Histamine Intolerance and the Altered Micobiome

A week or so ago, a reader wrote to me asking if I had ever heard of an intolerance to fermented foods.  Indeed I had:  histamine intolerance.  I have worked with a very few nutrition clients over the years who have suffered from this syndrome, and while it is still somewhat controversial (I’m not sure why, as the mechanism of action is actually at least partially known), there is no doubt in my mind that it exists.

Anyway, this inspired me to do some searching and I came across an article published last year which correlates histamine intolerance to alterations in the gut bacteria. [i]

Why are none of us surprised?

Histamine intolerance (HIT) is defined in this article as, “…an adverse reaction of ingested histamine that affects different organ systems and results in various intestinal and extra-intestinal symptoms.” Some common symptoms of HIT include flushing, pruritus (skin itching), nausea, vomiting, diarrhea and abdominal pain.  Every organ system can be affected, including the respiratory tract, skin, cardiovascular, nervous, and digestive systems.) Foods that contain histamine include shellfish, peanuts, chickpeas, vinegar, chocolate,  cheese, red wine, beer, like sauerkraut, pickles and more.  (Below see a link for a more complete list.)

As I mentioned above, the exact mechanism of action is not entirely understood, but we do know that many people with this issue have a reduced level of an enzyme called diamine oxidase (DAO) in their intestines.  This enzyme degrades histamine, and thus, if it’s level is low, more histamines from foods will make their way into the blood stream and cause symptoms.

Several species of gut bacteria are known to convert histidine (an amino acid) into histamine, including some of the lactic acid producing bacteria like Lactobacillus reuteri, Lactobacillus casei, etc:  “The presence of these bacteria in the human intestine might contribute to increased histamine levels and promote histamine sensitivity in some persons.”

In this study, 64 patients were broken up into 4 groups, for comparison: 25 were determined to have food hypersensitivities (FH), 21 had outright food allergy (FA), 8 had histamine intolerance (HIT) with decrease DAO activity, and 10 were healthy controls.  All contributed blood and stool samples for analysis.  To sum up the results:

  1. Surprisingly, there was no increase in histamine producing bacteria in those with HIT.  However, the authors do suggest that more research is needed in regards to this question.
  2. However…there were significant differences in gut bacteria in those with HIT, and FA and FH, in comparison to the healthy controls. Those with HIT had markedly higher levels of Proteobacteria, which are associated with dysbiosis.  Low grade inflammation is actually known to promote an increase in this species:  “An intestinal inflammation may cause an epithelial dysfunction and increase the oxygen levels in the colon.  This promotes the growth of facultative anaerobic bacteria, e.g. various species of Proteobacteria, that compete against obligate anaerobic bacteria comprising beneficial ones like Bifidobacteria.  There, an increase in Proteobacteria is also suggested as a marker for epithelial dysfunction [i.e. leaky gut].”  A leaky gut would, of course, permit the excess histamine to enter the blood stream more readily.
  3. Since DAO is synthesized in the enterocytes (cells that line the intestine) and stored in these mucosal cells, any disruption of these cells by inflammation will lead to reduced DAO production, which, in turn, leads to higher levels of histamine in an inflamed and leaky gut. This study did not look at the gut inflammation in depth, and the authors suggest that this is a prime area for future work.  (I will keep an eye out!)
  4. Zonulin is a protein that regulates the tight junctions between the cells in the gut. Patients with HIT were found to have increased zonulin in their stools, which “…suggests a mild alteration of gut permeability in patients with a high intestinal histamine exposure.”
  5. “In summary, our results suggest an alteration of the microbial composition in food intolerances, especially in patients with histamine intolerance. The increase abundance of Proteobacteria, the decreased abundance of Bifidobacteriaceae/Bifidobacterium and the lower bacterial diversity points to a dysbiosis and an impaired intestinal barrier in this patient group.  The positive correlation between intestinal histamine and stool zonulin levels indicates a negative effect of histamine on gut permeability.”

In other words, those with HIT are caught in a vicious cycle.  Raised levels of histamine in the gut (from improper breakdown of food derived histamine) leads to compromised gut wall integrity and inflammation…which in turn leads to lower levels of the enzyme necessary to break down histamine…which leads to higher levels of histamine…and so on.  Which is the chicken and which is the egg, no one yet knows.

How to break the vicious cycle?  Firstly avoid foods with histamine.  Here is a list of good and bad foods for you to consider.  Secondly, for those of you who suspect leaky gut issues:  prior research has shown that supplementation of Bifidobacterium bifidum enhances “…epithelial function by promoting the epithelial tight junction integrity…” in humans.  Supplementation with that probiotic may help over time.

Also, be aware that certain medicines can interfere with DAO activity, including antibiotics, antidepressants, aspirin, and many more.  Look at this page for more info.

While considered rare, you really do have to wonder if HIT is actually more common than believed, and just infrequently recognized by doctors unfamiliar with it.


[i] Schink, M, et. al. Microbial patterns in patients with histamine intolerance.  Journal of Physiology and Pharmacology. 2018;69(4):579-593.

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