Dear Mark: Histamine Intolerance

For today’s edition of Dear Mark, I’m answering one question. But it’s a doozy: histamine intolerance and what to do about it. Now, this is a huge question. As you’ll read below, there are numerous causes, many overlapping. There’s no easy fix. There may not even be a hard fix. However, we can almost certainly improve the situation. In today’s post, I offer Laura my take on what to do about histamine intolerance based on my reading of the available literature. It’s not perfect, mind you. It’s complex and often seemingly contradictory. But that’s how it is with the human body, isn’t it?

Let’s go:

Hi Mark,

I hope you can one day shed some light on histamine intolerance. I am extremely sensitive to histamine and also found out that I am mutated for the DAO enzyme, making my problem even worse. I’ve found it very hard to eat primally, since most of the foods promoted like bacon, sausage, cheese, wine, onions, lemons, vinegar, keifer/kombucha/kimchi, bone broth, and a lot of veggies and fruit, etc., all either contain high histamine or induce mast cells to release histamine, causing a huge reaction. I’m sure other people in the primal community are suffering from this as well and would also appreciate any insight you might have.



Great question, Laura.

Just so everyone knows, histamine isn’t “bad.” It’s a normal biochemical produced by immune cells during certain immune responses that produces some unpleasant but necessary effects. The stuffy nose we get during seasonal allergies is histamine’s most famous product, but it’s also involved in bronchoconstriction, hives, the immune response to bug bites and stings, alterations in blood pressure, and vasodilation. Histamine also promotes gastric acid secretion and acts as a neurotransmitter that can increase and inhibit the release of other neurotransmitters. Histamine is only bad when your body can’t break it down fast enough or you simply make too much.

Why might a person make too much histamine?

Bad gut bacteria: Many gut bacteria produce histamine themselves. If these histamine-producing strains are overrepresented in your gut, you may suffer negative symptoms from any extra histamine.

Mast cell activation syndrome: Mast cells are immune cells that produce histamine as part of the immune response. In the recently-identified-but-still-relatively-mysterious mast cell activation syndrome, a person’s mast cells release excessive amounts of histamine.

Why might a person be unable to break down histamine?

Bad gut bacteria: Many gut bacteria also degrade histamine. A dearth of these histamine-degrading strains in the gut may lead to impaired histamine degradation and increased histamine load.

Diamine oxidase deficiency: Some histamine intolerance stems from a simple deficiency in diamine oxidase, the enzyme that breaks down histamine in the body. Without adequate diamine oxidase, histamine builds up and causes problems where it shouldn’t.

HNMT deficiency: We produce another histamine-degrading enzyme called HNMT, or histamine N-methyltransferase. HNMT deficiency is largely genetic, as various HNMT polymorphisms determine endogenous histamine levels.

A Primal lifestyle is a good idea, but it’s not everything. And because many of our favorite Primal foods are high in histamine or, as you mention, induce the mast cells to release it, when you can’t break down histamine effectively, even eating cherished Primal fare can produce negative symptoms. These foods include but are not limited to:

Anything fermented: pickles, sauerkraut, kimchi, kefir, cheese, yogurt, fish sauce, kombucha, wine, vinegar.

Anything cured: salami, bacon, cold cuts, sausage, ham.

The longer a food is exposed to bacteria or yeasts (even recently cooked food sitting out, IOW leftovers), the more time those microbes have to convert the amino acid histidine present in foods to histamine.

Many slow cooked foods, like bone broth, also increase histamine content and can be problematic in sensitive individuals. For a complete list, check out Chris Kresser’s post on histamine-rich foods (and prepare to be sad). They won’t trigger everyone with histamine intolerance, but it helps to know the potential offenders.

What can you do except avoid histamine-rich or histamine-producing foods forever?

Focus on gut health. I may sound like a broken record, but the gut may be everything when it comes to histamine tolerance. Certain probiotics are histamine-producing (which may worsen your symptoms), histamine-neutral (which will have no direct effect), or histamine-degrading (which should improve your symptoms). If the histamine-producing ones colonize your gut, that’s bad news.

  • Among the histamine-producing, foremost are Lactobacillus casei, Lactobacillus delbrueckii, and Lactobacillus bulgaricus, all of which are found in most yogurts. Avoid those. That’s why fermented dairy is a no-go for most people with histamine intolerance.
  • Take a probiotic that contains histamine-degrading strains, like Lactobacillus plantarum (my own probiotic supplement is one example). Soil-based organisms may also reduce histamine.
  • Eat prebiotic fibers and resistant starch. When choosing a resistant starch source, consider going with unripened green bananas (great frozen in smoothies, not so great as straight-up snacks) and/or cooked and cooled potatoes over raw potato starch. Raw potato starch may aggravate your symptoms, as potato lectins can induce mast cells to release histamine.

Check your intake of nutrients, foods, and supplements that support histamine metabolism and tolerance. Will they cure you? No, unless a frank deficiency in said nutrient is the proximate cause of your histamine intolerance. Might they make you feel better in the short term (which is incredibly important and shouldn’t be discounted)? Yes.

  • Selenium has been shown to reduce mast cell activation and attenuate allergic symptoms.
  • Quercetin, found in capers, apples, citrus, onions, and pretty much every fruit and vegetable, is a potent inhibitor of mast cell activation and histamine release. Supplements are widely available.
  • Vitamin C can regulate mast cell activity. Many histamine intolerance supplements (like quercetin) will often come with vitamin C.
  • Stinging nettle can reduce the amount of histamine the body produces in response to an allergen. In one study, almost half of subjects found stinging nettle to be as effective as over the counter anti-histamine drugs.
  • ECGC, the primary catechin in green tea, also inhibits mast cell activation. You can drink green tea or take supplements.
  • Diamine oxidase is the enzyme that actually breaks down histamine in the body, and it’s available in supplemental form.
  • Common antihistamines like Claritin are fairly well-tolerated, too.

Support the liver. As HNMT (the other enzyme that nullifies histamine) activity takes place in the liver, a healthy liver is crucial for histamine intolerance.

  • Avoid oxidized PUFAs (refined seed oils, bad restaurant food, fried foods). Eat healthy monounsaturated fats and saturated fat instead.
  • Avoid excess sugar, especially refined sugar, and carbohydrates.
  • Eat colorful fruits and vegetables rich in polyphenols.
  • Exercise regularly and stay physically active throughout the day. Deplete your glycogen regularly, as a liver with fully-stocked glycogen stores cannot store incoming glucose/fructose and must convert and store it as fat.

Avoid alcohol. Alcohol is a major DAO inhibitor, making red wine a double whammy for the histamine intolerant.

Watch stress. Corticotropin-releasing hormone (CRH) stimulates mast cells to release histamine. But CRH also releases cortisol, which inhibits histamine secretion. In normal circumstances, with acute, short-lived stress, this works to oppose excessive histamine. In chronic stress, things change. We become resistant to stress hormones, and cortisol loses a bit of its histamine-inhibiting luster. We’re releasing massive amounts of histamine-stimulating CRH, but the cortisol is unable to stem the tide. So: watch stress. Avoid it, limit it, mitigate it, or rethink it. And consider an effective adaptogen/herbal supplement to get yourself over the hump when you need it. (I swear by this one.)

Maintain optimal sleep hygiene. The activity of mast cells adhere to one’s circadian rhythm, so getting inadequate light during the day, excessive light at night, going to bed too late, and neglecting one’s circadian hygiene in general will likely perturb histamine tolerance.

It’s a messy story with too many threads to easily follow, but you can try a few things. Let me know how things go for you, Laura. And everyone else, let’s hear about your experiences with histamine intolerance down below. What worked? What didn’t? What else should Laura try?

Thanks for reading, all!


TAGS:  immune health

About the Author

Mark Sisson is the founder of Mark’s Daily Apple, godfather to the Primal food and lifestyle movement, and the New York Times bestselling author of The Keto Reset Diet. His latest book is Keto for Life, where he discusses how he combines the keto diet with a Primal lifestyle for optimal health and longevity. Mark is the author of numerous other books as well, including The Primal Blueprint, which was credited with turbocharging the growth of the primal/paleo movement back in 2009. After spending three decades researching and educating folks on why food is the key component to achieving and maintaining optimal wellness, Mark launched Primal Kitchen, a real-food company that creates Primal/paleo, keto, and Whole30-friendly kitchen staples.

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