Managing histamine intolerance 2


With its broad range of (and often seemingly unrelated) symptoms, histamine intolerance often goes undetected during a standard consultation.  As we look a little deeper into our client’s medication and lifestyle history and explore more about their current eating habits, the clues often come together, allowing us to offer a range of diet and lifestyle changes that can have a significant positive outcome on that individual’s quality of life.

Understanding histamine intolerance

Histamine can be synthesised endogenously or ingested via food and, in a healthy individual, is broken down on a regular basis by two enzymes: diamine oxidase (DAO) and histamine N-methyltransferase (HNMT). DAO is the main enzyme for the metabolism of ingested histamine (and hence stops histamine entering the circulation) while HNMT converts histamine via intracellular methylation.   For some individuals, a reduced capacity to break down histamine results in a histamine excess and, given histamine’s multiple actions at multiple sites throughout the body, a range of unpleasant and often unrelated symptoms can arise.

Table 1: Location and action of histamine receptors
H1 receptors are located on endothelial cells of the blood vessels, smooth muscle tissue, the central nervous system and heart, and are involved in allergies that occur in the nasal airway and lung.  Common over-the-counter antihistamine drugs bind to H1 receptors and can provide relief from H1-specific symptoms (but not from H2-4).
H2 receptors are found on the gastric parietal cells, responsible for the production of stomach acid.  Low acid (which can be a consequence of low histamine) can result in poor digestion while overactivity can lead to the development of ulcers.

H2 receptors are also located on the endothelial cells of the heart, uterus, vascular and smooth muscles.

H3 histamine receptors  located in the central nervous system affect the release of neurotransmitters that control both skeletal and smooth muscles (acetylcholine), arousal (dopamine and noradrenaline) and drowsiness (serotonin).
H4 receptors are located on immune cells including mast cells, eosinophil cells, T cells and dendritic cells.

 

Table 2:  Common symptoms associated with histamine intolerance
Skin problems

Skin rashes, itchiness

Eczema

Urticaria (hives)

Acne (pimples)

Digestive tract

Irritable bowel syndrome (constipation/diarrhoea)

Flatulence and feeling of fullness

Stomach cramps /stomach ache

Nausea/vomiting

Symptoms affecting head and face

Flushing of face and/or chest (very common symptom)

Headaches/migraine

Runny nose and weepy eyes (with no clinical sign of allergies)

Dizziness/extreme tiredness, fatigue (often feeling cold/shivery)

Oedema (swellings mostly appearing around eyes and lips, sometimes in the area of the throat)

Chest area/cardiovascular

Asthma

Cardiac arrhythmia, such as a fast-beating or irregular heart beat

Low blood pressure

 

Women

Dysmenorrhoea (severe period pains)

Symptoms of histamine intolerance often improve during pregnancy (due to up-regulation of DAO) and return after birth of child

Mood

Sudden psychological changes (e.g. aggressiveness, inattentiveness, lack of concentration)

Anxiety/depression

Sleep issue (insomnia/early waking)

Citrus fruits are one of the most common histamine-rich food sources

Ingested histamine can become problematic in these cases, and sufferers often present with different tolerance levels and may react differently to different foods.  If the client identifies ‘trigger’ foods such as fermented or highly processed products, it is more than likely that they have a high histamine load.  Furthermore, meat and fish contain naturally high levels of the amino acid histidine which is converted to histamine by naturally-occurring bacteria.  Eating spoiled, or leftover foods can also contribute to the histamine burden via similar mechanisms.  Certain vegetables, such as tomatoes and spinach, are also identified as culprits as they are also high in histamine, with some fruits that are high in benzoates contributing to histamine intolerance via their ability to ‘release’ histamine.

Table 3:  Histamine and  food
Histamine-rich foods:

•        Fermented alcoholic beverages, especially wine, champagne and beer

•        Fermented foods: sauerkraut, vinegar, soy sauce, kefir, yogurt, kombucha, etc

•        Vinegar-containing foods: pickles, mayonnaise, olives

•        Cured meats: bacon, salami, pepperoni, luncheon meats and hot dogs

•        Soured foods: sour cream, sour milk, buttermilk, soured bread, etc

•        Dried fruit: apricots, prunes, dates, figs, raisins

•        Most citrus fruits

•        Aged cheese including goat cheese

•        Nuts: walnuts, cashews and peanuts

•        Vegetables: avocados, eggplant, spinach and tomatoes

•        Smoked fish and certain species of fish: mackerel, mahi-mahi, tuna, anchovies, sardines

Histamine-releasing foods:

•        Alcohol

•        Bananas

•        Chocolate

•        Cow’s milk

•        Nuts

•        Papaya

•        Pineapple

•        Shellfish

•        Strawberries

•        Tomatoes

•        Wheat germ

•        Many artificial preservatives and dyes

DAO-blocking foods:

•        Alcohol

•        Energy drinks

•        Black tea

•        Mate tea

•        Green tea

 

Pre-existing gut disorders can negatively impact DAO activity

As such, if histamine intolerance is suspected, we can learn a lot by asking a client to keep a relatively short food diary (even 2-3 days can be of value). In addition to a food diary, learning about the client’s exposure to chemicals and drugs can also provide insight.  DAO activity can be reduced by a number of foods (blockers) and drugs (from standard NSAIDs to antidepressants) (Table 4), with diets low in the cofactors vitamin B6, magnesium and copper also known to exacerbate histamine intolerance symptoms by directly hindering DAO activity. The enzyme HNMT degrades histamine using the major methyl donor S-adenosylmethionine (SAMe) as a co-factor.  It stands to reason that insufficient SAMe (or methylation cofactors such as vitamins B6, B12 and folate) may result in high levels of histamine and that high histamine can deplete SAMe, thereby reducing its availability for other methylation reactions.  In addition, a number of SNPs in histamine-metabolising enzymes have been identified as factors that can predispose an individual to the condition.  Interestingly, intolerance is often seen in individuals with pre-existing gastrointestinal disorders such as IBD, IBS, coeliac or SIBO, conditions associated either with poor barrier function, dysregulated gut microbiota diversity (as a consequence of antibiotic use, for example) or gut-associated inflammation, all of which can negatively impact on DAO activity.  In the case of female clients, those who exhibit clear signs of oestrogen dominance may have histamine issues.  Oestrogen excess down-regulates DAO, leading to elevated levels of histamine, which in turn then stimulates further oestrogen production.

Table 4: Pharmaceuticals known to reduce the activity of DAO and/or DNMT
Non-steroidal anti-inflammatory drugs

                Ibuprofen & aspirin

Antidepressants

(Cymbalta, Effexor, Prozac, Zoloft)

Immune modulators:

Humira & Enbrel: rheumatoid arthritis, psoriatic arthritis, Ankylosing spondylitis, Crohn’s disease, ulcerative colitis, chronic psoriasis

               Plaquenil: Malaria & rheumatoid arthritis

Antiarrhythmics (propanolol, metaprolol, Cardizem, Norvasc)

Antihistamines (Allegra, Zyrtec, Benadryl)

Histamine (H2) blockers:

Tagamet: duodenal and benign gastric ulceration

                Pepcid & Zantac: heartburn

Managing histamine intolerance

Reduce histamine burden

Adopting a low-histamine (and low-protein) diet has been shown to be a therapeutically useful, simple and cost-free tool to decrease symptoms and increase quality of life in individuals with histamine-related symptoms.  Ensuring nutritional adequacy and compliance to a low-histamine diet can be challenging for some clients due to the potential severity of a restriction diet in terms of foods that need to be excluded.  Relief from symptoms is usually experienced within 4-6 weeks.

SNP analysis?

Some practitioners may recommend genetic testing to identify predisposition; current evidence, however, suggests that it is unlikely that genetic variants alone would be wholly responsible for the development of intolerance and that the interplay of genetic and environmental factors is more likely.  SNP analysis may therefore not offer as much value as testing for DAO activity, which can be conducted relatively cheaply and non-invasively via a simple home test such as provided by Medichecks.com. Testing DAO activity may be particularly useful when implementing a gut-healing protocol to improve DAO production.

DAO supplements

Though not available in the UK, DAO supplements (such as Daosin) can be purchased online and studies appear to support the reduction in histamine-related symptoms;  however, DAO supplements increase DAO (and degrade histamine) specifically within the digestive tract and do not increase systemic DAO levels.

Heal the gut

As DAO is produced within the gut enterocyte, damage to the gut mucosa will disrupt normal DAO production (as well as digestive enzymes).  A gut-healing protocol should be recommended as a priority in order to optimise gut barrier function and help restore normal enzyme function. Vitamins A and D3 are particularly important for mucosal health, alongside glutamine, prebiotics and probiotics. Dysbiosis (which often occurs as a result of poor dietary choices, high levels of stress coupled with overuse of NSAIDs and antibiotics) can disrupt the diversity of the gut microbiota, leading to an overgrowth of histamine-producing microbes (converting histidine from dietary protein). Probiotics can also shift immune activity to a more intracellular Th1 response rather than the extracellular Th2 response that characterises excessive histamine activity in allergy, asthma and autoimmune diseases.

Cofactors

When the body is low in B-vitamins, vitamin C and copper, histamine may not break down sufficiently to overcome symptoms of intolerance. Copper and vitamin C are crucial components of the DAO enzyme and B6 is a key cofactor that enables DAO to degrade histamine.  Furthermore, B-vitamins are methylation co-factors required for HNMT activity.  We would recommend supplementing with Pure Essentials MULTIVITAMIN & MINERALS™ which provides 22 essential vitamins & minerals in superior body-ready and active forms for enhanced absorption and utilisation. Our sustained slow-release system optimises blood nutrient levels for longer-lasting action.

Food-sourced anti-inflammatory agents

Polyphenols such as quercetin, grape seed extract, pycnogenol and curcumin alongside omega-3 EPA can be particularly useful to include in the diet.  Polyphenols act directly on mast cells, reducing the release of histamine into the system and, alongside EPA, are potent anti-inflammatory nutrients acting synergistically to dampen the inflammatory response initiated by histamine.  As standard curcumin has low bioavailability we’d recommend taking our optimised Longvida Curcumin, in combination with our Pharmepa RESTORE pure EPA.

Summary

Histamine intolerance affects around 1% of the population, making it likely that as practitioners we will come into contact with clients with some degree of histamine-associated health condition.  Understanding the complexity of the condition and the factors that influence its progression can help in identifying those clients who may respond to an appropriate intervention. Identifying and removing the source of the problem is an important part of the process when managing histamine intolerance.   In addition to a low histamine diet, the practitioner should focus on improving gut function and gut flora diversity, stabilising histamine release and accelerating histamine degradation via dietary and supplemental intervention. Such a multifaceted approach offers the client the best chance of symptom resolution.

References

Chung BY, Cho SI, Ahn IS, Lee HB, Kim HO, Park CW, Lee CH. Treatment of Atopic Dermatitis with a Low-histamine Diet. Ann Dermatol. 2011 Sep;23 Suppl 1:S91-5

Guida B, De Martino CD, De Martino SD, Tritto G, Patella V, Trio R, D’Agostino C, Pecoraro P, D’Agostino L. Histamine plasma levels and elimination diet in chronic idiopathic urticaria. Eur J Clin Nutr. 2000 Feb;54(2):155-8.

Joneja, J. V. & Carmona-Silva, C., 2001. Outcome of a histamine-restricted diet based on chart audit. Journal of Nutritional and Environmental Medicine, Volume 11, pp. 249-262.

Maintz, L. and Novak, N. Histamine and histamine intolerance. Am J Clin Nutr. 2007; 85: 1185–1196

Wagner N, Dirk D, Peveling-Oberhag A, Reese I, Rady-Pizarro U, Mitzel H, Staubach P. A Popular myth – low-histamine diet improves chronic spontaneous urticaria – fact or fiction? J Eur Acad Dermatol Venereol. 2017 Apr;31(4):650-655.

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Dr Nina Bailey

About Dr Nina Bailey

Nina is a leading expert in marine fatty acids and their role in health and disease. Nina holds a master’s degree in Clinical Nutrition and received her doctorate from Cambridge University. Nina’s main area of interest is the role of essential fatty acids in inflammatory disorders. She is a published scientist and regularly features in national health publications and has featured as a nutrition expert on several leading and regional radio stations including SKY.FM, various BBC stations and London’s Biggest Conversation. Nina regularly holds training workshops and webinars both with the public and health practitioners.

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