JES
Senior Member
- Messages
- 1,323
Correlation doesn't prove causation, which sounds like a mantra, but this point cannot be stressed highly enough. Even if we grant that MTHFR defect is present more commonly in autoimmune diseases, that doesn't tell us whether MTHFR is the causative factor behind them. It could be, but to oversimplify a bit, I could claim that having two X chromosomes causes autoimmune diseases, because almost every autoimmune disease is more common in women than men, including ME/CFS. But obviously I think we all agree that being a woman cannot be considered a direct disease causative factor.
Now one possible mechanism, as you mention, for MTHFR actually causing ME/CFS would be from the resulting decrease in methylation. Here it is worth mentioning that heterozygous and homozygous MTHFR mutations have a different degree of effect, so not everyone with one or more MTHFR polymorphims has necessarily a much reduced methylation as a consequence. But to the extent that for example a homozygous MTHFR mutation would cause decreased methylation, the next question would be does this have any much impact in ME/CFS? I would say there is little evidence to show that methylation and methylation treatments are of particular importance in ME/CFS. You linked to a CFS/ME study with B12 supplementation, but that study did not have a placebo group and participants rated themselves improved or not improved, very much like in the PACE trial.
I would look at the methylation section of this forum rather than rely on one small scale study. Thousands of PhoenixRising users have tried various methylation protocols over the years and the effect has been overall disappointing. The late Rich van Konynenburg provided much insight into these treatments, but it seems B12 and methylfolate does not help us any more than other popular supplements like Omega-3's, magnesium, LDN, etc. For me, attempting to treat methylation was the single most disappointing experiment, but I don't deny its value completely. With a homozygous MTHFR mutation, folate supplementation does make sense either way to be safe.
Now one possible mechanism, as you mention, for MTHFR actually causing ME/CFS would be from the resulting decrease in methylation. Here it is worth mentioning that heterozygous and homozygous MTHFR mutations have a different degree of effect, so not everyone with one or more MTHFR polymorphims has necessarily a much reduced methylation as a consequence. But to the extent that for example a homozygous MTHFR mutation would cause decreased methylation, the next question would be does this have any much impact in ME/CFS? I would say there is little evidence to show that methylation and methylation treatments are of particular importance in ME/CFS. You linked to a CFS/ME study with B12 supplementation, but that study did not have a placebo group and participants rated themselves improved or not improved, very much like in the PACE trial.
I would look at the methylation section of this forum rather than rely on one small scale study. Thousands of PhoenixRising users have tried various methylation protocols over the years and the effect has been overall disappointing. The late Rich van Konynenburg provided much insight into these treatments, but it seems B12 and methylfolate does not help us any more than other popular supplements like Omega-3's, magnesium, LDN, etc. For me, attempting to treat methylation was the single most disappointing experiment, but I don't deny its value completely. With a homozygous MTHFR mutation, folate supplementation does make sense either way to be safe.