioNTech and Moderna’s COVID-19 vaccine clinical trials, and they are not included in any ongoing trials for vaccines manufactured by other companies. That means there is no safety data available to know for sure whether these ‘vaccines’ are safe for people who are pregnant or breastfeeding. It is not known if or how these experimental drugs will affect fertility in the short or long term. What is known is that there have been several reports to Vaccine Adverse Event Reporting System (VAERS) of miscarriages following the shot.

 

Viral Messenger RNA as a Synthetic Pathogen of Unknown Risk

 

The central dogma of biology states that DNA makes RNA and RNA make proteins.However, there are many different types of RNAs, and only one of them, the messenger RNA (mRNA), gives rise to proteins. Messenger ribonucleic acids (mRNAs) transfer the information from DNA to the cell machinery that makes proteins. Specifically, mRNA delivers the information encoded in one or more genes from the DNA to the ribosome, a specialized cellular structure, or organelle, where that information is decoded into a protein. Ribosomes read the mRNA and translate the message into functional proteins in a process called ‘translation’. Depending on the newly synthesized protein’s structure and function, it will be further modified by the cell, exported to the extracellular space, or will remain inside the cell. The primary function of mRNA is to act as an intermediary between the genetic information in DNA and the amino acid sequence of proteins. Thus, messenger RNA is an intermediary between the gene, and the product, the protein.

 

In vaccines, it is the protein that ultimately elicits the immune response, not the RNA. Historically, vaccines are proteins, either viral, or bacterial, and it is the vaccine’s protein that, if all goes well, develops an immune response to elicit neutralizing antibodies. Vaccine-mediated immunity is often multifactorial, and the best protection is likely to be elicited by the combination of strong humoral and cell-mediated immune responses.

 

So, by definition, an mRNA ‘vaccine’ is not a true vaccine. First, because it is not a protein that directly elicits an immune response. It first must be decoded into protein, and it is then that protein that in turn creates the desired immune response. Secondly, by FDA definition, since it is a component used as a treatment to affect a body’s function, it is by legal definition a ‘medical device’ or a physical ‘device’ that comes in a molecular-sized package. Thus, strictly speaking, this messenger RNA device is a synthetic pathogen utilizing a genetic engineering process as a biological response modifier, not at all like a classical vaccine. In principle, biological response modifiers are biologically active agents including antibodies, small peptides, and/or other (small) molecules of mRNA, DNA, that can influence the immune response. Most importantly, this synthetic viral pathogen device is a new and different molecular platform, one that has never been injected into the public’s arm.

 

With these mRNA synthetic pathogens, what is injected into the body is not a weakened virus or even selected antigens, but rather protein-coding instructions that tell your body’s cells how to make the antigens on their own. Again, that process is called “translation.”

 

Erroneously referring to this intervention as a ‘vaccine’ exploits the public’s ingrained trust in previous vaccination programs. It keeps us in the illusion of vaccine safety in place of taking the necessary measures to investigate the impact of this new experimental device on our health. In studies of vaccination decision-making, risk perception is often intricately linked with ideas of trust in health professionals, in government, or public health institutions and the interplay between these actors. When medical professionals or institutions no longer fulfill their obligation of information transparency and disclosure of potential risks, this is a harmful violation of trust. Many people do not understand what FDA Emergency Use Authorization entails. It means it is still experimental and carries risk yet unknown. The public becomes the experiment.

 

Another wrinkle in information disclosure is the manufacturer’s complete lack of liability. As I described in the previous article, the Public Readiness and Emergency Preparedness Act of 2005 has now allowed vaccine manufacturers unlimited freedom to create, develop, and market COVID-19 vaccines without any liability whatsoever. All liability is protected by the PREP Act, which means if anyone has an adverse event or death caused by this vaccine there really is no recourse. This was put into the Federal Register in March of 2020 and does not expire till the end of 2024. So, anything that is developed over the next four years that has to do with a biological agent, such as a vaccine or drug or biotechnology, no matter how nefarious, is protected from liability under the umbrella of COVID-19.

 
 

Messenger RNA

 

This mRNA experimental synthetic pathogen carries mRNA genetic material from SARS-CoV-2 coronavirus into cells where that cellular machinery with the synthetic pathogen produces a protein to which the body mounts an immune response. In the case of COVID-19, inert spike (S) antigen proteins are produced. This then enables SARS-CoV-2 coronavirus particles to enter host cells and triggers humoral (antibody-mediated) acquired immunity. So, what could possibly go wrong with bodily cells that are artificially programmed to produce foreign viral proteins to which the immune system is going mount an immune response? Well, that biochemical reaction could create an autoimmune reaction. As this mRNA platform has never been used in humans before, the potential for this to go wrong and elicit widespread autoimmune diseases and deaths is enormous.

 

Pfizer, Moderna, Dr. Anthony Fauci, and Dr. Soumya Swaminathan, the WHO’s chief scientist, have now made it abundantly clear that the novel mRNA strand entering the cell is not intended to stop transmission but rather as a treatment. However, America’s Frontline Doctors and numerous other doctors have been censored from public discourse on the profoundly viable and formerly ubiquitous treatments such as hydroxychloroquine, ivermectin, zinc, vitamin C, and vitamin D3. If these effective treatments had not been denied us, both in access and scientific data, but disseminated to the global community, we might not have needed an ‘emergency use’ technology at all. Bear in mind for FDA to issue an emergency use authorization, there must be no adequate, approved, and available alternative to the candidate product for diagnosing, preventing, or treating the disease or condition. Could this be why these available and effective alternative products are constantly censored in the media and social media?

 

Antibodies and Vaccines

 

To understand how vaccines create immune responses it is necessary to briefly clarify and review the function of antibodies and both the adaptive and innate immune system. Antibodies, also known as immunoglobulins (Ig), are specialized proteins that bind to a uniquely shaped object – called an antigen – that is found on the surface of a pathogen. These pathogens can be things such as bacteria or viruses. Antibodies are produced by B lymphocytes, known as B cells, which are specialized white blood cells of the immune system. B cells have antibodies on their cell surface that allow them to recognize anything foreign. When they encounter a pathogen such as a virus, the B cells transform into plasma cells, which start producing antibodies that are designed to bind to an antigen that is specific to that pathogen.

 

B-plasma cells release large amounts of antibodies into the body’s circulation. This protects us in two main ways. First, antibodies can bind to antigens on the outside of the pathogen to stop it from entering our cells. This is particularly important for viruses, which enter human cells to replicate. Second, by binding to antigens on the pathogen, antibodies also signal other white blood cells known as phagocytic cells, which engulf and destroy the pathogen. So, in short, antibodies can both neutralize a virus and mark it for destruction.

 

Antibodies form part of our adaptive immune response, which is a refined, targeted response to a specific antigen. The first time we encounter a virus, some of our B cells become plasma cells, but others transform into memory B cells. The second time you are exposed to the same pathogen, these memory cells quickly transform into plasma cells that produce large amounts of antigen-specific antibodies to fight the infection.

 

There are many types of antibodies, each with different purposes, which are created in response to chemical signals. Different B cells in the body will produce multiple different antibodies that bind to different sites, but only binding to some of these sites will inactivate the virus. For a vaccine to work, it must produce a binding or neutralizing antibody. It is never certain that a vaccine will produce neutralizing antibodies. One important difference in antibodies produced from vaccines and antibodies from natural infections is that the immune system does not form as many different types of antibodies from a vaccination as it would in the course of a natural infection. Thus, natural infection often protects the individual for life, whereas artificial infection from a vaccine usually requires repeated boosters to maintain antibody levels.

 

However, in some circumstances, the binding of an antibody might worsen an infection. For example, antibodies might bind to a virus in such a way that helps the virus enter cells more easily. This might mean that a person re-infected after an initial mild infection might then have a more severe disease. Or it might mean that a person could have a worse response to a potential infection (like with COVID-19) if they have previously been vaccinated for the disease. This scenario has been called “antibody-dependent enhancement” (ADE) and will be discussed later in this article.

 

Three main types of antibodies are produced in response to infection: IgA, IgG, and IgM. IgM rises soonest and typically declines after infection. IgG and IgA persist and usually reflect longer-term immune responses. The detection of IgM antibodies is sometimes used as a test for recent infection. For example, an IgM antibody is commonly used to check for recent coronavirus infection. A particularly important type is IgG antibodies, which tend to be more long-lived than IgM antibodies. This subtype of antibodies is critical not just for controlling the initial disease but for preventing future disease if you are later re-exposed. It is observed that IgM levels increased during the first week after SARS-CoV-2 infection, peak 2 weeks later, and then they are reduced to near-background levels in most patients. IgG has been detectable after 1 week and may be maintained at a high level for a long period.

 

Some people make many high-quality antibodies that are good at recognizing the relevant antigen and binding to it. If this happens, the virus is rapidly bound by antibodies and eliminated before it can even cause an infection. Other people make antibodies, but they are not as effective at binding the pathogen. In this situation, the antibodies only provide partial protection at best. Then there are also those people who either produce little or no antibodies or poor-quality antibodies. Generally, many elderly fall into this category. In this case, vaccine immunity is not so effective, so they may experience a prolonged infection with more severe symptoms. They are also likely to be re-infected at a later point in time. This is part of the reason vaccines do not always confer immunity or confer only partial immunity for a limited period.

 

The adaptive immune system involves more than just B cells, plasma cells, and antibodies – it also includes T cells. T cells are another population of white blood cells that can develop into memory cells, just as B cells can. They can also differentiate into specialized cells that kill virus-infected cells. The functions of T cells and B cells are different. B cells develop into plasma cells that produce antibodies (T cells do not); T cells directly kill virus-infected cells (B cells do not). Sometimes individuals with a very vigorous T cell immune response will be protected from a pathogen even though they produce low amounts of antibody. The T cell immune response is much more difficult to measure than the antibody response and is usually only evaluated in a specialized laboratory or research setting. Our adaptive immune response is important because once developed, it is highly specific for the pathogen and provides us with immunologic memory.

 

We also have another type of immune system known as the innate immune system. The innate immune system is our frontline defense, the first system to respond to a new infection. This includes cells such as neutrophils, macrophages, and dendritic cells. Unlike the adaptive immune system, which includes antigen-specific antibodies that take time to develop, the innate immune system responds to antigens very quickly but in a non-specific way. It attacks anything that “looks” foreign to the body, like components of a bacterial cell wall, or viral RNA and DNA. Quite often, the innate immune response will take care of an infection before the adaptive immune system even has a chance to start manufacturing antibodies.

 

SARS-CoV-2 Antibody Blood Test

 

Many people are now taking the COVID-19 antibody blood test. This immune response test detects the immune proteins or antibodies that the body produces in response to the virus. It does not detect the virus itself; thus, an antibody test does not determine whether you are currently infected with the COVID-19 virus. Antibody testing is best undertaken at least two weeks after the onset of symptoms. Because SARS-CoV-2 belongs to a large family of coronaviruses, the test may inadvertently detect the antibody of related coronavirus strains (such as the HKU1, NL63, OC43, or 229E strains) and trigger a false-positive reading. False-negatives are even more common with SARS-CoV-2 antibody tests, due in part to the variable sensitivities of the tests. The sensitivity and specificity of antibody tests vary over time and results should be interpreted in the context of clinical history. Compared to venous blood tests, rapid finger-stick tests tend to be less reliable and more likely to return a false-negative result. In short, the evidence is currently insufficient to know whether individuals with SARS-CoV-2 antibodies have protective immunity.

 

Current SARS-CoV-2 ‘Vaccines’

 

At the time of this writing, there are 2 experimental mRNA SARS-CoV-2vaccines’ publicly available, one by Pfizer/BioNTech the other from Moderna, and one viral vector vaccine by Johnson and Johnson. As previously mentioned, mRNA-based ‘vaccines’ have never before been used on humans and these two are still not FDA licensed for human use, though they have been made publicly available through Emergency Use Authorization. These mRNA formulas contain a synthetic sequence of messenger RNA that is concealed within a patented lipid nanoparticle delivery system. After entering cellular ribosomes (that house the transcription machinery of the cells) of the muscle cells into which the synthetic pathogenic mRNA is injected, it then instructs cells to produce a copy of the spike protein of the virus. In essence, it means that the human body becomes the vaccine factory of the protein. This process is genetic engineering. Even more concerning, is that these synthetic pathogen devices place a novel molecule, spike protein, in/on the surface of host cells. This spike protein then becomes a potential receptor for another possibly novel pathogenic infectious agent.

 

Recently the Janssen Vaccines, a subsidiary of Johnson and Johnson has also received FDA Emergency Use Authorization for the company’s single-shot COVID-19 vaccine for adults 18 and older. Thus, it is now the third vaccine available in the U.S. This vaccine is based on an adenovirus vector Ad26 (not a mRNA vaccine like Pfizer or Moderna). Ad26.COV2.S expresses the full-length spike protein, stabilized by furin cleavage site mutations and two consecutive proline stabilizing mutations in the hinge region. It contains the wild-type signal peptide. The science behind recombinant adenoviral vector vaccines has been around for a long time, but the only commercially available adenovirus-based vaccine is a rabies vaccine for animals. Viral vector vaccines are more of a conventional vaccine platform, unlike mRNA vaccines. Viral vector vaccine work by carrying a DNA express or antigen(s) into host cells, thereby eliciting cell-mediated immunity in addition to the humoral immune responses. Adenovirus-based vaccines may also pose some problems in that the adenovirus is so common that the vaccine may not be as effective once booster doses are given, or that some people may already have immunity to the virus used in the vaccine. Additionally, incorporating a spike protein into the viral vector vaccine potentially creates this protein receptor to attract another novel pathogenic infectious agent.

 

Another frontrunner is the non-replicating viral vector vaccine by the AstraZeneca/Oxford University group. This also employs a genetically modified (non-replicating) chimpanzee viral vector vaccine, now designated AZD1222. The AstraZeneca/Oxford’s vaccine instead of utilizing a human adenovirus in its vaccine uses a genetically modified chimpanzee-derived adenovirus that encodes the spike protein of Middle East respiratory syndrome coronavirus (MERS-CoV).

 

According to the recent World Health Organization’s Draft landscape of COVID-19 candidate vaccines, there are currently 64 candidate vaccines in clinical development with a further 173 in pre-clinical development, these relying on 8 different vaccine platforms in addition to the two already relied on by the 3 frontrunners. Most (31%) rely on the more conventional protein subunit platform that has been widely used for seasonal influenza vaccines.

 

This article will continue to focus on mRNA vaccines, not viral vector vaccines.

 

SARS-CoV-2 Autoimmunity and Inflammatory Cytokines

 

Autoimmune disease occurs when the body’s immune system cannot discern the difference between its cells and foreign cells, and in turn, this causes the body to attack its normal cells. Simply speaking, in autoimmunity the patient’s immune system is activated against the body’s proteins. Molecular mimicry is an antigenic similarity between molecules found on some disease- causing microorganisms and specific previously healthy body cells or tissues. In short, molecular mimicry occurs when a pathogen expresses a protein that is remarkably similar in sequence or shape to a protein in the host. It has been suggested that molecular mimicry may contribute to a potential adverse reaction to the SARS-CoV-2 mRNA shot. Thus, antibodies to SARS-CoV-2 cross-reacting with structurally similar host protein sequences and raising an acute autoimmune response against them.

 

Cytokines are the hormonal messengers responsible for many of the biological effects in the immune system, such as cell-mediated immunity and allergic-type responses. Although they are numerous, cytokines can be functionally divided into two groups: those that are proinflammatory and those that are essentially anti-inflammatory but that promote allergic responses. As previously discussed, T cell lymphocytes play a central role in the adaptive immune response. T lymphocytes are also a major source of cytokines. These cells bear antigen-specific receptors on their cell surface to allow recognition of foreign pathogens. They can also recognize normal tissue during episodes of autoimmune diseases. There are two main subsets of T lymphocytes, distinguished by the presence of cell surface molecules known as CD4 and CD8. T lymphocytes expressing CD4 are also known as helper T cells, and these are regarded as being the most prolific cytokine producers. This subset can be further subdivided into Th1 and Th2, and the cytokines they produce are known as Th1-type cytokines and Th2-type cytokines.

 

Th1 or Th2 differ in a few important ways. The most apparent difference is that Th1 cytokines are produced by Th1 helper cells, as opposed to Th2 helper cells. Whether an attacking virus or bacteria invades inside or outside of cells is also important, as intracellular invaders tend to trigger Th1 cytokine responses, while outside agents call upon Th2 cytokine responses. As such, Th1 cytokines activate white blood cells called macrophages inside of tissues. In contrast, Th2 cytokines activate antibodies in what is known as a humoral immune response, and this type of response will most likely occur when the concentration of an invading substance (virus) is high.

 

Th1-type cytokines tend to produce the pro-inflammatory responses responsible for killing microorganisms and for perpetuating autoimmune responses. Interferon-gamma is the main Th1 cytokine. Excessive pro-inflammatory responses can lead to uncontrolled tissue damage, so there needs to be a mechanism to counteract this. The Th2-type cytokines include interleukins 4, 5, and 13, which are associated with the promotion of IgE and eosinophilic responses. Over-expression of IL-5 significantly increases eosinophil numbers and antibody levels. It has been proposed that IL-5 be used as a biomarker for antibody-dependent enhancement or pathogenic priming.

 

Regulatory T-cells (formerly called suppressor T cells) are a component of the immune system that suppresses the immune responses of other cells. Th1 assists in the activation of these regulatory T-cells which are meant to slow down B-cells and cytotoxic T-cells. If the regulatory T-cells are malfunctioning or deficient due to a decrease in Th1, the cytotoxic T-cells may take over and start killing healthy cells (autoimmune). This leads to increased immune stimulation, followed by an inflammatory cytokine storm and potential for autoimmune disorders. It is observed that some people find themselves with an autoimmune condition after a traumatic event or stressful event (e.g., a parent or sibling passing away). The physiological stress response caused Th1 to decrease, which lead to Th2 dominance.

 

Additionally, excess Th2 responses will counteract the Th1 mediated microbicidal action. The optimal scenario would therefore seem to be that humans should produce a well-balanced Th1 and Th2 response, suited to the immune challenge. Unfortunately, vaccines being an artificial induced immune response, historically have been implicated in creating an imbalance in this Th1 and Th2 response, resulting in pro-inflammatory Th2-type cytokines.

 

In chronic inflammatory autoimmune diseases, white cells such as neutrophils and other leukocytes are constitutively recruited by these proinflammatory cytokines and chemokines, resulting in tissue damage. This inflammatory reaction is called a ‘cytokine storm’. It is an overreaction of the immune system, in which an excess of certain proinflammatory cytokines trigger an onslaught of white blood cells that attack an area or organ of the body resulting in tissue damage, and in extreme cases, organ failure. An example of a cytokine storm in the lungs of a COVID-19 patient can draw inflammatory causing white blood cells into the spaces between air sacs, blocking oxygen from reaching the blood, which can prove fatal. Both genetic and environmental factors are thought to contribute both to the severity of viral infections and in determining who potentially develops an autoimmune condition.

 

Thus, it is observed that severe/fatal cases of COVID-19 are associated with immune hyperactivation and excessive cytokine release, leading to multiorgan failure. A broad range of mechanisms appears to be involved. However, it has been suggested that ‘molecular mimicry’ may contribute to this problem, with antibodies to SARS-CoV-2 spike glycoproteins cross-reacting with structurally similar host heptapeptide protein sequences (for example, in interleukin-7 and alveolar surfactant proteins), and raising an acute autoimmune response against them.1 Auto-inflammatory dysregulation in genetically susceptible individuals might also contribute to acute but also chronic autoimmunity during and after COVID-19.2

 

Though the exact etiology of many autoimmune diseases remain unknown, various factors are believed to contribute to the emergence of autoimmune disease in people including the genetic predisposition, corruption of the internal milieu resulting in microbe triggers such as bacterial, viral, fungal, and parasitic infections, including imbalances of the gut microbiota (dysbiosis of the intestinal microbiome), as well as numerous toxicological environmental agents, hormonal factors, and the host’s immune system dysregulation. All these factors interplay was coined by Shoenfeld et al., many years ago in “The Mosaic of Autoimmunity.”3

 

Certain viruses have long been implicated in the initiation of chronic inflammatory or autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, Sjogren’s syndrome, multiple sclerosis, polymyositis, uveitis, Henoch–Schönlein purpura, systemic juvenile idiopathic arthritis, and others.4 In May 2020 a German study entitled “COVID-19-induced acute respiratory failure: an exacerbation of organ-specific autoimmunity?”, examined a group of 22 patients for the possible role of autoimmunity in SARS-CoV-2 -associated respiratory failure. Based on serological, radiological, and histomorphology similarities between Covid-19-associated ARDS and acute exacerbation of connective tissue disease-induced interstitial lung disease, the authors suggest that SARS-CoV-2 infection might trigger or simulate a form of organ-specific autoimmunity in predisposed patients.5 In a similar retrospective study from China of 21 patients with critical SARS-CoV-2 pneumonia, the authors showed a prevalence of between 20 and 50% of autoimmune disease-related autoantibodies.6

 

Autopsies of Chinese citizens who have died from COVID-19 following SARS-CoV-19 infection show evidence of lung interstitial changes, suggesting the development of pulmonary fibrosis. This suggests, at least partly, an autoimmunology basis of the pathogenesis of COVID-19.

 

Vaccine Autoimmunity

 

In the past few decades, the study of autoimmune biology, the failure to recognize self-antigens as “self”, has grown immensely. One in five Americans has an autoimmune condition. Vaccines, particularly viral vaccines, have been observed playing a role in inducing autoimmune disease for a long time. Autoimmune reactions are among the most serious adverse events observed in vaccines. An example is Guillain-Barré syndrome (GBS), an autoimmune polyneuropathy. GBS has been attributed to certain vaccinations, particularly, with monovalent or combination measles, mumps, and rubella vaccines, influenza vaccine, oral polio vaccine, diphtheria, and tetanus toxoids. GBS has also been associated with the 1976 swine-influenza vaccine. 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 Some studies have shown an increased risk of GBS following receipt of seasonal H1N1 monovalent influenza vaccines.17,18 Bear in mind GBS is not the only autoimmune disease that has been documented as an adverse reaction to vaccination.

 

Vaccine autoimmunity reactions occur from several causes. One explanation is that they may be induced via “molecular mimicry”, and often, in specific families who happen to have a genomic mutation that makes one of their proteins more like the protein in the vaccine. It appears that in addition to molecular mimicry there are other mechanisms by which this SARS-CoV-2 mRNA “vaccine” could induce a hyperinflammatory autoimmune syndrome. One of the most documented is ‘pathogenic priming’ or ‘disease enhancement’, euphemistically called in literature ‘antibody-dependent enhancement or ADE’.

 

Pathogenic priming or disease enhancement occurs after vaccination or when an infection a person can experience more serious, enhanced disease when later being exposed to the pathogen against which that the vaccine was intended to protect. When the enhancement is specifically related to a vaccine, it is sometimes called vaccine-associated hypersensitivity (VAH). Pathogenic priming or disease enhancement has been demonstrated in SARS-CoV infection years ago, mediated by antibodies directed to the envelope spike proteins.19 Thus, a simple definition of pathogenic priming or ADE is increasing specific antibodies that do not protect, but instead, make a viral infection even worse. This unwanted antibody reaction has long been a thorn in the side of vaccine manufacturers. There are “neutralizing” antibodies as opposed to non-neutralizing ones – a neutralizing antibody, as the name implies, binds to its target in a way that shuts its function down. That is generally done by blocking the receptor of a given protein target or smothering the binding surface that it would need to function. For the coronavirus, a straightforward example of a neutralizing antibody would be one that binds to the tip of the spike protein, the receptor-binding domain that is the part that recognizes and binds to the human ACE2 protein on a cell surface. Block that thoroughly enough, and it would follow that you have blocked the virus’s ability to infect your cells.

 

More technically, in antibody-mediated viral neutralization, neutralizing antibodies binding to the receptor-binding domain of the viral spike protein, as well as other domains, prevent the virus from docking onto its entry receptor, ACE2. In antibody-dependent enhancement, low quality, low quantity, non-neutralizing antibodies bind to virus particles through the antigen-binding fragment or Fab domains. Fc receptors (FcRs) expressed on monocytes or macrophages bind to Fc domains of antibodies and facilitate viral entry and infection. (An Fc receptor is a protein found on the surface of certain cells – including, among others, B lymphocytes, follicular dendritic cells, natural killer cells, macrophages, neutrophils, eosinophils, basophils, human platelets, and mast cells – that contribute to the protective functions of the immune system.) Upon engagement by the Fc domains on antibodies, activating FcRs with ITAMs initiate signaling to upregulate pro-inflammatory cytokines and downregulate anti-inflammatory cytokines. This causes what is commonly described as a cytokine storm. Immune complexes and viral RNA in the endosomes can signal through Toll-like receptor 3 (TLR3), TLR7, and/or TLR8 to activate host cells, resulting in immunopathology.

 

(ITAM is an immunoreceptor tyrosine-based activation motif. A conserved sequence of four amino acids repeated twice in the cytoplasmic tails of non-catalytic tyrosine-phosphorylated receptors, cell-surface proteins found mainly on immune cells. Its major role is being an integral component for the initiation of a variety of signaling pathways and subsequently the activation of immune cells, although different functions have been described, for example, an osteoclast maturation.)

 

Thus, the concern about disease enhancement or ADE arises from the possibility that antibodies present at the time of infection may increase the severity of an illness. Uptake of SARS-CoV through ADE in macrophages led to elevated production of TNF and IL-6.20

 

In mice infected with SARS-CoV, ADE was associated with decreased levels of the anti-inflammatory cytokines IL-10 and TGFβ and increased levels of the pro-inflammatory chemokines CCL2 and CCL3. 21

 

Furthermore, immunization of non-human primates with a modified vaccinia Ankara (MVA) virus encoding the full-length S protein of SARS-CoV promoted activation of alveolar macrophages, leading to acute lung injury.22

 

The enhancement of disease by ADE or pathogenic priming has been described clinically in several studies such as children given formalin-inactivated respiratory syncytial virus (RSV) or measles vaccines in the 1960s, and in dengue hemorrhagic fever due to secondary infection with a heterologous dengue serotype.23, 24, 25, 26

 

ADE is a primary reason why vaccines for SARS-1 and MERS, were not previously manufactured commercially. Early researchers concluded coronavirus vaccines were too dangerous to proceed to human studies, as demonstrated in animal studies and were no longer necessary because SARS and MERS had waned naturally.

 

For example, previous vaccine studies in mice, with several whole-inactivated SARS-CoV candidates (with and without aluminum adjuvants) reduced lung viral titer and/or mortality upon viral challenge, but at the same time induced increased lung immunopathology in the form of eosinophilic infiltration (i.e., unusual presence of eosinophilic cells in the lung tissue) upon infection.27, 28, 29 Importantly, one study showed that in older mice, protection was lower and eosinophilic immune infiltration was exacerbated as compared to younger mice.30 Similarly, an inactivated MERS-CoV vaccine in aluminum adjuvant resulted in the production of neutralizing antibody and reduced lung viral titers (upon viral challenge), but induced increased eosinophil infiltration upon homologous coronavirus challenge, despite reducing lung viral titer and/or mortality.31

 

There has been expressed by many doctors a genuine concern over the risk of pathogenic priming or ADE with these new experimental viral mRNA synthetic pathogen platforms. The results from the fast-tracked human trials and subsequent emergency authorization are not sufficient to rigorously evaluate their true potential risk. The fact that only hundreds (not tens of thousands) of people for each vaccine who have been vaccinated have also been exposed to wild SARS-CoV-2 is not adequate to know if sub-groups of people could be susceptible to disease enhancement following exposure to the virus.

 

These concerns are sufficient enough for Drs Anne Arvin, Herbert Virgin, and colleagues from Vir Biotechnology in San Francisco and Stanford, writing in one of the world’s most prestigious journals, Nature, to have stated in July 2020 that ADE is “…a general concern for the development of vaccines and antibody therapies because the mechanisms that underlie antibody protection against any virus have a theoretical potential to amplify the infection or trigger harmful immunopathology. This possibility requires careful consideration at this critical point in the pandemic of coronavirus disease 2019”.32

 

Another concerned voice is, J. Patrick Whelan, MD, PhD, a pediatric rheumatologist, who has warned the FDA about the potential for mRNA vaccines designed to create immunity to the SARS-CoV-2 spike protein to instead cause injuries. Whelan’s training (at Harvard, Texas Children’s Hospital and Baylor College of Medicine) includes degrees in biochemistry, medicine, and rheumatology. For 20 years, he worked as a pediatric rheumatologist. Whelan warned that a recently infected patient who is subject to covid-19 vaccination is likely to suffer from autoimmune attacks along the ACE-2 receptors present in the heart, and in the microvasculature of the brain, liver, and kidney. The risk is doubled because two shots are required.

 

It is a well-documented fact that SARS-CoV-2 readily targets humans through the vascular endothelium. The virus is known to enter endothelial cells through the ACE-2 receptor on the endothelium. Because of this unique gain-of-function, one of the medical emergencies that may occur in covid-19 patients is thromboembolic complications (formation of a blood clot inside a blood vessel). If viral antigens are present in the endothelial lining of blood vessels, then the vaccine will cause an antigen-specific immune response that attacks those precious tissues, potentially causing cardiovascular events. Research warns that the vaccine may damage the vascular endothelium, especially in the elderly. Dr. Whelan claims that vaccine-induced endothelial inflammation is “certain to cause blood clot formation with the potential for major thromboembolic complications in a subset of such patients. The potential to cause microvascular injury (inflammation and small blood clots called microthrombi) to the brain, heart, liver and kidney … were not assessed in the safety trials.”

 

An essential stage in any vaccine licensing process should involve a careful analysis for potential of ADE/pathogenic priming, yet in the political and socioeconomic rush towards mass ‘vaccination’ this has been skipped as no longer-term safety testing has been conducted. At a minimum laboratory assessment of interleukin-5 should have been conducted in the human test trials to determine any evidence of eosinophilia autoimmune responses or pathogenic priming.

 

Current Adverse Reactions

 

Worldwide there have now been hundreds of deaths and thousands of serious adverse reactions reported after receiving the viral mRNA injection. The Vaccine Adverse Event Reporting System (VAERS), a co-managed program by the CDC and FDA, has accumulated an extensive list of these adverse reactions here in the U.S.

 

As of Feb. 12th, 929 deaths, 616 life-threatening adverse events, 316 cases of permanent disability, and more than 5,000 hospitalizations and emergency room visits after COVID vaccinations were reported to VAERS. 33 Fifty-three percent of those who died were male, forty-four percent were female, the remaining death reports did not include the gender of the deceased. The average age of those who died was 77, the youngest was a 23-year-old. The Pfizer shot was taken by 58% of those who died, while the Moderna shot was taken by 41%. As of February 4th, there had been 163 cases of Bell’s Palsy reported and 775 reports of anaphylaxis.34

 

According to the CDC VAERS website, “VAERS reports alone cannot be used to determine if a vaccine caused or contributed to an adverse event or illness.” Rather, it is considered to be a tool for detecting “signals” or patterns of significant problems with vaccines. While the VAERS database numbers are sobering, according to a U.S. Department of Health and Human Services study,35 the actual number of adverse events is likely significantly higher. VAERS is a passive surveillance system that relies on the willingness of individuals and professionals to submit reports voluntarily. Thus, we really do not know the full extent of adverse reactions to these products. Globally there are reports of hundreds of nursing home residents dying immediately of a day or two after the shot.

 

The medical establishment and its controlled media networks are downplaying the numerous severe adverse events caused by these mRNA products, either calling them coincidental, blaming them on a new viral variant, or claiming their “rare” occurrence is from the toxic additive known as polyethylene glycol (PEG). Though PEG reaction is real and widespread, the experimental mRNA synthetic pathogen technology will probably prove to be the real culprit.

 

Both the Moderna and Pfizer-BioNTech mRNA product contains polyethylene glycol. To be clear, we know that PEG is harmful and should not be injected into humans. It has never been used in other vaccines to date. Growing evidence suggests that a large percentage of people can generate allergic immune responses to PEG-modified therapeutics. The presence of anti-PEG antibodies has been associated with anaphylactic or hypersensitivity reactions after the administration of PEG- containing formulation.36, 37, 38.

 

A 2016 study reported an astonishing 72% of specimens possessed anti-PEG antibodies with 8% of those being extremely elevated more than 500 ng/mL. The authors concluded that the widespread prevalence of pre-existing anti-PEG antibodies underscores the importance of screening patients for anti-PEG Ab levels before the administration of PEG-containing products.39

 

In contrast to the popular assumption that PEG is biologically inert, PEG is both immunogenic and antigenic. While PEGylation of therapeutic agents have shown and will continue to show, a great value in medicine to address toxicity, immunogenicity, and rapid clearance of an unconjugated drug while maintaining efficacy in the treatment of many diseases, it is possible that a subset of patients with anti-PEG may not benefit from treatment with PEG-conjugated agents.

 

The PEG delivery system allows the mRNA spike protein to be expressed by any cell not just the cells with entry receptors like the wild-type viral sequence. Afterward the cell goes through programmed cell death. One question is what happens when cells like dopaminergic neurons go through this process and die? Instant Parkinson’s?

 

Conclusion

 

Currently, Pfizer/BioNTech and Moderna mRNA products have been approved by the FDA under an Emergency Use Authorization (EUA) but are still FDA unlicensed biologicals. This mRNA technology is being labeled as ‘vaccines’, when by legal definition they are viral mRNA synthetic-pathogen devices. These experimental products are presently being distributed to millions and eventually potentially billions of people worldwide. Both products were expedited or “fast-tracked” through human trials and have not had adequate evaluation or surveillance for any long-term side effects. The historic timeline for taking a vaccine from concept to licensed product is estimated at 10–15 years, though some licensed vaccines have taken up to 30 years.40

 

This extended timeline is due largely to the stringent pre-clinical and clinical testing that is required of human vaccine candidates. The extremely short duration human trials of these experimental products are unprecedented, and their performance and safety profiles are still largely unknown. The profit-motivated rush to deploy mRNA vaccines for treatment of the Wuhan coronavirus has caused regulators and researchers to skip (or accelerate) many critical steps in quality control and clinical trials.

 

Remembering that previous efforts to develop vaccines against human coronaviruses have faced challenges, with several preclinical studies demonstrating disease enhancement and death in vaccinated animals after viral challenge. This was characterized by eosinophilic infiltrates resulting in immunopathology, after the induction of a T helper cell type 2 (Th2)-biased response, or a weak neutralizing antibody response that might contribute to antibody-dependent enhancement of infection.41

 

Analyzing the induction of immune responses after vaccination is driven, in part, by concerns about enhanced disease from potentially immunopathologic Th2 responses, as seen in animal studies of vaccines against other coronaviruses.42, 43, 44, 45

 

Hence, one of the side effects of giving a mass vaccine could be an emergence of an epidemic of autoimmune diseases, especially in individuals who are genetically prone to autoimmunity. After many years, and considerable attention, the understanding of pathogenic priming or ADE of disease after vaccination is insufficient to confidently predict that a given immune intervention for a viral infection will not have certain negative and grave outcomes in humans.

 

The remaining elephant in the room is that of the greatest unknown, of tampering with the human genome. The possibility that synthetic viral mRNA fragments might, through some currently unknown process, permanently alter the genome of the host. mRNA ‘vaccine’ manufacturers currently claim this is impossible, but the history of medicine is full of examples of arrogant scientists making catastrophic assumptions about the human body that turned out to be overly optimistic. Using viral mRNA to create proteins has unknown long-term consequences. There is much we have yet to comprehend of the complexity of the human body and immune system. RNA expresses proteins but it has many other functions, specifically as an epigenetic modifier. RNA can modify genetics without being reverse transcribed into DNA.46 RNA has multiple mechanisms of modifying DNA expression including modifying DNA promoter regions.47 In short, the viral pathogen mRNA technology being used has many unknown long-term effects on the human genome.

 

If this human experiment does prove to cause adverse problems in time, it will already have been administered to millions worldwide and will be too late. This synthetic pathogenic genetic engineering cannot be removed, and it cannot be turned off. It will have been irretrievably unleashed into the cellular system of humankind.

 

There are many other potential adverse events that can be induced by the experimental mRNA based ‘vaccines’ against COVID-19 undisclosed here. These synthetic pathogen devices place a novel molecule to create a spike protein, in/on the surface of host cells. This spike protein can become a potential receptor for another possibly novel pathogenic infectious agent. Data is not publicly available to provide information on how long the mRNA is translated in the vaccine recipient and how long after translation the spike protein will be present in the recipient’s cells. Forever? What is done here genetically cannot be undone. Genetic diversity protects species from mass casualties caused by infectious agents. One individual may be killed by a virus while another may have no ill effects from the same virus. By placing the identical receptor, the spike protein, on cells of everyone in a population, the genetic diversity for at least one potential receptor disappears. Everyone in the population now becomes potentially susceptible to binding with the same infectious agent.

 

Research into mRNA vaccines is still in its infancy, even though various biotech pioneers have been working on ways to achieve mRNA vaccines for around two decades. Yet more decades of research will likely be required to achieve acceptable levels of safety and efficacy. Unfortunately, we have become the test animal.

 

For manufacturers mRNA “vaccines” offer economic advantages over traditional vaccines. They are cheaper and faster to manufacture. They typically require no adjuvants or other toxic additives to work as intended (aside from the potentially antigenic and toxic lipids that envelope the naked mRNA). Furthermore, they can direct the body to manufacture almost any protein imaginable. That is how it works in theory, of course.

 

But they also present enormous risks of which the results could be catastrophic and irreparable. mRNA “vaccines” could inadvertently trick the human body into attacking its critical functions such as fertility, neurological function, cell repair, and other indispensable processes. Additionally, mRNA “vaccines” could be maliciously exploited to weaponize vaccines to target essential physiological functions in humans. This is similar in effect to “RNA interference” technology which is a gene suppressing innovation that has been studied for use as an insect-killing pesticide technology in crops. Although the mechanisms of mRNA vaccines and RNA interference technology are vastly different, they can achieve many of the same outcomes such as induced infertility or death in targeted organisms, which could include humans. Technically, this could also be exploited to target specific genetic subgroups of humans – the elderly.

 

Any COVID ‘vaccine(s)’ approved for emergency use should be voluntary, since the ‘vaccine(s)’ are considered investigational and are held to a much lower standard for both efficacy and safety. For example, compared to the non-emergency approval process to get full licensure, an emergency approval allows for a vaccine that “may” be effective, compared to the non-emergency approval process where a vaccine must demonstrate “substantial” effectiveness. Emergency Use Authorization (EUA) law is clear: States are barred from mandating a vaccine approved for emergency usage. (See Section VI. Preemption.) It also should be illegal for private businesses, airlines, or your employer to mandate a vaccination while it is approved under a EUA.

 

Lastly, the manufacturers have been exempted from any liability that they may inflict on the public. In February, Health and Human Services Secretary Alex Azar invoked the Public Readiness and Emergency Preparedness Act. The 2005 law empowers the HHS secretary to provide legal protection to companies making or distributing critical medical supplies, such as vaccines and treatments unless there’s “willful misconduct” by the company. The protection lasts until 2024. That means that for the next four years, these companies “cannot be sued for money damages in court” over injuries related to the administration or use of products to treat or protect against SARS-CoV. Thus, there is not a manufacturer nor government in the world that will be held financially accountable when people succumb to grave harm.

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COVID-19 mRNA Vaccines

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COVID-19 mRNA Vaccines

James Odell, OMD, ND, L.Ac.

Editorial – The material published in this editorial is intended to foster scholarly inquiry and a rich discussion of the controversial topic of bioethics and health policy. The views expressed in this article are solely the authors and do not represent the policy or position of the Bioregulatory Medicine Institute (BRMI), nor any of its Board Advisors or contributors. The views expressed are not intended to malign any religious or ethnic group, organization, company, individual, or any other. Every effort has been made to attribute the sources of this article to the rightful authors listed in references.

With the recent licensing and roll out of COVID-19 vaccines in the U.K., Canada, the U.S. (Pfizer/ BioNTech and Moderna), and Russia (Sputnik) there are several serious safety concerns that have not been addressed or even mentioned in the medical media. In short, it is beyond reckless and totally unnecessary to administer these experimental vaccines to millions of people when there is only limited short term safety data. Absolutely no long-term safety studies have been done to ensure that any of these vaccines do not cause cancer, seizures, heart disease, allergies, and autoimmune diseases, as seen with other vaccines and observed in earlier coronavirus vaccine animal studies. Because animal studies were bypassed for these vaccines due to ‘fast-tracking’, millions of humans are now the primary test animal. Additionally, these vaccines were developed using a completely new mRNA technology that has never been licensed for human use. In essence, we have absolutely no knowledge of what to expect from these new mRNA vaccines. Since viruses mutate frequently, the chance of any vaccine working for more than a year is unlikely. That is why the influenza (flu) vaccine changes every year. This editorial comprehensively discloses current COVID-19 vaccine development, administration, and safety concerns in detail.

 

Ribonucleic acid (RNA) is a nucleic acid present in all living cells. Its principal role is to act as a messenger carrying instructions from DNA for controlling the synthesis of proteins. Although in some viruses’ RNA rather than DNA carries the genetic information. In each cell of a living organism, DNA is the molecule that contains the genetic information of the organism. It is composed of a series of four building blocks, whose sequence gives the instructions to fabricate proteins. This process requires a transient intermediary called messenger RNA that carries the genetic information to the cell machinery responsible for protein synthesis. RNA is the only molecule known to recapitulate all biochemical functions of life: definition, control, and transmission of genetic information, creation of defined three-dimensional structures, enzymatic activities, and storage of energy.

 

RNA became the focus of intense research in molecular medicine at the beginning of the millennium. Messenger viral RNA (mRNA) is now developed as a vaccine and this technology poses many questions and serious health concerns that have been left unanswered by the vaccine manufacturers. Unlike previous vaccines an mRNA vaccine is a new type of vaccine that inserts fragments of viral mRNA into human cells, which are reprogrammed to produce pathogen antigens, which then if all goes well, stimulate an adaptive immune response against the targeted pathogen. That seems straightforward, but what else is in the vaccines, and is this new technology truly proven safe and effective?

 

History of Coronavirus Vaccine Animal Studies and

Antibody Dependent Enhancement (ADE)

 

Researchers have been trying to develop a coronavirus vaccine since the Severe Acute Respiratory Syndrome (SARS-1) outbreak in 2002. Thus, over a span of 18 years there have been numerous coronavirus vaccine animal studies conducted, which unfortunately demonstrated significant and serious side-effects. Either the animals were not completely protected, became severely ill with accelerated autoimmune conditions, or died.1, 2, 3, 4, 5, 6, 7

 

Animal side effects and deaths were primarily attributed to what is called Antibody-Dependent Enhancement (ADE). In the 1960s, immunologists discovered ADE and since then have extensively researched and identified its mechanism. Virus ADE is a biochemical mechanism in which virus-specific antibodies (usually from a vaccine) promote the entry and/or the replication of another virus into white cells such as monocytes/macrophages and granulocytic cells. This then modulates an overly strong immune response (abnormally enhances it) and induces chronic inflammation, lymphopenia, and/or a ‘cytokine storm’, one or more of which have been reported to cause severe illness and even death. Essentially, ADE is a disease dissemination cycle causing individuals with secondary infection to be more immunologically upregulated than during their first infection (or prior vaccination) by a different strain. ADE of disease is always a concern for the development of vaccines and antibody therapies because the mechanisms that underlie antibody protection against any virus has a theoretical potential to amplify the infection or trigger harmful immunopathology.8, 9, 10 ADE of the viral entry has been observed and its mechanism described for many viruses including coronaviruses.11, 12, 13 Basically, it was shown that antibodies target one serotype of viruses but only sub neutralize another, leading to ADE of the latter exposed viruses. Thus, ADA of viral entry has been a major concern and stumbling block for vaccine development and antibody-based drug therapy. For example, it has been shown that when patients are infected by one serotype of dengue virus (i.e., primary infection), they produce neutralizing antibodies targeting the same serotype of the virus. However, if they are later infected by another serotype of dengue virus (i.e., secondary infection), the preexisting antibodies cannot fully neutralize the virus. Instead, the antibodies first bind to the virus and then bind to the IgG Fc receptors on immune cells and mediate viral entry into these cells.14 A similar mechanism has been observed for HIV, Ebola, and influenza viruses. Thus, sub neutralizing antibodies (or non-neutralizing antibodies in some cases) are responsible for ADE of these viruses.15, 16, 17, 18, 19, 20

 

Generally, the conclusion of some of those studies was that great caution needs to be exercised when moving forward to human trials primarily because of the potential of accelerated autoimmunity reaction. Because ADE has been demonstrated in animals21, coronavirus vaccine research never progressed to human trials, at least not till the recent SARS coronavirus-2 fast-track campaign.

 

More technical Understanding of SARS-CoV-2 ADE Mechanisms

 

As a forementioned, a potential barrier to the development of safe and efficacious COVID-19 vaccines is the risk that insufficient titers of neutralizing antibodies might trigger ADE of disease. Previous research in SARS-CoV infection demonstrated ADE is mediated by the engagement of Fc receptors (FcRs) expressed on different immune cells, including monocytes, macrophages and B cells.22, 23, 24 A Fc receptor is a protein found on the surface of certain cells – including, among others, B lymphocytes, follicular dendritic cells, natural killer cells, macrophages, neutrophils, eosinophils, basophils, human platelets, and mast cells – that contribute to the protective functions of the immune system.

 

Akiko Iwasaki and colleagues describe this coronavirus ADE mechanism in more detail in their 2020 research published in Nature Reviews Immunology.25 They confirm that pre-existing SARS-CoV-specific antibodies may thus promote viral entry into FcR-expressing cells. This process is independent of ACE2 expression and endosomal pH and proteases, suggesting distinct cellular pathways of ACE2-mediated and FcR-mediated viral entry.

In short, previous experience with veterinary coronavirus vaccines and animal models of SARS-CoV and MERS-CoV infection has raised safety concerns about the potential for ADE and/or vaccine-associated enhanced respiratory disease. These events were associated either with macrophage-tropic coronaviruses susceptible to antibody-dependent enhancement of replication or with vaccine antigens that induced antibodies with poor neutralizing activity and Th2-biased responses.

 

After two decades of failed animal trials, the question is posed as to why fast-tracking coronavirus vaccine will now result in a different outcome? Given that many of these fast-track trials have bypassed animal studies, are only performed on healthy volunteers and children (not the elderly or those with pre-morbidities), and that trials are conducted without an inert double-blind placebo-controlled environment, and are not given sufficient time to observe effects on the human trials, there is a serious safety concern. Many, many virologists, and epidemiologists feel this fast-track policy is a recipe for mass disaster. Microbiologist Dr. Sucharit Bhakdi and Dr. Karina Reiss in their new book Corona, False Alarm? give clarity to many of the issues surrounding the pandemic, especially the current coronavirus vaccines.26

 

Traditional vs. mRNA Vaccines

 

Historically, the manufacturing process for creating vaccines involves many trade secrets and numerous other ingredients as adjuvants and preservatives.27, 28 ‘Traditional or classical vaccines’ may contain attenuated or inactivated viruses and bacteria or proteins, as well as adjuvants, such as aluminum, to stimulate an immune response that produces artificial immunity, as well as a host of other ingredients called “excipients”. For example, older viral vaccines for smallpox and measles vaccine contain live attenuated viruses; injectable influenza vaccines contain inactivated viruses; the recombinant hepatitis B virus vaccine is a protein subunit vaccine, while the newer human papillomavirus (HPV) virus vaccine contains virus-like particles.

 

To date, there are several different types of potential vaccines for COVID-19 in development, including:

  • Inactivated or weakened virus vaccines, which use a form of the virus that has been inactivated or weakened, but still generates an artificial immune response.

  • Protein-based vaccines, which use fragments of proteins or protein shells that mimic the COVID-19 virus to generate an artificial immune response.

  • Viral vector vaccines, which use a virus that has been genetically engineered to generate an artificial immune response.

  • RNA and DNA vaccines, that uses genetically engineered RNA or DNA to generate a protein that itself prompts an artificial immune response.

For the past two decades, researchers have been experimenting with new technology platforms, notably ones that introduce foreign DNA and RNA into cells of the body, to develop experimental vaccines for SARS, MERS, HIV, and other diseases but, historically none have been proven effective and safe for humans.

 

Thus, for a traditional vaccine, the antigen is introduced in the body to produce an immune response. However, in the case of DNA- or RNA-based vaccines, no antigen is introduced, only the RNA or DNA containing the genetic information to produce the antigen. That is, for this specific class of vaccines, the introduction of DNA and RNA provides the instructions to the body to produce the antigen itself.29

 

mRNA vaccines differ greatly in their design and biochemical mechanisms from traditional vaccines. Traditional vaccines stimulate an antibody response by injecting a human with antigens (proteins or peptides), or an attenuated virus, or a recombinant antigen-encoding viral vector. These ingredients are prepared and grown outside of the human body, which takes time, and even when they are injected into the bloodstream, they do not enter the human cell.30

 

In contrast, mRNA vaccines insert a synthetically created fragment or snip of the virus RNA sequence directly into the human cells (known as transfection). This snip of viral RNA material then activates an enzyme called reverse transcriptase which replicates that RNA snip repeatedly. This then reprograms the cells to produce their own viral antigens, which, if all goes as planned, stimulates an adaptive immune response, resulting in the production of new antibodies that bind to the antigen and activate T-cells.31, 32, 33

 

Simply speaking, the new mRNA vaccines inject (transfects) molecules of synthetic genetic material from non-human sources (viral sequences) into our cells. Once in the cells, the genetic material interacts with our transfer RNA (tRNA) to make a foreign protein that supposedly teaches the body to destroy the virus being coded for. These created proteins are not regulated by our own DNA and are thus completely foreign to our cells. What they are fully capable of doing is completely unknown.

 

Till now, messenger-RNA vaccines have never been licensed for public use. In the last two decades, there has been deep-pocket funding for the development of mRNA vaccines against infectious diseases, particularly with the currently declared pandemic and vaccine fast track campaign. Historically, their application has until recently been restricted by the instability and inefficient in vivo delivery of mRNA. New technological advancements in RNA biology, chemistry, stability, and delivery systems have now accelerated the development of fully synthetic mRNA vaccines. The consensus is that mRNA vaccines are faster and cheaper to produce than traditional vaccines and for vaccine manufacturers, more cost-effectiveness translates to greater profits. Certainly, there are unique and unknown risks to messenger RNA vaccines, including local and systemic (ADE) inflammatory responses that could lead to autoimmune conditions.

 

mRNA Vaccines Mechanisms

 

mRNA vaccines have strands of genetic material called mRNA inside a special coating. That coating protects the mRNA from enzymes in the body that would otherwise break it down. It also helps the mRNA enter the muscle cells near the vaccination site. mRNA vaccines use a different approach that takes advantage of the process that cells use to make proteins: cells use DNA as the template to make messenger RNA (mRNA) molecules, which are then translated to build proteins. An RNA vaccine consists of an mRNA strand that codes for a disease-specific antigen. Once the mRNA is in the cell, human biology takes over. Ribosomes read the code and build the protein, and the cells express the protein in the body. Thus, cells use the genetic information to produce the disease-specific antigen. This antigen is then displayed on the cell surface, where it is recognized by the immune system.34

 

mRNA vaccines have been studied before for influenza, Zika, rabies, and cytomegalovirus. The concept for the development of an mRNA vaccine is rather straightforward. Once the antigen of choice from the pathogen target is identified, the gene is sequenced, synthesized, and cloned into the DNA template plasmid. mRNA is then transcribed in vitro, and the vaccine is delivered to the subject. The mRNA vaccine utilizes the host cell machinery for in vivo translation of mRNA into the corresponding antigen, thereby mimicking a viral infection to elicit potent humoral and cellular immune responses. The final cellular location of the antigen is determined by the signal peptide and transmembrane domain. This can be intrinsic to the natural protein sequence or engineered to direct the protein to the desired cellular compartment.35, 36

 

Once the viral mRNA is injected into the body, it faces immune responses that are programmed to destroy it. Our cells have evolved elaborate defense mechanisms intended to destroy foreign, unprotected, or “naked” RNA. However, the susceptibility of mRNA to degradation can be reduced by modifying the RNA during synthesis. One modification is to add in ‘nucleoside analogs’ that resemble the normal nucleosides found within RNA (A, U, C and G,) but have minor structural changes that make the RNA more resistant to enzyme degradation by the body’s ribonucleases. (Nucleosides are the structural subunit of nucleic acids such as DNA and RNA.)

 

Additional structural modifications and the inclusion of regulatory sequences can also improve the stability of mRNA.37 For example,the vaccine viral mRNA is delivered in the form of a complex with lipid nanoparticles, to stabilize the mRNA, making it easier to penetrate the cell, and increases the amount of antigen produced per cell.38 Lipid nanoparticle formulations also elicit a stronger immune response compared to naked mRNA.39This is where it gets tricky and potentially dangerous because some of the lipid nanoparticles developed for these mRNA vaccines can be strongly immunologically reactive and elicit an unwanted autoimmune reaction.

 

PEGylated Lipid Nanoparticles

 

Thus, mRNA is threatened by rapid degradation by ubiquitous extracellular ribonucleases before being taken up by cells.40 The mRNA molecule is also vulnerable to destruction from temperature changes as well as our immune system. Thus, the efficacy of mRNA vaccines requires ‘complexing agents’ which protect RNA from degradation. Complexation may also enhance uptake by cells and/or improve delivery to the translation machinery in the cytoplasm. To this end, mRNA is often complexed with either lipids or polymers. These mRNA vaccines are coated with PEGylated lipid nanoparticles (polyethylene glycol). This coating hides the mRNA from our immune system which ordinarily would attack and destroy kill any foreign material injected into the body. PEGylated lipid nanoparticles have been used in several different drugs for years. Unfortunately, PEGylated lipid nanoparticles have been shown to imbalance certain immune responses and can induce allergies and even autoimmune diseases.41, 42, 43, 44, 45, 46

 

A 2016 study in Analytical Chemistry reported detectable and sometimes high levels of anti-PEG antibodies (including first line-of-defense IgM antibodies and later stage IgG antibodies) in approximately 72% of contemporary human samples and about 56% of historical specimens from the 1970s through the 1990s. Of the 72% with PEG IgG antibodies, 8% had anti-PEG IgG antibodies > 500ng/ml., which is considered extremely elevated.47 Extrapolated to the U.S. population of 330 million who may receive this vaccine, 16.6 million may have anti-PEG antibody levels associated with adverse effects.The researchers confessed that the results were entirely unexpected. The authors concluded that:

 

“…sensitive detection and precise quantitation of anti-PEG Ab levels in a clinical setting will be essential to ensuring the safe use of PEGylated drugs in all target patient populations going forward.”

 

Multiple previous studies regarding the prevalence of anti-PEG antibodies in the population have stated that pre-screening should be done prior to any administration of a PEG-containing medication. Screening is likely to be even more important in the case of a vaccine intended for parenteral administration to as many people as possible that contains a substance to which a majority of the population unknowingly has anti-PEG antibodies.

 

Production of mRNA vaccines

 

To further understand PEGylated lipid nanoparticles and their role in vaccine delivery, it is helpful to understand a little more about how an mRNA vaccine is manufactured. A major manufacturing advantage of mRNA vaccines is that RNA can be produced in the laboratory from a DNA template using readily available materials, again less expensively and faster than conventional vaccine production, which utilize a variety of cell types such as chicken eggs or other mammalian cells such a fetal material.48 This all comes down to economics. It is faster and cheaper to make.

 

Traditional vaccines normally contain a strong adjuvant (often aluminum) supplying an enhanced signal for the initiation of the adaptive immune response. However, it is thought that mRNA vaccines sort of have their own adjuvant effect by themselves, partly by virtue of being foreign nucleic acids. It has not been disclosed if any of these candidates (from any company) have an adjuvant added to them. (More information on adjuvants later in this article.)

 

Moreover, according to Arcturus, the company manufacturing the Pfizer/BioNTech lipid delivery system, this involves a multi-component delivery system called LUNAR® (Lipid-enabled and Unlocked Nucleomonomer Agent modified RNA). “This system has access to over 150 proprietary lipids that have been utilized for mRNA-based COVID-19 vaccines.”49 Basically, all we know is this involves proprietary PEGylated lipid nanoparticles.

 

Current mRNA Vaccines and Potential Side-Effects

 

According to the WHO and the Milken Institute, as of August 2020, there were 202 companies and universities worldwide working on a coronavirus vaccine. The vaccine types vary from traditionally established vaccines (e.g., inactivated, and live attenuated) to vaccines that have only recently gained clinical approval (e.g., subunit) to those that have never been licensed for human use, till now (e.g., mRNA, DNA, non replicating viral vector, replicating viral vector). A striking feature of the vaccine development landscape for SARS coronavirus-2 is the range of technology platforms being evaluated, including nucleic acid (DNA and RNA), virus-like particle, peptide, viral vector (replicating and non-replicating), recombinant protein, live attenuated virus and inactivated virus approaches. Since November 9th, Moderna, the pharma giant Pfizer and its German collaborator BioNTech, and a Russian Institute have all offered “preliminary evidence that their mRNA spike-based vaccines can achieve greater than 90% protective efficacy.”

 

The vaccine pharmaceutical industry contends that an mRNA-based vaccine is “safer for the patient” than classical vaccines. But is that verified true? The manufacturer’s rationale is that mRNA is a non-infectious, non-integrating platform, there is no potential risk of infection or insertional mutagenesis. Since mRNA vaccines have never been licensed and have not undergone long-term testing, we cannot know this for certain. Additionally, there is also concern that these vaccine mRNA may have long-standing dire consequences on the body’s immunity, fertility, and DNA integrity.

 

According to researchers at the University of Pennsylvania and Duke University50, mRNA vaccines have these potential safety issues:

  • Local and systemic inflammation.

  • The biodistribution and persistence of expressed immunogen.

  • Stimulation of auto-reactive antibodies.

  • Induction of a potent type 1 interferon response, which has been associated with inflammation and potential autoimmunity. Thus, identification of individuals at an increased risk of autoimmune reactions before mRNA vaccination should be undertaken.

  • Presence of extracellular RNA, which may contribute to edema and pathogenic thrombus formation (blood clots). Extracellular naked RNA has been shown to increase the permeability of tightly packed endothelial cells and may thus contribute to edema.51 Another study showed that extracellular RNA promoted blood coagulation and pathological thrombus formation.52

  • Potential toxic effects of any non-native nucleotides and delivery system components (particularly those that have not been disclosed by manufacturers).

There is also concern about potential mRNA modifications to the genetics of the body. Once injected into the body mRNA vaccines take the RNA from the virus into the cell where it may create unwanted detrimental genetic modifications. Over the last five years, there has been an enormous increase in the amount of research into RNA modifications; this field is called epitranscriptomics. The role of DNA modification in gene regulation is well established, but much less is known about how mRNA modification influences the way genes are expressed. In fact, numerous studies have shown viral mRNAs to be implicated as a driver in some forms of cancer and autoimmune diseases.53, 54, 55, 56

 

Thus, long-term safety evaluation is essential and should precede the licensing of different mRNA modalities and delivery systems. Normally, vaccine development is a lengthy and complicated process, often lasting 10-15 years and involving a combination of public and private involvement. Unfortunately, the rapid worldwide competition between pharmaceutical companies to develop a COVID-19 vaccine has bypassed multiple safety controls, rendering the result both dubious and potentially dangerous for the public. Financial interests have taken precedence over the health and safety of the public. Hasty development of vaccines is always risky, and only thorough research employing all the safety precautions will lead to a safe and effective vaccine.

 

The current licensed COVID-19 vaccine is not being offered to pregnant women. This is because researchers do not know enough about how COVID-19 vaccination can affect children, pregnant women, or their babies. There is also no data on the safety of COVID-19 vaccines for breastfeeding women. The Pfizer/BioNTech vaccine is not available to children under age 16.

 

Moderna and Pfizer Vaccine Ingredients and Dosage

 

As unbelievable as it sounds, neither Pfizer/BioNTech nor Moderna have ‘completely’ disclosed everything in their vaccines. Apparently, to be licensed by the FDA they do not have to disclose to the public the entire composition of their vaccine. This is what we do know. Both Moderna and Pfizer/ BioNTech vaccines are mRNA vaccines and they are different in composition, delivery, and storage. They have different nucleoside analogs, and each has unique ways to essentially attenuate the capacity of messenger RNA to induce innate immunity. They each have a different complex liquid delivery system, and this is one reason why one is much more amenable to shipping and storing at minus 20º whereas the other requires shipping and storing at minus 70º.

 

Moderna’s vaccine uses 100 micrograms of RNA per dose, while Pfizer-BioNTech’s uses only 30 micrograms. In both the Moderna and Pfizer-BioNTech vaccines the mRNA is encapsulated in lipid nanoparticles (LPN). These microscopic droplets of oily liquid — about 0.1 micron in diameter — enclose and protect the mRNA as they are manufactured, transported, and injected into people.As previously mentioned, the composition of the lipid nanoparticles is different in the two vaccines.

 

Pfizer/BioNTech obtains their nanoparticles from Acuitas, a specialist Canadian company, while Moderna has developed its own lipid technology.

 

Listed ingredients of the Pfizer/BioNTech COVID-19 vaccine include:

  • 30 mcg of a nucleoside-modified messenger RNA (modRNA) encoding the viral spike (S) glycoprotein of SARS-CoV-2

  • lipids (0.43 mg (4-hydroxybutyl)azanediyl)bis (hexane-6,1-diyl) bis (2-hexyldecanoic)

  • .05 mg 2[polyethylene glycol)-2000]-N,N-ditetradecylacetamide

  • .09 mg 1,2-distearoyl-sn-glycero-3-phosphocholine, and 0.2 mg cholesterol)

  • .01 potassium chloride

  • .01 mg monobasic potassium phosphate

  • .36 mg sodium chloride

  • .07 mg dibasic sodium phosphate dehydrate

  • 6 mg sucrose

  • the diluent (.09 percent Sodium Chloride Injection) contributes an additional 2.16 mg sodium chloride per dose

So far as revealed in the public domain Moderna’s vaccine (mRNA-1273) specifically contains lipid nanoparticle dispersion containing an mRNA that encodes for the prefusion stabilized spike protein 2019-nCoV. mRNA-1273 consists of an mRNA drug substance that is manufactured into LNPs composed of the proprietary ionizable lipid, SM-102, and 3 commercially available lipids, cholesterol, DSPC (1,2-distearoyl-sn-glycero-3-phosphocholine is a phosphatidylcholine with alkyl chain comprising 18 carbons), and PEG2000 DMG (1,2-dimyristoyl-rac-glycero-3-methoxypolyethylene glycol-2000). Adjuvants and other biotechnology if added have not been publicly disclosed. This vaccine requires two injections given 28 days apart.

 

For more information on clinical trials of all corona vaccines in development visit the Regulatory Affairs Professionals Society (RAPS).58

 

mRNA Vaccine Viral Shedding and Viral Vaccine Interference

 

Vaccine shedding is a term used for the release of virus following administration of a live-virus vaccine. This has been particularly observed in the administration of live polio vaccines. Neither of the vaccines in distribution or in development use the live virus that causes COVID-19. Thus, current consensus among vaccine developers is that vaccine viral shedding is not expected with mRNA vaccines. However, bear in mind mRNA viral vaccines is a new platform, and this issue is in unknown territory.

Viral interference describes the situation whereby infection or vaccine inoculation with one virus limits infection and replication of a second virus. For example, epidemiological studies show that following infection with influenza virus, there is a short period during which a host experiences a lower susceptibility to infection with other similar viruses. This viral interference appears to be independent of any antigenic similarities between the viruses. It certainly is possible that the mRNA vaccine may elicit vaccine viral interference and causes people to be more susceptible to other viruses, such as influenza.

 

SARS-CoV-2 Spike Protein Shares Sequence with a Human Protein Syncytin-1

 

Syncytin-1 is a protein that functions for placental development and therefore is essential for fertility. Fifteen years ago, it was proposed that a synthetic Syncytin-1 vaccine could be developed as a contraceptive that would work to produce antibodies against human Syncytin-1.59

 

It is proposed by some doctors that the Pfizer COVID vaccine may elicit an antibody response against Syncythin-1 and cause infertility because of a similar or shared amino acid sequence in the spike protein of SARS-CoV-2 and the Syncythin-1 placental protein. Pharmaceutically sponsored fact-checkers, and Pfizer employed virologists were quick to discount such an idea as “unlikely”. They claim that this amino acid sequence is too short for the immune system to meaningfully confuse it with this important placental protein. However unlikely, if this later proves true for some susceptible women, then that could cause infertility of an unspecified duration. Consider that scientific consensus is not 100 percent sure these similar amino acid sequences will cause Syncythin-1 antibodies to be produced. The role of retroviral proteins, especially syncytins, in the trophoblastic fusion process and placental morphogenesis were only identified and hypothesized about 20years ago.60 There is still much to learn, and much we still do not know about similar amino acid sequences and their effect on human physiology. Thus, this issue warrants further research, and until then we should proceed with caution and assume that it may possibly cause public harm.

 

Adjuvants

 

Adjuvants are immunostimulatory molecules administered together with the vaccine to help boost immune responses mainly by activating additional molecular receptors that predominantly recognize pathogens or danger signals. These pathways function primarily within the innate immune system, and each adjuvant generally has a different range of stimulation of these pathogen or danger receptors. While the vaccine goal is to stimulate recognition and response by lymphocytes, not innate cells, the activation of the innate immune cells is required to activate the lymphocytes to obtain both B and T-cell responses. Many adjuvants have previously failed in the clinic due to toxicity issues. These chemicals can have a wide range of compositions, including lipids, proteins, nucleic acids, and even inorganic material, such as aluminum salts. What they all have in common is that they hyper-stimulate receptors in immune cells and most do this through their cellular toxicity.

 

Pfizer/BioNTech and Moderna do not explicitly state the use of an adjuvant within their vaccines, but RNA already contains immunostimulatory properties and signals through pathogen recognition receptors. It remains to be seen whether the immunostimulation from RNA is strong enough to confer full protection against SARS-CoV-2. There is also a possibility that the lipid nanoparticle carriers they utilize confer adjuvant properties themselves. Or for that matter, elicit an abnormal autoimmune reaction.

 

It is unknown if any future licensed COVID-19 mRNA vaccines will contain aluminum or something else as an adjuvant, as commonly used in other viral vaccines. Despite almost 90 years of widespread use of aluminum adjuvants, medical science’s understanding of their mechanisms of action is still remarkably poor. There is also a concerning scarcity of data on toxicology and pharmacokinetics of these compounds. Despite this, the false notion that aluminium in vaccines is safe appears to be widely accepted. Experimental research clearly shows that aluminum adjuvants have a potential to induce serious immunological disorders in humans. Aluminum in adjuvant form carries a risk for autoimmunity, long-term brain inflammation, and associated neurological complications and may thus have profound and widespread adverse health consequences.61

 

Stability and Storage

 

These mRNA vaccines require cold storage to maintain the nanoparticles and to stop the mRNA from degrading. The Pfizer/BioNTech vaccine (BNT162b2) is to be stored at a temperature of -94 degrees Fahrenheit (-70 Celsius) and will last for only 24 hours at refrigerated temps between 35.6° and 46.4° Fahrenheit. It will be shipped on dry-ice (–80°C). The Moderna vaccine (mRNA-1273), must be stored at -4° Fahrenheit (-20 C) and shipped at this –20°C temperature using gel packs.62

Thus, preserving this constant cold temperature is a major hurdle for the implementation of its vaccine marketing campaign, particularly the Pfizer/BioNTech vaccine. Given those constraints, analysts argued that Pfizer’s vaccine could only be used at certain hospitals and clinics with the proper equipment, and would require intensive one-day vaccination events at such sites that would cover a fraction of the healthy population. Not only do most vaccination sites lack the freezing requirements needed, but also shipping companies are currently unable to ship mass quantities of ultracold vaccines. Pfizer has partnered with UPS to develop ultracold shipping containers that can hold the vaccine at the required temperature. The packages utilize cold-resistant glass vials to hold the vaccine and dry ice to maintain cold temperatures. Although this may seem like a sustainable solution, the US presently has a shortage of both dry-ice (due to a shortage in CO2) and cold-resistant glass.63 Mass shipping using these containers would cause a huge strain on the supply chain and likely would require investments of billions of dollars.64

 

Deployment

 

Pfizer-BioNTech has said that they will be able to supply 50 million doses by the end of this year and around 1.3 billion by the end of 2021. If licensed, Moderna has said it intends to provide the US government with 20 million doses by the end of this year, and manufacture between 500 million and one billion doses globally throughout 2021. There are currently more than 320 Covid-19 vaccine candidates in development. Several of them, including the Oxford/AstraZeneca vaccine, are emerging from phase III trials, so we can expect more announcements like this soon.

 

No Liability Due to the PREP Act

With the upcoming SARS coronavirus-2 vaccines the vaccine industry is completely liability-free (not legally liable). The governmental nonliability guarantee for vaccine the manufacturers of current mRNA vaccines being implemented, or any future vaccines chosen to fast-track, comes out of the Emergency Use Authorization Authority (EUA Authority) that originated out of Project Bioshield. The Project Bioshield Act was an act passed by the United States Congress in 2004 calling for $5 billion for purchasing vaccines that would be used in the event of a bioterrorist attack. This was further defined by the PREP Act of 2005, the Public Readiness and Emergency Preparedness Act, which further granted the non-liability of vaccine manufacturers previously outlined in the 1986 Injury Compensation Program for childhood vaccines. On March 10, 2020, the Secretary invoked the PREP Act and determined that COVID-19 constitutes a public health emergency. Therefore, the HHS declaration authorizes PREP Act immunity for the “manufacture, testing, development, distribution, administration, and use” of covered countermeasures. An amendment to the PREP Act, which was updated in April65, stipulates that companies “cannot be sued for money damages in court” over injuries caused by medical countermeasures for Covid-19. Such countermeasures include vaccines, therapeutics, and respiratory devices. The only exception to this immunity is if death or serious physical injury is caused by “willful misconduct.” And even then, the people who are harmed will have to meet heightened standards for “willful misconduct” that are favorable to defendants.66

 

While people harmed by vaccines for other diseases are able to file claims with the National Vaccine Injury Compensation Program, which was established in 1986, the PREP Act now bars anyone who feels they were harmed by a vaccine for the coronavirus from using that program.

 

The PREP Act has allowed vaccine manufacturers unlimited freedom to create, develop, and market vaccines without any liability whatsoever. Manufacturers have been allowed to bypass animal studies and go directly to human trials. They also can add anything they deem important to the vaccine formula they choose – whether it be a known toxin or carcinogen. All liability is protected by the PREP Act, which means if anyone has an adverse event, or death caused by this vaccine there really is no recourse. This was put into the Federal Register in March of 2020 and does not expire till the end of 2024. So, anything that is developed over the next four years that has to do with a biological agent, such as a vaccine or drug or biotechnology, no matter how nefarious, is protected from liability under the umbrella of COVID-19.

 

Conclusion

 

The world, pushed by the pharmaceutical owned media, is clamoring for a safe, effective COVID-19 vaccine. Many laboratories and companies have scrambled to rapidly develop these vaccines, resulting in more than 200 vaccine candidates. Without proceeding with animal studies, many of these companies have entered human phase I, II and III clinical trials within a short period of 6 months. Pfizer/BioNTech and Moderna ‘vaccines’ moved quickly through human testing, without giving time for proper evaluation of earlier phases. They have not been approved or licensed by the U.S. Food and Drug Administration (FDA) ,but instead have received authorization for emergency use by the FDA under an Emergency Use Authorization (EUA) for use in individuals 16 years of age and older and are being injected into millions of people. Dangers arise due to the fast-tracking process that limits the time available for large-scale studies. Owing to the accelerated development process, the interim data from ongoing clinical and preclinical vaccine studies are being published almost in real time. As a result, crucial information about the longevity and quality of vaccine-induced protective immunity is unavailable. Fast-tracking leads companies to push out the vaccine before the results of a large-scale study show the safety and efficacy of the vaccine. Scientists and epidemiologists emphatically confirm that the primary focus of vaccine research is to prove it safe for a large population or group before being unleashed. The trials should offer clear datasets before releasing the vaccine to the public (millions if not billions of people). Without clear time-tested datasets of a large population, it is not possible to ensure that the vaccine is safe for most people in the country.

Pfizer released a Peer Review study entitled Safety and Efficacy of the BNT162b2mRNA Covid-19 Vaccine, recently published in the New England Journal of Medicine.67 In the Pfizer/BioNTech COVID-19 vaccine trials conducted in the United States, there were more allergic reactions reported in the vaccine group than in the placebo control group.68 While allergic reactions occurred in less than one percent of those receiving the COVID vaccine, it is important to note that individuals with a “history of severe adverse reaction associated with a vaccine and/or severe allergic reaction (e.g., anaphylaxis) to any component of the study intervention(s)” were excluded from Pfizer’s clinical trials.69, 70

 

Further testing and adequate time-testing may also identify specific health conditions, allergies, or related concerns of individuals that may not be qualified to take the vaccine. By fast-tracking the vaccine, the possibility of harm due to allergic reactions, autoimmune reactions, complications with an existing health condition, interactions with certain medications or other related concerns may increase when compared to a longer time frame for trials. In short, tests must prove that the vaccine is safe, which in vaccine time usually requires years rather than months.

 

Numbers reveal the death rate from COVID resumed to the normal flu death rate in early September 2020. Many scientists now view that the coronavirus pandemic is over. Therefore, a vaccine is no longer needed; it is totally unnecessary and comes with a potential danger. Perhaps the saddest part of this worldwide rush to the vaccine is seeing how little faith people have in their own immune systems. Somehow the powers that should not be have managed to convince the majority of the people that the immune system is just a conspiracy theory, and rather than strengthening our own innate ability to heal and regenerate our bodies, we should give our faith into the hands of pharmaceutical corporations, who profit from sickness.

 

When we pause for just one moment to marvel the ability of your own skin to heal a wound or a bone to mend itself, we will realize that our bodies have their own bioregulatory intelligence. This organic living intelligence is far beyond the capacities of any nanotechnology or lab-created synthetic concoctions which merely try to mimic nature and its grand design. Our immune system and a healthy biological terrain are our best defense for pathogens and there are several proven ways to keep it active. The mineral zinc is important for numerous immunological enzymes and may be taken daily. Vitamin D3 has been shown to be low or deficient in individuals that develop a serious coronavirus infection. Thus, taking vitamin D3 is preventive and may be taken daily to keep body levels therapeutic. Also, vitamin C has been extensively proven effective for infection protection. Getting fresh air and sunlight, staying active and well hydrated, and enjoying joyous social activities are all helpful in staying well.

 

Lastly, mRNA vaccines have never been licensed before, and now they are being administered to millions of people with no manufacturer liability. The public has become the testing ground for this new technology. If these coronavirus mRNA vaccines later prove to be harmful to fragile genetic cellular structures, then that cannot be undone. Essentially, we need a much better understanding of their potential side effects, and more evidence of their long-term efficacy. Vaccine development takes time as the vaccines must not only be proven protective but also safe. Unlike other drugs that are delivered into sick patients, vaccines are administered into healthy patients and thus require very high safety margins. There is still a lot of research that should have been done around safety before mRNA vaccines become used on the public. Unfortunately, that is not what is happening now, and consequently this has a potential to turn into a disaster on a massive scale.

 

Note:

Vaccine providers are supposed to report adverse events that occur after vaccinations to VAERS but vaccinated persons who experienced the reaction or a family member also can file a report if a health care provider does not do it. According to one government funded study in 2011, fewer than one percent of all vaccine reactions are reported to VAERS. Report vaccine side effects to the FDA/CDC Vaccine Adverse Event Reporting System (VAERS). The VAERS toll-free number is 1-800-822-7967 or report online to https://vaers.hhs.gov/reportevent.html and include ‘Pfizer/BioNTech COVID-19 Vaccine EUA’ in the first line of box #18 of the report form.

 

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Recent Posts

Okoubaka aubrevillei: A Remedy for Modern Day Intoxications

Okoubaka aubrevillei: A Remedy for Modern Day Intoxications

October 22, 2020

Okoubaka aubrevillei: A Remedy for Modern Day Intoxications

James Odell, OMD, ND, L.Ac.

Okoubaka aubrevillei is a deciduous, monoecious tropophyte tree of the equatorial forest in West Africa, particularly in Ghana, Nigeria and on the Ivory Coast. It can grow to 40 meters in height and 3 meters in diameter. It belongs to the family of the Santalaceae, or the sandalwood family. In 1944, the tree was mistakenly categorized as being a member of the Octonemataceae family and it was not until 1957 that the tree was correctly categorized as a member of the Santalaceae family.  However, the earlier taxonomy mistake crops up in literature again and again, even in more recent publications.1

 

The tree has a magnificent crown with drooping branches, pendulums, with oval and serrated leaves of about 15 cm. long and 10 cm. wide. Tiny, gray flowers appear on old branches, their fruits turn a strong yellow when ripe. 

It is a semi-parasitic tree in which its roots attach to those of neighboring plants. This allows it to destroy surrounding plants likely to compete for water, light, and food. This explains why other plants around it do not thrive, an observation that has traditionally contributed to the belief that the tree has magical powers. The name Oku Baka is from the Anyin language, a Niger-Congo language spoken mainly in Côte d’Ivoire and Ghana. It translates as ‘tree of death’ due to its effect on surrounding vegetation.

 

Based on the records available for this genus, the population of Okoubaka aubrevillei in its range is probably less than 250 mature trees. The populations of the tree appear to have declined sharply (over 25%) in the last 60 years, in many locations – Cameroon, Ghana, Sierra Leone, and Côte d’Ivoire.2, 3 Though the distribution range is more than 100 km2, it has been shown to be rare in all its reported locations. This scarcity is due to massive deforestation in western Africa, high demand for its bark and seeds for medicine, as well as its highly-priced wood. Thus, it is currently ranked as endangered and is subject to special monitoring. Despite the fact that the tree is reported in protected areas in many parts of its ranges, strict protection and management of protected areas have been characterized by widespread encroachment, poor staffing, inadequate funding, presence of enclave villages, land conversion to farming, and several other illegal activities in Nigeria4, 5, and other African countries.6, 7, 8

 

Folk Lore and Traditional Usage

 

Okoubaka has long been viewed as a mysterious medicinal tree, used both for its wood and therapeutic properties by shamans in West Africa. Traditional African medicine and shamanism were the dominant medical system for centuries successfully treating millions of people in Africa prior to the arrival of the Europeans. Formerly clouded in the secrecy of the magical realm of the African shamans and traditional healers, Okoubaka was used for stomach and intestinal conditions, food poisoning, various intoxications, infections, and even diseases of the skin.

 

The bark, leaves, and seeds of the plant have traditionally been used as a talisman to ward off evil spirits. The tree is considered invaluable for this reason and has been associated with the most stringent of taboos. Its usage was strictly reserved for local shamans. In order to prevent themselves from being poisoned the bark of the tree was chewed by African chiefs to protect themselves before meetings and visits to foreign tribe members. To resolve tribal feuds, adding poisons to food was commonly used. Many tasters’ of a tribal chief possibly owe his life to this bark. Current day African herbalists still prepare a powder from the tree’s bark which is used against all kinds of poisoning.

 

There have emerged numerous records of Okoubaka being used for a wide variety of afflictions and conditions. The bark and seed have been used for the treatment of mental conditions (insanity)9 and for treatment of convulsions, as an aphrodisiac, for rituals and prevention of miscarriage.10 The bark and leaves have also been reported as a treatment for reducing swollen testicles (orchitis) among Edo people of Nigeria.11

 

In Akoase, Southern Ghana, the seeds were used in postnatal care, and its branches were tied on a broken limb, along with other plants, for the healing of the limbs.12 The bark is also reported to be used as an antidote for venomous stings and bites etc., and in the treatment of dropsy, swellings, gout, heart, leprosy, and venereal diseases.13

 

Current Research

 

Much of its traditional use by the African shaman and herbalist define its use in the western world today. Okoubaka was first mentioned in O.A Julian’s Materia Medica in 1981.14 Since then studies have been few, but demonstrate its ability to stimulate the body’s defense mechanisms against poisonings. Effectiveness has been seen with food-poisoning, pesticide poisoning, and many self-poisoning (auto-toxic) diseases.15, 16, 17, 18, 19, 20

 

Journal of Biology and Life Science

ISSN 2157-6076

2015, Vol. 6, No. 1

Map of Distribution of Okoubaka aubrevillei in West and Central Africa

 

Chemical Analysis

 

The bark and stems contain various catechins with antioxidant properties: gallocathechins, epicatechin gallates and epigallocatechin gallates. It also contains gallic acid, b-sitosterol, and stigmasterol. These polyphenols have detoxifying, antibacterial and anti-inflammatory effects on the liver and digestive system. The presence of phenolic compounds gives the bark antimicrobial and immunostimulant properties.20

In all its native range, the tree is used for various medicinal purposes. The main parts used are the bark and the seeds. The bark is used for treatment of insanity (Osemeobo, 2007). van Andel

Availability and Preparations

 

Okoubaka is available as powdered bark and as a homeopathic tincture. Several companies now manufacture okoubaka in a homeopathic form. Dried bark from the branches of the Okoubaka tree is pulverized, macerated in alcohol, and then potentized to the desired dilution. Dosage is to be individualized. Some examples of commercial homeopathic okoubaka are depicted below.

Indications:

As a homeopathic remedy the main therapeutic indications given by Magdalena Kunst22 and others 23, 24, 25, 26, 27, 28 are the following:

  • Food poisoning

  • Alimentary infections or infestations – parasitism, bacterial or yeast dysbiosis

  • Residual toxic conditions after intestinal infections

  • Environmental intoxication – xenobiotics

  • Side effect of cytotoxic chemotherapy

  • Nicotine toxicity

  • During and after childhood diseases – mumps, measles, rubella

  • Prophylactic use when traveling and consuming foreign food and water

Okoubaka holds promise as an herbal medicine for numerous modern-day intoxications. Unfortunately, there is concern over its endangerment. Medicinal plants are an important source of healthcare and livelihood for a large proportion of the human population in Africa. However, many medicinal plants such as Okoubaka are endangered because of unsustainable harvesting, and loss of habitats. Accompanying the loss of medicinal species is the loss of associated indigenous knowledge. Poverty, lack of adequate policies and lack of effort to enforce current existing policies and laws, are the major contributing factors for this endangerment.

 

References:

1. Lebacq, Lucien, Roger Dechamps, André Georges, Jean Hermans, and Justin Katondi. Essias d’identification anatomique des bois de l’Afrique centrale. 1964.

 

2. Bagot, Jean-Lionel. “Indications of Okoubaka aubrevillei in oncological supportive care.” Allgemeine Homöopathische Zeitung 265, no. 04 (2020): 21-24.

 

3. Ladipo DO, Adebisi AA, Bosch CH. Okoubaka aubrevillei Pellegr. & Normand. In: Schmelzer GH, Gurib-Fakim, editors. A Medicinal plants. Prota; 2008. p. 11.

 

4. Meduna, A. J., Ogunjinmi, A. A., & Onadeko, S. A. (2009). Biodiversity Conservation Problems and their Implications on Ecotourism in Kainji Lake National Park, Nigeria. J. Sust. Dev. Afr. 10(4), 59-73.

 

5. Oseni, J. O. (2007). Ensuring Peaceful Coexistence between Man and Animal in Protected Areas in Nigeria. Available at: http://peaceparks2007.whsites.net/papers/oseni_peaceful

 

6. Struhsaker, T. T., Struhsaker, P. J., & Siex, S. K. (2005). Conserving Africa’s rain forests: problems in protected areas and possible solutions. Biol. Cons. 123, 45-54. http://dx.doi.org/10.1016/j.biocon.2004.10.00.

 

7. Jachmann, H. (2008). Monitoring law-enforcement performance in nine protected areas in Ghana. Biol. Cons. 141, 89-99. http://dx.doi.org/10.1016/j.biocon.2007.09.012

 

8. Weladji, R. B., & M. N. Tchamba (2003). Conflict between people and protected areas within the Bénoué Wildlife Conservation Area, North Cameroon. Oryx, 37(1), 72-79. http://dx.doi.org/10.1017/S0030605303000140

 

9. Osemeobo, G. J. (2007). Who decides on access to genetic resources? Towards implementation of the convention on biological diversity in Nigeria. Small-scale For. 6. 93-109. http://dx.doi.org/10.1007/s11842-007-9000-8

 

10. van Andel, T., Myren, B., & Onselen, S. V. (2012). Ghana’s herbal market. J. Ethnopharm. 140. 368-378. http://dx.doi.org/10.1016/j.jep.2012.01.028

 

11. Idu, M., & Onyibe, H. I. (2007). Medicinal plants of Edo State, Nigeria. Res. J. Med. Plants, 1(2), 32-41.

 

12. Myren, B. (2011). Magic plants in the south of Ghana. Report of Research internship. Biology Leiden University, Belgium. 52 pp.

 

13. Burkill, H. M. (1985). The Useful Plants of West Tropical Africa, Vol. 1, Families A-D, Royal Botanical Gardens, Kew. 960 pp.

 

14. Julian OA. Dictionnaire de Matière Médicale Homéopathique :les 130 nouveaux homéothérapiques. Ed. Masson; 1981. p.278–9.

 

15. Journal of Biology and Life Science ISSN 2157-6076 2015, Vol. 6, No. 1

 

16. Normand, D. “Note sur l’anatomie du bois du genre nouveau Okoubaka.” Bulletin de la Société Botanique de France 91, no. 1-3 (1944): 20-25.

 

17. Normand, Didier. Atlas des bois de la Côte d’Ivoire. CTFT, 1950.

 

18. Normand, Didier, Pierre Détienne, Paulette Jacquet, Alain Mariaux, and Jacqueline Paquis. “Manuel d’identification des bois commerciaux. Tome 1: Généralités. Tome 2: Afrique guinéo-congolaise. Tome 3: Guyane française.” (1972).

 

19. Normand, Didier, and Jacqueline Paquis. Manuel d’identification des bois commerciaux. Tome 2: Afrique guinéo-congolaise. GERDAT-CTFT, 1976.

 

20. Peter, Achukwu U., Ufelle A. Silas, Onyekwelu C. Kenechukwu, Amadi N. Millicent, Achukwu O. Ngozika, and Amadi N. Francis. “EFFECTS OF STEM-BARK EXTRACT OF OKOUBAKA AUBREVILLIE ON SOME VISCERAL ORGANS OF WISTAR RATS.” African Journal of Traditional, Complementary and Alternative Medicines 15, no. 3 (2018): 57-63.

 

21. Wagner, H., B. Kreutzkamp, and K. Jurcic. “Inhaltsstoffe und pharmakologie der Okoubaka aubrevillei-Rinde.” Planta medica 51, no. 05 (1985): 404-407.

 

22. Kunst,. “Okoubaka, ein neues homöopathische Arzneimittel.” Allgemeine Homöopathische Zeitung 217, no. 03 (1972): 116-121.

 

23. Bagot, Jean-Lionel. “Okoubaka aubrevillei. A new homeopathic medicine for the side effects of chemotherapy.” La Revue d’Homéopathie 6, no. 2 (2015): e1-e6.

 

24. Bagot, Jean-Lionel. “Indications of Okoubaka aubrevillei in oncological supportive care.” Allgemeine Homöopathische Zeitung 265, no. 04 (2020): 21-24.

 

25. Bagot, Jean-Lionel. “Okoubaka aubrevillei: un nouveau médicament pour les soins de support en cancérologie.” La Revue d’Homéopathie 6, no. 2 (2015): 46-51.

 

26. Schlüren, E., 1991. Okoubaka aubrevillei-ein klinischer Erfahrungsbericht. Allgemeine Homöopathische Zeitung236(06), pp.225-231.

 

27. Buchheim-Schmidt, Susann, Uwe Peters, Cindy Duysburgh, Pieter Van den Abbeele, Massimo Marzorati, Thomas Keller, Petra Klement, and Stephan Baumgartner. “In-vitro Evaluation of the Anti-pathogenic Activity of Okoubaka aubrevillei Mother Tincture/3x in the Human Gastrointestinal Tract Using the SHIME Technology Platform.” Homeopathy 109, no. 01 (2020): A003.

 

28. Riley, David S. “Okoubaka aubrevillei.” In Materia Medica of New and Old Homeopathic Medicines, pp. 189-190. Springer, Berlin, Heidelberg, 2018.

The information in this monograph is intended for informational purposes only and is meant to help users better understand health concerns. Information is based on review of scientific research data, historical practice patterns, and clinical experience. This information should not be interpreted as specific medical advice. Users should consult with a qualified healthcare provider for specific questions regarding therapies, diagnosis and/or health conditions, prior to making therapeutic decisions.

Recent Posts

Aluminum Adjuvants in Vaccines

Aluminum Adjuvants in Vaccines

October 21, 2020

Aluminum Adjuvants in Vaccines

by James Odell, ND, OMD, L.Ac.

Aluminum is used as a vaccine adjuvant—a substance that when mixed with an antigen from a virus or bacteria, elicits a greater inflammatory immune response and theoretically a higher response of protective antibodies. Aluminum-containing adjuvants are often simply referred to as “alum.” This term should be avoided for two reasons. First, alum is the name of a specific chemical compound, hydrated potassium aluminum sulfate, KAl(SO4)2·12 H2O. Precipitation of a solution of alum and antigen was originally used for the preparation of aluminum-adjuvanted vaccines. The chemical composition of the aluminum precipitate depends on the type of ions present in the antigen solution. The precipitation method is difficult to reproduce in a consistent manner and has largely been replaced by adsorption of antigens to aluminum-containing gels. The second reason to avoid the term alum is that it fails to specify which type of aluminum-containing adjuvant was used for the vaccine preparation. The two main types of aluminum adjuvants that are commercially available are aluminum hydroxide adjuvant (AH) and aluminum phosphate adjuvant (AP). The physical and chemical composition of AH and AP are quite different and this has important implications for the formulation with antigens.

 

Thus, there are two aluminium based adjuvants (ABAs) commonly used in vaccines. Alhydrogel® is a semi-crystalline form of aluminium oxyhydroxide and AdjuPhos® is an amorphous salt of aluminium hydroxyphosphate. A sulphate salt of the latter (AAHS) is also listed as being one component of an adjuvant system used in HPV vaccinations. Alhydrogel® and AdjuPhos® are commonly referred to as ‘clinically approved ABAs’, however, this is not the case. There are no ABAs which have been approved for intramuscular or subcutaneous injection into humans. Aluminium salts are the most common type of vaccine adjuvant in use, despite abundant science establishing aluminium as a neurotoxin. Generally, live vaccines will not contain aluminum. Only vaccines made with killed/inactivated viruses and so-called “toxoid” vaccines may contain it, and this goes for both childhood and adult vaccines. In 2002, only two childhood vaccines contained aluminum adjuvants, but the aluminium picture had changed dramatically by 2016, when children received five aluminium-containing vaccines from birth to age three and at least two more in the teenage years. Thus, in the United States, Canada, Europe, Australia, and many other parts of the world, infants and young children receive high quantities of aluminium from multiple inoculations.

 

Adjuvants are classed as a vaccine excipient. The following link summarizes most other vaccine excipients: https://www.cdc.gov/vaccines/pubs/pinkbook/downloads/appendices/B/excipient-table-2.pdf

 

Excipient List:

  • Preservatives used to prevent contamination. For example, thimerosal.

  • Adjuvants used to stimulate a stronger immune response. For example, aluminum salts.

  • Stabilizers used to keep the vaccine potent during transportation and storage. For example, sugars or gelatin.

  • Inactivating ingredients used to kill viruses or inactivate toxins. For example, formaldehyde.

  • Antibiotics used to prevent contamination by bacteria. For example, neomycin.

  • Others are residual trace amounts of materials that were used during the manufacturing process and removed. These can include: Cell culture materials, used to grow the vaccine antigens. For example, egg protein, various culture media.

Despite almost 90 years of widespread use of aluminium adjuvants, medical science’s understanding about their mechanisms of action is still remarkably poor. There is also a concerning scarcity of data on toxicology and pharmacokinetics of these compounds. Despite this, the false notion that aluminium in vaccines is safe appears to be widely accepted. Experimental research clearly shows that aluminium adjuvants have a potential to induce serious immunological disorders in humans. Aluminium in adjuvant form carries a risk for autoimmunity, long-term brain inflammation and associated neurological complications and may thus have profound and widespread adverse health consequences.

 

When you orally ingest aluminium, your body will absorb between 0.2 to 1.5% of it. When aluminum is injected into muscle, your body absorbs 100%, which is why aluminum-containing vaccines are likely far more dangerous than eating aluminium. Numerous studies provide compelling evidence that injected aluminium is detrimental to health. In a paper by Lyons-Weiler and colleagues published in the Journal of Trace Elements in Medicine and Biology, the researchers methodically show that current levels of aluminum in vaccines are wrongly termed “safe” by the Food and Drug Administration and derive from “outdated information, unwarranted assumptions and errors.” They further state that “the levels of aluminium currently present in individual vaccines and in the modern vaccine schedule as a whole are “problematically high.

 

Another paper by Tomljenovic and Shaw affirmed that aluminium is a neurotoxin and may be a co-factor in several neurodegenerative disorders and diseases, including Alzheimer’s, Parkinson’s, multiple sclerosis, amyotrophic lateral sclerosis (ALS), autism, and epilepsy. According to the authors, “The continued use of aluminium adjuvants in various vaccines for children as well as the general public may be of significant concern. In particular, aluminium presented in this form carries a risk for autoimmunity, long-term brain inflammation and associated neurological complications and may thus have profound and widespread adverse health consequences.”

 

Recent data by Perricone et al. showed that aluminium adjuvants in vaccines have been linked to multiple sclerosis, systemic lupus erythematosus, chronic fatigue syndrome, Gulf War syndrome, macrophagic myofasciitis, arthritis, and autoimmune/inflammatory syndrome induced by adjuvants (ASIA syndrome), an autoimmune disease with neurological and cognitive manifestations. Clinical symptoms associated with vaccine-induced autoimmunity can take months or years to manifest, much longer than the time intervals utilized in most vaccine safety studies

 

In another study by Morris et al. published in Metabolic Brain Disease, the authors concluded, “Accordingly, it is recommended that the use of aluminium salts in immunizations should be discontinued and that adults should take steps to minimize their exposure to environmental aluminium.”

There is now abundant scientific data that clearly confirms aluminium as used as an vaccine adjuvant is a dangerous neurotoxin and should be immediately removed form vaccines. The following are selected articles on the health dangers and toxicity of aluminium adjuvants in vaccines.

 

Sources:

 

Cerpa-Cruz, S., P. Paredes-Casillas, E. Landeros Navarro, A. G. Bernard-Medina, G. Martinez-Bonilla, and S. Gutierrez-Urena. Adverse events following immunization with vaccines containing adjuvants.” Immunologic research 56, no. 2-3 (2013): 299-303. 

A traditional infectious disease vaccine is a preparation of live attenuated, inactivated or killed pathogen that stimulates immunity. Vaccine immunologic adjuvants are compounds incorporated into vaccines to enhance immunogenicity. Adjuvants have recently been implicated in the new syndrome named ASIA autoimmune/inflammatory syndrome induced by adjuvants. The objective describes the frequencies of post-vaccination clinical syndrome induced by adjuvants. We performed a cross-sectional study; adverse event following immunization was defined as any untoward medical occurrence that follows immunization 54 days prior to the event. Data on vaccinations and other risk factors were obtained from daily epidemiologic surveillance. Descriptive statistics were done using means and standard deviation, and odds ratio adjusted for potential confounding variables was calculated with SPSS 17 software. Forty-three out of 120 patients with moderate or severe manifestations following immunization were hospitalized from 2008 to 2011. All patients fulfilled at least 2 major and 1 minor criteria suggested by Shoenfeld and Agmon–Levin for ASIA diagnosis. The most frequent clinical findings were pyrexia 68 %, arthralgias 47 %, cutaneous disorders 33 %, muscle weakness 16 % and myalgias 14 %. Three patients had diagnosis of Guillain–Barre syndrome, one patient had Adult-Still’s disease 3 days after vaccination. A total of 76 % of the events occurred in the first 3 days post-vaccination. Two patients with previous autoimmune disease showed severe adverse reactions with the reactivation of their illness. Minor local reactions were present in 49 % of patients. Vaccines containing adjuvants may be associated with an increased risk of autoimmune/inflammatory adverse events following immunization.

Couette, Maryline, Marie-Françoise Boisse, Patrick Maison, Pierre Brugieres, Pierre Cesaro, Xavier Chevalier, Romain K. Gherardi, Anne-Catherine Bachoud-Levi, and François-Jérôme Authier. “Long-term persistence of vaccine-derived aluminum hydroxide is associated with chronic cognitive dysfunction.” Journal of inorganic biochemistry 103, no. 11 (2009): 1571-1578.

Macrophagic myofasciitis (MMF) is an emerging condition, characterized by specific muscle lesions assessing long-term persistence of aluminum hydroxide within macrophages at the site of previous immunization. Affected patients mainly complain of arthromyalgias, chronic fatigue, and cognitive difficulties. We designed a comprehensive battery of neuropsychological tests to prospectively delineate MMF-associated cognitive dysfunction (MACD). Compared to control patients with arthritis and chronic pain, MMF patients had pronounced and specific cognitive impairment. MACD mainly affected (i) both visual and verbal memory; (ii) executive functions, including attention, working memory, and planning; and (iii) left ear extinction at dichotic listening test. Cognitive deficits did not correlate with pain, fatigue, depression, or disease duration. Pathophysiological mechanisms underlying MACD remain to be determined. In conclusion, long-term persistence of vaccine-derived aluminum hydroxide within the body assessed by MMF is associated with cognitive dysfunction, not solely due to chronic pain, fatigue and depression.

Dórea, José G. “Exposure to mercury and aluminum in early life: developmental vulnerability as a modifying factor in neurologic and immunologic effects.” International Journal of Environmental Research and Public Health 12, no. 2 (2015): 1295-1313.

Currently, ethyl mercury (EtHg) and adjuvant-Al are the dominating interventional exposures encountered by fetuses, newborns, and infants due to immunization with Thimerosal-containing vaccines (TCVs). Despite their long use as active agents of medicines and fungicides, the safety levels of these substances have never been determined, either for animals or for adult humans—much less for fetuses, newborns, infants, and children. I reviewed the literature for papers reporting on outcomes associated with (a) multiple exposures and metabolism of EtHg and Al during early life; (b) physiological and metabolic characteristics of newborns, neonates, and infants relevant to xenobiotic exposure and effects; (c) neurobehavioral, immunological, and inflammatory reactions to Thimerosal and Al-adjuvants resulting from TCV exposure in infancy. Immunological and neurobehavioral effects of Thimerosal-EtHg and Al-adjuvants are not extraordinary; rather, these effects are easily detected in high- and low-income countries, with co-exposure to methylmercury (MeHg) or other neurotoxicants. Rigorous and replicable studies (in different animal species) have shown evidence of EtHg and Al toxicities. More research attention has been given to EtHg and findings have showed a solid link with neurotoxic effects in humans; however, the potential synergic effect of both toxic agents has not been properly studied. Therefore, early life exposure to both EtHg and Al deserves due consideration.

Dórea, José G., and Rejane C. Marques. “Infants’ exposure to aluminum from vaccines and breast milk during the first 6 months.” Journal of Exposure Science & Environmental Epidemiology 20, no. 7 (2010): 598-601.

The success of vaccination programs in reducing and eliminating infectious diseases has contributed to an ever-increasing number of vaccines given at earlier ages (newborns and infants). Exposure to low levels of environmental toxic substances (including metals) at an early age raises plausible concerns over increasingly lower neuro-cognitive rates. Current immunization schedules with vaccines containing aluminum (as adjuvant) are given to infants, but thimerosal (as preservative) is found mostly in vaccines used in non-industrialized countries. Exclusively, breastfed infants (in Brazil) receiving a full recommended schedule of immunizations showed an exceedingly high exposure of Al (225 to 1750 μg per dose) when compared with estimated levels absorbed from breast milk (2.0 μg). This study does not dispute the safety of vaccines but reinforces the need to study long-term effects of early exposure to neuro-toxic substances on the developing brain. Pragmatic vaccine safety needs to embrace conventional toxicology, addressing especial characteristics of unborn fetuses, neonates and infants exposed to low levels of aluminum, and ethyl mercury traditionally considered innocuous to the central nervous system.

Exley, Christopher, Louise Swarbrick, Rhomain K. Gherardi, and Francois-Jérôme Authier. A role for the body burden of aluminium in vaccine-associated macrophagic myofasciitis and chronic fatigue syndrome.” Medical hypotheses 72, no. 2 (2009): 135-139.

Macrophagic myofasciitis and chronic fatigue syndrome are severely disabling conditions which may be caused by adverse reactions to aluminium-containing adjuvants in vaccines. While a little is known of disease aetiology both conditions are characterised by an aberrant immune response, have a number of prominent symptoms in common and are coincident in many individuals. Herein, we have described a case of vaccine-associated chronic fatigue syndrome and macrophagic myofasciitis in an individual demonstrating aluminium overload. This is the first report linking the latter with either of these two conditions and the possibility is considered that the coincident aluminium overload contributed significantly to the severity of these conditions in this individual. This case has highlighted potential dangers associated with aluminium-containing adjuvants and we have elucidated a possible mechanism whereby vaccination involving aluminium-containing adjuvants could trigger the cascade of immunological events which are associated with autoimmune conditions including chronic fatigue syndrome and macrophagic myofasciitis.

Fanni, Daniela, Rossano Ambu, Clara Gerosa, Sonia Nemolato, Nicoletta Iacovidou, Peter Van Eyken, Vassilios Fanos, Marco Zaffanello, and Gavino Faa. “Aluminum exposure and toxicity in neonates: a practical guide to halt aluminum overload in the prenatal and perinatal periods.” World Journal of Pediatrics 10, no. 2 (2014): 101-107.

Pediatricians and neonatologists must be more concerned about aluminum content in all products our newborns are exposed to, starting from monitoring aluminum concentrations in milk- and soybased formulas in which, on the on the basis of recent studies, there is still too much aluminum.

Fanni, Daniela, Rossano Ambu, Clara Gerosa, Sonia Nemolato, Nicoletta Iacovidou, Peter Van Eyken, Vassilios Fanos, Marco Zaffanello, and Gavino Faa. “Aluminum exposure and toxicity in neonates: a practical guide to halt aluminum overload in the prenatal and perinatal periods.” World Journal of Pediatrics 10, no. 2 (2014): 101-107.

Background: During the last years, human newborns have been overexposed to biologically reactive aluminum, with possible relevant consequences on their future health and on their susceptibility to a variety of diseases. Children, newborns and particularly preterm neonates are at an increased risk of aluminum toxicity because of their relative immaturity.

Data sources: Based on recent original publications and classical data of the literatures, we reviewed the aluminum content in mother’s food during the intrauterine life as well as in breast milk and infant formula during lactation. We also determined the possible role of aluminum in parenteral nutrition solutions, in adjuvants of vaccines and in pharmaceutical products. A special focus is placed on the relationship between aluminum overexposure and the insurgence of bone diseases. 

Results: Practical points of management and prevention are suggested. Aluminum sources that infants may receive during the first 6 months of life are presented. In the context of prevention of possible adverse effects of aluminum overload in fetal tissues during development, simple suggestions to pregnant women are described. Finally, practical points of management and prevention are suggested. 

Conclusions: Pediatricians and neonatologists must be more concerned about aluminum content in all products our newborns are exposed to, starting from monitoring aluminum concentrations in milk- and soy based formulas in which, on the basis of recent studies, there is still too much aluminum.

Gherardi, Romain K., Guillemette Crépeaux, François-Jerome Authier, and Lluis Lujan. “Animal studies are mandatory to investigate the poorly understood fate and effects of aluminum adjuvants administered to billions of humans and animals worldwide.” Autoimmunity reviews 17, no. 7 (2018): 735-737.

Gherardi, Romain K., Guillemette Crépeaux, and François-Jérome Authier. “Myalgia and chronic fatigue syndrome following immunization: macrophagic myofasciitis and animal studies support linkage to aluminum adjuvant persistency and diffusion in the immune system.” Autoimmunity reviews 18, no. 7 (2019): 691-705.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a multifactorial and poorly undersood disabling disease. We present epidemiological, clinical and experimental evidence that ME/CFS constitutes a major type of adverse effect of vaccines, especially those containing poorly degradable particulate aluminum adjuvants. Evidence has emerged very slowly due to the multiplicity, lack of specificity, delayed onset, and frequent medical underestimation of ME/CFS symptoms. It was supported by an epidemiological study comparing vaccinated vs unvaccinated militaries that remained undeployed during Gulf War II. Affected patients suffer from cognitive dysfunction affecting attention, memory and inter-hemispheric connections, well correlated to brain perfusion defects and associated with a stereotyped and distinctive pattern of cerebral glucose hypometabolism. Deltoid muscle biopsy performed to investigate myalgia typically yields macrophagic myofasciitis (MMF), a histological biomarker assessing longstanding persistency of aluminum agglomerates within innate immune cells at site of previous immunization. MMF is seemingly linked to altered mineral particle detoxification by the xeno/ autophagy machinery. Comparing toxicology of different forms of aluminum and different types of exposure is misleading and inadequate and small animal experiments have turned old dogma upside down. Instead of being rapidly solubilized in the extracellular space, injected aluminum particles are quickly captured by immune cells and transported to distant organs and the brain where they elicit an inflammatory response and exert selective low dose long-term neurotoxicity. Clinical observations and experiments in sheep, a large animal like humans, confirmed both systemic diffusion and neurotoxic effects of aluminum adjuvants. Post-immunization ME/CFS represents the core manifestation of “autoimmune/inflammatory syndrome induced by adjuvants”

.

Igbokwe, Ikechukwu Onyebuchi, Ephraim Igwenagu, and Nanacha Afifi Igbokwe. “Aluminium toxicosis: a review of toxic actions and effects.” Interdisciplinary Toxicology 12, no. 2 (2019): 45-70.

Aluminium (Al) is frequently accessible to animal and human populations to the extent that intoxications may occur. Intake of Al is by inhalation of aerosols or particles, ingestion of food, water and medicaments, skin contact, vaccination, dialysis and infusions. Toxic actions of Al induce oxidative stress, immunologic alterations, genotoxicity, pro-inflammatory effect, peptide denaturation or transformation, enzymatic dysfunction, metabolic derangement, amyloidogenesis, membrane perturbation, iron dyshomeostasis, apoptosis, necrosis and dysplasia. The pathological conditions associated with Al toxicosis are desquamative interstitial pneumonia, pulmonary alveolar proteinosis, granulomas, granulomatosis and fibrosis, toxic myocarditis, thrombosis and ischemic stroke, granulomatous enteritis, Crohn’s disease, inflammatory bowel diseases, anemia, Alzheimer’s disease, dementia, sclerosis, autism, macrophagic myofasciitis, osteomalacia, oligospermia and infertility, hepatorenal disease, breast cancer and cyst, pancreatitis, pancreatic necrosis and diabetes mellitus. The review provides a broad overview of Al toxicosis as a background for sustained investigations of the toxicology of Al compounds of public health importance.

Katzav, A., S. Kivity, M. Blank, Y. Shoenfeld, and J. Chapman. “Adjuvant immunization induces high levels of pathogenic antiphospholipid antibodies in genetically prone mice: another facet of the ASIA syndrome.” Lupus 21, no. 2 (2012): 210-216.

Adjuvants may induce autoimmune diseases in susceptible individuals, a phenomenon recently defined as autoimmune/inflammatory syndrome induced by adjuvants (ASIA). Patients with both antiphospholipid antibodies (aPL) and the genetic coagulopathy factor V Leiden (FVL) are frequently found. We therefore evaluated whether adjuvant can induce aPL in heterozygous FVL mice. aPL were measured in naı¨ve mice and at 1 and 5 months after immunization with either complete or incomplete Freund’s adjuvant (CFA, IFA) in FVL and control C57/ B6 background mice. We defined antibody levels 3 SD above the mean of C57/B6 mice immunized with adjuvant as positive (specificity of 99%). For b2GPI-dependent aPL, 28.6% (6/21) of FVL mice 5 months after immunization with adjuvant (both IFA and CFA) were positive compared with 4.8% (1/22) of FVL mice 1 month after adjuvant and 0% of naı¨ve FVL and C57/B6 mice (0/16, p < 0.001). aPL levels correlated with behavioral hyperactivity in the staircase test. FVL mice immunized with adjuvant did not develop b2GPIindependent aPL. We hypothesize that the FVL aPL association is not a coincidence, but that chronic coagulation defects combined with external inflammatory stimuli analogous to adjuvant may induce aPL and also antiphospholipid syndrome, thus supporting the notion of ASIA. 

Lyons-Weiler, James, and Robert Ricketson. “Reconsideration of the immunotherapeutic pediatric safe dose levels of aluminum.” Journal of Trace Elements in Medicine and Biology 48 (2018): 67-73.

FDA regulations require safety testing of constituent ingredients in drugs (21 CFR 610.15). With the exception of extraneous proteins, no component safety testing is required for vaccines or vaccine schedules. The dosing of aluminum in vaccines is based on the production of antibody titers, not safety science. Here we estimate a Pediatric Dose Limit that considers body weight. We identify several serious historical missteps in past analyses of provisional safe levels of aluminum in vaccines, and provide updates relevant to infant aluminum exposure in the pediatric schedule considering pediatric body weight. When aluminum doses are estimated from Federal Regulatory Code given body weight, exposure from the current vaccine schedule are found to exceed our estimate of a weight-corrected Pediatric Dose Limit. Our calculations show that the levels of aluminum suggested by the currently used limits place infants at risk of acute, repeated, and possibly chronic exposures of toxic levels of aluminum in modern vaccine schedules. Individual adult exposures are on par with Provisional Tolerable Weekly Intake “limits”, but some individuals may be aluminum intolerant due to genetics or previous exposures. Vaccination in neonates and low birth-weight infants must be re-assessed; other implications for the use of aluminum-containing vaccines, and additional limitations in our understanding of neurotoxicity and safety levels of aluminum in biologics are discussed.

Masson, Jean-Daniel, Guillemette Crépeaux, François-Jérôme Authier, Christopher Exley, and Romain K. Gherardi. “Critical analysis of reference studies on the toxicokinetics of aluminum-based adjuvants.” Journal of Inorganic Biochemistry 181 (2018): 87-95.

We reviewed the three toxicokinetic reference studies commonly used to suggest that aluminum (Al)-based adjuvants are innocuous. A single experimental study was carried out using isotopic 26Al (Flarend et al., Vaccine, 1997). This study used aluminum salts resembling those used in vaccines but ignored adjuvant uptake by cells that was not fully documented at the time. It was conducted over a short period of time (28 days) and used only two rabbits per adjuvant. At the endpoint, Al elimination in the urine accounted for 6% for Al hydroxide and 22% for Al phosphate, both results being incompatible with rapid elimination of vaccine-derived Al in urine. Two theoretical studies have evaluated the potential risk of vaccine Al in infants, by reference to an oral “minimal risk level” (MRL) extrapolated from animal studies. Keith et al. (Vaccine, 2002) used a high MRL (2 mg/kg/d), an erroneous model of 100% immediate absorption of vaccine Al and did not consider renal and blood-brain barrier immaturity. Mitkus et al. (Vaccine, 2011) only considered solubilized Al, with erroneous calculations of absorption duration. Systemic Al particle diffusion and neuro-inflammatory potential were omitted. The MRL they used was both inappropriate (oral Al vs. injected adjuvant) and still too high (1 mg/kg/d) regarding recent animal studies. Both paucity and serious weaknesses of reference studies strongly suggest that novel experimental studies of Al adjuvants toxicokinetics should be performed on the long-term, including both neonatal and adult exposures, to ensure their safety and restore population confidence in Al-containing vaccines.

McFarland, G., La Joie, E., Thomas, P., & Lyons-Weiler, J. (2020). “Acute exposure and chronic retention of aluminum in three vaccine schedules and effects of genetic and environmental variation.” Journal of Trace Elements in Medicine and Biology, 58, 126444.

Like the mechanisms of action as adjuvants, the pharmacodynamics of injected forms of aluminum commonly used in vaccines are not well-characterized, particularly with respect to how differences in schedules impact accumulation and how factors such as genetics and environmental influences on detoxification influence clearance. Previous modeling efforts are based on very little empirical data, with the model by Priest based on whole-body clearance rates estimated from a study involving a single human subject. In this analysis, we explore the expected acute exposures and longer-term whole-body accumulation/clearance across three vaccination schedules: the current US Centers for Disease Control and Prevention (CDC) schedule, the current CDC schedule using low aluminum or no aluminum vaccines, and Dr. Paul Thomas’ “Vaccine Friendly Plan” schedule. We then study the effects of an implicit assumption of the Priest model on whether clearance dynamics from successive doses are influenced by the current level of aluminum or modeled by the assumption that a new dose has its own whole-body dynamics “reset” on the day of injection. We model two additional factors: variation (deficiency) in aluminum detoxification, and a factor added to the Priest equation to model the potential impact of aluminum itself on cellular and whole-body detoxification. These explorations are compared to a previously estimated pediatric dose limit (PDL) of whole-body aluminum exposure and provide a new statistic: %alumTox, the (expected) percentage of days (or weeks) an infant is in aluminum toxicity, reflecting chronic toxicity. We show that among three schedules, the CDC schedule results in the highest %alumTox regardless of model assumptions, and the Vaccine Friendly Plan schedule, which avoids >1 ACV per office visit results in the lowest (expected) %alumTox. These results are conservative, as the MSL is derived from data used by FDA to estimate safety of aluminum in adult humans. These results demonstrate high potential utility of modeling variation in patient responses to aluminum. More empirical data from individuals who are suspected of being intolerant of aluminum from vaccines, evidenced by high aluminum retention, neurodevelopmental disorders and/or a myriad of chronic illnesses would help answer questions on whether the model predictions can be used to estimate parameter values tied to genetic factors including genomic sequence variation and family history of chronic illnesses tied to aluminum exposure.

Miller, Neil Z. “Aluminum in childhood vaccines is unsafe.” Journal of American Physicians and Surgeons 21, no. 4 (2016): 109-117.

Aluminum is a neurotoxin, yet infants and young children are repeatedly injected with aluminum adjuvants from multiple vaccines during critical periods of brain development. Numerous studies provide credible evidence that aluminum adversely affects important biological functions and may contribute to neurodegenerative and autoimmune disorders. It is impossible to predetermine which vaccinated babies will succumb to aluminum poisoning. Aluminum-free health options are needed.

Mold, Matthew, Dorcas Umar, Andrew King, and Christopher Exley. “Aluminum in brain tissue in autism.” Journal of Trace Elements in Medicine and Biology 46 (2018): 76-82.

Autism spectrum disorder is a neurodevelopmental disorder of unknown aetiology. It is suggested to involve both genetic susceptibility and environmental factors including in the latter environmental toxins. Human exposure to the environmental toxin aluminum has been linked, if tentatively, to autism spectrum disorder. Herein we have used transversely heated graphite furnace atomic absorption spectrometry to measure, for the first time, the aluminum content of brain tissue from donors with a diagnosis of autism. We have also used an aluminum-selective fluor to identify aluminum in brain tissue using fluorescence microscopy. The aluminum content of brain tissue in autism was consistently high. The mean (standard deviation) aluminum content across all 5 individuals for each lobe were 3.82(5.42), 2.30(2.00), 2.79(4.05) and 3.82(5.17) μg/g dry wt. for the occipital, frontal, temporal and parietal lobes respectively. These are some of the highest values for aluminum in human brain tissue yet recorded and one has to question why, for example, the aluminum content of the occipital lobe of a 15 year old boy would be 8.74 (11.59) μg/g dry wt.? Aluminum-selective fluorescence microscopy was used to identify aluminum in brain tissue in 10 donors. While aluminum was imaged associated with neurones it appeared to be present intracellularly in microglia-like cells and other inflammatory non-neuronal cells in the meninges, vasculature, grey and white matter. The pre-eminence of intracellular aluminum associated with non-neuronal cells was a standout observation in autism brain tissue and may offer clues as to both the origin of the brain aluminum as well as a putative role in autism spectrum disorder.

Morris, Gerwyn, Basant K. Puri, and Richard E. Frye. “The putative role of environmental aluminium in the development of chronic neuropathology in adults and children. How strong is the evidence and what could be the mechanisms involved?.” Metabolic brain disease 32, no. 5 (2017): 1335-1355.

The conceptualization of autistic spectrum disorder and Alzheimer’s disease has undergone something of a paradigm shift in recent years and rather than being viewed as single illnesses with a unitary pathogenesis and pathophysiology they are increasingly considered to be heterogeneous syndromes with a complex multifactorial aetiopathogenesis, involving a highly complex and diverse combination of genetic, epigenetic and environmental factors. One such environmental factor implicated as a potential cause in both syndromes is aluminum, as an element or as part of a salt, received, for example, in oral form or as an adjuvant. Such administration has the potential to induce pathology via several routes such as provoking dysfunction and/or activation of glial cells which play an indispensable role in the regulation of central nervous system homeostasis and neurodevelopment. Other routes include the generation of oxidative stress, depletion of reduced glutathione, direct and indirect reductions in mitochondrial performance and integrity, and increasing the production of proinflammatory cytokines in both the brain and peripherally. The mechanisms whereby environmental aluminum could contribute to the development of the highly specific pattern of neuropathology seen in Alzheimer’s disease are described. Also detailed are several mechanisms whereby significant quantities of aluminum introduced via immunization could produce chronic neuropathology in genetically susceptible children. Accordingly, it is recommended that the use of aluminum salts in immunizations should be discontinued and that adults should take steps to minimize their exposure to environmental aluminum.

Parker, Albert. “Testing new hypotheses of neurological and immunological outcomes with aluminum-containing vaccines is warranted.” Journal of trace elements in medicine and biology: organ of the Society for Minerals and Trace Elements (GMS) 51 (2019): 28.

Petrik, Michael S., Margaret C. Wong, Rena C. Tabata, Robert F. Garry, and Christopher A. Shaw. “Aluminum adjuvant linked to Gulf War illness induces motor neuron death in mice.” NeuroMolecular Medicine 9, no. 1 (2007): 83-100.

Gulf War illness (GWI) affects a significant percentage of veterans of the 1991 conflict, but its origin remains unknown. Associated with some cases of GWI are increased incidences of amyotrophic lateral sclerosis and other neurological disorders. Whereas many environmental factors have been linked to GWI, the role of the anthrax vaccine has come under increasing scrutiny. Among the vaccine’s potentially toxic components are the adjuvants aluminum hydroxide and squalene. To examine whether these compounds might contribute to neuronal deficits associated with GWI, an animal model for examining the potential neurological impact of aluminum hydroxide, squalene, or aluminum hydroxide combined with squalene was developed. Young, male colony CD-1 mice were injected with the adjuvants at doses equivalent to those given to US military service personnel. All mice were subjected to a battery of motor and cognitive-behavioral tests over a 6-mo period postinjections. Following sacrifice, central nervous system tissues were examined using immunohistochemistry for evidence of inflammation and cell death. Behavioral testing showed motor deficits in the aluminum treatment group that expressed as a progressive decrease in strength measured by the wire-mesh hang test (final deficit at 24 wk; about 50%). Significant cognitive deficits in water-maze learning were observed in the combined aluminum and squalene group (4.3 errors per trial) compared with the controls (0.2 errors per trial) after 20 wk. Apoptotic neurons were identified in aluminum-injected animals that showed significantly increased activated caspase-3 labeling in lumbar spinal cord (255%) and primary motor cortex (192%) compared with the controls. Aluminum-treated groups also showed significant motor neuron loss (35%) and increased numbers of astrocytes (350%) in the lumbar spinal cord. The findings suggest a possible role for the aluminum adjuvant in some neurological features associated with GWI and possibly an additional role for the combination of adjuvants.

Perricone C, Colafrancesco S, Mazor RD, et al. “Autoimmune/inflammatory syndrome induced by adjuvants.” (ASIA) 2013: Unveiling the pathogenic, clinical and diagnostic aspects. J Autoimmun 2013;47(Dec):1-16

In 2011 a new syndrome termed ‘ASIA Autoimmune/Inflammatory Syndrome Induced by Adjuvants’ was defined pointing to summarize for the first time the spectrum of immune-mediated diseases triggered by an adjuvant stimulus such as chronic exposure to silicone, tetramethylpentadecane, pristane, aluminum and other adjuvants, as well as infectious components, that also may have an adjuvant effect. All these environmental factors have been found to induce autoimmunity by themselves both in animal models and in humans: for instance, silicone was associated with siliconosis, aluminum hydroxide with postvaccination phenomena and macrophagic myofasciitis syndrome. Several mechanisms have been hypothesized to be involved in the onset of adjuvant-induced autoimmunity; a genetic favorable background plays a key role in the appearance on such vaccine-related diseases and also justifies the rarity of these phenomena. This paper will focus on protean facets which are part of ASIA, focusing on the roles and mechanisms of action of different adjuvants which lead to the autoimmune/inflammatory response. The data herein illustrate the critical role of environmental factors in the induction of autoimmunity. Indeed, it is the interplay of genetic susceptibility and environment that is the major player for the initiation of breach of tolerance.

Shaw, Christopher A., Dan Li, and Lucija Tomljenovic. “Are there negative CNS impacts of aluminum adjuvants used in vaccines and immunotherapy?.” Immunotherapy 6, no. 10 (2014): 1055-1071.

In spite of a common view that aluminum (Al) salts are inert and therefore harmless as vaccine adjuvants or in immunotherapy, the reality is quite different. In the following article we briefly review the literature on Al neurotoxicity and the use of Al salts as vaccine adjuvants and consider not only direct toxic actions on the nervous system, but also the potential impact for triggering autoimmunity. Autoimmune and inflammatory responses affecting the CNS appear to underlie some forms of neurological disease, including developmental disorders. Al has been demonstrated to impact the CNS at every level, including by changing gene expression. These outcomes should raise concerns about the increasing use of Al salts as vaccine adjuvants and for the application as more general immune stimulants.

Shaw, Christopher A., and Michael S. Petrik. “Aluminum hydroxide injections lead to motor deficits and motor neuron degeneration.” Journal of inorganic biochemistry 103, no. 11 (2009): 1555-1562.

Gulf War Syndrome is a multi-system disorder afflicting many veterans of Western armies in the 1990–1991 Gulf War. A number of those afflicted may show neurological deficits including various cognitive dysfunctions and motor neuron disease, the latter expression virtually indistinguishable from classical amyotrophic lateral sclerosis (ALS) except for the age of onset. This ALS “cluster” represents the second such ALS cluster described in the literature to date. Possible causes of GWS include several of the adjuvants in the anthrax vaccine and others. The most likely culprit appears to be aluminum hydroxide. In an initial series of experiments, we examined the potential toxicity of aluminum hydroxide in male, outbred CD-1 mice injected subcutaneously in two equivalent-to-human doses. After sacrifice, spinal cord and motor cortex samples were examined by immunohistochemistry. Aluminum-treated mice showed significantly increased apoptosis of motor neurons and increases in reactive astrocytes and microglial proliferation within the spinal cord and cortex. Morin stain detected the presence of aluminum in the cytoplasm of motor neurons with some neurons also testing positive for the presence of hyper-phosphorylated tau protein, a pathological hallmark of various neurological diseases, including Alzheimer’s disease and frontotemporal dementia. A second series of experiments was conducted on mice injected with six doses of aluminum hydroxide. Behavioural analyses in these mice revealed significant impairments in a number of motor functions as well as diminished spatial memory capacity. The demonstrated neurotoxicity of aluminum hydroxide and its relative ubiquity as an adjuvant suggest that greater scrutiny by the scientific community is warranted.

Sheth, Sneha KS, Yongling Li, and Christopher A. Shaw. “Is exposure to aluminium adjuvants associated with social impairments in mice? A pilot study.” Journal of inorganic biochemistry 181 (2018): 96-103.

This is the first experimental study, to our knowledge, to demonstrate that aluminum adjuvants can impair social behaviour if applied in the early period of postnatal development. The study, however, is insufficient to make any assertive claims about the link between aluminium adjuvants and ASD in humans.

Strunecka, Anna, Russell L. Blaylock, Jiri Patocka, and Otakar Strunecky. “Immunoexcitotoxicity as the central mechanism of etiopathology and treatment of autism spectrum disorders: A possible role of fluoride and aluminum.” Surgical Neurology International 9 (2018).

Our review suggests that most autism spectrum disorder (ASD) risk factors are connected, either directly or indirectly, to immunoexcitotoxicity. Chronic brain inflammation is known to enhance the sensitivity of glutamate receptors and interfere with glutamate removal from the extraneuronal space, where it can trigger excitotoxicity over a prolonged period. Neuroscience studies have clearly shown that sequential systemic immune stimulation can activate the brain’s immune system, microglia, and astrocytes, and that with initial immune stimulation, there occurs CNS microglial priming. Children are exposed to such sequential immune stimulation via a growing number of environmental excitotoxins, vaccines, and persistent viral infections. We demonstrate that fluoride and aluminum (Al3+) can exacerbate the pathological problems by worsening excitotoxicity and inflammation. While Al3+ appears among the key suspicious factors of ASD, fluoride is rarely recognized as a causative culprit. A long-term burden of these ubiquitous toxins has several health effects with a striking resemblance to the symptoms of ASD. In addition, their synergistic action in molecules of aluminofluoride complexes can affect cell signaling, neurodevelopment, and CNS functions at several times lower concentrations than either Al3+ or fluoride acting alone. Our review opens the door to a number of new treatment modes that naturally reduce excitotoxicity and microglial priming.

Tomljenovic, Lucija, and C. A. Shaw. “Mechanisms of aluminum adjuvant toxicity and autoimmunity in pediatric populations.” Lupus 21, no. 2 (2012): 223-230.

Immune challenges during early development, including those vaccine-induced, can lead to permanent detrimental alterations of the brain and immune function. Experimental evidence also shows that simultaneous administration of as little as two to three immune adjuvants can overcome genetic resistance to autoimmunity. In some developed countries, by the time children are 4 to 6 years old, they will have received a total of 126 antigenic compounds along with high amounts of aluminum (Al) adjuvants through routine vaccinations. According to the US Food and Drug Administration, safety assessments for vaccines have often not included appropriate toxicity studies because vaccines have not been viewed as inherently toxic. Taken together, these observations raise plausible concerns about the overall safety of current childhood vaccination programs. When assessing adjuvant toxicity in children, several key points ought to be considered: (i) infants and children should not be viewed as “small adults” with regard to toxicological risk as their unique physiology makes them much more vulnerable to toxic insults; (ii) in adult humans Al vaccine adjuvants have been linked to a variety of serious autoimmune and inflammatory conditions (i.e., “ASIA”), yet children are regularly exposed to much higher amounts of Al from vaccines than adults; (iii) it is often assumed that peripheral immune responses do not affect brain function. However, it is now clearly established that there is a bidirectional neuro-immune crosstalk that plays crucial roles in immunoregulation as well as brain function. In turn, perturbations of the neuro-immune axis have been demonstrated in many autoimmune diseases encompassed in “ASIA” and are thought to be driven by a hyperactive immune response; and (iv) the same components of the neuro-immune axis that play key roles in brain development and immune function are heavily targeted by Al adjuvants. In summary, research evidence shows that increasing concerns about current vaccination practices may indeed be warranted. Because children may be most at risk of vaccine-induced complications, a rigorous evaluation of the vaccine-related adverse health impacts in the pediatric population is urgently needed.

Tomljenovic, Lucija, and Christopher A. Shaw. “Do aluminum vaccine adjuvants contribute to the rising prevalence of autism?.” Journal of inorganic biochemistry 105, no. 11 (2011): 1489-1499.

Autism spectrum disorders (ASD) are serious multisystem developmental disorders and an urgent global public health concern. Dysfunctional immunity and impaired brain function are core deficits in ASD. Aluminum (Al), the most commonly used vaccine adjuvant, is a demonstrated neurotoxin and a strong immune stimulator. Hence, adjuvant Al has the potential to induce neuroimmune disorders. When assessing adjuvant toxicity in children, two key points ought to be considered: (i) children should not be viewed as “small adults” as their unique physiology makes them much more vulnerable to toxic insults; and (ii) if exposure to Al from only few vaccines can lead to cognitive impairment and autoimmunity in adults, is it unreasonable to question whether the current pediatric schedules, often containing 18 Al adjuvanted vaccines, are safe for children? By applying Hill’s criteria for establishing causality between exposure and outcome we investigated whether exposure to Al from vaccines could be contributing to the rise in ASD prevalence in the Western world. Our results show that: 

1. children from countries with the highest ASD prevalence appear to have the highest exposure to Al from vaccines.

 

2. the increase in exposure to Al adjuvants significantly correlates with the increase in ASD prevalence in the United States observed over the last two decades (Pearson r = 0.92, p < 0.0001); and

 

3. a significant correlation exists between the amounts of Al administered to preschool children and the current prevalence of ASD in seven Western countries, particularly at 3–4 months of age (Pearson r = 0.89–0.94, p = 0.0018–0.0248). The application of the Hill’s criteria to these data indicates that the correlation between Al in vaccines and ASD may be causal. Because children represent a fraction of the population most at risk for complications following exposure to Al, a more rigorous evaluation of Al adjuvant safety seems warranted.

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Honeybee Venom Therapy

Honeybee Venom Therapy

August 31, 2020

Honeybee Venom Therapy

James Odell, OMD, ND, L.Ac.

All content in this article is created and published online for informational purposes only. It is not intended to be a substitute for professional medical advice and should not be relied on as health or personal advice. Always seek the guidance of your doctor or other qualified health professional with any questions you may have regarding your health or a medical condition. Never disregard the advice of a medical professional, or delay in seeking it because of something you have read in this article or e-journal. Honeybee venom is toxic and may cause serious life-threatening reactions. If you choose to rely on any information provided in this article, you do so solely at your own risk.

 

To make a prairie it takes a clover and one bee, One clover, and a bee . . . ~ Emily Dickinson ~

 

Practicing the use of honeybee venom for medical conditions is part of apitherapy. Apitherapy, or therapy from honeybee products, such as honey, propolis, royal jelly, bee pollen and bee wax, has been practiced in many countries for centuries. Honeybee venom therapy (BVT), the use of live bee stings (or injectable venom), has been used for more than 3000 years in the treatment of numerous types of acute and chronic afflictions. BVT has been practiced in ancient Egypt, Greece and China — three Great Civilizations known for their highly developed medical systems. Hippocrates, a Greek physician known as the “Father of Medicine”, recognized the healing virtues of bee venom in the treatment of arthritis and other joint problems. Throughout the world many physicians are now successfully using honeybee venom therapy with success in the treatment of arthritis, multiple sclerosis, ALS, Lyme disease, psoriasis, epilepsy, asthma, and some types of cancer. The world scientific literature contains more than 1500 articles on the medicinal value of BVT.

Egyptian Hieroglyph of Honeybee

 

Honeybee venom is a complex mixture of various chemical compounds such as peptides, enzymes, biologically active amines and non-peptide components, some of which have strong neurological, immunological, and anti-inflammatory effects.

 

Honeybee venom contains more than 18 active components, of which mellitin (40-50%) is the main active peptide that exhibits anti-inflammatory, antibacterial, antiviral, and anti-carcinogenic properties.

 

Other components of honeybee venom:

 

Apamin – increases the production of cortisol in the adrenal gland.

Adolapin – contributes 2–5% of the peptides, acts as an anti-inflammatory and analgesic agent because it blocks cyclooxygenase-2, an enzyme responsible for inflammation and pain.

Phospholipase A2 – amounts to 10–12% of peptides and is the most destructive component of apitoxin. It is an enzyme that degrades the phospholipids which compose cellular membranes. It also lowers blood pressure and inhibits blood coagulation. Phospholipase A2 activates arachidonic acid that is metabolized in the cyclooxygenase-cycle to form prostaglandins. Prostaglandins regulate the body’s inflammatory response.

Hyaluronidase – contributes 1–3% of peptides, dilates the capillaries that cause the spread of inflammation.

Histamine – contributes 0.5–2% and is contributes to allergic reactions.

Dopamine and noradrenaline – contribute 1–2% increase in the pulse rate.

Protease-inhibitors – contribute 2% and act as anti-inflammatory agents and stop bleeding.

∙Tertiapin

 

Unlike many other types of insect venom, honeybee venom is water-soluble, not fat-soluble. In order to be effective it is injected just under the skin into moist tissue. It’s hemorrhagic, unlike the viper snake venom, which is a coagulant. In short, honeybee venom contains anti-inflammatory properties, is mildly cytotoxic and has the contradictory effects of inhibiting the nervous system, while stimulating the heart and adrenal glands.

 

Mechanisms

 

Honeybee venom therapy is not a single mechanism, which explains why it has such a wide range of treatment applications. Several mechanisms have been proposed to describe its efficacy for the treatment of many different types of diseases. The immune system is a complicated web of communication between cells and organs, and honeybee venom stimulates key centers in the immune system by eliciting a nonspecific response. Some key mechanisms are that it stimulates the cortisone secretion, enhances antibody production, and affects cytokine production. It is also a potent inhibitor of prostaglandin formation and possesses antioxidant properties.

 

Conditions Treated with Honeybee Venom

 

Due to its bioactive substances that exhibit antioxidant, anticoagulant, and anti-inflammatory properties, honeybee venom is used to treat many disorders. In the case of chronic pain disorders such as rheumatism and arthritis, bee venom is used to control inflammation and the degeneration of connective tissue. Neurological disorders such as migraine, peripheral neuritis and chronic back pain have also been treated successfully. In the case of autoimmune disorders such as multiple sclerosis and lupus, it restores movement and mobility by enhancing the body’s natural defense mechanism. In addition, dermatological conditions such as eczema, psoriasis, and herpes may be treated effectively. Most recently, bee venom is also being investigated for treatment of cancerous tumors. 1-5Due to its antibacterial and antiviral properties, honeybee venom is also used to treat certain infectious diseases, such as Lyme disease.6, 7

 

Antimicrobial Effects

 

Honeybee venom contains a complex mixture of therapeutic compounds, including antimicrobial peptides, which allows bees to defend their hives against predators and external threats. The melittin peptide, the predominant component of bee venom (40–48%, w/w), has been substantially investigated and exhibits potent cytolytic and antimicrobial activity. Potential actions of Honeybee venom against parasites, bacteria, and viruses have been extensively examined and verified with minimal toxicity in vitro and in vivo.8, 9, 10

 

Inflammation and Arthritis

 

Inflammation is a pervasive phenomenon triggered by the innate and adaptive immune systems to maintain homeostasis. The phenomenon usually leads to recovery from infection and healing, but when not properly phased, inflammation may cause immune disorders. Honeybee venom has been widely used in the Orient as an anti-inflammatory medicine for the treatment of chronic inflammatory diseases. Bee venom and its major component, melittin, are potential means of reducing excessive immune responses and provide new options for the treatment of inflammatory diseases. Melittin is a potent anti-inflammatory agent that induces the production of cortisol in the body. Recent studies show that the anti-inflammatory properties of honeybee venom can be applied therapeutically for several types of inflammatory conditions, particularly rheumatoid and osteoarthritis.

 

Exact mechanisms through which honeybee venom reduces inflammation is still being investigated. The nuclear factor NF-κB pathway has long been considered a prototypical proinflammatory signaling pathway, largely based on the role of NF-κB in the expression of proinflammatory genes including cytokines, chemokines, and adhesion molecules. Melittin has been shown to inhibit the activity of NF-κB. Other proposed mechanisms of reducing inflammation, such as the activation of the central and spinal opioid receptors, and α2-adrenergic activity, as well as activation of the descending serotonergic pathway have also been suggested.11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23

 

Nervous System Diseases

 

Recent clinical trials have shown that honeybee venom and its derived active components are applicable to a wide variety of neurodegenerative diseases, including multiple sclerosis and Parkinson’s disease. Such effects of honeybee venom are known to be partly mediated by modulating immune cells in the periphery and glial cells and neurons in the central nervous system.24, 25, 26

 

Honeybee venom has different effects on the central and peripheral nervous system and used to treat various neurological conditions such as multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), Alzheimer’s, and Parkinson’s disease.27, 28 There are several excellent YouTube videos on the use of honeybee venom in the treatment of MS.

 

Changes in glutamate, the predominant excitatory neurotransmitter in the central nervous system, alters the activity of glutamate transporters in many neurodegenerative diseases, including Parkinson’s disease, Alzheimer’s disease, and amyotrophic lateral sclerosis. Honeybee venom assists in reducing glutamatergic cell toxicity in neurodegenerative diseases as it protects cell death and significantly inhibits the cellular toxicity of glutamate. In one study it was shown that pretreatment with honeybee venom altered MAP kinase activation following exposure to glutamate.29

 

Cancer

 

Venoms of several animal species including honeybees have shown promising therapeutic potential against certain forms of cancer. Several studies have demonstrated that honeybee venom and/or melittin have anti-cancer effects including ovarian, prostate, liver, breast, cervical, and renal cancer cells.30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40

 

Honeybee venom has been widely used in the treatment of certain immune-related diseases, as well as recently in the treatment of tumors. Apoptosis, necrosis, and lysis of tumor cells have been suggested as possible mechanisms by which bee venom inhibits tumor growth. Several cancer cells, including renal, lung, liver, prostate, bladder, and mammary cancer cells as well as leukemia cells, may be targets of bee venom peptides such as melittin and phospholipase A2. The cell cytotoxic effects due to the activation of PLA2 by melittin have been suggested as a critical mechanism for the anti-cancer activity of honeybee venom. The induction of apoptotic cell death through several cancer cell death mechanisms, including the activation of caspase and matrix metalloproteinases, is essential for the melittin-induced anti-cancer effects.

 

Administering Honeybee Venom

 

Traditionally, honeybee venom has been administered with live bees by stimulating them to sting in the affected area or in traditional Chinese medicine (TCM) administered on a specific acupuncture point. Current day varieties of honeybee venom products include injectable liquid venom, creams, liniments, ointments, and oral homeopathic preparations such as liquids, tablets, or capsules. Practitioners may choose the most suitable application for the condition being treated and the characteristics of the patient.

 

Next to the effect of a live honeybee, injectable venom solution is a standard method to administer BVT. The solution of the injectable venom is prepared from pure honeybee venom. The solution is administered under the skin to mimic the effect of a bee sting and each injection is equal to or less than the average dry venom sac content of a honeybee. Another popular way of administering BVT is with topical creams and ointments applied to the affected part of the body. For rare cases of an allergic reaction, epinephrine and Benadryl must be present before injection or administration of honeybee venom.

Acupuncture with Honeybee Venom (Api-acupuncture)

 

The stinging of acupuncture points with honeybees, knows as api-acupuncture, has been traditionally used in China and Japan for centuries. Bee venom acupuncture is a form of acupuncture in which bee venom is applied to acupoints on the skin by using the tips of acupuncture needles, stingers extracted from bees, or bees are held by an instrument exposing the stinger.

 

Collecting Honeybee Venom

 

Honeybee venom is synthesized in the venom glands of worker and queen bees and stored in their venom sacs. It is expressed via the sting apparatus during the stinging process. BVT is most effective when it comes from bees during the late spring to the early fall season. This is when bees have an abundant source of pollen to produce potent venom. Their venom during the winter season is less potent. The venom is normally obtained by means of electric shock stimulation. Bees come into contact with a collector frame that is covered with a wire grid and experience a mild electrical shock that causes them to release their venom. The venom is then allowed to air dry, gathered and processed. Approximately a minimum of 4000 bee stings are needed to produce 1 gram of bee venom. Traditional collection methods used up to until now typically killed the bees. However, the bee venom collected using an electro-stimulant method does not harm bees.

 

Reactions and Sensitivity

 

Honeybee venom reactions and sensitivity for most individuals typically include some redness, swelling, and itching that generally improves within a few hours. Nonetheless, an allergic individual may have a longer lasting and more severe reaction. Many individuals are allergic to the wasp, hornet, and yellow jacket stings, but few are allergic to honeybee venom. There is no cross allergy between wasp, hornet, or yellow jacket venom and honeybee venom. Because of their vegetarian nature, the chemical peptides from honeybees are different and less toxic than their carnivorous cousins. Honeybee stings are estimated to account for less than 5% of all adverse stinging insect reactions. The side effects of bee venom therapy are usually minimal as the inflammation, swelling, and itching is expected. The risk of an anaphylactic allergic reaction to honeybee venom is rare but real. It is therefore essential to have a bee sting allergy kit on hand.

 

Generally, a person who is not hypersensitive to bee stings can tolerate one to five stings at a time. This is followed by mild local symptoms accompanied by swelling, redness, and itchy skin. Initially, the symptoms are a little painful, but later change to a pleasant and warm sensation. 

 

Conclusions

 

The use of honeybee venom for medicinal purposes can be traced back thousands of years. The therapeutic interests of honeybee venom and/or its main compounds, particularly melittin, are discussed here. The latter grants broad anti-inflammatory properties by influencing primary inflammation signaling pathways and inducing the inhibition of pro-inflammatory chemicals. Honeybee venom also exhibits neuroprotective ability in neurodegenerative diseases such as MS, Parkinson’s disease, Alzheimer’s, and ALS by significantly blocking their progression and enhancing cognitive functioning in mice models. In terms of antitumor activity, both melittin and honeybee venom have a cytotoxic effect on cancer cells and significant anti-metastatic function. The antimicrobial activity of honeybee venom also has a positive effect against a broad-spectrum of viruses, and bacteria including Borrelia b., which causes Lyme disease. The clinical acceptance of honeybee venom therapy into mainstream medicine still has a long way to go, but researchers believe that the ongoing work on this topic will eventually allow honeybee venom to be a frontline treatment for numerous diseases in upcoming years.

 

References:

1. Ram, S. K. M., Jayapal, N., Nanaiah, P., Aswal, G. S., Ramnarayan, B. K., & Taher, S. M. (2014). The therapeutic benefits of bee venom. Int. J. Curr. Microbiol. App. Sci, 3(11), 377-381.

 

2. Castro, J. I Mendez-Lnocenio, B. Omidvar, J. Omidvar, J. Santilli, H. S. Jr Nielsen, A. P. Pavot, J. R. Richert, J. A. Bellanti. 2005. “A phase I study of the safety of honeybee venom extract as a possible treatment for patients with progressive forms of multiple sclerosis”. Allergy and Asthma Proceedings. 26(6): 470- 476.

 

3. Lee, J D; Park, H J; Chae, Y; Lim, S (2005). An overview of bee venom acupuncture in the treatment of arthritis. Evidence-based complementary and alternative medicine 2 (1): 79- 84.

 

4. Liu, H.and F. Tong,( 2003). “Advances in the study of bee venom and its clinical uses”. Zhong Yao Cai. Jun; 26(6):456-458.

 

5. Hwang, D. S., Kim, S. K., & Bae, H. (2015). Therapeutic effects of bee venom on immunological and neurological diseases. Toxins, 7(7), 2413-2421. Kim, H. J., & Jeon, B. S. (2014). Is acupuncture efficacious therapy in Parkinson’s disease?. Journal of the neurological sciences, 341(1), 1-7.

 

6. Han, SangMi, KwangGil Lee, JooHong Yeo, HaJu Baek, and Kwankyu Park. “Antibacterial and anti-inflammatory effects of honeybee (Apis mellifera) venom against acne-inducing bacteria.” Journal of Medicinal Plants Research 4, no. 6 (2010): 459-464.

 

7. Leandro, Luís F., Carlos A. Mendes, Luciana A. Casemiro, Adriana HC Vinholis, Wilson R. Cunha, Rosana de Almeida, and Carlos HG Martins. “Antimicrobial activity of apitoxin, melittin and phospholipase A2 of honey bee (Apis mellifera) venom against oral pathogens.” Anais da Academia Brasileira de Ciências 87, no. 1 (2015): 147-155.

 

8. Adade, Camila M., Isabelle RS Oliveira, Joana AR Pais, and Thaïs Souto-Padrón. “Melittin peptide kills Trypanosoma cruzi parasites by inducing different cell death pathways.” Toxicon 69 (2013): 227-239.

 

9. Choi, Ji Hae, A. Yeung Jang, Shunmei Lin, Sangyong Lim, Dongho Kim, Kyungho Park, Sang-Mi Han, Joo-Hong Yeo, and Ho Seong Seo. “Melittin, a honeybee venom-derived antimicrobial peptide, may target methicillin-resistant Staphylococcus aureus.” Molecular medicine reports 12, no. 5 (2015): 6483-6490.

 

10. Dosler, Sibel, Elif Karaaslan, and A. Alev Gerceker. “Antibacterial and anti-biofilm activities of melittin and colistin, alone and in combination with antibiotics against Gram-negative bacteria.” Journal of Chemotherapy 28, no. 2 (2016): 95-103.

 

11. Chang, Yi-Han, and Marcia L. Bliven. “Anti-arthritic effect of bee venom.” Agents and actions 9, no. 2 (1979): 205-211.

 

12. Eiseman, Julie L., Jurgen Von Bredow, and Alvito P. Alvares. “Effect of honeybee (Apis mellifera) venom on the course of adjuvant-induced arthritis and depression of drug metabolism in the rat.” Biochemical pharmacology 31, no. 6 (1982): 1139-1146.

 

13. Fisher, R. B. “Bee venom and chronic inflammatory disease.” The New Zealand medical journal 99, no. 808 (1986): 639.

 

14. Kwon, Young Bae, Hye Jung Lee, Ho Jae Han, Woung Chon Mar, Sung Keel Kang, Ok Byung Yoon, Alvin J. Beitz, and Jang Hern Lee. “The water-soluble fraction of bee venom produces antinociceptive and anti-inflammatory effects on rheumatoid arthritis in rats.” Life sciences 71, no. 2 (2002): 191-204.

 

15. Kwon, Young-bae, Jae-dong Lee, Hye-jung Lee, Ho-jae Han, Woung-chon Mar, Sung-keel Kang, Alvin J. Beitz, and Jang-hern Lee. “Bee venom injection into an acupuncture point reduces arthritis associated edema and nociceptive responses.” Pain 90, no. 3 (2001): 271-280.

 

16. Lee, Gihyun, and Hyunsu Bae. “Anti-inflammatory applications of melittin, a major component of bee venom: Detailed mechanism of action and adverse effects.” Molecules 21, no. 5 (2016): 616.

 

17. Lee, Jae-Dong, Hi-Joon Park, Younbyoung Chae, and Sabina Lim. “An overview of bee venom acupuncture in the treatment of arthritis.” Evidence-based complementary and alternative medicine 2 (2005).

 

18. Lee, Jae-Dong, Su-Young Kim, Tae-Woo Kim, Sang-Hoon Lee, Hyung-In Yang, Doo-Ik Lee, and Yun-Ho Lee. “Anti-inflammatory effect of bee venom on type II collagen-induced arthritis.” The American journal of Chinese medicine 32, no. 03 (2004): 361-367.

 

19. Lee, Ju Ah, Mi Ju Son, Jiae Choi, Ji Hee Jun, Jong-In Kim, and Myeong Soo Lee. “Bee venom acupuncture for rheumatoid arthritis: a systematic review of randomised clinical trials.” BMJ open 4, no. 11 (2014).

 

20. Lee, Myeong Soo, Max H. Pittler, Byung-Cheul Shin, Jae Cheol Kong, and Edzard Ernst. “Bee venom acupuncture for musculoskeletal pain: a review.” The Journal of Pain 9, no. 4 (2008): 289-297.

 

21. Won, Choong-Hee, Seong-Sun Hong, Christopher MH Kim, Chong-Hee Won, Seung-Back Kang, D-Hoon Lee, Young-Do Ko, Bong-Soon Chang, and You-Young Lee. “Efficacy of apitox (bee venom) for osteoarthritis: A randomized active-controlled trial.” Journal of the American Apitherapy Society 7, no. 3 (2000): 53-60.

 

22. Park, Hye Ji, Seong Ho Lee, Dong Ju Son, Ki Wan Oh, Ki Hyun Kim, Ho Sueb Song, Goon Joung Kim, Goo Taeg Oh, Do Young Yoon, and Jin Tae Hong. “Antiarthritic effect of bee venom: Inhibition of inflammation mediator generation by suppression of NF‐κB through interaction with the p50 subunit.” Arthritis & rheumatism 50, no. 11 (2004): 3504-3515.

 

23. Zurier, R. B., H. Mitnick, D. Bloomgarden, and G. Weissmann. “Effect of bee venom on experimental arthritis.” Annals of the rheumatic diseases 32, no. 5 (1973): 466.

 

24. Chung, Eun Sook, Himchan Kim, Gihyun Lee, Soojin Park, Hyunseong Kim, and Hyunsu Bae. “Neuro-protective effects of bee venom by suppression of neuroinflammatory responses in a mouse model of Parkinson’s disease: role of regulatory T cells.” Brain, behavior, and immunity 26, no. 8 (2012): 1322-1330.

 

25. Hwang, Deok-Sang, Sun Kwang Kim, and Hyunsu Bae. “Therapeutic effects of bee venom on immunological and neurological diseases.” Toxins 7, no. 7 (2015): 2413-2421.

 

26. Karimi, Akbar, Farhad Ahmadi, Kazem Parivar, Mohammad Nabiuni, Saied Haghighi, Sohrab Imani, and Hossein Afrouzi. “Effect of honey bee venom on lewis rats with experimental allergic encephalomyelitis, a model for multiple sclerosis.” Iranian journal of pharmaceutical research: IJPR 11, no. 2 (2012): 671.

 

27. Hwang, Deok-Sang, Sun Kwang Kim, and Hyunsu Bae. “Therapeutic effects of bee venom on immunological and neurological diseases.” Toxins 7, no. 7 (2015): 2413-2421.

 

28. Silva, J., Monge-Fuentes, V., Gomes, F., Lopes, K., Anjos, L. D., Campos, G., and Campos, L. (2015). Pharmacological alternatives for the treatment of neurodegenerative disorders: Wasp and bee venoms and their components as new neuroactive tools. Toxins,7(8), 3179-3209.

 

29. Lee, Sang Min, Eun Jin Yang, Sun-Mi Choi, Seon Hwy Kim, Myung Gi Baek, and Jing Hua Jiang. “Effects of bee venom on glutamate-induced toxicity in neuronal and glial cells.” Evidence-based complementary and alternative medicine: eCAM 2012 (2012).

 

30. Alizadehnohi, Masoumehzaman, Mohammad Nabiuni, Zahra Nazari, Zahra Safaeinejad, and Saeed Irian. “The synergistic cytotoxic effect of cisplatin and honey bee venom on human ovarian cancer cell line A2780cp.” Journal of venom research 3 (2012): 22.

 

31. Amini, Elaheh, Javad Baharara, Najmeh Nikdel, and Farzaneh Salek Abdollahi. “Cytotoxic and Pro-Apoptotic Effects of Honey Bee Venom and Chrysin on Human Ovarian Cancer Cells.” Asia Pacific Journal of Medical Toxicology 4, no. 2 (2015): 68-73.

 

32. Huh, Jeong-Eun, Yong-Hyeon Baek, Min-Ho Lee, Do-Young Choi, Dong-Suk Park, and Jae-Dong Lee. “Bee venom inhibits tumor angiogenesis and metastasis by inhibiting tyrosine phosphorylation of VEGFR-2 in LLC-tumor-bearing mice.” Cancer letters 292, no. 1 (2010): 98-110.

 

33. Jang, Mi-Hyeon, Min-Chul Shin, Sabina Lim, Seung-Moo Han, Hi-Joon Park, Insop Shin, Ji-Suk Lee, Kyoung-Ah Kim, Ee-Hwa Kim, and Chang-Ju Kim. “Bee venom induces apoptosis and inhibits expression of cyclooxygenase-2 mRNA in human lung cancer cell line NCI-H1299.” Journal of pharmacological sciences 91, no. 2 (2003): 95-104.

 

34. Kim, Yong-Wan, Pankaj Kumar Chaturvedi, Sung Nam Chun, Yang Gu Lee, and Woong Shick Ahn. “Honeybee venom possesses anticancer and antiviral effects by differential inhibition of HPV E6 and E7 expression on cervical cancer cell line.” Oncology reports 33, no. 4 (2015): 1675-1682.

 

35. Liu, Xing, Dawei Chen, Liping Xie, and Rongqing Zhang. “Effect of honey bee venom on proliferation of K1735M2 mouse melanoma cells in‐vitro and growth of murine B16 melanomas in‐vivo.” Journal of pharmacy and pharmacology 54, no. 8 (2002): 1083-1089.

 

36. Mahmoodzadeh, Amir, Hannaneh Zarrinnahad, Kamran Pooshang Bagheri, Ali Moradia, and Delavar Shahbazzadeh. “First report on the isolation of melittin from Iranian honey bee venom and evaluation of its toxicity on gastric cancer AGS cells.” Journal of the Chinese Medical Association 78, no. 10 (2015): 574-583.

 

37. Oršolić, Nada, Lidija Šver, Srđan Verstovšek, Svjetlana Terzić, and Ivan Bašić. “Inhibition of mammary carcinoma cell proliferation in vitro and tumor growth in vivo by bee venom.” Toxicon 41, no. 7 (2003): 861-870.

 

38. Rady, Islam, Imtiaz A. Siddiqui, Mohamad Rady, and Hasan Mukhtar. “Melittin, a major peptide component of bee venom, and its conjugates in cancer therapy.” Cancer letters 402 (2017): 16-31.

 

39. Russell, Pamela J., Dean Hewish, Teresa Carter, Katy Sterling-Levis, Kim Ow, Meghan Hattarki, Larissa Doughty et al. “Cytotoxic properties of immunoconjugates containing melittin-like peptide 101 against prostate cancer: in vitro and in vivo studies.” Cancer Immunology, Immunotherapy 53, no. 5 (2004): 411-421.

 

40. Zarrinnahad, Hannaneh, Amir Mahmoodzadeh, Monireh Parviz Hamidi, Mehdi Mahdavi, Ali Moradi, Kamran Pooshang Bagheri, and Delavar Shahbazzadeh. “Apoptotic effect of melittin purified from Iranian honey bee venom on human cervical cancer hela cell line.” International journal of peptide research and therapeutics 24, no. 4 (2018): 563-570.

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Artemisia Annua: A Potent Antimicrobial

Artemisia Annua: A Potent Antimicrobial

August 31, 2020

Artemisia Annua: A Potent Antimicrobial

by James Odell, OMD, ND, L.Ac.

Artemisia annua has been used in China for more than 2000 years to treat fevers and more recently used in the treatment of the chloroquine-resistant and cerebral malaria (Plasmodium falciparum). Much focus has now been paid to its effectiveness in the treatment of SARS-CoV-2 (Covid-19). Its ancient Chinese name Qing Hao literally means “green herb.” Qing Hao was mentioned in the ancient text (168BC) Wu Shi Er Bing Fang or “Recipes for Fifty-Two Ailments”, as a remedy for fevers. The genus Artemisia consists of over 400 species, many of which have an aromatic, bitter taste. Herbal extracts of Artemisia annua have been used for thousands of years in other parts of the world, particularly Southeast Asia, Africa, India, and South America, to treat malaria and a variety of infectious diseases. Apart from its anti-malarial properties, Artemisia annua has been used in traditional Chinese medicine to stimulate hair growth, to promote longevity, as a food additive, as an anti-inflammatory, as well as a treatment for numerous external illnesses including hemorrhoids, lice and boils. 

 

Botanical Aspects

 

Artemisia is a large, diverse plant genus with between 200 and 400 species and consists of hardy herbs and shrubs belonging to the Magnoliopsida class of flowering plants. Artemisia annua is an annual shrub of 50–150 cm in height. The shrub grows in temperate climates and is most widespread in China and Vietnam, but is also cultivated in East Africa, the United States, Russia, India, Brazil, and several other countries.1, 2 The reproduction of the shrub occurs by insects, self-pollination, and wind distribution.3

 

Artemisia annua Chemical Properties

 

The essential oil of Artemisia annua is rich in mono- and sesquiterpenes with numerous medicinal properties. Significant variations in its percentage and composition have been identified (main constituents may be camphor (up to 48%), germacrene D (up to 18.9%), artemisia ketone (up to 68%), and 1,8 cineole (up to 51.5%)). The oil has been subjected to numerous studies supporting exciting antiparasitic, antibacterial, antiviral, and antifungal activities. One of the more medicinal components found in Artemisia annua is artemisinin, first isolated in China in 1971.4

 

Artemisinin is the constituent with the greatest antimalarial activity. Up to 42% of the total artemisinin content is found in the upper leaves, where it accumulates in the glandular trichomes of the leaves. Artemisinin has been found in only two other species, Artemisia apiacea and Artemisia lance 5, and since that time its efficacy against malaria has been amply demonstrated.6, 7, 8, 9, 10, 11

 

The total amount of artemisinin found in different varieties of Artemisia annua varies slightly depending on extraction methods, different collection periods, different sample preparation, and different environmental influences.12 The artemisinin content in the plant exhibits the highest quantities usually just before flowering. Except for Artemisia annua, artemisinin is also present in Artemisia apiacea and Artemisia lancea, but only in minor quantities.13

 

Nowadays, many researchers are still investigating the effect of artemisinin and its analogues on the malarial parasite (Plasmodium) by modifying the structure of peroxides, ethers and ozonides in artemisinin. This improves the killing rate of plasmodium parasites for both in vitro and in vivo models as well as a faster clinical response for humans.14

 

Antimalarial Mechanism of Action of Artemisia annua

 

Malaria is one of the most severe public health problems worldwide. It is a leading cause of death and disease in many developing countries, where young children and pregnant women are the groups most affected. Worldwide an estimated 450,000 deaths annually (around 1200 per day) are attributed to malaria. This infection is caused primarily by the Plasmodium falciparum parasite, which largely reside in red blood cells and contains iron-rich heme-groups (in the form of hemozoin). Such hematophagous organisms digest hemoglobin and release high quantities of free heme, which is the non-protein component of hemoglobin. As a result, hemozoin pigment and other toxic factors such as glycosylphosphatidylinositol (GPI) are also released into the blood. These products, particularly the GPI, activate macrophages and endothelial cells to secrete cytokines and inflammatory mediators such as tumor necrosis factor, interferon-γ, interleukin-1, IL-6, IL-8, macrophage colony-stimulating factor, and lymphotoxin, as well as superoxide and nitric oxide. These inflammatory cytokines and mediators can cause significant damage to organs and tissues.15, 16, 17

 

The parasite is fairly shielded from attack by the body’s immune system since it resides within the liver and blood cells for much of its human life cycle and is relatively invisible to immune surveillance. However, circulating infected blood cells are destroyed in the spleen. To avoid this fate, the Plasmodium falciparum parasite displays adhesive proteins on the surface of the infected blood cells, causing the blood cells to stick to the walls of small blood vessels, thus sequestering the parasite from passage through the general circulation and the spleen. Sequestered red blood cells can breach the blood-brain barrier and cause cerebral malaria. Artemisinin is also active against other parasite species such as Toxoplasma and Babesia that do not contain hematin.

 

Chemically, artemisinin is a sesquiterpene lactone that contains an unusual peroxide bridge. This 1, 2, 4-trioxane ring of endoperoxide is responsible for the drug’s mechanism of action.  Thus, the proposed antimalarial mechanism of action of artemisinin involves cleavage of endoperoxide bridges by iron, producing free radicals (hypervalent iron-oxo species, epoxides, aldehydes, and dicarbonyl compounds) which damage biological macromolecules causing oxidative stress in the cells of the parasite.18, 19

 

Artemisinins have also been investigated for their anti-proliferative activity against a wide range of cancer cell lines. Artemisinin results in decreased proliferation, increased levels of oxidative stress, induction of apoptosis and inhibition of angiogenesis in cancer cells. Artemisinins have also been shown to inhibit the falcipains, a papain family cysteine protease that aids hemoglobin degradation.20

 

Cultivation

 

Over the last ten years as the worldwide demand for artemisinin has become evident, Chinese, Vietnamese, African, and Indian plant breeding institutes have developed high-yielding Artemisia hybrids. Factories were developed in all three countries to extract artemisinin and manufacture its anti-malarial compounds. East African factories are currently exporting artemisinin to pharmaceutical factories in India and Europe, where the final products are made.

 

Drug resistance is a growing issue for the treatment of malaria in the 21st-century. Resistance is now common against all classes of antimalarial drugs except for artemisinins. Artemisinin treatment of resistant drug strains has therefore become increasingly popular. Unfortunately, while the cost of cultivation and production of artemisia is lower than that of other competitive pharmaceuticals, politics involving the pharmaceutical industry have restricted their use in the developing world.

From Quinine to Chloroquine to Hydroxychloroquine to Artemisinin

 

In 1820, the first antimalarial drug quinine was extracted from cinchona bark by French pharmacists Pelletier and Caventou.21 In the 1940s, limited by the raw materials for quinine extraction, German scientists synthesized chloroquine, which is similar to natural quinine in chemical structure.

In 1950, chemists Alexander Surrey and Henry Hammer published the synthesis of hydroxychloroquine which was even more effective with less toxicity.

By the mid-20th century, malaria was gradually controlled in China. However, parts of Africa still suffer high epidemic proportions of malaria. In the 1960’s an epidemic broke out which spread rapidly in Southeast Asia and South America. In addition, the plasmodium falciparum parasite was developing a resistance to chloroquine and hydroxychloroquine. Inspired by ancient books of traditional Chinese medicine, Youyou Tu, a Chinese scientist, successfully extracted artemisinin from Artemisia annua. With a 100% inhibition rate against plasmodium, artemisinin is now used for chloroquine and hydroxychloroquine resistant malaria. For her work, Tu was awarded the 2011 Lasker Award in clinical medicine and the 2015 Nobel Prize in Physiology or Medicine jointly with William Campbell and Satoshi Ōmura. Tu is the first Chinese Nobel laureate in physiology or medicine and the first female citizen of the People’s Republic of China to receive a Nobel Prize in any category.22

Antiviral Effects of Chloroquine and Hydroxychloroquine

 

To better understand the therapeutic antiviral similarities of chloroquine derivatives and Artemisia annua extracts it is beneficial to review the antiviral background of chloroquine. Chloroquine has been confirmed to be effective during epidemics of various infectious diseases, especially Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome Coronavirus (MERS). In 2003, SARS broke out in China. According to the World Health Organization, a total of 8,098 people worldwide became sick with SARS during this outbreak, of whom 774 died. In 2004, MarcVan Ranst and colleagues found that chloroquine effectively inhibited SARS coronavirus replication in vitro.23

 

In 2005, Stuart Nichol and colleagues found that chloroquine suppressed SARS virus replication both before and after infection, suggesting a preventative and therapeutic role of chloroquine against SARS.24

 

In 2014 Eric Snijder and colleagues successfully inhibited MERS coronavirus replication by chloroquine in monkeys, with similar suppressive effect against SARS and human coronavirus.25 Additionally, chloroquine has also been reported to inhibit Human Immunodeficiency Virus (HIV), Zika virus (ZIKV), and dengue virus (DENV).26 Chloroquine phosphate was also reported to alleviate lung autophagy induced by avian influenza A (H5N1) and reduce alveolar injury in mice.27

 

February 2020, Wuhan Virus Research Institute of the Chinese Academy of Sciences and other units jointly published the results on cell research, which showed that chloroquine phosphate effectively inhibited SARS-Cov-2 and such inhibition was superior as compared to Remdesivir.28 Other recent studies have validated those findings.29, 30

 

The antiviral mechanisms of chloroquine and hydroxychloroquine on SARS-Cov-2 is proposed as follows:

 

1) To weaken the binding of the virus to the receptor by interfering with the terminal glycosylation of the receptor protein angiotensin 2 receptor invertase of coronavirus.

2) As an alkaline drug, chloroquine increases pH value inside endosomes which was not conducive for virus-cell fusion.

3) Inhibits cell autophagy and regulates host immune reaction to suppress viral infection and replication.

4) Suppresses transcription and translation of virus protein by binding to viral protease; and

5) Alleviates cytokine storm through inhibiting the production and release of TNF-α and IL-6.

 

In June 2020, the U.S. Food and Drug Administration revoked the emergency use authorization that allowed for chloroquine phosphate and hydroxychloroquine sulfate to be used to treat certain hospitalized patients with COVID-19 when a clinical trial was unavailable, or participation in a clinical trial was not feasible. More than 35 states have now restricted prescriptions for hydroxychloroquine, and at least five of those have rules specifically prohibiting prescribing the drug as a preventive measure. Fortunately, we still have artemisia extracts and other immunological nutrients (vitamin D3, zinc, vitamin C) available – for now.

 

Artemisia annua Extracts Effective Against Viruses

 

Due to its similar history to chloroquine in the treatment of malaria and viruses, scientists at several institutions have researched whether extracts of Artemisia annua – pure artemisinin and related derivatives – may be effective against the COVID-19 virus. These compounds would be attractive candidates for immediate use as they have an excellent safety profile, are readily available, and are relatively inexpensive.

 

Numerous in vitro studies have reported that artemisinins have antiviral properties. Artemisinins reduce replication rates of hepatitis B and C viruses 31, 32, a range of human herpes viruses 33, 34, 35, HIV-1 36, influenza virus A 37, 38, and a bovine viral diarrhea virus39, in the low micromolar range. 

 

Like chloroquine, Artemisia annua extracts have even shown significant activity against the SARS coronavirus. In 2003, Li and colleagues showed that artemisinin was effective in treating SARS-CoV in vitro.40 Since the beginning of the COVID-19 pandemic, formulations of Artemisia annua have been used in Africa, Madagascar, and China for both COVID-19 prevention and treatment.41

 

Last June 2020, chemists at the Max Planck Institute of Colloids and Interfaces (Potsdam, Germany) in close collaboration with virologists at Freie Universität Berlin demonstrated in laboratory studies that aqueous and ethanolic extracts Artemisia annua are active against the SARS-CoV-2 (COIVID-19) virus. Human clinical trials to test the efficacy of both teas and coffee containing Artemisia annua are about to begin at the University of Kentucky’s academic medical center.42 Artemisia annua leaves, from a cultivated seed line grown by ArtemiLife Inc.in Kentucky, USA, when extracted with absolute ethanol or distilled water produces the strongest antiviral activity. The addition of either ethanolic or aqueous Artemisia annua extracts prior to the introduction of the virus resulted in significantly reduced plaque formation. The most active extract of both Artemisia annua and coffee was found to be ethanolic. However, artemisinin alone does not present much antiviral activity. “I was surprised to find that A. annua extracts worked significantly better than pure artemisinin derivatives and that the addition of coffee further enhanced the activity” says Klaus Osterrieder, Professor of Virology at Freie Universität Berlin who conducted all activity assays.

 

In SARS-CoV-2 (COVID-19), cellular adaptive immunity is primarily involved, in particular, CD8 and CD4 lymphocytes that stimulate the B lymphocytes responsible for the production of antibodies targeting the coronavirus. In addition, there is a cytokine storm in patients infected with SARS-CoV-2 which is responsible for a major inflammatory response and their very severe progressive clinical state. The increase in interleukin-10 and TNF alpha reduces CD4 counts, causes functional exhaustion of immune cells, and induces, at their site of action (liver, vascular endothelium), runaway production and action of inflammatory proteins, resulting in secondary aggravation of COVID-19 patients.

 

Artemisia annua has extensively recognized antiviral activity (anti HSV1, Poliovirus, RSV, hepatitis C anti-virus, type 2 dengue virus, hantavirus, human cytomegalovirus) and anti-HIV in vitro, due in partto the artemisinin, flavonoids, quercetin and dicaffeoylquinic acids it contains. These molecules have been shown to inhibit the enzymatic activity of CLPro (Chymotrypsin-like protease), an enzyme produced by SARS-CoV-2.

 

The antiviral action of Artemisia annua, which is achieved by stimulating adaptive immunity, regulating the production of the pro-inflammatory cytokines prostaglandin E2 (PGE2), IL-6, IL-10, TNF alpha, and increasing the genesis of CD4, CD8 and interferon gamma, involves many minerals and biomolecules: the properties of flavonoids, polyphenols, triterpenes, sterols, saponins, polysaccharides, artemisinin and its derivatives, the concentration of zinc, gallium and selenium in the plant play a role in the immune, antiviral, antioxidant and anti-inflammatory response.

 

The plant is rich in vitamins A and E, of which one, when supplemented, is known to reduce morbidity and mortality in viral infections, notably HIV among others, and the other is a powerful antioxidant. Therefore the combination of these biomolecules and the intake of Artemisia annua may strengthen the exhausted adaptive immunity and modulate the runaway inflammatory response during COVID-19 infection, as has already been demonstrated in other serious viral and parasitic infections.

 

As more research develops it is likely that Artemisia annua extracts will take their place as a first-line defense against coronaviruses. Given that this plant has been extensively used for more than 2000 years in traditional Chinese medicine for treatment of fever, viruses, and malaria, the evidence argues for the inclusion of inexpensive Artemisia annua dried leaf tablets, capsules, or teas into the arsenal of remedies to combat coronavirus.

 

Lastly, malaria treatment is more complicated for human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) patients. Malaria and HIV co-infection represents a major health burden in Africa, primarily because it is now well known that HIV infection results in a higher incidence and more severe manifestations of malaria. With a compromised immune system, AIDS patients are more susceptible to malaria and respond slower to malaria therapy. In several studies and in clinical observation, Artemisia annua has demonstrated anti-HIV activity.43, 44 Hence, the use of Artemisia annua not only treats malaria but should also enhance the well-being of HIV/AIDS patients.

 

Preparation and Dosage

 

Artemisia annua is typically prepared as a tea extracted with water according to the rules of traditional Chinese medicine. There have been few well-controlled studies investigating the extraction, recovery, and stabilization of artemisinin and other compounds in Artemisia annua tea infusions. A systematic study of preparations of Artemisia annua therapeutic tea infusion was performed by van der Kooy and colleagues.45 This study showed that nearly 93% of available artemisinin was extracted from dried Artemisia annua leaves, but only under certain conditions. The best preparation method was: 9 g dried leaves/L, for 5 min at 100 °C. Subsequent storage of the tea infusion at room temperature showed that the concentration of artemisinin was stable for more than 24 hours. This is important for malaria-endemic locations where there is no refrigeration. Other studies using the same extraction protocol also measured the extraction and stability of artemisinin and certain key flavonoids in the tea. Artemisinin was found to be stable at room temperature for up to 48 hours.46 However, some flavonoids were poorly extracted and not stable at room temperature, therefore it may be best to refrigerate after the infusion is complete.47

 

Clearly, if a tea infusion is to be a therapeutic option, it must be prepared and consumed consistently and reliably.  Artemisia annua is also available commercially in extracts such as capsules and tinctures. As with all herbal remedies, the correct dosage depends on a variety factors such as the illness treated, the age of the person, health status, and number of other conditions.

 

Herb-Drug Reactions

 

Artemisinin has no reported toxicity if taken in recommended doses for a limited period of time.51 In animal studies, artemisinin has been used in high oral doses in dogs and rabbits52 and at 200-300 mg/kg BW in mice53 without toxicity. Artemisinin has been effective against Plasmodium in humans at doses of approximately 30 mg/kg BW, but it has poor bioavailability and a short half-life that is quickly eliminated from the body.54, 55 Artemisinin derivatives (dihydroartemisinin, artesunate, artemether, arteether) present better bioavailability and antimalarial activity than artemisinin, but have different safety margins than artemisinin. The bioavailability and half-lives also vary with the delivery mechanism (intramuscular, intravenous, intraperitoneal, oral).

 

Conclusion

 

Evidence is mounting for the therapeutic effectiveness of the use of Artemisia annua not only in the treatment of malaria, but also for various viruses, including coronaviruses. The complex mixture of antiparasitic compounds in the plant appears to account for its therapeutic activity with the animal and human trials supporting this claim. It is also clear that the cost of using Artemisia annua is a fraction of that for any other existing or potential antimalarial or antiviral treatment. Considering that for more than 2000 years this plant was used in traditional Chinese medicine for the treatment of fever with little to no significant toxicity and no clear signs of artemisinin drug resistance. Thus, the cumulative evidence argues for the inclusion of Artemisia annua extracts,tinctures, and teas into the arsenal of remedies to not only combat malaria, but also numerous other diseases, particularly viruses.

 

References

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2. Bhakuni, D.S., Goel, A.K., Jain, S., Mehrotra, B.N., Srimal, R.C., 1990. Screening of Indian plants for biological activity: part XIV. Indian Journal of Experimental Biology 28, 619–637.

 

3. Bown, Deni. The Royal Horticultural Society encyclopedia of herbs & their uses. Dorling Kindersley Limited, 1995.

 

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5. Tan, Ren Xhiang, W. F. Zheng, and H. Q. Tang. “Biologically active substances from the genus Artemisia.” Planta medica 64, no. 04 (1998): 295-302.

 

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7. Mueller, Markus S., I. B. Karhagomba, Hans Martin Hirt, and Emmanuel Wemakor. “The potential of Artemisia annua L. as a locally produced remedy for malaria in the tropics: agricultural, chemical and clinical aspects.” Journal of ethnopharmacology 73, no. 3 (2000): 487-493.

 

8. Mueller, Markus S., Nyabuhanga Runyambo, Irmela Wagner, Steffen Borrmann, Klaus Dietz, and Lutz Heide. “Randomized controlled trial of a traditional preparation of Artemisia annua L.(Annual Wormwood) in the treatment of malaria.” Transactions of the Royal Society of Tropical Medicine and Hygiene 98, no. 5 (2004): 318-321.

 

9. Balint, Gabor A. “Artemisinin and its derivatives: an important new class of antimalarial agents.” Pharmacology & therapeutics 90, no. 2-3 (2001): 261-265.

 

10. Van Agtmael, Michiel A., Teunis A. Eggelte, and Chris J. van Boxtel. “Artemisinin drugs in the treatment of malaria: from medicinal herb to registered medication.” Trends in Pharmacological Sciences 20, no. 5 (1999): 199-205.

 

11. De Ridder, Sanne, Frank Van der Kooy, and Robert Verpoorte. “Artemisia annua as a self-reliant treatment for malaria in developing countries.” Journal of ethnopharmacology 120, no. 3 (2008): 302-314.

 

12. Delabays, N., Simonnet, X., Gaudin, M., 2001. The genetics of artemisinin content in Artemisia annua L. and the breeding of high yielding cultivars. Current Medicinal Chemistry 8, 1795–1801.

 

13. Hsu, E., 2006. The history of Qing Hao in the Chinese Materia medica. Transactions of the Royal Society of Tropical Medicine and Hygiene 100, 505–508.

 

14. De Ridder, Sanne, Frank Van der Kooy, and Robert Verpoorte. “Artemisia annua as a self-reliant treatment for malaria in developing countries.” Journal of ethnopharmacology 120, no. 3 (2008): 302-314.

 

15. Fakhreldin M. Omer, J. Brian de Souza, Eleanor M. Riley. Differential Induction of TGF-{beta} Regulates Proinflammatory Cytokine Production and Determines the Outcome of Lethal and Nonlethal Plasmodium yoelii Infections. J. Immunol. 2003;171;5430-5436.

 

16. Claire L. Mackintosh, James G. Beeson, Kevin Marsh. Clinical features and pathogenesis of severe malaria. Trends in Parasitology December 2004;20(12):597-603.

 

17. Ian A Clark, Alison C Budd, Lisa M Alleva, William B Cowden. Human malarial disease: a consequence of inflammatory cytokine release. Malaria Journal. 2006;5:85.

 

18. Cumming, Jared N., Poonsakdi Ploypradith, and Gary H. Posner. “Antimalarial activity of artemisinin (qinghaosu) and related trioxanes: mechanism (s) of action.” In Advances in pharmacology, vol. 37, pp. 253-297. Academic Press, 1996.

 

19. Posner, Gary H., and Paul M. O’Neill. “Knowledge of the proposed chemical mechanism of action and cytochrome P450 metabolism of antimalarial trioxanes like artemisinin allows rational design of new antimalarial peroxides.” Accounts of chemical research 37, no. 6 (2004): 397-404.

 

20. O’neill, Paul M., Victoria E. Barton, and Stephen A. Ward. “The molecular mechanism of action of artemisinin—the debate continues.” Molecules 15, no. 3 (2010): 1705-1721.

 

21. Pai-Dhungat, J. V. “Caventou, Pelletier &-History Of Quinine.” Journal of the Association of Physicians of India 63 (2015).

 

22. Chang, Zengyi. “The discovery of Qinghaosu (artemisinin) as an effective anti-malaria drug: a unique China story.” Science China Life Sciences 59, no. 1 (2016): 81-88.

 

23. Keyaerts, Els, Leen Vijgen, Piet Maes, Johan Neyts, and Marc Van Ranst. “In vitro inhibition of severe acute respiratory syndrome coronavirus by chloroquine.” Biochemical and biophysical research communications 323, no. 1 (2004): 264-268.

 

24. Vincent, Martin J., Eric Bergeron, Suzanne Benjannet, Bobbie R. Erickson, Pierre E. Rollin, Thomas G. Ksiazek, Nabil G. Seidah, and Stuart T. Nichol. “Chloroquine is a potent inhibitor of SARS coronavirus infection and spread.” Virology journal 2, no. 1 (2005): 1-10.

 

25. De Wilde, Adriaan H., Dirk Jochmans, Clara C. Posthuma, Jessika C. Zevenhoven-Dobbe, Stefan Van Nieuwkoop, Theo M. Bestebroer, Bernadette G. Van Den Hoogen, Johan Neyts, and Eric J. Snijder. “Screening of an FDA-approved compound library identifies four small-molecule inhibitors of Middle East respiratory syndrome coronavirus replication in cell culture.” Antimicrobial agents and chemotherapy 58, no. 8 (2014): 4875-4884.

 

26. Al-Bari MAA. Targeting endosomal acidification by Chloroquine analogs as a promising strategy for the treatment of emerging viral diseases. Pharmacol Res Perspect 2017, 5: e00293

 

27. Yan Y, Zou Z, Sun Y, et al. Anti-malaria drug Chloroquine is highly effective in treating Avian Influenza A H5N1 virus infection in an animal model. Cell Res 2013, 23: 300-2.

 

28. Wang, Manli, Ruiyuan Cao, Leike Zhang, Xinglou Yang, Jia Liu, Mingyue Xu, Zhengli Shi, Zhihong Hu, Wu Zhong, and Gengfu Xiao. “Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro.” Cell research 30, no. 3 (2020): 269-271.

 

29. Gao, Jianjun, Zhenxue Tian, and Xu Yang. “Breakthrough: Chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies.” Bioscience trends (2020).

 

30. Gautret, Philippe, Jean-Christophe Lagier, Philippe Parola, Line Meddeb, Morgane Mailhe, Barbara Doudier, Johan Courjon et al. “Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial.” International journal of antimicrobial agents (2020): 105949.

 

31. Paeshuyse, Jan, Lotte Coelmont, Inge Vliegen, Jan Vandenkerckhove, Eric Peys, Benedikt Sas, Erik De Clercq, and Johan Neyts. “Hemin potentiates the anti-hepatitis C virus activity of the antimalarial drug artemisinin.” Biochemical and biophysical research communications 348, no. 1 (2006): 139-144.

 

32. Romero, Marta R., Thomas Efferth, Maria A. Serrano, Beatriz Castaño, Rocio IR Macias, Oscar Briz, and Jose JG Marin. “Effect of artemisinin/artesunate as inhibitors of hepatitis B virus production in an “in vitro” replicative system.” Antiviral research 68, no. 2 (2005): 75-83.

 

33. Efferth, Thomas, Manfred Marschall, Xin Wang, Shu-Mei Huong, Ilona Hauber, Armin Olbrich, Martina Kronschnabl, Thomas Stamminger, and Eng-Shang Huang. “Antiviral activity of artesunate towards wild-type, recombinant, and ganciclovir-resistant human cytomegaloviruses.” Journal of molecular medicine 80, no. 4 (2002): 233-242.

 

34. Kaptein, Suzanne JF, Thomas Efferth, Martina Leis, Sabine Rechter, Sabrina Auerochs, Martina Kalmer, Cathrien A. Bruggeman, Cornelis Vink, Thomas Stamminger, and Manfred Marschall. “The anti-malaria drug artesunate inhibits replication of cytomegalovirus in vitro and in vivo.” Antiviral research 69, no. 2 (2006): 60-69.

 

35. Naesens, Lieve, Pascale Bonnafous, Henri Agut, and Erik De Clercq. “Antiviral activity of diverse classes of broad-acting agents and natural compounds in HHV-6-infected lymphoblasts.” Journal of clinical virology 37 (2006): S69-S75.

 

36. Naesens, Lieve, Pascale Bonnafous, Henri Agut, and Erik De Clercq. “Antiviral activity of diverse classes of broad-acting agents and natural compounds in HHV-6-infected lymphoblasts.” Journal of clinical virology 37 (2006): S69-S75.

 

37. Efferth, Thomas, Manfred Marschall, Xin Wang, Shu-Mei Huong, Ilona Hauber, Armin Olbrich, Martina Kronschnabl, Thomas Stamminger, and Eng-Shang Huang. “Antiviral activity of artesunate towards wild-type, recombinant, and ganciclovir-resistant human cytomegaloviruses.” Journal of molecular medicine 80, no. 4 (2002): 233-242.

 

38. Qian, R. S., Z. L. Li, J. L. Yu, and D. J. Ma. “The immunologic and antiviral effect of qinghaosu.” Journal of traditional Chinese medicine= Chung i tsa chih ying wen pan 2, no. 4 (1982): 271.

 

39. Romero, Marta R., Maria A. Serrano, Marta Vallejo, Thomas Efferth, Marcelino Alvarez, and Jose JG Marin. “Antiviral effect of artemisinin from Artemisia annua against a model member of the Flaviviridae family, the bovine viral diarrhoea virus (BVDV).” Planta medica 72, no. 13 (2006): 1169-1174.

 

40. Lin, L., Han, Y., & Yang, Z. M. (2003). Clinical observation on 103 patients of severe acute respiratory syndrome treated by integrative traditional Chinese and Western Medicine. Zhongguo Zhong xi yi jie he za zhi Zhongguo Zhongxiyi jiehe zazhi= Chinese journal of integrated traditional and Western medicine, 23(6), 409.

 

41. Suryanarayana, Lakavath, and Dhanalaxmi Banavath. “A Review On Identification of Antiviral Potential Medicinal Plant Compounds Against with COVID-19.” International Journal of Research in Engineering, Science and Management 3, no. 3 (2020): 675-679.

 

42. Gilmore, K.; Osterrieder, K.; Seeberger, P.H. (2020): “Artemisia annua Plant Extracts are Active Against SARS-CoV-2 In Vitro”, in: submitted for publication

 

43. Marchand, Els, Magnus A. Atemnkeng, Stijn Vanermen, and Jacqueline Plaizier‐Vercammen. “Development and validation of a simple thin layer chromatographic method for the analysis of artemisinin in Artemisia annua L. plant extracts.” Biomedical chromatography 22, no. 5 (2008): 454-459.

 

44. Lubbe, Andrea, Isabell Seibert, Thomas Klimkait, and Frank Van der Kooy. “Ethnopharmacology in overdrive: the remarkable anti-HIV activity of Artemisia annua.” Journal of ethnopharmacology 141, no. 3 (2012): 854-859.

 

45. van der Kooy, Frank, and Robert Verpoorte. “The content of artemisinin in the Artemisia annua tea infusion.” Planta Medica-Natural Products and MedicinalPlant Research 77, no. 15 (2011): 1754.

 

46. Carbonara, Teresa, Rossana Pascale, Maria Pia Argentieri, Paride Papadia, Francesco Paolo Fanizzi, Luciano Villanova, and Pinarosa Avato. “Phytochemical analysis of a herbal tea from Artemisia annua L.” Journal of Pharmaceutical and Biomedical Analysis 62 (2012): 79-86.

 

47. Weathers, Pamela J., and Melissa J. Towler. “The flavonoids casticin and artemetin are poorly extracted and are unstable in an Artemisia annua tea infusion.” Planta medica 78, no. 10 (2012): 1024.

 

48. Xing J, Kirby BJ, Whittington D, et al. Evaluation of P450 inhibition and induction by artemisinin antimalarials in human liver microsomes and primary human hepatocytes. Drug Metab Dispos. 2012 Sep;40(9):1757-64.

 

49. Burk, O., Arnold, K.A., Nussler, A.K., Schaeffeler, E., Efimova, E., Avery, B.A., Avery, M.A., Fromm, M.F., Eichelbaum, M., 2005. Antimalarial artemisinin drugs induce cytochrome P450 and MDR1 expression by activation of xenosensors pregnane X receptor and constitutive androstane receptor. Molecular Pharmacology 67, 1954–1965.

 

50. Svensson, Ulrika SH, and M. Ashton. “Identification of the human cytochrome P450 enzymes involved in the in vitro metabolism of artemisinin.” British journal of clinical pharmacology 48, no. 4 (1999): 528.

 

51. Meshnick, Steven R. “Artemisinin: mechanisms of action, resistance and toxicity.” International journal for parasitology 32, no. 13 (2002): 1655-1660.

 

52. Zhao, K., Song, Z., 1990. The pharmacokinetics of dihydroqinghaosu given orally to rabits and dogs (chinese). Acta Pharmaceutica Sinica 25:161–163.

 

53. Shuhua, X., Catto, B.A., 1989. In vitro and in vivo studies of the effect of artemether on Schistosoma mansoni. Antimicrobial Agents and Chemotherapy 33:1557–1562.

 

54. Titulaer, H.A.C., Zuidema, J., Kager, P.A., Wetsteyn, J.C.F.M., Lugt, C.B., Merkus, F.W.H.M., 1990. The pharmacokinetics of artemisinin after oral, intramuscular and rectal administration to volunteers. J. Pharm. Pharmacol. 42:810–813.

 

55. Navaratman, V., Mansor, S.M., Chin, L.K., Mordi, M.N., Asokan, M., Nair, N.K., 1995. Determination of artemether and dihydroartemisinin in blood plasma by highperformance liquid chromatography for application in clinical pharmacological studies. J.Chrom. 669:289–294.

Recent Posts

Overview of Lyme Borreliosis (A Bioregulatory Medicine Approach)

Overview of Lyme Borreliosis (A Bioregulatory Medicine Approach)

July 1, 2020

Overview of Lyme Borreliosis (A Bioregulatory Medicine Approach)

by: James Odell, OMD, ND, L.Ac., BRMI Medical Director

The information in this monograph is intended to help users better understand current diagnostic and bioregulatory medicine treatment protocols related to tick-borne illnesses. Information is based on review of scientific research data, historical practice patterns, and clinical experience. This information should not be interpreted as specific medical advice. The management of tick-borne illnesses in any given patient must be approached on an individual basis using the practitioner’s best judgment. Users should seek the advice of a physician before using any protocol listed in this monograph. The protocols raise many issues that are subject to change as new data emerge. The reader assumes the risk of any injuries. None of the suggested protocol regimens can guarantee health benefits. Users should consult with a qualified healthcare provider for specific questions regarding therapies, diagnosis and/or health conditions, prior to making therapeutic decisions. ——————— Lyme disease, also called Borreliosis, might be the most insidious and least understood of infectious diseases of our day. Lyme disease is an infection that is caused by different genospecies of the Borrelia bacteria and primarily transmitted by the bite of an infected tick. According to Center for Disease Control (CDC) reports, Lyme disease caused by Borrelia is currently the most common vector-borne disease in the United States.1 There are several species, subspecies and strains of this bacteria. This great diversity of species and strains contributes to its ability to evade the immune system and antibiotic therapy, thus leading to a chronic infection (post-treatment Lyme disease syndrome or PTLDS). PTLDS is often associated with neurological symptoms that are both debilitating and increasingly difficult to treat with conventional antibiotics.2 The Borrelia spirochete has developed numerous adaptive features that makes it unique among pathogenic bacteria and thus can lead to PTLDS.3

Borrelia’s Adaptive Features

Borrelia’s adaptive features ensure its survival and confer resistance to antibiotics. Borrelia, like the bacteria that causes syphilis, is a spirochete. Spirochetes are a group of bacteria that have a unique mode of motility by means of axial filaments called endoflagella. When these filaments rotate, the spirochetes move in cork-screw fashion. This type of movement is thought to be an adaptation to viscous environments, such as aquatic sediments, biofilms, mucosal tissues, collagen tissue and the intestinal tracts of animals. This feature allows the spirochetes to hide their flagella from the host immune defenses. Borrelia’s membrane has a composition like the cells of mammals in that it contains phosphatidylcholine (PC), a type of phospholipid. Phospholipids are a class of lipids or fats that are a major component of all cell membranes. Because our nervous system is rich in PC, the spirochete tends to associate itself with our nervous system as a source of PC for its membrane. Hence, it feeds on us. It has also been suggested that having a cell membrane high in PC, and therefore “looking” like one of our own cells, may aid Borrelia in its effort to avoid our immune system.4

Borrelia has one of the most advanced and complex DNA structures of any bacteria known. This allows it to assess its surrounding chemistry and alter its cell membrane to ensure its survival. Thus, Borrelia is the ultimate escape artist. It can invade a variety of cells, including endothelium, fibroblasts, lymphocytes, macrophages, keratinocytes, synovium, and most recently neuronal and glial cells. By “hiding” inside these cells, the spirochete can evade the immune system and be protected to varying degrees against white cells and antibiotics, allowing the infection to persist.5 The spirochete can change its form to rounded forms, sometimes called spheroplasts, which either lack a cell wall or have a damaged cell wall.6 This too is a survival technique that can protect it from antibiotics. Data suggest these rounded cells are virulent and infectious, can survive under adverse environmental conditions, and may revert to the spiral form, once conditions are more favorable. Antibiotics are ineffective against these spheroplasts.7, 8, 9

Stages and Manifestations of Lyme Borreliosis

The disease is described as having three stages: early localized, early disseminated and late disseminated. However, the stages can overlap and not all patients go through all three. A bull’s-eye rash is usually considered one of the first signs of infection, but many people develop a different kind of rash or none at all. The last stage, because of domination of neurologic symptomatology, is called “neuroborreliosis”. The brain has a highly selective permeable barrier called the blood-brain barrier that normally protects the brain from foreign invaders. However, Borrelia‘s unique characteristics allow it to penetrate this protective barrier. Thus, neurological symptoms are present with chronic Lyme disease because Borrelia and its endotoxins (neurotoxins) infect the brain and central nervous system causing inflammation and various neurological symptoms such as pain, headaches, tremors, seizures, and brain fog.10

It has been said that the longer one is ill with Lyme the more endotoxin/neurotoxin is present in the body.  It probably is stored in fatty tissues, and once present, persists for a very long time.  This may be because of enterohepatic circulation, where the toxin is excreted via the bile into the intestinal tract, but then is reabsorbed from the intestinal tract back into the blood stream. Mainstream infectious disease doctors argue that there is no evidence that Lyme borreliosis remains in the body after a few weeks to a month of antibiotic treatment. The laundry list of symptoms in patients may be persistent, but these conventional doctors claim that it is not due to a chronic Lyme infection. On the other side, many doctors that specialize in Lyme disease blame Borrelia and coinfections for triggering chronic neurological and psychiatric symptoms.

A comprehensive therapeutic bioregulatory medicine approach considers the stage as well as the individual’s unique constitution and the biological terrain that is affected.

Spirochetes have an affinity for connective tissue. The following are 5 tissues that are commonly infected:

  • ligaments and joints (asymmetric affliction of large joints, especially hip and knee)

  • skin and subcutaneous tissues (collagen breakdown and premature aging)

  • meninges and astroglia (connective tissue of brain)

  • heart tissue

  • aqueous humor of the eye

Symptoms Borrelia spirochete releases bacterial lipoproteins (BLP) which cause numerous symptoms. The following is a checklist of common symptoms seen in various stages of Lyme disease:

Localized Early (Acute) Stage:

  • Solid red or bull’s-eye rash, usually at site of bite

  • Swelling of lymph glands near tick bite

  • Generalized achiness

  • Headache

Early Disseminated Stage:

  • Two or more rashes not at site of bite

  • Migrating pains in joints/tendons

  • Headache

  • Stiff, aching neck

  • Facial palsy (facial paralysis like Bell’s palsy)

  • Tingling or numbness in extremities

  • Multiple enlarged lymph glands

  • Abnormal pulse

  • Sore throat

  • Changes in vision

  • Fever of 100 to 102 F

  • Severe fatigue

Late Stage:

  • Arthritis (pain/swelling) of one or two large joints

  • Disabling neurological disorders (disorientation; confusion; dizziness; short-term memory loss; inability to concentrate, finish sentences or follow conversations; mental “fog”)

  • Numbness in arms/hands or legs/feet

Basic Bioregulatory Medicine Approaches for Lyme and its Co-infections The goals in treating Lyme disease are to eliminate the Borrelia infection, to resolve symptoms and return patients to their prior quality of life, and to prevent patients from experiencing recurrent episodes from an untreated or inadequately treated infection. There are at least five basic guiding principles used to achieve this goal.

1. Decrease pathogenic microbial load

 

2. Improve the intestinal and oral microbiome

 

3. Decrease total toxic body burden

 

4. Balance and modulate the immune system, thereby improving the bodies’ natural defenses and reducing inflammation

 

5. Improve bioregulatory mechanisms (heme synthesis and methylation) with supplementation

To achieve this, it is necessary to utilize a comprehensive multitherapeutic approach in the treatment of Lyme and its coinfections. The following list (though far from complete) describes therapies used towards these principles:

  • Identify food allergens and eliminate those foods. Diets that are pro-inflammatory and depleted of nutrients (i.e., the average American diet) cause imbalances in the body’s biochemistry. Specifically, the body will become more acidic and inflamed, and less oxygen will be available on the cellular level. Consider a low lectin11, anti-inflammatory diet as described in The Plant Paradox by Steven Gundry, MD.

  • Decrease microbial load using plant-based antimicrobials, IV ozone therapy and ozonated rizols (Biopure). There are several herbs that have been clinically used to treat Lyme and its co-infections. Some are used solo, some work better in combination, and there are many specific formulations available as well. This, as all therapy, needs to be individually assessed as to dosage, timing and herbal alterations or rotations. An excellent text on plant-based antimicrobials is Healing Lyme by Stephen Buhner – http://buhnerhealinglyme.com/ (see APPENDIUM 1)

  • Identify and supplement nutritional deficiencies

  • Improve errors in heme synthesis. Heme is an iron-containing molecule that occurs naturally in every single plant and animal. It is an essential molecular building block of life and gives the blood its ability to carry oxygen. Kryptopyrroluria, also called hemopyrrollactamuria (HPU), is a metabolic disorder disrupting heme synthesis. This disorder results in a significant loss of zinc, vitamin B6, biotin, manganese, and other important nutrients from the body via the kidneys. It has been proposed that the incidence of HPU in Lyme disease may be 80% or higher, particularly in patients with toxic element excess (lead, mercury, cadmium, and others).12, 13 Thus, patients with symptoms of chronic Lyme disease might benefit from kryptopyrrole testing, and if positive, a supplemental treatment protocol that addresses nutritional deficiencies.14

  • Detoxify environmental toxins – these can make Borrelia more virulent and difficult to treat. Decrease the total toxic body-burden (toxic element excess) by activating organs of detoxification – liver, spleen, intestine, lung, kidneys and skin. There are several nutrients, such as chlorella and cilantro, that help facilitate toxic element removal. Sauna is also very helpful.

  • Get enough sleep; practice sleep hygiene – EMF and WIFI Free Sleep

  • Improve lymphatic circulation – Lymph massage, dry brushing, and colon hydrotherapy.

  • Minimize Herxheimer reactions when using antimicrobials. A ‘Jarisch–Herxheimer reaction’ is a body reaction to endotoxin-like products released by the death of harmful microorganisms within the body, usually during antibiotic treatment. Antimicrobial therapy results in lysis (destruction) of bacterial cell membranes, and in the consequent release into the bloodstream of bacterial toxins, resulting in a systemic inflammatory response. This reaction may occur between 1–12 hours after antibiotics are initiated but can also occur later and last for a few hours or up to two days. Symptoms include a worsening of fever, chills, muscle pains and headache. If this occurs, patients are advised to consult their doctor.15, 16, 17

  • Resolve psychoemotional trauma and stress associated with the tick-borne illness. Journaling important past traumatic events; meditation; taijiquan (Tai Chi); movement and dance.

  • Modulate immunity using medicinal mushrooms, honeybee propolis and immunological herbs.18

  • Focus on reducing overall inflammation; may use curcumin and proteolytic enzymes.

  • Improve methylation with methyl donors such as methylated B12 and methylated folate.19

  • Balance intestinal microbiome with pre- and probiotics; internal bentonite clay helps remove toxic intestinal biofilm.

  • Resolve structural misalignments.

  • Improve the oral microbiome -resolve dental foci such as root canal treated teeth and cavitations.

The types and duration of treatments vary with the stage and nature of the infection(s) and must be evaluated by a physician on a case-by-case basis

. Co–infections of Lyme Disease

Ticks carry many bacteria, viruses, fungi and protozoans all at the same time and can transmit them in a single bite. Hence, a huge body of research shows that many chronic Lyme patients have co-infections with multiple tick-borne pathogens.20, 21 Microbes exist in communities: bacteria, viruses, mycoplasma, parasites and molds co-habitate. One species supports and mutually benefits from the other. Studies have shown that co-infection results in a more severe clinical presentation, with more organ damage, and the pathogens become more difficult to eradicate.22 It is not uncommon to see 4 or more combinations of infections in chronic Lyme disease patients. The first three organisms of the following list are the most prevalent coinfections and will be briefly discussed.

  • Babesia (protozoa)

  • Bartonella (bacteria)

  • Ehrlichia (rickettsia)

  • Mycoplasma (L-form)

  • Anaplasma (rickettsia)

  • Coxiella (rickettsia)

  • Chlamydia (bacteria)

  • Viruses (EBV; CMV)

Babesia (Piroplasmosis or Babesiosis)

Babesia is a tiny parasite that infects red blood cells. It has been published that as many as 32% of Lyme patients show serologic evidence of co-infection with Babesia microti.23 Babesia infections can range in severity from mild, subclinical infection, to potentially life-threatening illness. Subclinical infection is often missed because the symptoms are incorrectly ascribed to Lyme. Babesia infections, even mild ones, may recur even after treatment and cause severe illness. This phenomenon has been reported to occur at any time, including up to several years after the initial infection. Babesiosis symptomology presents with a more acute initial illness. Patients often recall a high fever and chills at the onset of their Lyme. They also remember night sweats, air hunger, an occasional cough, persistent migraine-like headaches, a vague sense of imbalance without true vertigo, encephalopathy and fatigue.

Diagnostic tests for Babesiosis are insensitive and problematic. Standard blood smears reportedly are reliable for only the first two weeks of infection, thus are not useful for diagnosing later infections and milder ones including carrier states where the parasite load is too low to be detected. It is best to treat based on clinical presentation, even with negative tests. These parasites are not bacteria, they are protozoans. Therefore, they will not be eradicated by any of the currently used antibiotic Lyme treatment regimens. Therein lies the significance of co-infections – if a Lyme patient has been extensively treated yet is still ill, and especially if they are experiencing atypical symptoms, suspect a co-infection. Treating Babesia is often unsuccessful with Rx therapy. Newer conventional medicine regimens involve a combination of atovaquone (Mepron, Malarone), 750 mg, twice daily, plus an erythromycin-type drug, such as azithromycin (Zithromax), clarithromycin (Biaxin), or telithromycin (Ketek) in standard doses. This combination has resulted in slightly improved success over previous Rx meds; however, atovaquone is very expensive and side effects from these drugs can be severe. Instead, a safe and effective herb treatment for Babesia, like malaria, is Artemisia annula. Specifically, as Artemisinin capsules – 100 mg, 3 times daily for 4 to 6 weeks.

Ehrlichia

The potential transmission of Ehrlichia during tick bites is the main reason why doxycycline is now the first pharmaceutical choice in treating tick bites and early Lyme, before serologies can become positive. When present alone or co-infecting with Lyme, persistent leukopenia (low white count) is an important clue. Thrombocytopenia (low platelets) and elevated liver enzymes, common in acute infection, are less often seen in those who are chronically infected, but likewise should not be ignored. Headaches, myalgias, and ongoing fatigue suggest this illness, but are extremely difficult to separate from symptoms caused by Lyme.24

Testing is problematic with Ehrlichia, like the situation with Babesiosis. More species are known to be present in ticks than can be tested for with clinically available serologies and PCRs. In addition, serologies and PCRs are of unknown sensitivity and specificity. Consider this diagnosis in a Lyme Borreliosis patient not responding well to Lyme therapy who has symptoms suggestive of Ehrlichia. Standard conventional medicine treatment consists of doxycycline, 200 mg daily, for two to four weeks. A safe and effective herbal remedy for Ehrlichia is the homeopathic (mother tincture) of Colchicum Autumnale (Autumn Crocus) – 20 drops daily for seven days, repeat 10 days if necessary.

Bartonella

Bartonella is a genesis of gram-negative bacteria considered to be the most common of all tick-borne pathogens. It can also be transmitted by other insect vectors such as fleas, sand flies, and lice. There seems to be a distinct clinical syndrome when this type of organism is present in the chronic Lyme patient.25 Early signs of bartonellosis include fever, fatigue, headache, poor appetite, and an unusual streaked rash that resembles “stretch marks” from pregnancy (Bart marks). Swollen glands are typical, especially around the head, neck and arms.   Bartonella, like bacterial some other bacterial, can cause abnormal angiogenesis, or the development of microvessels.

The conventional medicine drug of choice to treat Bartonella is the toxic and often problematic levofloxacin. Levofloxacin is usually never used for Lyme or Babesia. Levofloxacin and drugs in this family may cause permanent damage to the connective tissue. It should not be given to those under the age of 18, so other Rx alternatives, such as azithromycin, are used instead in children. A safe triple-herb regime of choice for Bartonella is Polygonum cuspidatum to counteract the angiogenesis actions of the organisms and reduce inflammation, Eupatorium perfoliatum (boneset) to stimulate immune response, and Ceanothus americanus (red root) to clear the lymphatics.

Antibiotic Limitations

The traditional recommended treatment, upon finding an engorged tick and making the clinical diagnosis, is a seven to ten-day regimen of oral doxycycline at 100 mg twice daily for ages greater than eight, excluding pregnant women. This regimen has the advantage of sometimes curing the disease Ehrlichiosis, caused by a gram-negative bacterium carried by Ixodes ticks and a frequent co-infection in endemic areas. Second line Rx therapy includes medications such as amoxicillin and cefuroxime. However, failures are common with this traditional approach and, in fact, many published studies report less than perfect response rates with doxycycline, amoxicillin, and other oral antibiotic programs. While many patients may appear cured with a 2-4-week antibiotic therapy (symptoms abated), a significant percent of patients continue to suffer persistent symptoms of fatigue, pain or joint and muscle aches, and neurocognitive disorders despite the treatment. This condition is called post-treatment Lyme disease syndrome (PTLDS). The cause for PTLDS is unclear but one strong possibility is persistent infection with Borrelia which is known to develop morphological variant forms such as round bodies (spheroplasts) and aggregated biofilm-like microcolonies.26, 27, 28

Antibiotics do not destroy the mycotoxins or help the body rid itself of the BLP (bacteria lipoprotein neurotoxins) caused by Borrelia. Antibiotics are not effective in treating the various viral, fungal, and parasitic co-infections attendant to Lyme disease. The pharmaceutical challenge of Lyme disease centers on the lack of evidence to support use of antibiotics for longer than 4 weeks.29, 30 There have been several “point and counterpoint” editorials on the benefits and detrimental consequences of long-term antibiotic treatment for Lyme disease. Generally, most studies do not recommend long-term antibiotics for Lyme disease.31, 32 Additionally, the Infectious Disease Society of America and the Center for Disease Control do not recommend prolonged treatment with antibiotics.33 Hence, many individuals develop chronic Lyme because they are solely and ineffectively treated with antibiotic therapy. In these cases, bioregulatory medicine using herbs and other multidisciplinary approaches, offers many advantages in both safety and efficacy.

Diagnosis and Testing

Diagnosing Lyme is often a complicated process and many physicians are not adequately qualified to identify Lyme disease. Additionally, the common tests (Western Blot and ELISA) used to confirm a Lyme diagnosis can report incorrect results 50% of the time.34 In the absence of a defining erythema migrans rash, or “bull’s eye rash”, the clinical symptoms for Borrelia infection are ill defined and ambiguous. In addition, the human antibody response to Borrelia infection develops slowly; this makes early detection challenging for antibody screening tests. First, if you suspect that you have Lyme disease and have not been tested, download and fill out the Horowitz Lyme-MSIDS Questionnaire.35 Physicians typically diagnose and initiate treatment for Lyme disease based on a combination of clinical symptoms and results from laboratory testing, but there are some exceptions. The Center for Disease Control (CDC), International Lyme and Associated Diseases Society, and the Infectious Diseases Society of America have developed guidelines for physicians to follow when diagnosing Lyme borreliosis. The CDC recommends that physicians follow a two-tier testing protocol. The first tier utilizes IgM or IgG-based ELISAs, or IFA, to determine if antibodies from exposure to Lyme Borrelia are present in the patient’s serum. According to the CDC, “if it tests negative, then no further testing is required.” However, also according to the CDC, “the diagnosis of Lyme disease is based primarily on clinical findings, and it is often appropriate to treat patients with early disease solely on the basis of objective signs and known exposure.”

The second tier is another round of immune response testing employing IgM and/or IgG Western blot methods. A Western blot looks for antibodies that are specific to different antigens produced by Borrelia. The CDC criteria for a surveillance case require that an IgM Western blot sample contain antibodies that are reactive to 2 out of 3 antigens to be considered positive. An IgG Western blot requires reactivity to 5 out of 10 antigens for a positive result that meets CDC criteria for surveillance reporting.

“Absence of proof is not proof of absence.”

However, currently, no test can rule out Lyme disease. A person can test negative, but still have Lyme disease. Lyme disease is a clinical diagnosis and testing can support clinical presentation, but not always. Diagnosis of Lyme disease should not be contingent on surveillance criteria which require a positive ELISA followed by five positive CDC bands on a Western Blot. Both the ELISA and Western Blot tests should ideally be conducted to get the most accurate blood testing results possible. Most insurance companies will only pay for one test, so the patient should consider paying out of pocket for the other. When used as part of a diagnostic evaluation for Lyme disease, the Western Blot should be performed by a laboratory that reads and reports all the bands related to Borrelia burgdorferi.’

Recommended Laboratory – IGeneX offers several Lyme and coinfection panels. (See Website)36

C6 Lyme Peptide ELISA Test – Oxford Immunotec

C6 Lyme Peptide ELISA test37 is based on the discovery of six (6) peptides on the surface of the spirochete, which are consistently present and do not evade detection by the laboratory as many of the other surface antigens of Borrelia do. This test detects all Borrelia burgdorferi strains and genospecies. It is highly specific and appears more sensitive than conventional tests for chronic Lyme disease. 38 It is also sensitive in early Lyme disease. Like other testing, negative test results should not be used to exclude Lyme disease.

“Treat the patient, not the lab test!”

Summary

Clinicians should be aware of the clinical signs of tick-transmitted diseases, because morbidity can increase substantially if there are delays in diagnosis and treatment. With the incidence of antibiotic failures and the potential of developing post-treatment Lyme disease syndrome, a more comprehensive biological regulatory medicine approach can help speed healing-time, enhance quality of life, and minimize the recurrence of Lyme disease. For more information on Bioregulatory Medicine and its treatments, visit the Bioregulatory Medicine Institute (BRMI) website at www.brmi.online. References

1.https://www.cdc.gov/lyme/datasurveillance/index.html

 

2.Ogrinc, K., et al., Course and Outcome of Early European Lyme Neuroborreliosis (Bannwarth Syndrome): Clinical and Laboratory Findings. Clinical Infectious Diseases, 2016. 63(3): p. 346-353.

 

3. Middelveen, Marianne, Eva Sapi, Jennie Burke, Katherine Filush, Agustin Franco, Melissa Fesler, and Raphael Stricker. Persistent Borrelia infection in patients with ongoing symptoms of Lyme disease. In Healthcare, vol. 6, no. 2, p. 33. Multidisciplinary Digital Publishing Institute, 2018.

 

4. Wang, Xing-Guo, Joanna P. Scagliotti, and Linden T. Hu. Phospholipid synthesis in Borrelia burgdorferi: BB0249 and BB0721 encode functional phosphatidylcholine synthase and phosphatidylglycerolphosphate synthase proteins. Microbiology150, no. 2 (2004): 391-397.

 

5. Kobryn, Kerri, Darius Z. Naigamwalla, and George Chaconas. Site‐specific DNA binding and bending by the Borrelia burgdorferi Hbb protein. Molecular microbiology37, no. 1 (2000): 145-155.

 

6. Mursic, Vera Preac, Sylvia Reinhardt, Bettina Wilske, U. Busch, G. Wanner, and W. Marget. Formation and cultivation ofBorrelia burgdorferi spheroplast-L-form variants. Infection24, no. 3 (1996): 218-226.

 

7. Murgia, Rossella, Chiara Piazzetta, and Marina Cinco. Cystic forms of Borrelia burgdorferi sensu lato: induction, development, and the role of RpoS. Wiener klinische Wochenschrift114, no. 13/14 (2002): 574-579.

 

8. Gruntar, Igor, Tadej Malovrh, Rossella Murgia, and Marina Cinco. Conversion of Borrelia garinii cystic forms to motile spirochetes in vivo Note. Apmis109, no. 5 (2001): 383-388.

 

9. Smith, Aaron J., John Oertle, and Dino Prato. Chronic Lyme disease: persistent clinical symptoms related to immune evasion, antibiotic resistance and various defense mechanisms of Borrelia burgdorferi. Open Journal of Medical Microbiology4, no. 04 (2014): 252.

 

10. Garcia‐Monco, Juan Carlos, and Jorge L. Benach. Lyme neuroborreliosis. Annals of Neurology: Official Journal of the American Neurological Association and the Child Neurology Society37, no. 6 (1995): 691-702.

 

11. Lectins are carbohydrate-binding proteins that can bind to cell membranes. For plants lectins are primarily a defense mechanism. Essentially, they are a low-level toxin. The purpose of lectins in plants is to discourage other animals from eating that plant or life form. By triggering a negative reaction in the predator, that life form is then viewed as an undesirable food source, thus, aiding its future survival. In short, lectins can interact with surface antigens found on the body’s cells, causing them to agglutinate or stick together. Hence, lectins are considered another major family of protein antinutrients. Lectins are like antibodies in their ability to agglutinate red blood cells. Essentially, they can cause inflammation in the body.

 

12. Dietrich Klinghardt, M. D. BIOTOXINS – http://klinghardtinstitute.com/wp-content/uploads/2015/06/1.-Biotoxin-chapter.pdf

 

13. Dietrich Klinghardt, M. D. Chronic Illness: the hidden causes. – https://aonm.org/wp-content/uploads/2018/01/Dr.-Dietrich-Klinghardt-AONM-15-Nov-2015-presentation-part1.pdf

 

14. For HPU diagnosis with urine analysis for Kryptopyrrol, suggest using The Great Plains Laboratory, Inc. 11813 W. 77th St.; Lenexa, KS 66214 USA 800-288-0383.

 

15. Belum, Geetanjali Reddy, Viswanath Reddy Belum, Sri Krishna Chaitanya Arudra, and B. S. N. Reddy. The jarisch–herxheimer reaction: Revisited. Travel medicine and infectious disease11, no. 4 (2013): 231-237.

 

16. Maloy, Anna L., Robert D. Black, and Romualdo J. Segurola Jr. Lyme disease complicated by the Jarisch-Herxheimer reaction. The Journal of emergency medicine16, no. 3 (1998): 437-438.

 

17. Moore, J. A. Jarisch-Herxheimer reaction in Lyme disease. Cutis39, no. 5 (1987): 397-398.

 

18. Stamets, Paul Edward. Antiviral and antibacterial activity from medicinal mushrooms. U.S. Patent 8,765,138 issued July 1, 2014.

 

19. Your DNA consists of four bases, called cytosine, guanine, adenine, and thymine. A chemical unit called a methyl group, which contains one carbon and three hydrogen atoms, can be added to cytosine. When this happens, that area of the DNA is ‘methylated’. When you lose that methyl group, the area becomes demethylated. DNA methylation often inhibits the expression of certain genes. For example, the methylation process might stop a tumor-causing gene from “turning on,” preventing cancer. Methyl groups are important for numerous cellular functions such as DNA methylation, phosphatidylcholine synthesis, and protein synthesis. The methyl group can directly be delivered by dietary methyl donors, including methionine, folate (folic acid), methylated B-12, betaine, and choline. Some individuals with Lyme disease lack methyl donors, and thus, have problems with methylation.

 

20. Moutailler, Sara, Claire Valiente Moro, Elise Vaumourin, Lorraine Michelet, Florence Hélène Tran, Elodie Devillers, Jean-François Cosson et al. Co-infection of ticks: the rule rather than the exception. PLoS neglected tropical diseases10, no. 3 (2016): e0004539.

 

21. Horowitz, Richard, Allen Richards, Megan Dulaney, Marna E. Ericson, Christine Green, Charles Lubelczyk, Ulrike Munderloh et al. Other Tick-Borne Diseases and Co-Infections. (2018).

 

22. Wormser, Gary P., Donna McKenna, Carol Scavarda, Denise Cooper, Marc Y. El Khoury, John Nowakowski, Praveen Sudhindra et al. Co-infections in Persons with Early Lyme Disease, New York, USA. Emerging Infectious Diseases25, no. 4 (2019): 748.

 

23. Djokic, Vitomir, LAVOISIER AKOOLO, Shekerah Primus, Samantha Schlachter, Kathleen Kelly, Purnima Bhanot, and Nikhat Parveen. Protozoan parasite Babesia microti subverts adaptive immunity and enhances Lyme disease severity. Frontiers in Microbiology10 (2019): 1596.

 

24. Dumler, J. Stephen, and Johan S. Bakken. Ehrlichial diseases of humans: emerging tick-borne infections. Clinical infectious diseases20, no. 5 (1995): 1102-1110.

 

25. Higgins, R. Emerging or re-emerging bacterial zoonotic diseases: bartonellosis, leptospirosis, Lyme borreliosis, Revue Scientifique et Technique-Office International des Epizooties 23, no. 2 (2004): 569-582.

 

26. Feng, Jie, Tingting Li, Yuting Yuan, Rebecca Yee, and Ying Zhang. Biofilm/Persister/Stationary Phase Bacteria Cause More Severe Disease Than Log Phase Bacteria I Biofilm Borrelia burgdorferi Not Only Display More Tolerance to Lyme Antibiotics but Also Cause More Severe Pathology in a Mouse Arthritis Model: Implications for Understanding Persistence, PTLDS and Treatment Failure. bioRxiv(2018): 440461.

 

27. Feng, Jie, and Ying Zhang. Proteomic Analyses of Morphological Variants of Borrelia burgdorferi Shed New Light on Persistence Mechanisms: Implications for Pathogenesis, Diagnosis and Treatment. bioRxiv(2018): 501080.

 

28. Rudenko, Natalie, Maryna Golovchenko, Katerina Kybicova, and Marie Vancova. Metamorphoses of Lyme disease spirochetes: phenomenon of Borrelia persisters. Parasites & vectors12, no. 1 (2019): 237.

 

29. Borchers AT, Keen CL, Huntley AC, Gershwin ME. Lyme disease: A rigorous review of diagnostic criteria and treatment. J. Autoimmun 2015;57:82– 115.

 

30. Rowe PM. Chronic Lyme disease: the debate goes on. Lancet 2000;355:1436.

 

31. Shaw, Gina. Prolonged Antibiotics Do Not Improve Neurocognitive Outcomes in Persistent Lyme Disease. Neurology Today19, no. 5 (2019): 27-31.

 

32. Auwaerter, Paul G. Point: antibiotic therapy is not the answer for patients with persisting symptoms attributable to lyme disease. Clinical Infectious Diseases45, no. 2 (2007): 143-148.

 

33. Wormser GP, Nadelman RB, Dattwyler RJ et al. Practice guidelines for the treatment of Lyme disease. The Infectious Diseases Society of America. Infect. Dis. 31(Suppl. 1), 1–14 (2000).

 

34. Lin Zhang, X.Z., Xuexia Hou, Zhen Geng, Hai Chen, and Qin Hao1, Test of 259 serums from patients with arthritis or neurological symptoms confirmed existence of Lyme disease in Hainan province, China. 2015, US National Library of Medicine.

 

35. http://lymeontario.com/wp-content/uploads/2015/03/Horowitz-Questionnaire.pdfigenex.com -797 San Antonio Rd., Palo Alto CA 800.832.3200.

 

36. C6 Lyme Peptide ELISA test (Boston Biomedica Inc DBA – BBI Clinical Laboratories, 75 N Mountain Rd, New Britain, CT,06053 Tel.: 1-800-676-1881 or 1-508-580-1900, test code: 556 – C6LPE).

 

37. Tjernberg, Ivar, G. Krüger, and Ingvar Eliasson. C6 peptide ELISA test in the serodiagnosis of Lyme borreliosis in Sweden. European Journal of Clinical Microbiology & Infectious Diseases26, no. 1 (2007): 37-42.

 

38. Jansson, C., S-A. Carlsson, H. Granlund, P. Wahlberg, and D. Nyman. Analysis of Borrelia burgdorferi IgG antibodies with a combination of IgG ELISA and VlsE C6 peptide ELISA. Clinical microbiology and infection11, no. 2 (2005): 147-150.

Additional Resources and References Books and Articles

  • Burrascano, Joseph J. , MD, Advanced Topics in Lyme Disease Diagnostic Hints and Treatment Guidelines for Lyme and Other Tick-Borne Illnesses; Sixteenth Edition Copyright October, 2008 – http://www.lymenet.org/BurrGuide200810.pdf

  • Buhner, Stephen Harrod.: Healing Lyme: Natural Prevention and Treatment of Lyme Borreliosis and Its Coinfections

  • Newby, Kris: Bitten – The Secret History of Lyme Disease and Biological Weapons

  • Horowitz, Richard – How Can I Get Better? An Action Plan for Treating Resistant Lyme and Chronic Disease

  • Horowitz, Richard – Herbs, Hormones & Heavy Metals: A study of CAM therapies in the Treatment of Chronic Lyme Disease

  • Singleton, Kenneth B – The Lyme Disease Solution

  • Weintraub, Pamela – Cure Unknown: Inside the Lyme Epidemic

Laboratories

Supplement Companies

Websites

ADDENDUM 1 – Overview of Lyme Borreliosis (A Bioregulatory Medicine Approach) Basic Principles:

  • Decrease Pathogenic Microbial Load (Plant-based Antimicrobials, IV Ozone, Rizols)

  • Improve Intestinal and Oral Microbiome

  • Decrease Total Toxic Body Burden

  • Balance and Modulate the Immune System

  • Improve Bioregulatory Mechanisms (Heme Synthesis, Methylation)

There are several herbs that have been clinically used to decrease pathogenic microbial load and treat Lyme and its co-infections. Some are used solo, some work better in combination, and there are many formulations available as well. This, as all therapy, needs to be individually assess as to which ones are appropriate, dosage, timing and herbal alterations or rotations. The following are some of the most commonly employed.

Artemisia annua (Sweet Wormwood; Qing Hao 青蒿) Bitter Flavor; cold property; liver and gallbladder meridians Actions:

  • Antibacterial effect

  • Anti-malarial

  • Anti-parasitical

  • Psycho-emotional Signature: Mental Clarification

Long been used in TCM for malaria; useful in treatment of Babesia co-infection; treating Babesia first will promote better outcome in the treatment of Lyme disease; can help reducing Herxheimer reaction; important to also stimulate lymphatics and support the spleen. Artemisia annua Dosage: babesia or malaria – 100 mg 2 – 3x daily for  two weeks, repeated again in one week with grapefruit juice;  2 weeks on, 1 week off; (30 to 60 days, some difficult cases may take 6 months to 1 year treatment for Babesia) Sources: Biopure – Artemisinin – powder – standardized extract, 24 grams, comes with spoon; serving is 1 scoop – 100 mg 2 x daily. At regular servings this equals 60 total servings per bottle. Allergy Research – 30:1 500 mg 100 capsules – 100mg 2 x daily

Andrographis paniculata (Chuan Xin Lian 穿心蓮) Bitter Flavor “King of Bitters”; cold property; lung, stomach, large intestine and bladder meridians Common Usage: prophylaxis and symptomatic treatment of upper respiratory infections, such as the common cold and uncomplicated sinusitis, bronchitis and tonsillitis, lower urinary tract infections and acute diarrhea. Actions:

  • Immune modulator

  • Anti-inflammatory

  • Protects and supports liver function

  • Protects CNS

  • Eliminates intestinal infestations

  • Historically, used to treat syphilis – it’s claimed to be anti-spirochetal

Andrographis paniculata: Contains: diterpene lactones known as andrographolides – andrographolide, deoxyandrographolide, neoandrographolide, 5,7, tetramethoxyflavanone and 5-hydroxy-7, trimethoxyflavone, as well as several other flavonoids and polyphenols. Often combined with other herbs in treatment of Lyme disease. Andrographis Initial dosage: 400 capsule 3x daily; gradually increase one capsule every 7 days till dosage is 3 capsules 1200mg 4x daily; after symptoms subside reduce slowly. Available: Standardized 10% andrographolides Smilax glabra (Sarsaparilla) Tu Fu Ling 土茯苓 Sweet bland flavor; neutral property Sarsaparilla contains: sarsasapogenin, smilagenin, sitosterol, stigmasterol, and pollinastanol; and the saponins sarsasaponin, smilasaponin, sarsaparilloside, and sitosterol glucoside, among others. Sarsaparilla Properties/Actions: Anti-inflammatory, anti-spirochetal; antibacterial, antifungal, blood cleanser, detoxifier, diuretic, hepatoprotective, protects brain cells, blood cleanser, immunomodulator, antimutagenic, detoxifier, tonic (tones, balances, strengthens overall body functions) Sarsaparilla has long been used in China for the treatment of syphilis. Clinical observations in China demonstrated that sarsaparilla was effective in treatment of syphilis (according to blood tests) in about 90% of acute and 50% of chronic cases. Useful as anti-Herxheimer reaction, with unresolved brain fog, confusion, weakness. Sarsaparilla Source and Dosage: Biopure tincture – available in 2 fluid oz. 1 drop per day for 4 days, doubling the dose every 4 days until the full dose of 16 drops per day is reached. If side effects are experienced, reduce to the last tolerable dose.

Polygonum cuspidatum (Japanese Knotweed) Hu Zhang 虎杖 Traditional Chinese medicine properties are sour, bitter, mildly pungent flavor; cold; enters liver, gallbladder and lung meridians; used traditionally in China for supporting the body’s natural detoxification pathways, to clear blood of toxic heat and eliminate blood stasis, as a cardiac tonic, mild laxative and as a diuretic Roots of P. cuspidatum contain compounds called stilbenes; one stilbene called resveratrol has several physiological activities.  Primarily, the root inhibits the growth of several bacteria and fungi (Kubo, et al, 1981) – including leptospira and Treponema denticola spirochetes. It is anti-inflammatory and helps reduce Herxheimer reactions.

Japanese Knotweed Actions: Its antimicrobial activity is not only due to resveratrol, but to 2-methoxy-6-acetyl-7-methyljuglone, a naphthoquinone (Kimura, et al, 1983a; Yamaki, et al, 1988). It protects against endotoxin damage and is a cardioprotector. Its constituents cross the blood-brain barrier and protects against oxidative damage and microbial endotoxins. Japanese Knotweed Sources and Dosage: Tincture (Biopure): 1 drop per day for 4 days, doubling the dose every 4 days until the full dose of 16 drops per day is reached. If side effects are experienced, go back to the last tolerable dose. Put drops in 1 – 2oz of filtered, organic apple juice to hide the bitter taste. Tablets (Source Naturals, Resveratrol Antioxidant Protection 40mg) 1 – 4 tablets 3-4 x daily beginning at lowest dose increasing every seven days. Maintain two months then lower to maintenance dose 8 to 12 months.

Quintessence Formula by Biopure Quintessence: Quintessence is a combination of five herbal tinctures that work together, creating a potent broad-spectrum approach to immune system support. Contains organic tinctures of Andrographis, Smilax, Stephania Root, Japanese Knotweed and Red Root. Source: Biopure – Dosage: The average adult may take up to 8 droppers full of Quintessence diluted in 1 liter of water and drunk throughout the day.

Coptis chinensis (Huang Lian 黃連) Root exhibits bitter flavor, cold property; disperses heat, dries dampness, purges fire, removes toxin; enters the heart, liver, gall bladder stomach and large intestine meridians Coptis chinensis actions: Anti-inflammatory, antibacterial, antifungal, antiviral (influenza viruses), vasodilator, anti-pyretic, anti-diarrhea, cholagogue, anti-ulcer, stomachic, anti-protozoal, immune stimulant. Coptis is a choleretic shown to triple bile secretion for 1.5 hours Coptis chinensis contains: Alkaloids: Berberine (7-9%), coptisine, atrorrhizine, palmatine, epiberberine, jatrorrhizine, urbenine, worenine, palmaline,, columbamine. Berberine and berberine-like alkaloids are primarily responsible for its antimicrobial activity. Clinically, berberine has been used to treat giardia, cholera, amebiasis, as well as visceral and cutaneous leishmaniasis. It strongly inhibits Streptococcus pneumoniae, Neisseria meningitis, and Staphylococcus aureus. Dosage: Coptis Tea Pills (Plum Flower Brand) 4-8, 3-4X daily            Source: Mayway Trading

Eight (8) Traditional Chinese Herbs for Lyme disease:

  • Andrographis paniculata (Chuan Xin Lian) – anti-spirochetal, antimicrobial, immune stimulant, anti-inflammatory, enhances liver function

  • Coptis chinensis (Huang Lian) Antitoxin heat clearing; strong antimicrobial

  • Scutellaria barbata (Ban Zhi Lian) Antitoxin heat clearing

  • Artemesia annua (Qing Hao) – Anti-parasitic

  • Smilax glabra (Tu Fu Ling) – Lymphatic cleanser, anti-spirochetal, anti-Herxheimer reaction

  • Flos Lonicerae japonicae (Jin Yin Hua) Antitoxin heat clearing

  • Fructus Forsythiae (Lian Qiao) Antitoxin heat clearing

  • Isatis root (Ban Lan Gen); Isatis leaf (Da Qing Ye) – Anti-toxin heat clearing

Traditional Chinese Medicine Formula for Lyme disease:

  • Huang Lian Jie Du Tang (Sun Ten Brand) – Coptis Scute Combination – 100 Sun Ten Capsules – General Dose 1-2 capsules 2-3 times per day. At full dose lasts approximately 16 days.

David Winston’s Spirolyd Compound Specific for spirochetes Contains Extracts of sarsapilla root, andrographis herb, guauacum wood, prickly ash bark, stillingia root. Dosage 40-60 drops (2-4 mL) in juice or water. Take 3 times per day. Shake well before using. Rain Forrest Herbs and Formulas Uncaria tomentosa; Uncaria guianensis (Cat’s Claw – uña de gato) Both South American Uncaria species are used by the indigenous peoples of the Amazon rainforest in very similar ways and have long histories of usage (2000 years) – for treating gastrointestinal and infectious diseases. Usages: all inflammatory conditions, immunological disorders, cancer and Lyme.

Cat’s Claw Chemical Properties:

  • Oxidole alkaloids – documented with immune-stimulant and antileukemic properties.

  • Carboxyl alkyl esters – immunostimulant, anti-inflammatory, anti-cancerous properties.

  • Quinovic acid glycosides -anti-inflammatory and antimicrobial actions.

  • Antioxidant chemicals – tannins, catechins and procyanidins

  • Plant sterols – beta-sitosterol, stigmasterol, campesterol exhibit anti-inflammatory properties.

Cat’s Claw Dosage: The best source of cat’s claw extract contains 3% total alkaloids.  For general immune and prevention benefits – 1 g daily of vine powder in tablets or capsules.  Therapeutic dosages of cat’s claw are from 5 to 20 g daily and average 2-3 grams two or three times daily. Supplementing with probiotics and digestive enzymes is advisable if Cat’s Claw is used for longer than 15 days.

Brosimum acutifolium (Tamamuri) Tamamuri is a large canopy tree of the Amazon; grows 15 to 25 m and produces light pink latex when the smooth trunk bark is wounded, or the leaf stems are broken from the branches. Tamamuri is found throughout lower elevations usually growing alongside streams and rivers where its fruits are eaten by fish when they fall from the tree. Tamamuri bark contains: flavans, flavanoids, lignans, phenylpropanoids, benezoids, and steroids. Many of these chemicals are novel ones never before discovered by scientists, including 6 chemicals they’ve named acutifolins and 13 chemicals they’ve named brosimacutins. Tamamuri Actions:

  • Antiinflammatory – In traditional medicine the bark is used as an anti-inflammatory and a treatment for rheumatism. Tamamuri’s long-standing use for arthritis and rheumatism has been the subject of research by Western scientists.

  • Anti-spirochete – It is both effective for Lyme and syphilis.

Tamamuri Dosage: As tincture: 60 drops 2 – 3 X daily; this plant is best prepared as a decoction. Use one teaspoon of powder for each cup of water. Bring to a boil and gently boil in a covered pot for 20 minutes. Allow to cool and settle for 10 minutes and strain warm liquid into a cup (leaving the settled powder in the bottom of the pan). It is traditionally taken in 1 cup dosages 3 times daily

Rainforest Amazon Spiro – Contains Six Herbal Ingredients:

  • Chanca piedra whole herb (Phyllanthus niruri)

  • Bellaco caspi bark (Himatanthus sucuuba)

  • Tamamuri bark (Brosimum acutifolium)

  • Matico leaf (Piper aduncum)

  • Huacapu bark (Minquartia guianensis)

  • Ajos sacha bark & leaf (Mansoa alliacea).

Rizols Rizols (as produced by Biopure) are ozonated castor oil remedies treated with high voltage electrolysis with added plant oils designed when taken orally to decrease microbial count. Rizols have strong and specific anti-microbial properties, are relatively easy and pleasant to take. Different Rizols:

  • Gamma Rizol contains: Oil of Artemisia, Clove Oil, Walnut Oil.

  • Zeta Rizol contains: Oil of Artemisia, Clove Oil, Black Cumin Oil, Moxa Oil, Walnut Oil

  • Epsilon Rizol contains: Oil of Artemisia, Clove Oil, Black Cumin Oil, Walnut Oil, Garlic Oil, Marjoram Oil

  • Kappa Rizol contains: Oil of Artemisia, Clove Oil, Black Cumin Oil, Walnut Oil Thyme Oil, Marjoram Oil

Rizols may be taken orally in two ways:

  • One or more drops may be dropped in an empty glass. Then good quality water is poured from a height so that the oil and water create half a glass of whitish emulsion. This may be taken on an empty stomach.

  • Alternatively, empty capsules may be filled with one or more drops of rizol, closed and swallowed with a glass of water.

Rizol Dosage – Practitioners may recommend adults building up from 1 drop to 15-20 drops of Rizol, 3 times per day for several months. Energetic testing to determine which rizol to start – usually Gamma and/or Zeta; Start slow, build up to full dose over 2-3 months. After 2-3 months test again – replace Zeta with Epsilon. Start slow!

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Honey – A Miraculous Medicine

Honey – A Miraculous Medicine

June 30, 2020

Honey – A Miraculous Medicine

James Odell, OMD, ND, L.Ac. with Addendum by Dr. Colin I. H. Perry

Humans have gathered honey for thousands of years. Rock art in Spain from 6000 B.C. shows people harvesting honey. Beeswax from around 8000 B.C. was found in cooking pots in Turkey. By 2400 B.C., the Egyptians were skilled beekeepers. When early people cleared forests into pastures, they created bee-friendly habitats where flowers and bushes grew. As farmers moved into new areas, honeybees followed. Honey is both a food and a medicine. This article describes only a few of the many miraculous qualities of honey

 

Chemical Properties and Composition of Honey

 

Honey is the sweet, viscous substance elaborated by the honeybee from the nectar of plants. This simple definition excludes honeydew honey, which is produced by the bee from honeydew excreted by various plant-sucking insects. Nectars vary considerably in quality and quantity, depending on the floral source. Similarly, honey varies; some honey is nearly colorless (like water), with a light, pleasing aroma, and some is as dark as crankcase oil, with a heavy-bodied aroma. Honey from most floral sources falls between these extremes. Bees convert nectar to honey by drying it down to a moisture content of 15 to 20 percent and by adding a salivary enzyme that changes sucrose (long-chain sugar) into glucose and fructose (two short-chain sugars). Hence, honey is composed of sugars, mainly fructose and glucose. Honey also contains trace amounts of minerals, enzymes, vitamins, and colloids. Honey is water soluble, may granulate between 10° and 18°C, and is acidic.

 

The high acidity of honey also plays an important role in the system that prevents bacterial growth. The pH of honey may vary from approximately 3.2 to 4.5 (average pH= 3.9). Honey acids account for less than 0.5 percent of the solids, this level not only contributes to the flavor, but is partly responsible for the excellent stability of honey against microorganisms. Several acids have been found in honey, gluconic acid being the major one. It arises from dextrose through the action of an enzyme called glucose oxidase. Other acids in honey are formic, acetic, butyric, lactic, oxalic, succinic, tartaric, maleic, pyruvic, pyroglutamic, a-ketoglutaric, glycolic, citric, malic, 2- or 3-phosphoglyceric acid, a– or B-glycerophosphate, and glucose 6-phosphate.

 

The amount of nitrogen in honey is low, 0.04 percent on the average, though it may range to 0.1 percent. Recent work has shown that only 40 to 65 percent of the total nitrogen in honey is in protein, and some nitrogen resides in substances other than proteins, namely the amino acids. Of the 8 to 11 proteins found in various honeys, 4 are common to all, and appear to originate in the bee, rather than the nectar. Little is known of the many proteins in honey, except that the enzymes fall into this class. The presence of proteins causes honey to have a lower surface tension than it would have otherwise, which produces a marked tendency to foam and form fine air bubbles. Beekeepers familiar with buckwheat honey know how readily it tends to foam and produce surface scum, which is largely due to its relatively high protein content.

 

One of the characteristics that differentiates honey from all other sweetening agents is the presence of enzymes. These conceivably arise from the bee, pollen, nectar, or even yeasts or microorganisms in the honey. Those most prominent are added by the bee during the conversion of nectar to honey. Enzymes are complex protein materials that under mild conditions bring about chemical changes, which may be exceedingly difficult to accomplish in a chemical laboratory without their aid. The changes that enzymes bring about throughout nature are essential to life. Some of the most important honey enzymes are invertase, diastase, and glucose oxidase.

 

Invertase, also known as sucrase, splits sucrose into its constituent simple sugars, dextrose and levulose. Recently, it was found that other more complex sugars formed in small quantities during this action and partly explained the complexity of the small sugars of honey. Although the work of invertase is completed when honey is ripened, the enzyme remains in the honey and retains its activity for some time. Even so, the sucrose content of honey never reaches zero. Since the enzyme also synthesizes sucrose, perhaps the final low value for the sucrose content of honey represents equilibrium between splitting and forming sucrose

.

Diastase (amylase) digests starch to simpler compounds, but no starch is found in nectar. What its function is in honey is not clear. Diastase appears to be present in varying amounts in nearly all honey, and it can be measured. It has probably had the greatest attention in the past because it has been used as a measure of honey quality in several European countries

.

Glucose oxidase converts dextrose to a related material, a gluconolactone, which in turn forms gluconic acid, the principal acid in honey. Since this enzyme was previously shown to be in the pharyngeal gland of the honeybee, this is the most likely source. Here, as with other enzymes, the amount varies in different honeys. In addition to gluconolactone, glucose oxidase forms hydrogen peroxide during its action on dextrose, which has been shown to be the basis of the heat-sensitive antibacterial activity of honey. Other enzymes are reported to be present in honey, including catalase and an acid phosphatase. All the honey enzymes can be destroyed or weakened by heat.

 

The glycemic index of honey varies from 32 to 85, depending on the botanical source which is lower than sucrose (table sugar – 60 to 110). Fructose-rich honeys such as acacia honey have an exceptionally low glycemic index. The low moisture content of honey is one of its most significant characteristics, as it affects quality, rate of granulation and body. Honey is hygroscopic (absorbs moisture) and will remove moisture from the air if the relative humidity exceeds 60 percent. Care must be taken in the handling and storage of honey to be sure that this does not happen. Hygroscopicity, however, is one of the traits making honey ideal for baking; honey-sweetened products stay moist for longer. The low moisture content of honey also forms an important part of the system that protects honey from attack by microorganisms. Because of the high concentration of solids and low moisture content honey’s hyperosmotic nature inhibits the growth of bacteria and yeasts as it extracts water from the organisms.

 

Medicinal Properties and Usage of Honey

 

Honey has had a valued place in traditional medicine for centuries. The prescription for a standard wound salve discovered in the Smith papyrus (an Egyptian text dating from between 2600 and 2200 BC) calls for a mixture of mrht (grease), byt (honey) and ftt (lint/fibre) as transliterated from hieroglyphic symbols. The ancient Egyptians, Assyrians, Chinese, Greeks and Romans employed honey for wounds and diseases of the gut. Honey was the most popular Egyptian drug being mentioned in hundreds of and hundreds of remedies.

 

Antimicrobial Effect in Wound Healing

 

Honey inhibits the growth of microorganisms and fungi. The antibacterial effect of honey, mostly against gram-positive bacteria, is well documented. Both bacteriostatic and bactericidal effects have been reported for numerous strains, many of them being pathogenic. The antimicrobial effect of honey is due to various substances and depends on the botanical origin of honey. As stated above the low water activity of honey inhibits bacterial growth. Honey glucose oxidase produces the antibacterial agent hydrogen peroxide, but the peroxide production capacity depends also on honey catalase activity. There are also other non-peroxide antibacterial substances with different chemical origin, e.g. aromatic acids, unknown compounds with different chemical properties and phenolics and flavonoids. The low pH of honey can also be responsible for the antibacterial activity.

 

There is rapidly increasing interest in the use of honey as a wound dressing because of its properties of rapid clearance of infection (including infection with antibiotic-resistant bacteria), rapid debridement of wounds, rapid suppression of inflammation, minimization of scarring and stimulation of angiogenesis and the growth of granulation tissue and epithelium. Early Egyptians were the first to use honey as a component (along with animal fats and vegetable fibers) in the topical treatment of wounds as evidenced from their writings in the Smith papyrus (1650 BC). In the time of Aristotle, it was recommended that honey, collected in specific regions and seasons (and therefore presumably from different floral sources), be used for the treatment of ailments. Although it appears that the honey from certain plants has better antibacterial activity than that from others, little work has been done to measure these variations. Honeydew honey from the conifer forests of the mountainous regions of central Europe has been found to have particularly high antibacterial activity, likewise, honey from Manuka (Leptospermum scoparium) in New Zealand has been found to have special antibacterial properties. Studies on the effectiveness against wound-infecting species of bacteria show that Manuka honey is more effective than other honeys for Escherichia coli and Staphylococcus aureus while other honey was superior for the other 5 tested species, including Salmonella, Streptococcus, and Pseudomonas.

 

Honey Treatment for Wounds and Burns

 

For centuries honey has been used as an effective remedy for wounds and burns. Honey can be used as a topical antibacterial agent to treat infections in a wide range of wound types. These include:

  • Leg ulcers

  • Pressure ulcers

  • Diabetic foot ulcers

  • Infected wound resulting from injury or surgery

  • Burns.

Recipe for Honey Wound Dressing

 

All difficult to heal wounds should be seen by a medical professional. The following are general tips on how honey may be used for wound care. Always seek professional advice before embarking on any new therapy. First, it is important to understand that you cannot go around squeezing regular store-bought honey on every wound or infection encountered. Manuka honey was approved by the U.S. Federal Drug Administration in 2007 as a recommended option for wound treatment.

The amount of honey used depends on the amount of fluid exuding from the wound. Large amounts of exudate require substantial amounts of honey to be applied. The amount of honey needed depends on the amount of fluid exuding from the wound. The benefits of honey on wound tissues will be reduced if honey becomes diluted. Typically, 20 ml of honey is used on a 10 cm X 10 cm dressing. Cover the wound with absorbent secondary dressings to prevent honey oozing out from the dressing. Change the dressings more frequently if the honey is being diluted with secretions. Otherwise change the dressing every day or two.

The frequency of dressing changes depends on how rapidly the honey is being diluted by the exudate. This should become less frequent as the honey starts to work on healing the wound.

 

Occlusive dressings help to prevent honey oozing out from the wound. It is best to spread the honey on a dressing and apply this to the wound then apply the honey directly onto the wound. Dressing pads pre-impregnated with honey are commercially available and provide an effective and less messy alternative.

 

Abscesses, cavity, or deep wounds need more honey to adequately penetrate deep into the wound tissues. The wound bed should be filled with honey before applying the honey dressing pad. Ensure that there is an even coverage of the wound surface with honey. Honey can be made fluid by stirring or warming. Cavities may be filled by pouring in fluidized honey, or more conveniently by using honey packed in squeeze-tubes. (Gamma-irradiated manuka honey in tubes is available commercially.) Spread the honey on the dressing pad rather than on the skin lesion. This is much easier to do and causes less discomfort for the patient.

 

Antimicrobial Effect in Peptic and Duodenal Ulcers

 

One of the many therapeutic effects of honey (particularly Manuka honey) is its healing effect on peptic and duodenal ulcers. Manuka honey is gathered in New Zealand from the manuka bush, Leptospermum scoparium, which grows uncultivated throughout the country. More recently, due to the systematic screening of Australian honeys, honey with the same properties is produced from Leptospermum polygalifolium, which grows uncultivated in a few parts of Australia. Manuka honey is being used to treat dyspepsia and peptic and duodenal ulcers. Not all manuka honey has this antibacterial activity, hence, Manuka honey is now laboratory tested and rated for its antibacterial effects. ‘Unique manuka factor’ (UMF) is the current rating used to indicate the levels of antibacterial properties. The UMF numbers are derived from the standard laboratory test for antibacterial activity, with honey being compared with a standard antiseptic (phenol) for potency. For example, a honey with a UMF rating of 4 would be equivalent to the antiseptic potency of 4% solution of phenol, a carbolic disinfectant; a honey with a rating of 10 would have potency equivalent to a 10% solution of phenol. In order to address any concerns about the possible risk of infection by using an unprocessed natural product on wounds, honey may be sterilized by gamma irradiation without losing any of its antibacterial activity.

 

However, the catalase enzyme present in body tissue and serum does not affect the unique manuka factor. This enzyme will break down the hydrogen peroxide to some degree, which is the major antibacterial factor found in other types of honey. If a honey without UMF were used to treat an infection, the potency of the honey’s antibacterial activity would most likely be reduced because of the action of catalase. The enzyme that produces hydrogen peroxide in honey is destroyed when honey is exposed to heat and light. But UMF is stable, so there is no concern about manuka honey losing its activity in storage. Also, the enzyme that produces hydrogen peroxide in honey becomes active only when honey is diluted. UMF is active in full strength honey, which will provide a more potent antibacterial action diffusing into the depth of infected tissues. A UMF rating of 10 – 15+ proves effective against H. Pylori and many other pathogenic bacteria.

 

These are just a few examples of the healing wonders of honey. For more information or how to successfully use honey as a medicinal remedy, speak to your clinician.

 

An Ayurveda Perspective of Honey by Dr. Colin Perry, ND, Podiatrist

 

Ayurveda considers that honey is Sattvic in nature and is regarded as the finest sweetener for food. Sattvic foods are foods that are abundant in Prana – the universal life-force that gives life to all sentient beings in both plant and animal kingdoms. They are foods such as fresh organic untainted fruits, vegetables, and honey. Honey is sweet, astringent, and pungent in taste, slightly warm in energy and sweet in post-digestive effect. It takes on the properties of the flowers from which it is made. For instance, sage flower honey will have nerve calming properties. Honey tends to balance the three constitutional Doshas, but in excess it can aggravate Pitta, so like everything else, it should be consumed wisely and not excessively. When it has matured slightly, it is the finest sweetener for a Kapha constitution. Whereas fresh raw honey is better for both Pitta and Vata constitutions. Internally, honey works as a demulcent, emollient, laxative, nutritive and a tonic. It can help discharge phlegm, dissolves fat and nourishes the mind and senses. It is rejuvenating and is considered good for improving immunity. Royal jelly is considered by some to be superior in this regard. Raw honey can be used for convalescents and to build vigor in children. Cooking honey is not at all a wise thing to do. This can denature it, resulting in the loss of its medicinal properties. So please only add honey to lukewarm food after it has been cooked and allowed to cool down slightly. Honey is a good Anupana and mixes well with health giving herbs helping to facilitate their penetration into the deeper tissues of the body allowing them to assist us. Externally, one can apply it to wounds and ulcers to utilize its excellent wound healing properties.

 

Dr. Colin I. H. Perry aka: theBEARFooTDOCTOR

Author of Provings: A collection of Poems

 

Editorial Note: Ayurvedic medicine (Ayurveda) is one of the world’s oldest holistic healing systems. Ayurveda is considered by many scholars to be the oldest healing science. In Sanskrit, Ayurveda means “The Science of Life.” Ayurvedic knowledge originated in India more than 5,000 years ago and is often called the “Mother of All Healing.” It stems from the ancient Vedic culture and was taught for many thousands of years in an oral tradition from accomplished masters to their disciples. Some of this knowledge was set to print a few thousand years ago, but much of it is inaccessible. The principles of many of the natural healing systems (bioregulatory medicine) now familiar in the West have their roots in Ayurveda.

 

References:

 

Ali ATMM: Natural honey prevents ischaemia-reperfusion-induced gastric mucosal lesions and increased vascular permeability in rats. Eur J Gastroenterol Hepatol 9:1101-1107, 1997.

 

Biswal BM, Zakaria A, Ahmad NM: Topical application of honey in the management of radiation mucositis. A preliminary study. Support Care Cancer 11:242-248, 2003.

 

Bogdanov S: Nature and origin of the antibacterial substances in honey. Lebensm.-Wiss -Technol 30:748-753, 1997.

 

Foster-Powell K, Holt SHA, Brand-Miller JC: International table of glycemic index and glycemic load values: 2002. Am J Clin Nutr 76:5-56, 2002.

 

Haffejee IE, Moosa A: Honey in the treatment of infantile gastroenteritis. Br Med J 290:1866-1867, 1985.

 

Kandil A, El-Banby M, Abdel-Wahed K, Abdel-Gawwad M, Fayez M: Curative properties of true floral and false nonfloral honeys and induced gastric ulcers. J Drug Res Egypt 17:103-106, 1987.

 

Menshikov FK, Feidman SI: Curing stomach ulcers with honey. Sovetskaya Meditsing 10:13-14, 1949.

 

Mladenov S: “Pcelnite produkti hrana i lekarstvo (BG) / The bee products – food and medicine.” Sofia: Medizina i Fizkultura, 1978.

 

Molan PC: The antibacterial activity of honey. 1. The nature of the antibacterial activity. Bee World 73:5-28, 1992.

 

Russell KM, Molan PC, Wilkins AL, Holland PT: Identification of some antibacterial constituents of New Zealand Manuka honey. J Agric Food Chem 38:10-13, 1988.

 

Salem SN: Honey regimen in gastrointestinal disorders. Bull Islamic Med 1:358- 362, 1981

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Shin H.S, Ustunol Z: Carbohydrate composition of honey from different floral sources and their influence on growth of selected intestinal bacteria: An in vitro comparison. Food Res Int 38:721-728, 2005.

 

Slobodianiuk AA, Slobodianiuk MS: Complex treatment of gastritis patients with high stomach secretion in combination with (and without) a 15-20% solution of honey. Ufa, Bashkir. Khniz. izd.-vo, 1969.

 

Weston RJ, Mitchell KR, Allen KL: Antibacterial phenolic components of New Zealand manuka honey. Food Chem 64:295-301, 1999.

 

Yatsunami K, Echigo T: Antibacterial action of honey and royal jelly (japanese). Honeybee Sci 5:125-130, 1984.

Recent Posts

Restoring a Canine’s Intestinal Microbiome

Restoring a Canine’s Intestinal Microbiome

April 28, 2020

Restoring a Canine’s Intestinal Microbiome

James Odell, OMD, ND, L.Ac

Dogs like humans have a complex gut microbiome composed of bacteria and other microorganisms. This microbiome must stay ecologically balanced to keep the animal healthy and immunologically strong. Like humans, much of the dog’s gut microbiota is non-harmful (commensal) and play many important roles in a canine’s health (Eckburg, Bik et al. 2005). Commensal bacteria perform the following important functions:

 
  • Form a protective barrier against toxins, heavy metals and allergens

  • Produce enzymes for digestion

  • Produce B vitamins

  • Change the genetic expression of cells

  • Contribute up to 90% of the body’s immune system

  • Crowd out unwanted bacteria and fungi

  • Produce serotonin and impact mood

 

Germ-free animal studies have shown that an absence of microbiota is associated with poor immune system development and increased nutrient requirement (Gordon 1971). When dogs have an imbalance in their gut microbiome, they will exhibit several symptoms and abnormal behavior. Diarrhea, bad breath, gas and bloating are common signs of such an imbalance, as is eating grass or other animals’ poop. Grass contains many soil microorganisms and eating grass for a dog is an instinctual way to attempt to replace the intestinal microbiome with bacteria. Of course, this is not ideal, as much yard grass is often contaminated with lawn chemicals. Also, grass is not an abundant source of beneficial bacteria either. Other animals’ feces contain bacteria and enzymes as well; unfortunately, some contain very harmful or pathogenic bacteria and may further aggravate the dog’s microbiome. As humans we take probiotics and fermented foods to balance our gut ecology. This strategy can help dogs too. There are several pet probiotics on the market now, but it is important to understand which ones are best and why.

 

Comparatively little work has been done to characterize the canine gut microbiota compared to that of humans. Several culture-based studies have been conducted profiling the canine gut microbiota (Greetham, Giffard et al. 2002; Greetham 2003). Gut microbiota are composed of different bacteria species taxonomically classified by species, genus, family, order, class, and phylum. Each dog’s gut microbiota changes during their lifetime and its composition depends on many factors and exposures (types of food, exposure to antibiotics and drugs, vaccines, age, breed, social interaction and psycho-emotional health). Essentially, each dog’s intestinal microbiome is unique, just like a fingerprint, because every dog is exposed to a unique environmental terrain and diet.

 

Bacteria live in all parts of a dog’s digestive tract. There are just a few that live in the stomach and as you travel from the small intestine to the large intestine, the numbers increase. But, by far, most of the bacteria thrive in a dog’s colon. This microbial community is usually dominated numerically by strictly anaerobic species, typically including members of the bacteroidetes, bifidobacteria and clostridia (Savage 1977; Gill, Pop et al. 2006). Essentially, types of bacteria change as you move down the digestive tract. (see diagram)

Dogs like people have the same 6 bacteria phyla in their guts. The two phyla Firmicutes and Bacteroidetes represent 90% of a dog’s gut microbiota. Though there are only 6 phyla, each phyla contains an astounding number of different bacteria species and strains. In fact, it is estimated there are several thousand strains of bacteria in the intestines. This complex microbiome also includes yeasts, but is mainly bacteria. These bacteria all function together, and they work as an organ. In fact, some scientists call the microbiome “the forgotten organ” (Backhed, Ley et al. 2005; O’Hara and Shanahan 2006). Balish observed that isolated dogs had an increased observed bacterial diversity (Balish, Cleven et al. 1977). It was suggested that this may have been due to disruption of the dominant microbiota leading to an increase in previously repressed groups.

 

Here are some of the bacteria families found in the top three phyla:

 

Firmicutes

  • Blautia

  • Clostridium

  • Lactobacillus

  • Bacillus Subtilis

  • Bacillus licheniformis

  • Pediococcus acidilactici

  • Enterococcus faecium

Bacteroidetes

  • Bacteroides

  • Prevotella

Actinobacteria

  • Bifidobacterium

Proteobacteria

Spirochaetes

Fusobacteria

 

Probiotics

 

Much like humans, there are several species and strains of probiotics (primarily derived from the Firmicutes and Actinobacteria phyla) that are commercially available and can help restore a canine’s intestinal microbiome: Lactobacillus acidophilus, Lactobacillus casei, Lactobacillus plantarum, Lactobacillus rhamnosus, Bifidobacterium longum, Enterococcus faecium, and the soil-based organisms – Bacillus Subtilis, Bacillus licheniformis, Bacillus coagulans, Bacillus indicus and Pediococcus acidilactici. All these organisms each have unique properties.

 

The soil-based probiotics are spore-forming. This means they can form a hard coating that protects them from heat, stomach acids and most antibiotics. The soil-based probiotics’ protective coating means they don’t need to be refrigerated. And unlike most probiotics that come from dairy (like Lactobacillus and Bifidobacterium), soil-based probiotics are hypoallergenic. That of course is better for dogs with food sensitivities and dairy allergies.

 

Probiotics can play an important part of a canine’s health plan (Biourge V 1998; Baillon, Marie-Louise A 2004; Kelly R 2010). They can help fight pathogenic bacteria and support the dog’s immune system (Pascher, M 2008). However, probiotic supplementation generally needs to be administered daily. In order to boost the numbers of diversity of bacteria in the dog’s microbiome it is also optimally better to periodically rotate species. 

 

Dog Food Considerations

 

Just like humans “dogs are what they eat”. What a canine’s diet is composed of hugely influences its overall health and their intestinal microbiome. To better understand what is best to feed a dog, it is useful to reference the history of commercial dog food. In 1918, WWI just ended and technology like cars and tractors eliminated the need for horses. This created a surplus of horses. A man named Phillip Chapel saw the opportunity to buy up cheap horse meat and sold the first canned dog food under the brand name Ken-L-Ration. Thus, Ken-L Ration became the first canned dog food in the United States. Though made of horse meat, it was carefully marketed as “lean, red meat” and only disclosed its ingredients in much smaller letters at the bottom of the packaging. By 1941, canned food was so successful that producers were breeding horses just for dog food and slaughtering 50,000 of them per year.

 

But when tin was rationed during World War II and pet food was classified as a “non-essential,” producers had to get creative. The combination of these imposed rations and pushback from animal lovers who were furious about the number of horses being killed every year for dog food, created a golden opportunity to introduce a new product in the pet food industry.

 

General Mills acquired Spratt’s in 1950, and Purina entered the dog food market in 1956 with the first ‘kibble’. Purina previously had been selling food for farm animals that was plant and grain-based for pigs and chickens. The Ralston Purina Company began experimenting with the machines they were using for their Chex breakfast cereal to create a more palatable dog food. Given the rations on tin cans, cardboard cereal boxes seemed like the perfect alternative for storing shelf-stable pet food. In 1956, the first dry kibble was produced through a process called extrusion

 

Extrusion is a method used for manufacturing large quantities of shelf-stable foods. It works like this: wet and dry ingredients are mixed to form a dough-like consistency, which is then fed into a machine called an expander. The dough is cooked under extreme pressurized steam and high temperatures before being extruded (or pushed) through a die cut machine and forming the small shapes we recognize as kibble today. This process, of course, destroys enzymes and many heat sensitive nutrients necessary for digestion and health. The extreme heat and drying remove beneficial vitamins, nutrients, and moisture that pets need to truly thrive. Different types of acrylamide and other carcinogens are also created in this process that could be detrimental to a canine’s long-term health. Kibble is a low-moisture product, which puts a dog in a constant state of dehydration. This created many diseases in dogs as pet food not only lacked enzymes and certain nutrients, but was composed of meat by-products and numerous toxic chemicals. Even worse is that these pet feeds were then allowed to contain diseased animal material and meat ingredients sourced from non-slaughtered animals – with no disclosure requirement. Of course, a dog’s intestinal microbiome suffers from such denatured, dehydrated food, as there is also a risk for bacteria and mycotoxins to be present. 

 

The use of extrusion for commercial kibble production gained momentum throughout the 1960s and 1970s as companies used the technology to create new flavors and varieties. Once kibble had been established as the leading pet food option, advertising strategies became more niche-based to differentiate brands. By the 1980s, Hill’s Pet Nutrition had introduced prescription kibble for different ailments (like kidney and liver failure) and continued to diversify by the 1990s, producing kibble based on individual activity level for weight management.

 

Today, pet food companies still produce kibble by extrusion because it facilitates flexibility and density control and better pasteurization. All ingredients (yes, even the high quality or organic variety) are cooked at the same extremely high temperatures and then dried after extrusion in order to remove moisture. While this process optimizes product shelf-life, it can also significantly impact the nutrient composition of the food and poses many other health risks. Additionally, much of the commercial pet food landscape has become increasingly unregulated and is marked by frequent recalls and health controversies.

 

Dogs are considered opportunistic carnivores, meaning they are primarily meat eaters but can supplement with food from other sources. Bottom line is individual dogs have different needs and should be fed as individuals, not a “one size fits all” diet. This means that different dogs may be better off eating different diets. However, there are some generalities that can be observed. The optimal diet for dogs includes fresh, whole foods made from human-grade ingredients. They should be grass-fed, free-range and organic, if possible. The optimal diet includes healthy fats, high moisture (around 70%) and is a healthy balance of protein, carbohydrates and other nutrients. One way to feed this balanced diet is with raw food. A raw diet for dogs includes simply fresh, whole foods that are uncooked and minimally processed. Meats and greens that are fresh, uncooked and wild make up the diet that dogs evolved to eat. It is what canine species in the wild still eat. The administration of a raw food diet has been shown to promote a more balanced growth of bacterial communities and a positive change of healthy gut functions in comparison to a commercial extruded diet of kibbles (Sandri, M 2016; Kim J 2017; Schmidt, M 2018; ).

 

Raw food is more easily absorbed and contains vital naturally occurring enzymes and vitamins that cooking destroys. Living foods that are unprocessed, fresh and whole enable our pets to thrive. And it’s the diet that lets dogs be their happiest and healthiest. Going raw does not have to be an all or nothing approach. Frozen raw dog food provides a complete and balanced, diversified diet. Most of these products can be obtained at health food stores or animal supply stores and contain 100% grass-fed beef, free-range poultry, and other non-factory farmed animal protein sources. Adding even small amounts of raw to a dog’s diet has shown to improve their overall health (Reinerth, S 2014; Stogdale, L 2003; Herstad K 2017).

 

When switching from dry food, it is common to see significant weight loss in the first week which is primarily water weight. After this, it is important that they lose no more than 1 – 2% of their body weight per week. It is highly recommended to consult and work with a holistic veterinarian to assist in monitoring your dog during any dietary transition.

 

Importance of Fiber

 

Every time a dog eats, the nutrients are not just feeding his cells, it is also feeding the intestinal bacteria. Thus, bacteria eat exactly much of what dogs eat. The commensal (friendly) bacteria love one food in particular: fiber. That is because dogs generally cannot digest fiber, so it passes undigested to the colon, creating short chain fatty acids (SCFAs) and benefiting the colonic bacteria (Gibson, 1995; Panasevich, M 2015). When bacteria eat fiber, they generate byproducts called short chain fatty acids. SCFAs either remain in the dog’s colon or they are excreted from their body. Either way, they play a critical role in a dog’s health and immunity:

 
  • SCFAs (especially butyrate) build important T-cells in the immune system, which helps reduce chronic inflammation.

  • SCFAs feed and grow more commensal bacteria and discourage the growth of harmful bacteria.

  • SCFAs help form the protective mucus layer in the gut. 

  • SCFAs keep the cells lining healthy preventing altered bowel permeability.

  • SCFAs reduce glucose levels, which protects against metabolic disease and obesity.

  • SCFAs protect against food allergens.

  • SCFAs help the body absorb calcium, magnesium, iron and other nutrients.

 

Conclusion

 

Like humans, gastrointestinal microbiome dysbiosis is common in dogs and can jeopardize their health leading to degenerative diseases and early death. The gut microbiota of dogs is significantly influenced by diet type (i.e., natural diet (raw) and commercial feed). Specifically, dogs fed a natural diet have more diverse and abundant microbial composition in the gut microbiota than dogs fed a commercial feed. Overall, some degree of a high-quality raw food diet containing nutrient rich fiber together with probiotic supplementation can yield tremendously beneficial effects on microbial populations and the systemic immune characteristics of a dog. 

 

Disclaimer:

 

The information in this article is not intended to replace the advice of your own veterinarian or doctor. This BRMI e-journal article is designed for information purposes only – so that you will know what options might be available to you and what questions and topics to ask your own veterinarian about. Only vets who have directly examined your pet can tell you which diet and supplements are most effective and safe for your animal. Recommendations as to diet, supplemental therapeutics and best standards of practice are constantly evolving in the veterinary industry and, at any one time and on any one point, opinions between professionals may differ. Please do not use this e-journal article as a sole source of information on any matter of veterinary or human health interest.

 

References:

 

Backhed, F., R. E. Ley, et al. (2005). “Host-Bacterial Mutualism in the Human Intestine.” Science 307(5717): 1915.

 

Balish, E., D. Cleven, et al. (1977). “Nose, throat, and fecal flora of beagle dogs housed in “locked” or “open” environments.” Applied and Environmental Microbiology 34(2): 207-221.

Baillon, Marie-Louise A., Zoe V. Marshall-Jones, and Richard F. Butterwick. “Effects of probiotic Lactobacillus acidophilus strain DSM13241 in healthy adult dogs.” American journal of veterinary research 65, no. 3 (2004): 338-343.

 

Biourge, Vincent, Celine Vallet, Anne Levesque, Renaud Sergheraert, Stéphane Chevalier, and Jean-Luc Roberton. “The use of probiotics in the diet of dogs.” The Journal of nutrition 128, no. 12 (1998): 2730S-2732S.

 

Eckburg, P. B., E. M. Bik, et al. (2005). “Diversity of the Human Intestinal Microbial Flora.” Science 308(5728): 1635-1638.

Gordon, H. L. a. L. P. (1971). “The Gnotobiotic Animal as a Tool in the Study of Host Microbial Relationships.” Bacteriological Reviews 35(4): 390-429.

 

Gibson, Glenn R., and Marcel B. Roberfroid. “Dietary modulation of the human colonic microbiota: introducing the concept of prebiotics.” The Journal of nutrition 125, no. 6 (1995): 1401-1412.

 

Gill, S. R., M. Pop, et al. (2006). “Metagenomic analysis of the human distal gut microbiome.” Science 312(5778): 1355-1359.

 

Greetham, H. L. (2003). “Diversity studies of the canine gastrointestinal microbiota.” Theses. Reading University. School of Food Biosciences. Greetham, H. L., M. D. Collins, et al. (2004). “Sutterella

 

Greetham, H. L., C. Giffard, et al. (2002). “Bacteriology of the Labrador dog gut: a cultural and genotypic approach.” Journal of Applied Microbiology 93(4): 640-646.

 

Hand, Daniel. “Exploring the breadth and depth of diversity within the canine gut microbiome.” PhD diss., University of Birmingham, 2011.

 

Herstad, Kristin MV, Karina Gajardo, Anne Marie Bakke, Lars Moe, Jane Ludvigsen, Knut Rudi, Ida Rud, Monika Sekelja, and Ellen Skancke. “A diet change from dry food to beef induces reversible changes on the faecal microbiota in healthy, adult client-owned dogs.” BMC veterinary research 13, no. 1 (2017): 147.

 

Jia, Jie, Nolan Frantz, Christina Khoo, Gibson Glenn R, Robert A. Rastall, and Anne L. McCartney. “Investigation of the faecal microbiota associated with canine chronic diarrhoea.” FEMS microbiology ecology 71, no. 2 (2009): 304-312.

 

Kelley, Russell L., J. Soon Park, Liam O’Mahony, Debbie Minikhiem, and Andrew Fix. “Safety and tolerance of dietary supplementation with a canine-derived probiotic (Bifidobacterium animalis strain AHC7) fed to growing dogs.” Vet Ther 11, no. 3 (2010): E1-E14.

 

Kim, Junhyung, Jae-Uk An, Woohyun Kim, Soomin Lee, and Seongbeom Cho. “Differences in the gut microbiota of dogs (Canis lupus familiaris) fed a natural diet or a commercial feed revealed by the Illumina MiSeq platform.” Gut pathogens 9, no. 1 (2017): 68.

 

O’Hara, A. M. and F. Shanahan (2006). “The gut flora as a forgotten organ.” EMBO Reports 2006: 688-693.

 

Panasevich, Matthew R., Katherine R. Kerr, Ryan N. Dilger, George C. Fahey, Laetitia Guérin-Deremaux, Gary L. Lynch, Daniel Wils et al. “Modulation of the faecal microbiome of healthy adult dogs by inclusion of potato fibre in the diet.” British Journal of Nutrition 113, no. 1 (2015): 125-133.

 

Pascher, Martina, Petra Hellweg, Annabella Khol-Parisini, and Jürgen Zentek. “Effects of a probiotic Lactobacillus acidophilus strain on feed tolerance in dogs with non-specific dietary sensitivity.” Archives of animal nutrition 62, no. 2 (2008): 107-116.

 

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Sandri, Misa, Simeone Dal Monego, Giuseppe Conte, Sandy Sgorlon, and Bruno Stefanon. “Raw meat-based diet influences faecal microbiome and end products of fermentation in healthy dogs.” BMC veterinary research 13, no. 1 (2016): 65.

 

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Recent Posts

Biological Regulatory Effects Associated with Exposure to Radiofrequency/Microwave Frequencies & 5G

Biological Regulatory Effects Associated with Exposure to Radiofrequency/Microwave Frequencies & 5G

April 28, 2020

Biological Regulatory Effects Associated with Exposure to Radiofrequency/Microwave Frequencies & 5G

James Odell, OMD, ND, L.Ac.

Mobile communication has exponentially grown worldwide over the last few decades due to an advancing revolution in wireless technology. This revolution began with 1G- the first generation and has advanced now to 5G- the fifth generation. The dependency on wireless technologies has greatly increased public exposure to broader and higher frequencies of the electromagnetic spectrum to transmit data through a variety of devices and infrastructure. Currently, throughout many urban and rural areasa new generation of even shorter high frequency 5G pulsed wavelengths is being implemented. Research is surfacing that the addition of this added pulsed, high frequency 5G radiation to an already complex mix of lower frequencies, will contribute to a negative public health outcome from both a physical and mental health perspective.

The following is a brief description of the advancement in mobile technology:

 
  • 1G – Analog- Advanced Mobile Phone Service (AMPS) was commercially introduced in the 1980’s and operated with voice only at 800 MHz with a continuous wave signal.

  • 2G – Global System for Mobile Communications (GSM) and Code Division Multiple Access (CDMA), are variants of 2G systems, introduced in the 1990’s, providing text messaging, multimedia messaging and internet access. These were used in the first digital cell phones. Frequencies are a combination of 850 and 1900 or 900 and 1800 MHz. (C.L. Russell Environmental Research 165 (2018) 484–495 486)

  • 3G – Universal Mobile Telecommunications Service (UMTS)- Introduced in 1998 with broadband features providing data transfer, mobile internet and video calling. There are dozens of frequency bands available in the 800–900 MHz range and the 1700–2100 MHz range depending on the carrier.

  • 4G – Long Term Evolution (LTE) –Was released in 2008 with higher frequency broadband supporting faster web access, gaming, video conferencing, and HD Mobile TV. These frequencies are in the 700 MHz, 1700/2100 MHz and the 2500–2690 MHz range.

  • 5G- Device-to-Device Communication, Proposed for expansion of the Internet of Things. Uses wavelengths from 30 to 95 GHz and possibly up to 300 GHz.

The study of the biological effects associated with exposure to electromagnetic energy at radiofrequency/microwave (RF/MW) frequencies is a mature scientific discipline. At present, there are well over 15,000 papers in the scientific literature that report the results of laboratory studies of exposed animals, humans, in vitro preparations, and other relevant studies. As can be imagined, the quality of the studies is uneven, ranging from poor and incomplete to excellent. Since many experimental maneuvers cannot be performed on human subjects, studies of animal subjects must often be substituted. Most studies that report biological effects have involved acute (minutes to hours) RF/MW exposures of animal subjects or in vitro preparations. Due to economic and technical concerns, only a few studies have investigated the consequences of long-term exposure of animals to controlled RF/MW fields.

 

Research and Controversy

 

The controversy over health effects of radiofrequency electromagnetic radiation from commonly used wireless devices such as cell phones, cordless phones, Wi-Fi routers and cell tower infrastructure remains problematic. Radiofrequency research in North America and many countries is poorly funded and even when a study is thorough it seems to not answer the question of long-term safety or provide appropriate precautionary limits.1

 

In 2011, the World Health Organization declared cellphones as a Class 2B: ‘Possibly Carcinogenic to Humans’, meaning the technology may be linked to cancer based on a thorough analysis of current scientific evidence. Some researchers feel this listing should be changed to a Group 2A: ‘Probably Carcinogenic to Humans’ or even to Group 1: ‘Carcinogenic to Humans’ classification.2, 3

 

Microwave radiation is silent and invisible, but with continuous exposure, cells are adversely affected. These extremely high and pulsed frequencies have been shown to cause disturbance in cell-to-cell communication. As cellular communication is vital to human bioregulation, studies have shown exposure to these pulsed microwave frequencies have a fundamental impact on biological processes in our body with the potential following detrimental effects:

 

Damage to reproductive health 4, 5, 6, 7, 8,

Damage to proteins and cellular membranes 9, 10, 11, 12, 13

Increased oxidative stress 14, 15, 16

DNA damage and alterations in gene expression in some human cell types 17, 18, 19

Alteration of the blood-brain barrier system 20, 21, 22

Altered electrical brain activity and cognition 23, 24, 25, 26

Risk of ocular damage – cataracts and lens toxicity 27, 28, 29, 30, 31, 32, 33, 34, 35

Increased behavioral problems in children 36, 37, 38, 39

Risks of some cancers 40, 41, 42, 43, 44, 45, 46

 

Additionally, damage goes well beyond humans, as there is growing evidence of harmful effects to both plant, wildlife and other biosystems. 47, 48, 49, 50, 51, 52, 53 The reported global reduction in bees and other insects is plausibly linked to the increased radiofrequency electromagnetic radiation in the environment. Honeybees are among the species that use magnetoreception, which is sensitive to anthropogenic electromagnetic fields, for navigation. When the honeybee suffers, so does agriculture, and so, potentially do all who depend on the bounty that comes from animal pollinated flowering plants from which we derive many of our most delicious and health-giving fruits and vegetables. Additionally, several million birds of 230 species die each year from collisions with telecommunications masts in the US during migration. Accidents happen mainly in the night, in fog, or bad weather, when birds might be using the earth’s magnetic field for navigation and could be seriously disoriented by the microwave radiation from telecommunication masts.

 

Review of Radiofrequency/Microwave and 5G Technology

 

Mobile phones, antennae of mobile towers, Wi-Fi, cordless phones, tablets and other such wireless equipment work on frequencies ranging from 700 Megahertz (700 million hertz) to 2.8 Gigahertz (2.8 billion hertz), and the new arrival of 5G operates within the extreme-high frequency range of 30 GHz to 300 GHz. Radio frequency is anything between 3Hz and 300 GHz but is subdivided depending on the actual frequency. Microwave is the general term used to describe radio frequency waves that start from ultra-high frequency to extremely high frequency which covers all frequencies between 300 Megahertz to 300 GHz. Lower frequencies are referred to as radio waves while higher frequencies are called millimeter waves.

 

In general, the longer the wavelength the longer it travels, and the farther apart broadcast stations are placed. The 5G short higher frequency millimeter wavelengths travel shorter distances (a few hundred meters); thus, to achieve a seamless integrated wireless system the “small cell” antenna needs to be installed about every 250 meters. Although antennas can be as small as a few millimeters, “small cell” antenna arrays may consist of dozens or even hundreds of antenna elements. Small cells communicate wirelessly with macrocell towers, other small cells, and individual mobile devices. Certain small cells connect directly to fiber cables while others provide support to wireless mesh networks that improve wireless coverage.

 

The all-powerful telecommunication industry has been pushing controversial legislation at the state and federal level to expedite the deployment of this fifth-generation technology. The legislation would block the rights of local governments and their citizens to control the installation of cellular antennas in the public “right-of-way.” Cell antennas may be installed on public utility poles every 10-20 houses in urban areas. According to the industry, as many as 50,000 new cell sites will be required in California alone and at 800,000 or more new cell sites nationwide. The added frequencies and proximity of small cell antenna in this dense network are a valid concern for residents. Although many major cities and newspapers have opposed this legislation, the potential health risks from the proliferation of new cellular antenna sites have been ignored.

 

These cell antennas will expose the population to new sources of radio frequency radiation including the ultra-high-frequency millimeter waves (MMWs). The characteristics of MMWs are different than the “low-band” (i.e., microwave) frequencies which are currently in use by the cellular and wireless industries. MMWs can transmit large amounts of data over short distances. The transmissions can be directed into narrow beams that travel by line-of-sight and can move data at high rates (e.g., up to 10 billion bits per second) with short lags (or latencies) between transmissions.54

 

Millimeter waves (MMWs) are mostly absorbed within 1 to 2 millimeters of human skin and in the surface layers of the cornea. Thus, the skin or near-surface zones of tissues are the primary targets of the radiation. Since skin contains capillaries and nerve endings, MMW bio-effects may be transmitted through molecular mechanisms by the skin or through the nervous system.

 

Thermal (or heating) effects occur when the power density of the waves is above 5–10 mW/cm2. Such high-intensity MMWs act on human skin and the cornea in a dose-dependent manner, beginning with heat sensation followed by pain and physical damage at higher exposures. Temperature elevation can impact the growth, morphology and metabolism of cells, induce production of free radicals, and damage DNA. The maximum permissible exposure that the FCC permits for the general public is 1.0 mW/cm2 averaged over 30 minutes for frequencies that range from 1.5 GHz to 100 GHz. This guideline was adopted in 1996 to protect humans from acute exposure to thermal levels of radiofrequency radiation. However, the guidelines were not designed to protect us from nonthermal risks that may occur with prolonged or long-term exposure to radiofrequency radiation.

 

With the deployment of fifth generation wireless infrastructure, much of the US and numerous other cities worldwide will be exposed to MMWs for the first time on a continuous basis. Due to FCC guidelines, these exposures will likely be of low intensity, at first. Hence, the health consequences of 5G exposure will be limited to non-thermal effects produced by prolonged exposure to MMWs in conjunction with exposure to low- and mid-band radiofrequency radiation.

 

Active Denial System

 

Another interestingly important consideration is that the Department of Defense sponsored studies in the late 1990s and early 2000s looking at the use of millimeter wavelengths as a non-lethal weapon (now called the Active Denial System).55, 56 This use of microwave was designed for area denial, perimeter security and crowd control. Thus, the military’s active denial technology employs very high-frequency millimeter wavelengths, above 94 GHz, to produce an intense burning sensation that penetrates the skin and stops when the transmitter is switched off or when the individual moves out of the beam. Informally, the weapon is also called the heat ray since it works by heating the surface of targets, such as the skin of targeted human subject. There are reports that Russia and China are developing their own versions of the Active Denial System.57

 

Conclusion

 

Industry and governments have turned a blind eye and are operating on the past assumption that there is and will be no health risks from this 5G advancement.58, 59 Consequently, this policy is largely been based on the recommendations of the International Commission on Non-Ionizing Radiation Protection (ICNIRP), published in 1998 (Guidelines for limiting exposure to time-varying electric, magnetic, and electromagnetic fields (up to 300GHz).60 This recommendation limits exposure in the 5G range to a power density of 10W/m2 for the general public and to 50W/m2 for occupational exposure (“Guidelines for limiting exposure to time-varying electric, magnetic, and electromagnetic fields (up to 300GHz).

 

It should be realized that biological effects of a prolonged or chronic MMW exposure of the whole body or a large body area have never been investigated. Safety limits for these types of exposures are based solely on predictions of energy deposition and MMW heating, but in view of recent studies this approach is not necessarily adequate. Common wisdom presented in the literature and media is that, if there are adverse impacts resulting from high-band 5G, the main impacts will be focused on near-surface phenomena, such as skin cancer, cataracts, and other skin conditions. However, there is evidence that biological responses to millimeter-wave irradiation can be initiated within the skin, and the subsequent systemic signaling in the skin can result in physiological effects on the nervous system, heart, and immune system.61

 

Since little research has been conducted on the health consequences from long-term exposure to MMWs, widespread deployment of 5G or 5th generation wireless infrastructure constitutes a massive experiment that may have adverse impacts on the public’s health. Considering the current science, lack of relevant exposure standards based on known biological effects and data gaps in research, we need to reduce our exposure to radiofrequency radiation wherever technically possible. Laws or policies which restrict the full integrity of science and the scientific community with regards to health and environmental effects of wireless technologies should be changed to enable unbiased, objective and precautionary science to drive necessary public policies and regulation.

 

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Lianhua Qingwen Capsule (granule) Approved for Treatment of COVID-19

Lianhua Qingwen Capsule (granule) Approved for Treatment of COVID-19

April 22, 2020

Lianhua Qingwen Capsule (granule) Approved for Treatment of COVID-19

Dr. James Odell, ND, OMD, L.Ac.

On April 14, 2020, Yiling Pharmaceutical announced that the traditional Chinese medicine herbal formulation Lianhua Qingwen capsules (granules) were approved by The State Administration for Market Regulation People’s Republic of China to add functional indications to the originally approved indications: “In the conventional treatment of novel coronavirus pneumonia, Lianhua Qingwen can be used for common type of fever, cough, and fatigue, in treatment lasting for 7-10 days.”

 

During the epidemic in China, Lianhua Qingwen capsules (granules) became the most frequently recommended Chinese herbal patent medicine for treatment of COVID 19. The efficacy of the Lianhua Qingwen capsule (granule) in the treatment of COVID and influenza viruses has been previously confirmed by numerous in vitro, animal and clinical studies (see references). In studies it exerted broad-spectrum antiviral effects on a series of influenza viruses and immune regulatory effects Recently, Runfeng, Li, and his team published a paper entitled “Lianhuaqingwen exerts anti-viral and anti-inflammatory activity against novel coronavirus (SARS-CoV-2).” in the international journal Pharmacology Research. This is the first basic research article demonstrating the effectiveness of this Chinese patent herbal medicine against SARS-Cov-2. In this study, it was found that “Lianhua Qingwen exerted its anti-coronavirus activity by inhibiting virus replication and reducing the cytokine release from host cells, which supported the clinical application of LH in combination with existing therapies to treat COVID-2019.” The authors further concluded, “ These findings indicate that LH protects against the virus attack, making its use a novel strategy for controlling the COVID-19 disease.”

 

Composition of Formula:

 

Lianhua-Qingwen capsule (LQC), developed from the two classical traditional Chinese medicine (TCM) formulae Maxing-Shigan-Tang and Yinqiao-San, both which have a long history of clinical application in the treatment of influenza. It has become a popular and commonly used traditional Chinese herbal preparation to treat viral influenza. It especially played an important role in the fight against severe acute respiratory syndrome (SARS) in 2002-2003 in China. LQC is composed of 11 herbs including Fructus Forsythiae (Lianqiao), Flos Lonicerae Japonicae (Jinyinhua), Herba Ephedrae (Mahuang), Semen Armeniacae Amarum (Kuxingren), Radix Isatidis (Banlangen), Rhizoma Dryopteridis Crassirhizomatis (Mianmaguanzhong), Herba Houttuyniae (Yuxingcao), Herba Pogostemonis (Guanghuoxiang), Radix et Rhizoma Rhei (Dahuang), Radix et Rhizoma Rhodiolae Crenulatae (Hongjingtian), and Radix et Rhizoma Glycyrrhizae (Gancao), along with menthol and a traditional Chinese mineral medicine, Gypsum Fibrosum (Shigao).

 

Availability:

 

Unfortunately, this formula must be ordered online. Thus, it may be a month or more wait when ordering this formula online.

 

References:

 

Ding, Yuewen, Lijuan Zeng, Runfeng Li, Qiaoyan Chen, Beixian Zhou, Qiaolian Chen, Pui leng Cheng et al. “The Chinese prescription lianhuaqingwen capsule exerts anti-influenza activity through the inhibition of viral propagation and impacts immune function.” BMC complementary and alternative medicine 17, no. 1 (2017): 130. https://link.springer.com/article/10.1186/s12906-017-1585-7

 

Duan, Zhong-ping, Zhen-hua Jia, Jian Zhang, Liu Shuang, Chen Yu, Lian-chun Liang, Chang-qing Zhang et al. “Natural herbal medicine Lianhuaqingwen capsule anti-influenza A (H1N1) trial: a randomized, double blind, positive controlled clinical trial.” Chinese medical journal 124, no. 18 (2011): 2925-2933.

https://journals.lww.com/cmj/Fulltext/2011/09020/Natural_herbal_medicine_Lianhuaqingwen_capsule.24.aspx

 

Hai, Guo, Yang Jin, Gong Jiening, and Zhang Qinghong. “Effect of Lianhua Qingwen Capsule on Pulmonary Index of Mice with Viral Infection [J].” Henan Traditional Chinese Medicine 3 (2007). http://en.cnki.com.cn/Article_en/CJFDTotal-HNZY200703016.htm

 

Jia, Weina, Chunhua Wang, Yuefei Wang, Guixiang Pan, Miaomiao Jiang, Zheng Li, and Yan Zhu. “Qualitative and quantitative analysis of the major constituents in Chinese medical preparation Lianhua-Qingwen capsule by UPLC-DAD-QTOF-MS.” The Scientific World Journal 2015 (2015).https://www.hindawi.com/journals/tswj/2015/731765/

 

Mo, Hongying, Changwen KE, Jingping ZHENG, and Nanshan ZHONG. “Anti-viral Effects of Lianhua Qingwen Capsule Against Influenza A Virus in Vitro [J].” Traditional Chinese Drug Research & Clinical Pharmacology 1 (2007). http://en.cnki.com.cn/Article_en/CJFDTotal-ZYXY200701002.htm

 

Ouyang, Huixiang, Qingyan TANG, Yongzhong CHEN, Yu WEI, and Guoshu LI. “Clinical observation of Lianhua Qingwen Department of Emergency, Capsules in treatment of the influenza A/H1N1 [J].” China Medical Herald 30 (2010). http://en.cnki.com.cn/Article_en/CJFDTotal-YYCY201030007.htm