Histamine intolerance – a possible CFS mechanism

In reviewing many sites dealing with histamine intolerance as well as PubMed articles, there is more speculation than fact (especially well constructed studies).

My approach is simple to the issue of reducing histamine levels:

  • Avoid foods that are already high in histamines before entering the mouth (which is the common wisdom out there)
  • Avoid food that with the wrong bacteria in your gut, would generate histamines in the guts (this does not appear to be commonly discussed).

To understand the histamine environment, I put together a simple diagram below


The second approach means reducing eating foods in histidine, an amino acid.  Unfortunately, there is no RDA for histidine, the WHO recommends 700 mg/day. To get this:

  • 33 gm (1/3 serving) of Soy protein isolate (1 oz)
  • 50 gm of Beef (2 oz of beef)

Additionally, encourage the breakdown of histamine by encouraging the DAO reaction on histamine.


A 2013 study found that diamine oxidase (DAO) levels are significantly low with histamine intolerance,  “our results showed the benefit of a histamine-free diet because after the diet the majority of symptoms disappeared and the serum DAO activity significantly increased.” More detail is available here. A 1993 study states that “diamine oxidase cannot be supplemented” and describe the low histamine diet as avoiding:

  • “Fish, cheese, hard cured sausages, pickled cabbage and alcoholic beverages had to be avoided.”

A 2007 article in Clinical Nutrition is available as full text and explains the process well and identifies histamine-N-methyltransferase (HNMT)  as another eliminator of histamines. A table of some foods with histamine content as well as troublesome drugs is also included.

  • “histamine intolerance seems to be acquired mostly through the impairment of DAO activity caused by gastrointestinal diseases or through the inhibition of DAO, “ which suggest that gut bacteria may be a factor for DAO levels.

Supplements that were shown effective are:

  • Vitamin C
  • Vitamin B-6 (which leaves the to supplement or to avoid question unclear)
  •  Flavonoids “Fisetin, kaempferol, myricetin, quercetin, and rutin inhibited …histamine release” [2008]

There is table of foods that release histamines (i.e. reduces the body stores of them). This list was actually confusing as several items are included that are the recommended CFS list of foods/supplements:

  • Liquorice,
  • Spices,
  • Chocolate
  • Pineapple (i.e. Bromelain!)
  • My old favorite foods during relapse:
    • nuts and
    • peanut butter!

Doing some further digging, it appears that these have not been confirmed by any clinical studies as having negative impact, rather they appear to be speculative beliefs.

A 2010 study, also available in full text, add further information such as:

  • “Some natural additives like glucose, spices, milk, vanillin, starch, orange juice, ascorbic and citric acids, showed an effective effect on disappearance of histamine and tyramine.”
  • “it was found that tomato showed a decrease in histamine and tyramine concentrations by adding spices. Strawberry and banana showed a clear decrease in histamine and tyramine concentrations by treating them with ascorbic acid [Vitamin C].”

This suggests that a proactive approach may be to soak meats and other foods with a high histamine risk in orange juice to reduce the risk or amount of histamine.


An old 1973 article reports: “The characteristics of histamine release induced by human leukocyte lysates were determined. Intact human leukocytes released histamine during incubation with leukocyte lysates. Maximal release occurred under physiological conditions of temperature and pH, and both Ca(2+) and Mg(2+) were required. The addition of ethylenediaminetetraacetic acid abruptly inhibited release.” and this 1976 article: “The activation of human serum complement by incubation with zymosan generates C5a which releases histamine from autologous basophils. The characteristics of the C5a-induced histamine release were investigated. It is similar to IgE-mediated reactions in requiring Ca++ and in being inhibited by EDTA.

Mangosteen, a Thai medicinal plant

A 2002 article reports: “These results suggest that the 40% ethanol extract of mangosteen has potent inhibitory activities of both histamine release and prostaglandin E2 synthesis.”

Histidine Intake Reduction

Histamine is produced from histidine. This suggests that consuming low histidine foods is beneficial. A low histidine diet with a low histamine diet should be considered. We are fortunate to have detail information of histidine levels available at various sites, including:


In my prior post, it is clear that you wish to avoid Lactobacillus bacteria (typically in yogurt and common probiotics) because they produce L-histidine decarboxylase which converts histidine into histamine.

  • Bifidobacterium infantis and Bifidobacterium longum reduces histamine levels [2008]
  • Bifidobacterium lactis Bb-12 also reduces [2000]

My inference is that the probiotics demonstrated to be effective for IBS are likely also histamine reducers.

Green Acres – Information

My last source of information is actually one that often has been very helpful — agriculture research . We find:

  • “higher diamine oxidase activities, transforming growth factor-α, trefoil factor family and MHC-II concentration occurred when feeding 10% wheat bran fibre (WBF) or 10% pea fibre (PF).” [2013]
  • “Tributyrin (TBU) is a good dietary source of butyrate … increases… diamine oxidase” [2014]
  • ” the activities of diamine oxidase .. higher with high fermentable protein (fCP)” [2013]
  • “Zinc … decreases  diamine oxidase” [2013] Zinc dosage: 30-40 mg/day see this post
  • Fish oil ..”decreased plasma diamine oxidase (DAO) activity and increased mucosal DAO activity’ [2012]
  • Copper deficiency associated with low DAO levels [2007] [1998]
  • “Glycinin, the main storage protein in soybean,…indicating that more histamine had been released in glycinin-fed piglets than in control” [2008]

The last study suggests that soy products should be avoided totally.

Major Histamine Producing Bacteria

A 2009 paper lists some species that produces a lot of histamines.

  • Morganella morganii
  • Providencia rustigianii
  • Proteus mirabilis
  • Raoutella planticola
  • R. ornithinolytica
  • Enterobacter aerogenes
  • E. gergoviae
  • Photobacterium damselae
  • Klebsiella oxitoca
  • Hafnia alvei
  • Vibrio alginolyticus
  • Citrobacter freundii

Both Enterobacter and Klebsiella are known overgrowths for CFS.  Streptococcus thermophilus(common in many yogurts)  isolates have the ability to form biogenic amines, especially histamine, and tyramine [2013].

Some Lactobacillus do not produce significant amount, for example Lactobacillus plantarum [2012] used in some cheeses.

The Acid-Basic Connection

  • “The alkalinity of the urine excreted after histamine injection, reaching pH 7.1 to 8.0, was high compared with 5.4 to 6.9 before the injections. ” [1926] This suggests that histamine producing bacteria favors higher (alkaline pH) and suggests that an alkaline biased diet may be beneficial. See this post for more details (the post could be retitled, how does excessive histamine production starts!)