The Promise of Niacin in Neurology.

Niacin (vitamin B3) is an essential nutrient that treats pellagra, and prior to the advent of statins, niacin was commonly used to counter dyslipidemia. Recent evidence has posited niacin as a promising therapeutic for several neurological disorders. In this review, we discuss the biochemistry of niacin, including its homeostatic roles in NAD+ supplementation and metabolism. Niacin also has roles outside of metabolism, largely through engaging hydroxycarboxylic acid receptor 2 (Hcar2). These receptor-mediated activities of niacin include regulation of immune responses, phagocytosis of myelin debris after demyelination or of amyloid beta in models of Alzheimer's disease, and cholesterol efflux from cells. We describe the neurological disorders in which niacin has been investigated or has been proposed as a candidate medication. These are multiple sclerosis, Alzheimer's disease, Parkinson's disease, glioblastoma and amyotrophic lateral sclerosis. Finally, we explore the proposed mechanisms through which niacin may ameliorate neuropathology. While several questions remain, the prospect of niacin as a therapeutic to alleviate neurological impairment is promising.

An Outbreak of Pellagra in the Kasese Catchment Area, Dowa, Malawi.

AbstractPellagra is a deficiency of niacin or its amino acid precursor, tryptophan, which presents with the classic four Ds: the characteristic dermatitis, diarrhea, dementia, and eventually death if left untreated. The incidence of pellagra is quite rare presently because of increased awareness and strategies such as vitamin fortification. However, the deficiency is still present in cultures that rely on maize as their primary source of sustenance. We report a recent outbreak in a catchment area in Kasese, Malawi, of 691 cases of pellagra which were successfully treated with niacin supplementation. We present this short report to highlight the importance of educating providers of at-risk populations about this diagnosis and to consider solutions for these populations to prevent further deficiencies.

Increase in conversion of tryptophan to niacin in pregnant rats.

There is the report that the deaths by pellagra in women is approximately twofold excess that in men. In the present experiment, in order to clarify a factor in the etiology of pellagra in female and to get basic information how much niacin should be supplemented in pregnant state, we investigated the effects of pregnant on the metabolism of tryptophan to niacin in rats. The daily urine samples were collected from day -17 and day +6 (the delivery day was designated as day 0) and the intermediates of tryptophan to niacin were measured. The metabolites such as kynurenic acid, xanthurenic acid, anthranilic acid, 3-hydroxyanthranilic acid, quinolinic acid, N1-methylnicotinamide, N1-methyl-2-pyridone-5-carboxamide, N1-methyl-4-pyridone-3-carboxamide were increased with progress in pregnant and returned to normal levels after the delivery. The catabolism of tryptophan is accelerated during pregnancy, indicataing that pregnancy would not be an etiology of pellagra and no niacin supplement needs but tryptohan supplement would need.

NADP+ biosynthesis by rats receiving a pellagragenic diet.

Rats showing signs of pellagra-like disease associated with gelatin ingestion were injected with [14C]-nicotinic acid into the portal vein and the incorporation of the label into hepatic NAD+ and NADP+ was determined. The quantity of NADP+ synthesized within 1 h after [14C]-nicotinic acid injection by the experimental group, supplemented or not with dietary niacin, was 75% lower than that synthesized by the control group fed a casein control diet (141 nmol h-1 g-1). The NAD+ and NADP+ contents of the liver of the experimental animals were 245 and 93 micrograms/g liver, respectively, i.e., significantly lower than those for the controls (597 and 210 micrograms/g, respectively). Dietary supplementation with niacin increased the NAD+ content to 317 micrograms/g liver but had no statistical effect on NADP+ content (75 micrograms/g liver) or NADP+ synthesis (46.5 in the free niacin group vs 37.0 nmol h-1 g-1 in the niacin-supplemented group). Therefore, NAD+ content did not seem to limit NADP+ synthesis. These results suggest that the lower availability of NADP+ is responsible, at least in part, for some metabolic derangements in pellagra-like disease, such as a decrease in the activity of NADP(+)-dependent enzymes observed in quail muscle.

Nadp+ biosynthesis by rats receiving a pellagragenic diet

Rats showing signs of pellagra-like disease associated with gelatin ingestion were injected with [14C}-nicotinic acid into the portal vein and the incorporation of the label into hepatic NAD+ and NADP+ was determined. The quantity of NADP+ synthesized within 1 h after [14C]-nicotine acid injection by the experimental group, supplemented or not with dietary niacin, was 75% lower than that synthesized by the control group fed a casein control diet (141nmol h-1 g-1). The NAD+ and NADP+ contents of the liverof the experimental animals were 245 and 93 *g/g liver, respectively, i. e., significantly lower than those for the controls (597 and 210 *g/g liver, respectively). Dietary supplementation with niacin increased the NAD+ content to 317 */g liver but had no statistical effect on NADP+ content (75 *g/g liver) or NADP+ synthesis (46.5 in the free niacin group vs 37.0 nmol h-1 g-1 in the niacin-supplemented group). Therefore, NAD+ content did not seem to limit NADP+ synthesis. These results that the lower availably of NADP+ is responsible, at least in part, for some metabolic derangements in pellagra-like disease, such as a decrease in the activity of NADP+-dependent enzymes observed in quail muscle

Interaction of niacin and zinc metabolism in patients with alcoholic pellagra.

The effect of zinc supplementation on the metabolism of tryptophan conversion to niacin was studied in 14 alcoholic patients with pellagra and in 7 male control subjects aged 21-45 y. The pellagrins received chemically defined diets based on crystalline amino acids through an enteral tube for 7 d. Patients were divided into two groups (A and B), both receiving a diet from which tryptophan, Zn, and niacin were excluded. Patients in group B, however, received 220 mg Zn sulfate orally. Upon admission the pellagra patients had low plasma Zn levels and low urinary excretion values of N'methylnicotinamide (N'MN) and N'methyl-2-pyridone-5-carboxamide (2-PYR) in relation to the control subjects (p less than 0.01). During the experimental period there was an increase in plasma Zn levels (p less than 0.005) and in urinary N'MN (p less than 0.05) and 2-PYR (p less than 0.05) excretion in the patients receiving Zn supplementation (group B). These results suggest that Zn interacts with niacin metabolism in alcoholic patients with pellagra through a probable mediation by vitamin B-6.