In the past I have written about the histamine subset of CFS patients. When there is too much histamine, the supplement/enzyme diamine oxidase can quickly reduce the histamine reaction. Often migraines will be shorten by this supplement.

• “We found that 10 out of 14 patients had serum DAO activity<10 U/mL, which was the threshold suggested as a cutoff for probable histamine intolerance…n patients with symptoms triggered by histamine-rich food, measuring the serum diamine oxidase activity can help identify subjects who can benefit from a histamine limitation diet and/or diamine oxidase supplementation.” [Serum diamine oxidase activity in patients with histamine intolerance. 2016]

” In humans, enzymatic inactivation of histamine occurs through the operation of two types of enzymes, diamine oxidase (DAO) and histamine N-methyltransferase (HMT) that have different characteristics (Rangachari 1992) …Laboratory findings of elevated plasma levels (> 2 ng/ml) of histamine and reduced DAO activity (0.7 nkat/L) have been suggested as indicators of reduced histamine catabolism (Jarisch and Wantke 1996; Bischoff and Manns 1998)… Diamine oxidase activity seems to predominate in the intestine, whereas, N-methyltransferase activity predominates in the brain (Holcslaw et al 1985; Schayer and Reilley 1973). DAO tends to exhibit a histamine-degrading capacity ten times higher than that of HMT (Huertz and Schwelberger 2003).

In contrast, 99% of histamine entering the [healthy] body in the digestive tract is prevented from reaching the circulation (Naranjo 1966) ” — thus intestinal barrier breakdown can be a significant contributor.

“The levels of urinary histamine and its metabolites seem to be greatly influenced by the level of histamine consumed in food, by the activity of bacteria in the digestive tract, and possibly in the vagina (Keyzer et al 1983).”

“Histamine from dietary sources and from the activity of intestinal microorganisms will normally be catabolised by diamine oxidase within the digestive tract before gaining access to circulating blood. However, if the enzymatic activity at this site is reduced, histamine will be transported from the gut lumen into circulation and augment the level of plasma histamine from endogenous sources ”

“At the present time there is no research data that may suggest a mechanism whereby up-regulation of diamine oxidase production or activity in human tissue can be achieved in situ.”

” Some preliminary research indicates that certain strains of bacteria, such as species of Lactobacillus, Leuconostoc, Escherichia faecium, Weisella and Sarcina (Figure 3) can produce diamine oxidase (Dapkevicius et al 2000; Leuschner et al 1998). ”

• “After intravenous administration of heparin, DAO is released from its capillary binding sites in the lamina propria into the peripheral circulation.” [1994]
• “The levels of diamine oxidase and D‑lactic acid in the plasma were analyzed as markers of the intestinal permeability” [2016]
• ” investigate the effects of cello-oligosaccharide (COS) on intestinal microbiota and epithelial barrier function … reduced plasma DAO
• “Increased D-lactate levels and DAO activities were observed in the model [respiratory issues] group (P < 0.01). Sequencing results revealed the presence of 3780 and 4142 species in the control and model groups, respectively. The percentage of shared species was 18.8419%

Diamine oxidase rs10156191 and rs2052129 variants are associated with the risk for migraine [2015].

Possible Model

We know that histamine is produced by bacteria, it also appears that diamine oxidase is also produced by some bacteria

• “hat the mean DA concentration is significantly higher in samples positive for microbial pathogens.” Enzymatic assay to test diamines produced by vaginal bacteria[2015].
• “PI-IBS mice treated either alone with Bifidobacterium or Lactobacillus (but not Streptococcus), or the mixture of the three exhibited not only decreased abdominal withdrawal reflex score and contractile response, but also reduced plasma DAO and D-lactate.” [2014]
• Bacterial translocation secondary to small intestinal mucosal ischemia during cardiopulmonary bypass. Measurement by diamine oxidase and peptidoglycan [2004].
• “Enzyme stimulation by S boulardii was associated with significant increases indiamine oxidase activity and mucosal polyamine concentrations.” [1999]

Bottom Line

I have written about S boulardii in an earlier post and concluded “There is no clean evidence of any significant improvement with CFS or any related condition“. There is just a single study (on rats). Histamine intolerance is a small subgroup of CFS patients — if you have  histamine over-sensitivity, you may wish to try S boulardii. You should track the amount of DAO you needed monthly before starting and then see if your need for DAO is reduced.