- Histamine is a neurotransmitter that supports our daily biological functions, but the histamine response can quickly turn destructive when oversensitized to external stimuli such as allergens and toxins.
- Histamine sensitivity is when the body releases histamine in response to certain compounds that should be considered harmless by the body, while histamine intolerance refers to an excess accumulation of histamine in the body.
- Histamine and sulfur sensitivity appear to be closely linked, but in some cases, excess sulfur and sulfur metabolism impairment may lead to histamine sensitivity.
- BodyBio Calm can help relieve histamine sensitivity with a unique combination of amino acids, trace minerals, and adaptogens.
Histamine is vital for our day-to-day biological rhythms. As a neurotransmitter, it promotes wakefulness, controls satiety, and is crucial to direct goal-oriented behaviors. Histamine H3 receptors are also connected to cognitive function and the maintenance of short and long-term memory.
However, the histamine response can become a disruptive force if it is not properly regulated. We are familiar with the ways histamine can produce a runny nose, or draw our attention to a mosquito bite, but histamine can also create hypersensitivity reactions. These can range from leaky gut and inflammatory bowel disease to mast cell activation syndrome (MCAS) and anxiety, contributing to neurological dysfunction.
Rather than writing off histamine as a bystander in common allergic reactions, we must consider histamine as a primary agent for various destabilizing effects in the body and a considerable source of systemic stress. Then, we can begin to manage and stabilize histamine for a better sense of overall balance in the body.
Table of Contents:
- What Does Histamine Do?
- Histamine Sensitivity Symptoms
- Histamine Sensitivity vs. Intolerance
- What Causes Histamine or Sulfur Imbalances?
- How to Calm Histamine Sensitivity
- Find Relief from (Histamine) Hypersensitivity
What Does Histamine Do?
Histamine acts as the body’s defense mechanism when it perceives a threat by a foreign or pathogenic invader. The release of histamine kicks off the body’s “attack mode,” making this monoamine the natural opposite of balance and calm. When uncontrolled, histamine is pure fight energy. Histamine also acts as a hormone regulator and helps keep us awake during the day, supports gut motility and gastric acid production, and contributes to feelings of satiety when we eat.
When an injury, pathogenic threat, or a toxic substance threatens the body, mast cells release histamine, causing the dilation of blood vessels. This dilation permits white blood cells and blood plasma proteins to slip into the bloodstream and travel to the location of the injury or toxin, where immune system cells can begin to fight the invasion (Branco et al., 2018).
In service of the immune response, histamine can also instigate a number of other reactions:
- Contracting smooth muscle tissues
- Lowering blood pressure
- Accelerating the heart rate
- Initiating chemical communication between nerve cells.
Sometimes these effects end up causing symptoms in those who have heightened histamine sensitivity.
Histamine Sensitivity Symptoms
Troubles in the body arise when histamine is over-secreted due to what are known as hypersensitivity reactions to various stimuli, some dangerous and others seemingly harmless. Hypersensitivity reactions refer to an immune response resulting in inflammation, tissue damage, and even chronic disease states (such as multiple sclerosis, colitis, arthritis, ADHD, anaphylaxis, and autoimmunity).
Symptoms of these reactions can include:
- Allergic conditions
- Gastrointestinal disease
- Low gastric acidity
- Sinus congestion
- Gallbladder impairment
- Chronic fatigue
Significantly, type II hypersensitivities, also known as cytotoxic hypersensitivities, occur when damage happens to our own cells. These reactions are initiated by the antibodies immunoglobulin G (IgG) and immunoglobulin M (IgM). Some common forms of type II hypersensitivities are when the specified immunoglobulins attack our own cells, often causing autoimmune disease (i.e. Graves’ Disease, hemolytic anemia, Myasthenia Gravis).
The most common points of entry for antigens (a substance provoking an immune response) are the skin, respiratory system, and digestive system. Every breath we take and every bite of food we eat offers an opportunity for new, unrecognizable substances, pathogens, and toxins to enter the body, where they must be identified, assessed for toxicity, and finally metabolized.
This is not something to be afraid of; our bodies are designed to do this. But in a hypersensitive system, the body looks to seek and destroy foreign materials under the assumption that they may be pathogenic — meaning that hypersensitivity may be directly related to excess secretion of histamine.
Histamine Sensitivity vs. Intolerance
However, note that histamine sensitivity is not the same as histamine intolerance. In cases of histamine intolerance, histamine is over-produced, altering the body’s ability to discern between human cells and antigens. Rather than a sensitivity to the compound, histamine intolerance is a sign that you’ve developed too much of it.
Histamine vs. Sulfur Sensitivity
Because histamine and gut health are so deeply linked, histamine-producing bacteria are of great concern in cases of mast cell activation syndrome (MCAS). Foods containing the amino acid histidine may be converted via certain types of gut bacteria into histamine.
However, sulfur metabolism impairment can act as a significant contributor to histamine intolerance, and a unique connection exists between the two.
Because sulfur and histamine intolerance are almost identical in symptomatology, they are easily, and often, confused. However, when we make the connection between impaired sulfur metabolism mechanisms and elevated levels of histamine in the body, it becomes clear that an inability to properly process sulfur is linked to a downstream inability to efficiently regulate histamine.
The body typically uses sulfur in the body as sulfate. When the conversion of sulfur to sulfate is slowed or compromised, concentrations of sulfate in the body are depleted, while concentrations of sulfur and sulfite may remain elevated.
Among other symptoms, this can result in:
- Allergic and inflammatory responses
- Compromised gut integrity
- Impaired cholesterol sulfate metabolism
- Decreased gallbladder function and bile acid activity
- Kidney stones and calcifications
The Role of Sulfur in Histamine Levels
Another factor that metabolizes sulfur is the CBS gene. A disruption of sulfur metabolism, and any mutations or impairments of the CBS gene may contribute to the depletion of the compound SAM-e, which has been linked to an increase in histamine levels in the body. An additional issue that may arise when the CBS gene is impaired is an excess accumulation of hydrogen sulfide gas (H2S) that may lead to gut dysbiosis or hydrogen sulfide SIBO.
Normal levels of hydrogen sulfide help regulate gut inflammation and motility, oxidative stress, ulcer healing, apoptosis, vascular tone, and hormone secretion. Imbalances in H2S due to gut dysbiosis may lead to Crohn’s disease, IBS, ulcerative colitis, SIBO, obesity, and sepsis.
Too much hydrogen sulfide may also be linked to adrenal insufficiency due to H2S helping to control mitochondrial function in the adrenal tissue (Wang et al., 2014). H2S imbalances could be linked to stress, excessive meat consumption, and high-sulfur diets, particularly if an individual has genetic predispositions that impair sulfur metabolism.
What Causes Histamine or Sulfur Imbalances?
We’ve mentioned a couple of times now that certain gut bacteria are involved in both processing sulfur and producing histamine. When these bacteria become imbalanced, levels of sulfur and histamine can easily get out of control.
Through clinical observation, our practitioners have identified a common thread between candida and SIBO cases (high histamine levels are a repeated symptom in this group), bacterial infections like Lyme Disease and its co-infections, mast cell activation syndrome, and sulfur intolerance. For comparison, here are the common symptoms of both sulfur and histamine intolerance:
Overlapping histamine intolerance and sulfur intolerance symptoms:
- Joint pain/Body pain
- Palpitations/Sudden blood pressure changes
- GI pain/Constipation/Diarrhea
- Shortness of breath
- Fatigue/Cognitive impairment
In cases of candida and SIBO, sulfate-reducing bacteria in the gut produce excess hydrogen sulfide gas when they ferment carbohydrates, further disrupting microbiome health, inducing an immune response, and increasing intestinal permeability and gut inflammation (Figliuolo et al., 2017).
Clients with candida or SIBO often present with an intolerance to sulfur-based medicines and foods, with symptoms that mirror those of histamine intolerance. One red flag for sulfur-sensitive clients is an intolerance to glutathione, a sulfur-based antioxidant. When the body cannot properly break down glutathione, one side effect is an increased production of hydrogen sulfide gas, especially in cases of SIBO. Hydrogen sulfide causes the breakdown of the mucus barrier, and reduces concentrations of the mineral molybdenum, which is crucial for the regulation of histamine.
How to Calm Histamine Sensitivity
BodyBio Calm is specifically designed to modulate the histamine response and bring the body back into balance, combining potent trace minerals, amino acids, and adrenal adaptogens to manage excess levels of histamine and support natural modulators of histamine in the body. The five key ingredients to achieving this are manganese, taurine, glycine, Rhodiola rosea, and phosphatidylserine.
One of the signature innovations of Calm is that it utilizes an underappreciated trace mineral, manganese. Manganese helps to promote a sense of calm by modulating the excitatory neurotransmitter histamine through the following mechanisms.
- Is a cofactor for the protein that forms superoxide dismutase (SOD), an enzyme that is crucial for the antioxidation of cells
- May support the suppression of mast cell activation
- May rebalance gut dysbiosis
The amount of manganese in Calm is small enough to ensure sustainable use, but potent enough to provide effective daily care.
Taurine, an amino acid linked to liver and nerve support, may also play a role in modulating:
- Inflammatory cytokines
- Mast cells
- Histamine release in the body
Modulating histamine and mast cell activity could contribute to a reduction in mast cell activation, and even rebalance the sympathetic nervous system response, regulating dopamine. This is of particular interest, as the improper regulation of dopamine can result in a histamine response. Taurine’s ability to act as a modulator for both dopamine and histamine make it a vital player in this formulation.
Glycine is also an amino acid, and a precursor to betaine that supports healthy levels of serotonin, promotes protein synthesis, and regulates cytokines. Crucially, glycine may reduce inflammation from digestive autoimmune diseases by lowering inflammation in the epithelial cells of the intestines.
Additionally, a study using mouse models found that oral administration of glycine significantly inhibited allergy development, indicated by a reduction in acute allergic skin response, anaphylaxis, and serum antibodies.
Two adrenal adaptogens are essential to Calm’s success: Rhodiola rosea and phosphatidylserine. When the adrenal glands are overworked, cortisol levels rise and may depart from normal ranges, depleting the body’s ability to relieve stress.
This is noteworthy because, as a natural anti-inflammatory agent, cortisol is key to the modulation of histamine, and strong adrenals are critical to maintaining the healthy production and management of cortisol. By supporting adrenal function with targeted adaptogens, Calm helps to modulate the stress response, which, in turn, modulates the histamine response.
Our first adaptogen, Rhodiola rosea, is an herb that helps to manage stress and mental fatigue, and may support the rebalancing of depressive symptoms. Acting as an adrenal adaptogen, Rhodiola has the potential to modulate the release of cortisol and reduce inflammatory markers in the body. As a modulator of cortisol, Rhodiola indirectly helps to support a balanced histamine response, and may modulate serotonin, contributing to a more balanced mood.
Calm’s final ingredient, phosphatidylserine, is a phospholipid found in the brain that supports healthy myelination, nerve cell structure, memory, and executive functioning. Phosphatidylserine may reduce the release of stress hormones such as ACTH and cortisol, indirectly managing histamine. Additionally, phosphatidylserine may also positively impact age-related cognitive decline, combat depression, and aid ADHD symptoms.
Find Relief from (Histamine) Hypersensitivity
BodyBio’s Calm Supplement provides comprehensive stress relief that goes beyond HPA axis support to target hidden and overlooked sources of stress, including the histamine response. By supporting a more balanced histamine response, Calm introduces a new way to soothe hypersensitive systems, addressing symptomatology that often goes overlooked but can significantly degrade an individual’s quality of life. From seasonal allergies to ADHD and mast cell activation syndrome, Calm is a secret weapon for hard-to-reach symptoms, providing a foundation for systemic balance.
Anghelescu, I.-G., Edwards, D., Seifritz, E., & Kasper, S. (2018, January 11). Stress management and the role of Rhodiola ROSEA: A review. Taylor & Francis. Retrieved September 14, 2021, from https://www.tandfonline.com/doi/full/10.1080/13651501.2017.1417442?scro ll=top&needAccess=true.
Bannai M, Kawai N, Nagao K, Nakano S, Matsuzawa D, Shimizu E. Oral administration of glycine increases extracellular serotonin but not dopamine in the prefrontal cortex of rats. Psychiatry Clin Neurosci. 2011 Mar;65(2):142-9. doi: 10.1111/j.1440-1819.2010.02181.x. PMID: 21414089.
Bergenhenegouwen, J. van, Braber, S., Loonstra, R., Buurman, N., Rutten, L., Knipping, K., Savelkoul, P.J., Harthoorn, L.F., Jahnsen, F.L., Garssen, J., Hartog, A. Oral exposure to the free amino acid glycine inhibits the acute allergic response in a model of cow's milk allergy in mice. Nutr Res. 2018 Oct;58:95-105. doi: 10.1016/j.nutres.2018.07.005. Epub 2018 Jul 10. PMID: 30340819.
Branco, A.C.C.C., Yoshikawa, F.S.Y., Pietrobon, A.J., Sato, M.N. Role of Histamine in Modulating the Immune Response and Inflammation. Mediators Inflamm. 2018 Aug 27;2018:9524075. doi: 10.1155/2018/9524075. PMID: 30224900; PMCID: PMC6129797.
Canani, R. B., Costanzo, M. D., Leone, L., Pedata, M., Meli, R., & Calignano, A. (2011, March 28). Potential beneficial ef ects of butyrate in intestinal and extraintestinal diseases. World journal of gastroenterology. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3070119/.
Cyr, J. (2020, April 1). The Role of Sulphur in Ulcerative Colitis. Gastrointestinal Society. https://badgut.org/information-centre/a-z-digestive-topics/the-role-of-sulphu r-in-uc/.
Figliuolo, V. R., Santos, L. M. dos, Abalo, A., Nanini, H., Santos, A., Brittes, N. M., Bernardazzi, C., Souza, H. S. P. de, Vieira, L. Q., Coutinho-Silva, R., & Coutinho, C. M. L. M. (2017, September 12). Sulfate-reducing bacteria stimulate gut immune responses and contribute to inflammation in experimental colitis. Life Sciences. https://www.sciencedirect.com/science/article/abs/pii/S002432051730454X.
Folkerts , J., Maurer, M., Stadhouders, R., Hendricks, R., Galli, S., Tam, S.-Y., Junt , T., van IJcken, W., de Bruijn, M., van den Berg, M., Blokhuis, B., Folkerts, G., & Redegeld, F. (2020, April 24). Butyrate inhibits human mast cell activation via epigenetic regulation of FcεRI-mediated signaling. Allergy. https://pubmed.ncbi.nlm.nih.gov/32112426/.
Glade, M. J., & Smith, K. (2014, November 4). Phosphatidylserine and the human brain. Nutrition. Retrieved September 23, 2021, from https://www.sciencedirect.com/science/article/abs/pii/S0899900714004523.
Haidari, F., Asadi, M., Mohammadi-Asl, J., & Ahmadi-Angali, K. (2019). Evaluation of the effect of oral taurine supplementation on fasting levels of fibroblast growth factors, β-Klotho co-receptor, some biochemical indices and body composition in obese women on a weight-loss diet: a study protocol for a double-blind, randomized controlled trial. Trials, 20(1), 315. https://doi.org/10.1186/s13063-019-3421-5
Hashioka, Sadayuki, Youn-Hee Han, Shunsuke Fujii, Takahiro Kato, Akira Monji, Hideo Utsumi, Makoto Sawada, Hiroshi Nakanishi, and Shigenobu Kanba. “Phosphatidylserine and phosphatidylcholine-containing liposomes inhibit amyloid β and interferon-γ-induced microglial activation.” Free Radical Biology and Medicine 42, no. 7 (2007): 945-954.
Heidari, A., Tongsook, C., Najafipour, R., Musante, L., Vasli, N., Garshasbi, M., Hu, H., Mittal, K., McNaughton, A. J. M., Sritharan, K., Hudson, M., Stehr, H., Talebi, S., Moradi, M., Darvish, H., Arshad Rafiq, M., Mozhdehipanah, H., Rashidinejad, A., Samiei, S., … Vincent, J. B. (2015, October 15). Mutations in the histamine N-methyltransferase gene, HNMT, are associated with nonsyndromic autosomal recessive intellectual disability. Human molecular genetics. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4581600/.
Hellhammer, J., Vogt, D., Franz, N., Freitas, U., & Rutenberg, D. (2014, July 31). A soy-based phosphatidylserine/ phosphatidic acid complex (PAS) normalizes the stress reactivity of hypothalamus-pituitary-adrenal-axis in chronically stressed male subjects: A randomized, placebo-controlled study. Lipids in Health and Disease. Retrieved September 23, 2021, from https://link.springer.com/article/10.1186/1476-511X-13-121.
Hirayama, S., Terasawa, K., Rabeler, R., Hirayama, T., Inoue, T., Tatsumi, Y., Purpura, M., & Jäger, R. (2013, March 17). The ef ect of phosphatidylserine administration on memory and symptoms of attention‐deficit hyperactivity disorder: A randomised, double‐blind, placebo‐controlled clinical trial. Wiley Online Library. Retrieved September 23, 2021, from https://onlinelibrary.wiley.com/doi/full/10.1111/jhn.12090.
Ishaque, S., Shamseer, L., Bukutu, C., & Vohra, S. (2012). Rhodiola rosea for physical and mental fatigue: a systematic review. BMC complementary and alternative medicine, 12, 70. https://doi.org/10.1186/1472-6882-12-70)
Kato-Kataoka, A., Sakai, M., Ebina, R., Nonaka, C., Asano, T., & Miyamori, T. (2010). Soybean-derived phosphatidylserine improves memory function of the elderly Japanese subjects with memory complaints. Journal of clinical biochemistry and nutrition, 47(3), 246–255. https://doi.org/10.3164/jcbn.10-62
Lee, Y. S., Choi, J.-H., Lee, J.-H., Lee, H.-W., Lee, W., Kim, W. T., & Kim, T.-Y. (2016). Extracellular superoxide dismutase ameliorates house dust mite-induced atopic dermatitis-like skin inflammation and inhibits mast cell activation in mice. Experimental Dermatology, 25(8), 630–635. https://doi.org/10.1111/exd.13028
Mannucci C, Navarra M, Calzavara E, Caputi AP, Calapai G. Serotonin involvement in Rhodiola rosea attenuation of nicotine withdrawal signs in rats. Phytomedicine. 2012 Sep 15;19(12):1117-24. doi: 10.1016/j.phymed.2012.07.001. Epub 2012 Aug 24. PMID: 22921986.
Nam, S.-Y., Kim, H.-M., & Jeong, H.-J. (2017, September 1). The potential protective role of taurine against experimental allergic inflammation. Life sciences. Retrieved September 22, 2021, from https://pubmed.ncbi.nlm.nih.gov/28694089/.
Patel, R. H. (2021, May 9). Biochemistry, Histamine. StatPearls [Internet]. https://www.ncbi.nlm.nih.gov/books/NBK557790/.
Pérez-Torres I, Zuniga-Munoz AM, Guarner-Lans V. Beneficial Effects of the Amino Acid Glycine. Mini Rev Med Chem. 2017;17(1):15-32. doi: 10.2174/1389557516666160609081602. PMID: 27292783.
Pituch, A., Walkowiak, J., & Banaszkiewicz, A. (2013, October 28). Butyric acid in functional constipation. Przeglad gastroenterologiczny. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4027827/.
Samsel, A., and Seneff, S. “Glyphosate’s Suppression of Cytochrome P450 Enzymes and Amino Acid Biosynthesis by the Gut Microbiome: Pathways to Modern Diseases.” Entropy, vol. 15, no. 12, 2013, pp. 1416–1463., doi:10.3390/e15041416.
Tan, J., McKenzie, C., Vuillermin, P. J., Goverse, G., Vinuesa, C. G., Mebius, R. E., Macia, L., & Mackay, C. R. (2016, June 21). Dietary fiber and bacterial SCFA enhance oral tolerance and protect against food allergy through diverse cellular pathways. Cell Reports. Retrieved November 29, 2021, from https://www.sciencedirect.com/science/article/pii/S2211124716306301.
Teigen, L. M., Geng, Z., Sadowsky, M. J., Vaughn, B. P., Hamilton, M. J., & Khoruts, A. (2019). Dietary Factors in Sulfur Metabolism and Pathogenesis of Ulcerative Colitis. Nutrients, 11(4), 931. https://doi.org/10.3390/nu11040931
The enzyme CBS: (Cystathione beta synthase): Energy Levels. Activate Your Happy Genes. https://myhappygenes.com/the-enzyme-cbs-cystathione-beta-synthase-energ\ y-levels/. Published July 5, 2020. Accessed November 23, 2021.
Wang, C.-N., Liu, Y.-J., Duan, G.-L., Zhao, W., Li, X.-H., Zhu, X.-Y., & Ni, X. (2014). CBS and CSE are critical for maintenance of mitochondrial function and glucocorticoid production in adrenal cortex. Antioxidants & Redox Signaling, 21(16), 2192–2207. https://doi.org/10.1089/ars.2013.5682
Xue, R., Zhang, H., Pan, J., Du, Z., Zhou, W., Zhang, Z., Tian, Z., Zhou, R., & Bai, L. (2018, October 17). Peripheral dopamine controlled by gut microbes inhibits invariant natural killer t cell-mediated hepatitis. Frontiers. https://www.frontiersin.org/articles/10.3389/fimmu.2018.02398/full.
Zhou, J., Lu, Y., Wu, W., & Feng, Y. (2021, June 19). Taurine promotes the production of cd4+cd25+foxp3+ treg cells through regulating il-35/stat1 pathway in a mouse allergic rhinitis model. Allergy, Asthma & Clinical Immunology. Retrieved September 22, 2021, from https://aacijournal.biomedcentral.com/articles/10.1186/s13223-021-00562-1.