I ran across this blog post as I was searching for answers to the anxiety and mood cycling I've been experiencing as I try to make forward progress on Freddd's Deadlock Quartet. The blogger had noticed the same post I'd found by Ben Lynch about nicotinic acid being a cofactor for COMT's breakdown of epinephrine. She also shares my COMT and MAO A status. The new bits of obscure biochemistry that brought me hope were learning that 1) epinephrine is broken down by the COMT andMAO enzymes, 2) that I've got slowish versions of both of these (heterozygous for COMT V158M and COMT H62H, and homozygous TT for MAO A R297R), and 3) that niacin is a cofactor that can increase the activity of COMT. The idea that epinephrine hangs around too long due to underperforming breakdown enzymes and conspires with the mutant beta receptors to cause the distressing jittery sensations seemed like a promising new lead. So, could additional niacin dosing help improve the breakdown efficiency and lead to less of that sort of feeling? I first encountered this possibility here while reading about methylation SNPs at mthfr.net. Dr. Lynch describes the use of ~50 mg of nicotinic acid (one of the two available supplement forms of niacin) to help a patient with anxiety caused by over-methylation. He says: "Nicotinic acid is a cofactor for the COMT enzyme. This enzyme helps breakdown norepinephrine and epinephrine – and estrogen. These are all commonly elevated in those with anxiety. Since the COMT enzyme sped up, the breakdown of these occurred faster." She goes on to trial adding SAM-E in to counterbalance the methylation-damping effects of the niacin. In a followup comment about six months later she says: I'm still doing it, and I still feel like it's helping. I've kept the SAM-e the same (one 200 mg tablet each morning), but have increased the dosage on the Niacin a couple times.... I'm also doing much much better in terms of energy, waking early, and wanting to be productive lately (started during trip to Amsterdam in early May for QSEU14 conference). I don't know to what extent the niacin/SAM-e strategy has contributed to that shift vs other factors (spring time, fresh salads from the garden, etc.), but I'm inclined to keep with what's currently working. I'm wondering if this makes sense to do at all. On the face of it it seems like jerking the methylation cycle on and off over and over again, but reading that niacin is a co-factor for COMT makes me wonder if it might not be useful to try. And if not, are there are other ways to address MAO A/COMT anxiety?