I found the following study interesting. It describes how the balance of B3 and methyl groups ultimately determine health status and aging. An illustration from the study: I must admit that I really don't have the knowledge to understand the implications of the article in depth. I'm hoping someone more knowledgeable than me will chime in. But as I understand it, both under- or overdosing B3 and methyl groups will lead to serious health problems. The question is, how do we find the right balance? From the full text: So what does this tell the many of us who are essentially megadosing on B vitamins and methyl donors? Is it safe at all? Or should we not supplement them? Are the problems related to ratio, dose or both? How would supplementing NAD or NADH change the picture? If I seem confused, it's because I am.