5-Methyltetrahydrofolate (5-MTHF) or Metafolin Hot

I recently had genomic testing which revealed I was homozygous for single nucleotide polymorphisms (SNPs) in both the C677T and A1298C variants of the MTHFR gene. This basically means that my MTHFR enzyme is very inefficient in the way it converts other forms of folate to the vital 5-MTHF form. As such I decided to try 5-MTHF supplements to essentially "bypass" this genetic block and ensure my body had enough 5-MTHF available to put into the methylation cycle. Important since poor methylation has been associated with both chronic fatigue syndrome and depression from which I have suffered for 20 and 15 years respectively.

While in theory 5-MTHF is an essential supplement for me, in practice things didn't quite work out. I initially felt I was getting some benefit and experienced a minor "detox reaction" and brighter mood when supplementing at 500mcg/day. However it quite quickly became apparent that the 5-MTHF was causing significant digestive upset. My intestines felt very sore indeed and this subsided once I stopped taking the 5-MTHF. I have discovered that all methyl donors (TMG, SAMe etc) cause the same reaction. I have read that digestive upset is common with SAMe supplements but nothing about this with 5-MTHF or TMG so I am unsure whether others will experience the same problems with 5-MTHF or not.

For those suffering from ME/CFS, depression, autism, or other illnesses in which methylation cycle deficits have been identified, and particularly those who know they have SNPs in MTHFR, a 5-MTHF supplement may very well help and therefore be worth a try. Just be aware of your 'gut reaction'!