I have been reading about the ideas of Bill Walsh, PhD., and I have to make some changes in my hypothesis and the NAD recipe in order to integrate his ideas about the methylation state of the histones, which seems to be the most important over and undermethylation effect, and doesn’t have anything to do with SAMe levels. First the change in the NAD recipe and then and explanation for those who want the technical part: Niacinamide should only be taken by overmethylators. Niacin should be used by undermethylators, but in smaller amounts. We are still experimenting to see what amount is needed. Otherwise the NAD recipe is the same, with ribose being the most important part. I know that some people here are familiar with Walsh’s ideas but I will give a brief overview for those who are not. How active a gene is depends on the amount of methylation in the histone tails of the histone that it is wrapped around. If the methylation level is high, the gene expression is low, if the methylation is low, the gene expression is high. These histone tails affect many processes, so it really isn't known yet all of the things that are affected by methylation levels that are too high or low, but one thing they are known to control is the number of neurotransmitter transporter proteins, which take the neurotransmitters out of the synapses. When these transporter proteins are more numerous the activity of the neurons will be less and so the methylation state of the histone controls how exposed to serotonin, dopamine and norepinephrine a neuron is. Naturally a person will have symptoms if the levels are either too high or too low. Folate is used by an enzyme called Histone Demethylase LSD1 which takes methyl groups off of histone. So folate, specifically THF, or tetrahydrofolate, can increase the expression of the gene which produces the neurotransmitter transporter proteins. Niacinamide inhibits sirtuins, which increase methylation of histone tails, so niacinamide has the same basic effect as folate, but sin sirtuins require NAD+, you have to have a large enough NAD/NADH pool so with these illnesses I think some regular niacin is needed, but not too much or the niacinamide levels will rise. So people who tend to have overmethylated histones need plenty of folate and niacinamide, and people who are undermethylators shouldn’t take much folate and only a limited amount of regular niacin. Methionine is supposed to help for undermethylators, too. I am studying a whole train of thought about how NAD is made and how it might have something to do with PEM (which at the moment I think might be caused by temporary axon damage in the brain) and neurological damage (more axon damage) but I haven't learned enough to post about it yet. I hope to have something in a few days.