I have a puzzle I'm hoping the biochemically minded folk on this forum may have some insight into. Brief background: I'm 30 years into the CFS journey, having knocked back chronic infections (C. pneumoniae, chronic yeast problems), and working on methylation issues (blood test identified MTHR C677T defect). My two big symptom concerns are fatigue and very significant brain fog. I've been working on methylation, now up to about 3000-4800mcg of folapro a day. I had an energy kick-in when I started to increase the methylcobalamin and dicobenzide. I keep expecting some improvement in the brain fog, but no dice so far. I had no negative reactions to either folapro or B12. Here's the puzzle piece- I've been low in Vitamin D levels for years, and my CFS doc has been working with me to get them up. I don't have my current levels, but they are likely approaching low normal ranges by now. The difficulty has been that any increase in dosing created reactions: fatigue, muscle and joint pain, gut disturbance. Increasing my D3 very gradually-- 400iu increment for a at least a month-- and I've gotten up to 2000iu a day. This has had a fabulous effect on my immune system, I seem to shrug off viruses and infections, remarkable for a CFS'er. BUT--- the other day I decided I was handling D so well that I decided to double my dose to 4000iu.:Retro redface: Next day I was completely flattened with brain fog and depressed mood. I couldn't think my way out of a paper bag! I'm not entirely certain if this is the D, but I recall this "side effect" from when I first started D, which at that time I attributed to viral/bacterial die-off. I'm thinking of stopping it entirely for a time to see if this is what's flattening me. Since my immune system clearly is better from D I don't want to undercut it, but this much brain fog isn't life. Curiously, I don't seem to get this effect from sunlight exposure, at least that I can recall. My wish here is to get some speculation by those more knowledgeable than I about the biochemical interactions on potential interactions of methylation problems, Vitamin D and brain chemistry. Could the increased D suppressing available neurotransmitters or interfere with methylation phases? Could I have a defect in metabolizing D3 that might render it toxic, much as I have a defect metabolizing folic acid?