There are times in our lives when it seems like we come full circle in our findings.
This is one of those times for me. Early on in my research into the HPV vaccines I knew that the L-Histidine, which is unique to this vaccine, played a major role in what I was hearing from parents and girls adversely injured by Gardasil®.
I made the connection between Histamine and IgE release.
I was able to make the connection with all the variety of symptoms to the various components of this vaccine. Because of personal experiences, I found that the majority of the injured experienced an anaphylactic type incident. The adverse events experienced from the HPV vaccines nearly mirror those of an autistic child even down to the regression.
Now I find that not only do the components of this vaccine play an integral part, but the main player in this scenario is the probable excessive histamine released because of injected L-Histidine.
So basically I am at the beginning, but with a sobering twist. Be prepared to be as shocked as I was, because of the simple answer that lay in front of me all these years.
NOTE: The information I am going to share with you has been extracted from peer reviewed studies and articles. References will be at the end of this article and definitions will be within brackets [ ] throughout the article. I have also underlined and italicized items I feel are of importance.
First, let me give you a little history about histamine.
“L-Histidine is an essential amino acid necessary for protein synthesis [creation] and various other functions in cells and tissues, e.g., as a precursor [foundation] for histamine. (8) Histamine was discovered in 1910 by Dale and Laidlaw (1, 2, 3), and it was identified as a mediator of anaphylactic reactions in 1932 (1, 2, 4). It is synthesized [created] by mast cells, basophils [white blood cell], platelets [piece of cell that helps blood clot], and some neurons, where it is stored intracellularly [within the cell] in vesicles [small sac or hollow organ in the body] and released on stimulation. It causes smooth muscle cell contraction, vasodilatation [widening of blood vessels], increased vascular permeability and mucus secretion, tachycardia [excessively rapid heartbeat], alterations of blood pressure, and arrhythmias [irregular heartbeat], and it stimulates gastric acid secretion and nociceptive [pain causing] nerve fibers. It is also known to play various roles in neurotransmission, immunomodulation [the suppression of the immune system], hematopoiesis [formation of red blood cells], wound healing, day-night rhythm [circadian rhythm], and the regulation of histamine and polyamine induced cell proliferation and angiogenesis [formation of new blood vessels] in tumor models. (1, 2, 5, 6), and intestinal ischemia [lack of blood](1, 2, 7).”
“Histamine is a biologically active substance that plays a key role in the body’s inflammatory reaction to injury caused by infection, physical damage or allergy. Histamine is released from cells in response to an antibody called immunoglobulin E (IgE). This antibody may be secreted in response to an invading pathogen such as a virus or bacteria, an allergenic substance such as pollen or in response to injury caused by toxins. Whatever triggers the release of IgE, the response is a flood of histamine that has various different effects depending on the histamine receptor it comes into contact with. (9)”
Reference 1 – Figure 1 (1)
Histamine effects according to plasma [blood] histamine concentration (ng/mL) [nanograms/milliliter]
Histamine Clinical effect
1–2 ↑ Gastric acid secretion ↑ Heart rate
3–5 Tachycardia [excessive rapid heart rate], headache, flush [a sudden intense warn/hot feeling], urticaria [rash], pruritus [intense feeling of itchiness]
6–8 ↓ Arterial pressure
7–12 Bronchospasm [acute, transient airway narrowing]
≈100 Cardiac arrest
Reference 1 – Table 1 (1)
Over the years I have heard from girls and their parents expressing various adverse events after administration of the HPV vaccine. I am only going to focus on the top five events that are most often experienced.
Migraine and recurrent headaches seem to be a common complaint among females and males adversely affected. The FDA, Merck and CDC know that headaches will be a common occurrence. The information that I am going to share is on page 30 of the Clinical Review of Biologics License Application for Human Papillomavirus dated June 8th, 2006 (26). This data was presented to the FDA prior to the actual clinical trials and approval was given to Merck to conduct the clinical trials on the HPV vaccine despite these findings.
“Note: Placebo – V501 HSS001 A001 (225 mcg aluminum as amorphous aluminum hydroxide sulfate or AAHS) – found on page 20 of the document.”
Systemic [affecting the whole body] clinical adverse experiences were generally comparable across treatment groups.
Overall incidence rates in different dose groups –
Placebo group: 96.3% (26/27)
10/40 mcg dose group: 92.3% (12/13)
40 mcg dose group: 82.2% (37/45)
80 mcg dose group: 91.7% (22/24)
The most common systemic clinical adverse experience was headache:
Placebo: 70.4% (19/27)
10/40 mcg dose group: 76.9% (10/13)
40 mcg dose group: 64.4% (29/45)
80 mcg dose group: 54.2% (13/24) (Source: Table 40, CSR 002, p. 169-73, not shown here)
Here is what the scientific community has discovered.
“Histamine is thought to play a role in the modulation of pain and has been shown to induce migraine, prompting investigation of histamine desensitization for prophylaxis against intractable migraine. (10) Headache can be induced dose-dependently by histamine in healthy persons as well as in patients with migraine (11, 12). Histamine-induced headache is a vascular headache… In migraine patients, plasma histamine concentrations have been shown to be elevated both during headache attacks and during symptom-free periods. An increase in the number of brain mast cells is associated with pathologic conditions such as migraine, cluster headache, and multiple sclerosis (13). (1)”
“High concentrations of histamine and histamine decarboxylase are found in neurons in the hypothalamus that send sparse but widespread projections to almost all regions of the brain and spinal cord. The central histamine projections mediate arousal and attention, similar to central Ach [adrenocortical hormone] and norepinephrine [is both a hormone and a neurotransmitter] projections. This partly explains why antihistamines that cross the blood-brain barrier, such as diphenhydramine (Benadryl®), act as sedatives. Histamine also is released from mast cells in response to allergic reactions or tissue damage. The close proximity of mast cells to blood vessels, together with the potent actions of histamine on blood vessels, raises the possibility that histamine may influence brain blood flow. (14)”
“According to Horton, in histamine headache the symptoms are caused by dilatation and constriction of the external and common carotid arteries. On the other hand, Wolff, Schumacher, Clark, Butler, Shuterland, and Pickering have proved, on the evidence of many cases, that the internal carotid is responsible for the quality and the intensity of histamine headache, and that the dilatation of the external carotid is of decisive importance in migraine. They demonstrated with photographs, taken during headache produced by the injection of histamine: (1) the amplitude of intracranial pulsation (which is increased); (2) the arterial blood pressure; (3) the pressure of the cerebrospinal fluid; and (4) the degree of pulsation in the temporal artery. (16)”
“In conclusion, we think that spontaneous migraine pain may be produced and maintained in the brain and that vasodilatation is an epiphenomenon [additional symptom]. Nevertheless, we believe possible that a transitory vasodilator effect (as that provoked by some drugs) can trigger undeﬁned central mechanisms which are able to provoke migraine attack, as any migraine trigger such as stress, hormonal variations, etc.. This interpretation may explain even the delayed headache provoked by vasodilator agents, at a time when vasodilatation has ended. (15)”
“It is well-documented that women have higher serum antibody concentrations compared to men. Furthermore, IgE binds mast cells causing degranulation [elimination of granules] and the release of histamine, IL-4, and IL-13. IgE levels in women have been shown to vary with hormonal status, which may play a part in premenstrual asthma exacerbations. …estrogen stimulates degranulation and increases histamine secretion in primed mast cells. This is a case where progesterone antagonizes the effects of estrogen in immune response… the overall inflammatory response may vary, as may occur in premenstrual asthma or in pregnancy. (21)”
“Histamine receptor mRNA in cultured human nasal epithelial cells and human mucosal microvascular [finer blood vessels] endothelial cells was increased by estrogen and progesterone (but not testosterone). Histamine is released in response to allergen stimuli, and hyperreactivity of nasal mucosa to histamine is a hallmark of allergic rhinitis. (21)”
“Therefore, we analyzed the responses of human airway cultures to allergic reactions. Three lines of evidence have been uncovered which indicate that mast-cell degranulation increases mucous secretion from cultured human airways. (a) Supernatant fluids from peripheral human lung tissue passively sensitized with human IgE and challenged [given more than one dose] with specific antigen contain a mixture of the mediators of anaphylaxis; these mediator-rich supernatant [surface liquid] solutions significantly increased mucous secretion. (b) Cultured airways themselves may be passively sensitized with IgE and challenged with a specific antigen; the resulting immunologic reaction induced the release of both histamine and increased quantities of mucus. (c) Antibodies directed against human IgE may interact with IgE molecules present on airway mast cells and cause mediator release; this reaction also caused increased mucous secretion. Thus, the mediators of anaphylaxis as well as reversed and direct anaphylaxis of airways induces mucous secretion. (22)”
“These data indicate that a product derived from degranulated lung mast cells is capable of stimulating mucous secretion. Histamine has previously been suggested as a mucous secretagogue [growth hormone releasing compound ](15), although other in vitro experiments have been inconsistent with this conclusion (5, 7, 16). Histamine (1-100 ,uM) increased mucous secretion maximally at 100 ,uM. Peripheral human lung contains 10, ug of histamine/g wet wt. It might be anticipated that the immunologic release of as little as 20% of total histamine (the mean percent histamine released by allergen-IgE interactions in human lung in vitro) would generate histamine concentrations in the interstitial [small opening] space around mast cells exceeding 100-1,000 ,mM [millimeter]. The effects of exogenous histamine on mucous secretion could be prevented by H-2 receptor antagonists and reproduced by H-2 agonists. H-1 receptor antagonists could not be studied as they appeared to be stimulatory; however, 2-methylhistamine, an H-1 agonist [competitor], was not effective. These data indicate that histamine stimulates mucous secretion by interacting with H-2 receptors. (22)”
Female Reproductive System
“Estrogens may support allergic reactivity in females by acting via the estrogen alpha receptor on mast cells, which might explain the peaking allergic reactions in females around menstruation and pregnancy, under oral contraceptives and hormone replacement therapy… For allergy, it is important to note that xenoestrogens interact equally well with the estrogen alpha and beta receptors and, thus, may either directly or in conjunction with an allergic reaction support the release of histamine (17, 18, 19)”
“It is possible that several immune reactions are at work in the process of hormone allergy. One of these possibilities may be that estrogen, progesterone, and their metabolites may act as antigens after binding to different proteins, promoting Th2 cell development, and thereby regulating the synthesis of IgE or other antibodies. The binding of these antibodies to mast cells with their corresponding antigens (hormones or metabolites) induces mast cell or basophile degranulation. This reaction leads to histamine release Th2 cytokine, and leukotriene secretion, resulting in Type I allergic disease. (17)”
“Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders, being found in 4–7% of women of reproductive age and accounting for about 75% of anovulatory [absence of ovulation] infertility. It is characterized by polycystic ovaries, hyperandrogenism [abnormally high levels of the androgen hormones] and chronic anovulation (Knochenhauer et al. 1998). PCOS is also associated with hirsutism [excessive hairiness on women], obesity, insulin resistance and compensatory hyperinsulinemia [excess levels of insulin circulating in the blood]. Hyperinsulinemia results in an increased risk of cardiovascular disorders and a sevenfold increase in risk of non-insulin-dependent diabetes mellitus (NIDDM) (Legro et al. 1999). Many lipid abnormalities (most notably, low high density lipoprotein cholesterol levels and elevated triglyceride levels) and impaired ﬁbrinolysis [process that prevents blood clots] are seen in women with PCOS. Long-standing unopposed estrogen stimulation leads to an increased risk of endometrial carcinoma. PCOS is also associated with an increased rate (30–40%) of early pregnancy loss (Watson et al. 1993). Early diagnosis of this syndrome, close long-term follow-up and screening for diabetes and cardiovascular diseases are warranted. (21)”
“Our study also revealed some other genes … HNMT (histamine N-methyltransferase), prothrombin [process of blood clotting ](Roach et al. 2002,) … (21)”
“Ovarian hyperstimulation syndrome (OHSS) – The syndrome is characterized by cystic enlargement of the ovaries and a fluid shift from the intravascular to the third space due to increased capillary permeability [leaks] and ovarian neoangiogenesis [new formation of blood vessels]. β-hCG and its analogs, estrogen, estradiol, prolactin, histamine and prostaglandins have all been implicated in OHSS but now it is increasingly better understood that the vasoactive [contracting or dilating blood vessels]substances such as interleukins, tumor necrosis factor-α, endothelin-1, and vascular endothelial growth factor (VEGF) secreted by the ovaries have been implicated in increasing vascular permeability. Enlargement of the ovaries causes abdominal pain, nausea and vomiting. Leakage of fluid from follicles, increased capillary permeability leading to third spacing (due to the release of vasoactive substances), or frank rupture of follicles can all cause ascites[fluid in abdomen]. (20)”
“The Arthritis Foundation reports the number of Americans with arthritis or chronic joint symptoms has risen from 35 million to 66 million (nearly 1 in 3 adults) in 2005. Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by inflammation of the lining, or synovium [the frictionless lining] of the joints. It is one of the most severe forms of arthritis and can lead to long-term joint damage, resulting in chronic pain, loss of function and disability. RA affects 1 percent of the U.S. population or 2.1 million Americans, mostly women. (24)”
“In their study, the researchers developed a new microscopic imaging method to visualize changes in blood vessel permeability in anesthetized mice. Within minutes following the delivery of arthritis-causing antibodies to the mice, the blood vessels around the joints became temporarily leaky, making it easier for the antibodies to enter the joint spaces. There, the antibodies set off a cascade of inflammatory cells and molecules, eventually resulting in arthritis. (24)”
“The big surprise was that the other blood vessels throughout the body did not become leaky, suggesting that there is something special about the vessels in the joints,” says Bryce Binstadt, M.D., Ph.D., of Joslin and Children’s Hospital Boston, lead author on the study. (24)”
“In trying to identify the special feature, the investigators made the even more unexpected discovery that histamine was responsible for the joint blood vessel leakiness – in fact, the researchers could mimic the effect of the antibodies on blood vessel leakiness by just injecting histamine. (24)”
“Histamine and IL-1 have been implicated in the pathogenesis of chronic inflammatory diseases, such as pulmonary allergic reactions and rheumatoid arthritis. (23)”
“These results suggest that mast cells may sustain chronic inflammatory processes by upregulating self-induction of IL-1 through histamine release. (J. Clin. Invest. 1993.92:281-287.) (23)”
“Our studies indicate that histamine enhances self-induction of IL-I: via H2 receptors. Because IL- 1 contributes to the eosinophil infiltration characteristic of the late phase response to antigen, histamine release by activated mast cells may sustain chronic inflammatory processes, in addition to its immediate inflammatory properties. (23)”
Foods with Histamine
Many individuals that I have communicated with have told me about the different food sensitivities they are experiencing. Foods that they loved are now causing an exacerbation of symptoms. Many have said that when they received an allergy test for the specific items the tests came back negative. This is why my last item is about foods. The foods that you eat if you are histamine intolerant have the potential to cause a mild to severe allergic reaction. You will find a link to the information below at reference 25.
It is important to eat foods that are low in histamine. Please always remember that there is no such thing as a histamine-free diet!
Low histamine level foods:
- Fresh meat (cooled, frozen or fresh)
- Freshly caught fish
- Chicken (skinned and fresh)
- Egg yolk
- Fresh fruits – with the exception of strawberries, most fresh fruits are considered to have a low histamine level (also see histamine liberators below)
- Fresh vegetables – with the exception of tomatoes
- Grains – rice noodles, yeast free rye bread, rice crisp bread, oats, puffed rice crackers, millet flour, pasta (spelt and corn based)
- Fresh pasteurized milk and milk products
- Milk substitutes – coconut milk, rice milk
- Cream cheese, butter (without the histamine generating rancidity)
- Most cooking oils – check suitability before use
- Most leafy herbs – check suitability before use
- Most non-citric fruit juices
- Herbal teas – with the exception of those listed below
High histamine level foods:
- Pickled or canned foods – sauerkrauts
- Matured cheeses
- Smoked meat products – salami, ham, sausages, etc.
- Beans and pulses – chickpeas, soy beans, peanuts
- Nuts – walnuts, cashew nuts
- Chocolates and other cocoa based products
- Most citric fruits
- Wheat based products
- Ready meals
- Salty snacks, sweets with preservatives and artificial colorings
- Most citric fruits – kiwi, lemon, lime, pineapple, plums…
- Cocoa and chocolate
- Beans and pulses
- Wheat germ
- Additives – benzoate, sulphites, nitrites, glutamate, food dyes
Diamine Oxidase (DAO) blockers: [the main enzyme for the metabolism of ingested histamine and may be responsible for scavenging extracellular histamine.]
- Black tea
- Energy drinks
- Green tea
- Mate tea
- Yogurt – depends on the bacteria culture used
- Egg white – it is a histamine liberator only when in its raw state
- Yeast – even though it does not contain histamine as such, yeast serves as a catalyst for histamine generation during manufacture. There is no yeast in the end product.
My opinion is simply this. Vaccinations are designed to cause an immune response to train the body to attack that specific antigen, pathogen or toxin to protect the body from harm. This is facilitated by the activation of the mast cells by IgE to release histamine. The HPV vaccine Gardasil had VLP’s (virus-like particles) cultured in yeast and has 0.78 mg of L-Histidine which is converted to histamine which increases the level of histamine in the body. This histamine response causes inflammation. The inflammation, depending on why or how the mast cells were activated, could be site specific or system wide. Considering that histamine generation can be produced in many organs and areas of the body like the reproductive system and the brain, this inflammation if chronic has the potential to cause auto-immune diseases, brain damage and even death if the histamine concentration is too high.
To estimate what 0.78 mg [micrograms] of L-Histidine is in ng [nanograms] I used a conversion calculator. This is what I found. 0.78 mg = 780 ng. It takes ~100ng to cause cardiac arrest as stated in Reference 1 – Table 1 at the beginning of this article.
Considering that the L-Histidine is injected intramuscularly, it has the potential to cause adverse events at the injection site (site specific). The L-Histidine is converted to histamine which now has access to the blood stream. Therefore, after the initial site specific reaction the newly created histamine will slowly be introduced to the rest of the body causing systemic reactions (system wide). This explains why we have the variety of adverse events and why they may happen hours to a few months later.
The mast cells have been primed because of the immune response to the vaccine to target histamine. Now every time a vaccine injured person eats certain foods there is the potential for a chronic anaphylactic histamine reaction from mild to severe.
I have found all this information plus much more to be shocking as to the fact that the majority of the information that I presented to you was prior to the approval of the HPV vaccine Gardasil in 2006.
I want to thank Leslie Carol Botha for being my sounding board over the years of my researching this vaccine and for her expertise in the effects of female hormones on the body. Also, for all the times I called her at all times of the day for opinions and to just sound off after speaking with another parent of a son or daughter who has been injured.
I want to thank Michelle from Florida who has two young children who are now suffering because of the adverse reactions following vaccination for bringing the possibility that Histamine Intolerance might be causation post-vaccination. This article is for you.
I want to thank little Jenny Tetlock for giving me the tenacity to never give up in my pursuit to find the truth with regards to the HPV vaccines. I never gave up Jenny. May you now rest in peace.
Lastly, I want to thank all the hundreds of parents whom I have communicated with over the years. You kept me going in my quest even when I thought no one was listening. You are the warriors and I love each and every one of you.
Now let us start to heal our children.
Cynthia Janak is a freelance journalist, mother of three, foster mother of one, grandmother of five, business owner, Chamber of Commerce member. Her expertise is as an administrative professional. Her specialties are adoptee and genealogy research and research journalism.
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