The Niacin Flush Pathway in Recovery from Schizophrenia and how Arginine and Glutamine may Provide Added Benefit 



known cholesterol-associated drug while also lowering triglycerides, total cholesterol, and very-low-density lipoprotein. However, there are many more uses for niacin, which have been overlooked by conventional mediAbstract A reduced niacin-mediated !ush is increasingly accepted today as a positive diagnostic indicator for schizophrenia. Schizophrenics that were successfully treated with high dose niacin (nicotinic acid) therapy by Dr. Abram Ho"er in the 1950s recovered from their otherwise previously reduced !ush response simultaneous with recovery from schizophrenia. Signi#cantly, some schizophrenics also recovered after high dose nicotinamide treatment, a di"erent nicotinamide adenine dinucleotide (NAD) precursor that does not cause a !ush response. Whether the niacin-!ush response is #rst due to replenishment of NAD de#ciency or due to a restoration of polyunsaturated fatty acid levels thus restoring niacin-!ush competence is not mutually exclusive. It is possible that nicotinic acid is #rst dedicated to intracellular NAD synthesis at the expense of the !ush response until the schizophrenic’s immediate needs for NAD are #nally met. $en the nicotinic acid, rather than entering the cell through transporters, instead becomes available to bind GPR109a, on the surface of the cell thus mediating the !ush pathway. Moreover the restored NAD levels may also revive the biosynthetic pathway required for generation of the known niacin-!ush vasodilatory molecules PGD2, PGE2, PGI2, and thromboxane A2. $e schizophrenic patient may potentially bene#t by additional supplementation with arginine to aid in restoration of the vasodilation, and glutamine to increase NAD synthesis. Arginine increases the amount of nitric oxide (NO) synthase substrate available towards more sustained niacin-NO-vasodilation pathways, while glutamine increases the amount of required substrate available for conversion of nicotinic acid adenine dinucleotide to NAD. $e addition of these two amino acids with high-dose niacin therapy has the potential to provide signi#cant additional therapeutic bene#ts when treating schizophrenia, especially the chronic cases.