MTHFR & Histamine Intolerance


I'm Joanne
I’m a Naturopath, MTHFR & Methylation Specialist. I’m dedicated to helping you achieve your health goals so you can live a vibrant & fulfilling life

MTHFR & Histamine Intolerance


There are so may links between MTHFR and histamine intolerance that it really deserves it’s own blog post.  I’ve made this post very simple, as I want to guide you step by step.

Here we go..

The MTHFR Gene governs the MTHFR enzyme which converts folate into the active form (methylfolate). Methylfolate is a key nutrient in methylation.
Those with an MTHFR gene mutation may have reduced methylfolate and therefore compromised methylation.
The proper functioning of the Histamine-N-Methyl-Transferase (HNMT) enzyme relies on methylation.
The proper functioning of the Catechol-O-Methyl-Transferase (COMT) enzyme also depends on methylation. Liver detoxification of estrogen necessitates the presence and activity of the COMT enzyme. Inadequate oestrogen detoxification causes a build up of oestrogen that stimulate mast cells to release histamine!
So if you have MTHFR and insufficient methylation, you don’t have enough methyls for the proper functioning of either HNMT or COMT, causing a significant build up of histamine.
Histamine also stimulates the production of oestrogen from the ovaries, so again, you have more oestrogen and then more histamine, then more oestrogen again!!!
Oestrogen then down regulates the DAO enzyme that degrades histamine in the gut, causing more histamine, then more oestrogen again!!!
Methylation produces phosphatidycholine which makes bile acids. Bile acids regulate the pH of the small intestine. Insufficient bile acids disrupt the pH of the small intestine which is a major cause of small intestinal bacterial overgrowth (SIBO).
SIBO causes inflammation and histamine release in the small intestine. The DAO enzyme then becomes overloaded with histamine.
When the DAO enzyme becomes overloaded with histamine, the HNMT enzyme takes over the degradation of histamine. If you have insufficient methylation, the HNMT enzyme will not function optimally.
When methylfolate is inadequate, the body utilizes choline to re-methylate homocysteine into methionine, contributing to the production of SAM, the primary methyl donor. You then have insufficient choline to make phosphatidylcholine and bile acids!!

“So you can see how essential it is to work on methylation in histamine intolerance.”

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