Note: I'm homozygous missense mutation for two enzymes in the methylation cycle. Pic attached. YMMV.

I noticed about 10 years ago that, while I get nothing from standard B vitamin complexes, that I get some attenuation of daytime tiredness from methylated B vitamins. I've been taking them almost daily since. Two years ago, I started taking stimulants for ADHD. The stimulant effects of these medications have mostly worn off by now.

A couple months ago, I saw that I had two mutations in the pathway of converting homocysteine to SAM-E, both of which should decrease efficacy, and with relative frequencies in the population of 5% and 5%. Geez, double whammy. I continued taking methyl b vitamin complex.

Then, I bought a sublingual 5-MTHF (methylfolate) to add to my methyl-B complex. I titrated up, and never got any negative side effects at any dose. I ended up taking 15mg (milligrams, not micrograms!) twice a day and found rapid attenuation of daytime tiredness, depressive symptoms, and body aches and pains. These effects last about 4 hours per dose -- I think I was really low on methylfolate.

When I took some of my stimulant ADHD medication alongside this methylfolate, all of the initial effects I got from the medication came back! Buzzing with energy, needing to stop myself from tippy tapping my fingers and teeth, talking a mile a minute. This lasted four hours, until the methylfolate (not the stimulant!) wore off.

What could possibly be the mechanism for this? I do not get the same effect from supplemental SAM-E at standard dosages. Does homocysteine itself suppress any signaling? If it is just the effect of SAM-E on dopamine, then can somebody explain this mechanism to me as well?