In my functional nutrition practice, I often hear the following: “I am having allergic reactions, but the doctor says I don’t have any allergies.” People come in with hives or red itchy bumps or breathing troubles, but with no identifiable true allergies.
In such cases, we explore food sensitivities, autoimmune conditions and other gastrointestinal (GI) issues. In addition, we know that there could be an underlying histamine problem. It’s not the first thing we investigate because many of those other issues can cause or exacerbate histamine problems. We like to start with the basics and move to considering complex conditions like histamine overload or mold toxicity only after we have optimized nutrition and GI function.
HISTAMINE AND ALLERGIES
Most people have heard of histamine because it is known to “cause” allergies. In fact, the body’s defense reaction to foreign proteins in the blood is what causes allergies. Part of that reaction includes the release of histamine from mast cells (a type of white blood cell that releases histamine and other substances). Although mast cells also release many other pro-inflammatory substances, histamine gets a particularly bad rap.
Histamine becomes problematic when people have too much histamine in their blood or tissue even though no allergic reaction is occurring. In the absence of true allergies (immunoglobulin E [IgE] reactions), there are essentially two major scenarios in which this can take place. The first and probably most common scenario, typically known as “histamine intolerance,” is when someone either absorbs too much histamine from the GI tract or does not break it down well in the liver (or both). Many foods contain histamine, and if the histamine is not successfully broken down in the gut, it can get absorbed in excessive amounts. Proper liver function is required to break down the histamine to be excreted as waste. When one or both of these functions is not working properly, histamine builds up in the blood.
In the second, much more complex and insidious scenario, called “mast cell activation syndrome” (MCAS), dysfunctional mast cells release too much histamine. In some people, of course, both things are happening, and there are other factors that can affect histamine levels as well. Any serious conversation about histamine “overload” thus needs to address the origin of the excess histamine. When the overload is due to improper breakdown of histamine in the gut or liver, the protocol will differ from when it originates from the mast cells.
There are at least two possible reasons why someone would absorb excess histamine from the gut. First, dysbiosis (or a disordered microbiome), so common these days, can certainly contribute to this problem and, in fact, is the leading cause of histamine intolerance. Microbial imbalance can inhibit the body’s ability to break down histamine in the gut.
Another confounding issue can be low levels of the enzyme that we naturally produce to break down histamine. This enzyme, called diamine oxidase (DAO), is responsible for breaking down histamine in the gut, the liver and other tissues. Some people are low in this enzyme due to genetic variations. Others may be low due to GI disorders such as small intestine bacterial overgrowth (SIBO), hormonal imbalances or any kind of persistent inflammation. Excess estrogen levels also can increase circulating histamine because estrogen suppresses DAO activity and stimulates mast cells.
In addition to the breakdown by DAO, histamine needs to be methylated in the liver before excretion by the kidneys. Methylation refers to the process of any molecule being transformed by the addition of a methyl group (CH3)—three hydrogen atoms bonded to a carbon atom. Histamine is methylated to a molecule called methylhistamine, which renders it much less toxic and ready for disposal through the urine.1
Low DAO activity in the GI tract and liver due to genetic variants, combined with gut inflammation, excess estrogen and insufficient levels of methyl groups can create a perfect storm for some people, causing major histamine overload. The approach to deal with this situation must be multifaceted.
MAST CELL ACTIVATION SYNDROME
When mast cells are activated, they release histamine, tryptase and other pro-inflammatory mediators. This is great when the mast cells are protecting us from pathogens or are involved in healing wounds. Sometimes, however, mast cells show up in excess (a rare condition known as mastocytosis), or, as in MCAS, they overproduce these pro-inflammatory molecules, flooding the system with them and mimicking an allergic response.
MCAS is not fully understood, and its treatments are even less clear. I like to think of MCAS as akin to an autoimmune condition because it involves mast cells (immune cells) that are overactive and somewhat trigger-happy in releasing their contents. Unfortunately, this can really wreak havoc in the body. Dr. Lawrence Afrin and Dr. Theoharis Theoharides are leading experts in MCAS, and their websites are excellent sources of information about this complex condition.2,3,4 However, individuals seeking to heal with a predominantly food-based approach will need additional help.
Symptoms of MCAS and the less complex histamine intolerance are not always clearly distinguishable. It can be challenging, therefore, to determine conclusively whether someone is suffering from MCAS or histamine intolerance or both.
In our functional nutrition practice, our initial approach focuses on improving the GI tract and liver function while supporting hormones, methylation and overall health. In this way, we are able to minimize histamine intolerance; if someone truly has MCAS, we will see some improvement but also will be able to recognize that more work needs to be done. We also will have set the stage for that person to do better on the pharmaceutical treatments that are so often necessary with MCAS.
SYMPTOMS AND TREATMENT
A first step is to be aware that both MCAS and histamine intolerance can coexist with other conditions, making it very difficult to parse out exactly what is going on. Next is the question of how they should be treated. A major component of the treatment for either condition is to reduce the dietary intake of histamine foods as well as histamine “liberators” (see below). We also use the DAO enzyme in a supplement form,5 in conjunction with a formula called NeuroProtek,6 which contains the bioflavonoids luteolin, quercetin and rutin. We have used both of these products with many patients over the past three years, and they have had a very high success rate in our clinical practice. There is research showing that DAO supplementation reduces histamine levels,7 and quercetin and luteolin reduce the release of histamine and tryptase from mast cells.8 More research is forthcoming in this area, including the results of a just-completed clinical trial.9
Histamine intolerance symptoms can include rashes, hives, itching, headache, migraine, anxiety, depression, fatigue, insomnia, vertigo and GI disorders. When treating histamine intolerance, we always try to address the GI disorders first, while supplementing with DAO and NeuroProtek. We also address methylation and, if needed, will supplement with vitamin C, additional B vitamins, copper, zinc and magnesium.
The dietary recommendations for individuals with histamine intolerance call for a diet rich in folate, vitamin B12, glycine and flavonoids such as quercetin and rutin. We also recommend juicing homemade pea sprouts (which are rich in the DAO enzyme) as well as eating rice bran (in “forbidden rice” or black or purple rice), which has been shown to reduce the release of histamine from mast cells. We exercise caution with probiotics, which can worsen the symptoms of histamine overload. We recommend only using the following bacterial strains: L. reuteri, L. rhamnosus, L. casei and B. bifidum.
Because people often have multiple food sensitivities due to intestinal permeability, or they have other food restrictions (such as low FODMAPs for SIBO), we do not recommend implementing a strict low-histamine diet; we do not want to be the ones telling people that they can only eat air from now on! However, we do encourage such people to limit or avoid the biggest offenders among histamine foods, which include alcohol, fermented foods, smoked or cured meats, citrus fruits, shellfish, canned fish or meat, fish and seafood in general (except salmon, cod and tuna frozen on the boat), vinegar, strawberries, nuts, tomatoes and cacao. This approach, coupled with addressing the major GI disorders, usually works very well.
For MCAS, the situation is much more complex. Symptoms can include rashes, hives, itching, flushing, fainting, headache, abdominal pain, nausea, vomiting, gastroesophageal reflux disease (GERD), fatigue, chronic pain, trouble breathing and many more. The conditions associated with MCAS are often complex in their own right. Related conditions may include allergies, autism, autoimmune disorders, cancer, diabetes, Ehler-Danlos syndrome, postural orthostatic tachycardia syndrome (POTS), fibromyalgia, Lyme disease, mastocytosis, migraines and obesity. When one adds MCAS symptoms on top of those conditions, the person may be extremely ill with twenty to thirty symptoms.
Unlike with histamine intolerance patients, it is imperative that MCAS patients implement a strict low-histamine diet (provided their diet is not already too restricted) and otherwise employ the same interventions that we use for histamine intolerance. However, due to the complexity of MCAS, it often requires much deeper investigative work (it is challenging even to get a diagnosis) and pharmaceutical interventions.
IMPLEMENTING A LOW-HISTAMINE DIET
The detailed low-histamine diet (next page) is as strict as they come. Individuals who are not sure about the extent to which histamine is affecting them might first want to try the less strict list described in the previous section, keeping in mind that many people do better with the stricter diet. We usually recommend following the stricter diet for six weeks before deciding whether it has helped or not, because sometimes it takes that long to reduce the body burden of histamine significantly. In most people, using the DAO enzyme and NeuroProtek will speed up the process.
Low-histamine food lists on the Internet may not be very reliable because they often derive from the author’s subjective experiences. This can make the whole subject very confusing. I recommend sticking to just one list and observing one’s body. Over time, it will become easier to identify foods that are particularly problematic. It helps to start off more strictly to establish some sort of baseline, experimenting with more variety as one starts to feel better.
HISTAMINE “LIBERATORS” TO AVOID
• Most citrus fruits
• Cocoa and chocolate
• Wheat germ
• Black tea energy drinks
• Green tea, mate tea
• Additives (benzoate, sulfites, nitrites, glutamate and food dyes)
FOODS TO ENCOURAGE
VEGETABLES: Add the following to dishes as much as possible: artichokes, basil, broccoli, celery, chives, cilantro, dill, garlic, onions (either cooked onions or spring onions in small amounts), oregano, parsley, rosemary, snap peas, watercress, and ancho, serrano and chili peppers. These are all high in quercetin and other phytonutrients, which help reduce the body burden of histamine. Capers are particularly rich in quercetin, but one should use only salt-dried capers (not capers in vinegar).10 Be sure to rinse the capers before using.
FRUIT: Apples and cranberries also are high in quercetin.
GRAINS: Rice bran (especially from black rice) reduces histamine. Heirloom black rice can be found in health food stores (often called “forbidden rice”) or online.11
PEA SPROUTS: Although consumption of pea sprouts is optional, it is encouraged when possible. Pea sprouts can be used liberally as they are high in the DAO enzyme, which helps break down histamine. The easiest way to use them is to juice or blend them and drink with meals. Sprouting peas to get the highest amount of DAO takes about ten days. The best time to drink pea sprout juice is with any meal containing meat or fish.
ALLOWED FOODS AND FOODS TO AVOID
The information below is adapted from the list provided in the book, Is Your Food Making You Sick? by James L. Gibb.12 Among the sources used by Gibb to compile the list are Dr. Janice Jones, Allergy UK, the Swiss Allergy Centre and the Swiss Interest Group Histamine Intolerance. Gibb’s list offers the strictest interpretation of what may constitute a problematic food for histamine; I have loosened it up a little to allow some sprouted beans. I also provide careful instructions on how to eat meat and fish.
ALLOWED: All fresh vegetables (except those on the “avoid” list). Water chestnuts can be used to make a starchy flour.
AVOID: Bell peppers, eggplant, onion (raw), pumpkin, purslane, spinach, tomatoes, winter squash, fermented vegetables (sauerkraut, pickles, etc.), overripe or rotten vegetables, all pickled vegetables (or anything that contains vinegar), prepackaged salad or other vegetables. Use caution with kale (small amounts only) due to its oxalate content.
ALLOWED: Apples, coconut, fig, goldenberries, longans, loquat, lychees, mango, melon, passionfruit, persimmon, pomegranate, quince, rhubarb and starfruit.
AVOID: All other fruit, especially strawberries, dried fruit that contains sulfur, overripe or rotten fruit, olives and avocado.
ALLOWED: Millet, oats, oat bran, rice (black, brown, purple, red or “regular”), rice bran, teff and wild rice. For baking, agar-agar, arrowroot, baking powder, baking soda, coconut flour, cornstarch (although this one is questionable in terms of general nutrition), guar gum, potato starch, rice flour, sago and water chestnut flour.
AVOID: Amaranth, buckwheat, quinoa and all wheat products. Avoid baked goods made with carrageenan, gelatin, tapioca starch, xanthan gum and yeast.
Histamine is present in small amounts in animal flesh but after death, histamine increases quickly (especially in fish that retain the guts). These foods may be problematic for extremely sensitive individuals and may need to be avoided completely. However, I encourage everyone to try consuming fish, poultry and red meat according to the guidelines below.
ALLOWED: Maximum one serving per day, or avoid altogether if symptoms do not subside within four to six weeks. AVOID: All shellfish, fish that has not been cleaned and frozen immediately, canned fish. All processed meat, aged meat, meat that has been cooked and not immediately frozen, leftovers from the fridge, meat that is not fresh, fermented meat and canned meat.
GUIDELINES: Fish should have the guts cleaned out on the boat and be frozen immediately. Salmon, snapper, Chilean sea bass, squid and octopus are commonly sold this way, but one should always check at the fish market. (When buying fish from a local market, make sure that the vendor is trustworthy and the fish is of the best quality.) Vital Choice is a good source of seafood because their king salmon, silver salmon, tuna and cod are guaranteed to be cleaned and frozen immediately on the boat, and they ship the fish frozen to the customer’s home. For meat and poultry, grassfed is best. Small farms often will freeze meat and poultry immediately after processing and can be good places to purchase meat. Buy in bulk and do not defrost until ready to cook. If buying from a butcher, only buy on the day the meat is processed. Do not buy already ground meat; instead, ask the butcher to grind the meat, place it in a cooler and rush home and cook or freeze. (Note: Freezing halts the bacteria-induced multiplication of histamine in animal flesh, but refrigeration does not. Cooking does not reduce or take away histamine, so once it’s there, it’s there.)
ALLOWED: Properly sprouted beans (except red beans and soybeans).
AVOID: All legumes that have not been sprouted, red beans, soybeans in any form and peanuts.
ALLOWED: Mascarpone, panir, quark, salted ricotta cheese (not the typical American kind that contains vinegar but the kind made in Italy, which may be hard to find, but is well worth the effort), fresh mozzarella, fresh cream, uncultured butter and buttermilk and fresh, raw milk. Some people tolerate any super fresh cheese such as non-aged chèvre and feta.
AVOID: Any cheeses not listed above, such as cheddar, Monterey Jack, processed cheeses, aged cheeses of all kinds, fermented dairy of any kind (yogurt, kefir, some types of cheese, sour cream, creme fraiche, etc.) and cottage cheese.
ALLOWED: Fresh raw and cooked egg yolks. If eating raw egg yolks, be sure to only use fresh, pasture-raised eggs from a known and reliable farmer; do not eat raw eggs from the supermarket. Many people tolerate cooked egg whites but some don’t, so use caution. If using as a protein source, make sure to use the whole egg. Pasture-raised eggs are ideal.
AVOID: All raw egg whites, raw commercial egg yolks and stale eggs. Use caution with cooked egg whites.
AVOID: All nuts (coconut is a fruit and is allowed), but especially almonds, pecans and walnuts.
ALLOWED: Soaked chia seeds, freshly ground and soaked flax seeds and their oils, and properly sprouted seeds. “Raw” is a good brand for sprouted seeds.
AVOID: Unsprouted seeds and sesame seeds.
HERBS AND SPICES
ALLOWED: Salt, pepper, fresh curry leaves, wasabi, fresh herbs and freshly ground spices (except those on the “avoid” list). Some allowed herbs and spices include: allspice, basil, bay leaf, caraway, cardamom, chives, coriander (cilantro), fenugreek, garlic, ginger root, marjoram, mint, myrtle leaf, oregano, parsley, peppermint, pimento leaf, rosemary, sage, savory, sumac, tarragon and turmeric. Black cumin seed (but not regular cumin) has antihistamine properties and is encouraged. Alcohol-free vanilla and other extracts are also allowed.
AVOID: Alcohol-based flavors, anise, artificial flavors, brewer’s yeast, cayenne pepper, chili, chocolate, cinnamon, cloves, cocoa, curry, mace, mustard seed, nutmeg, smoke flavor, soy sauce and all soy products, tamari, tamarind (fermented), thyme, vinegar of all kinds and any food containing vinegar.
ALLOWED: Coffee, fresh raw milk, mineral water, fresh water, chamomile tea, peppermint tea, dandelion tea, ginger tea, rooibos tea, coconut water and coconut milk.
AVOID: Soft drinks, all alcohol (but in particular wine and beer), anything fermented (such as kombucha and kefir), black tea, green tea, red raspberry tea, nettle tea, mate tea and energy drinks.
FATS AND OILS
ALLOWED: Cold pressed and unrefined seed and nut oils (Flora is the only brand I recommend), extra virgin olive oil, pure uncultured butter and cream, coconut butter and coconut cream, duck fat and goose fat.
AVOID: Vegetable oils, heat-treated or refined nut and seed oils, fried foods, processed foods, partially hydrogenated oils and fats, fish oil, avocado, olives, margarine and spreads such as Earth Balance and other fake fats.
ALLOWED: Pasteurized honey (or raw honey from a reliable source), maple syrup, brown rice syrup, coconut sugar, treacle, molasses, jaggery, palm sugar, pure jams, jellies and marmalade.
AVOID: Flavored syrups, prepared desserts and icings and dried fruit; high fructose corn syrup and agave. Caution with sugar alcohols such as xylitol (which can cause gas in those with compromised gut health).
1. Maintz L, Novak N. Histamine and histamine intolerance. Am J Clin Nutr 2007;85(5):1185-1196.
2. MastCellAware. http://www.mastcellaware.com/index.html.
3. Molecular Immunopharmacology & Drug Discovery Laboratory. http://www.mastcellmaster.com/index.php.
4. Armonk Integrative Medicine for Optimum Health. http://www.armonkmed.com/about/dr-afrin/.
5. Umbrellux™ DAO. https://www.umbrelluxdao.com/.
6. NeuroProtek®. http://algonot.com/product/neuroprotek/.
7. Manzotti G, Breda D, Di Gioacchino M, Burastero SE. Int J Immunopathol Pharmacol 2016;29(1):105-111.
8. Research: Dr. Theoharides at Tufts University. http://www.mastcellmaster.com/research.php.
9. Study to investigate the effect of an oral diamine oxidase substitution (DAOsin) in histamine intolerant patients on the low endogenous diamine oxidase serum activity. https://clinicaltrials.gov/ct2/show/NCT03298568.
11. Histamine intolerance. www.low-histamine.com.
12. Gibb JL. Is Food Making You Sick? The Strictly Low Histamine Diet. Brighton, Victoria: Leaves of Gold Press; 2014.
This article appeared in Wise Traditions in Food, Farming and the Healing Arts, the quarterly magazine of the Weston A. Price Foundation, Summer 2018.