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.
- Methylation is required for the proper functioning of the Histamine-N-Methyl-Transferase (HNMT) enzyme. The HNMT enzyme degrades histamine.
- Methylation is also required for the proper functioning of the Catechol-O-Methyl-Transferase (COMT) enzyme. The COMT enzyme is required for liver detoxification of oestrogen. 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.
- If there is insufficient methylfolate, choline is used for the re-methylation of homocysteine to methionine for the production of SAM (the major 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.