Nicotinic Acid, Nicotinamide, and Nicotinamide Riboside: A Molecular Evaluation of NAD⁺ Precursor Vitamins in Human Nutrition

Abstract

Although baseline requirements for nicotinamide adenine dinucleotide (NAD+) synthesis can be met either with dietary tryptophan or with less than 20 mg of daily niacin, which consists of nicotinic acid and/or nicotinamide, there is growing evidence that substantially greater rates of NAD+ synthesis may be beneficial to protect against neurological degeneration, Candida glabrata infection, and possibly to enhance reverse cholesterol transport. The distinct and tissue-specific biosynthetic and/or ligand activities of tryptophan, nicotinic acid, nicotinamide, and the newly identified NAD+ precursor, nicotinamide riboside, reviewed herein, are responsible for vitamin-specific effects and side effects. Because current data suggest that nicotinamide riboside may be the only vitamin precursor that supports neuronal NAD+ synthesis, we present prospects for human nicotinamide riboside supplementation and propose areas for future research.

NAD+ Levels Control Ca2+ Store Replenishment and Mitogen-induced Increase of Cytosolic Ca2+ by Cyclic ADP-ribose-dependent TRPM2 Channel Gating in Human T Lymphocytes

“…These data suggest the existence of a "threshold" level of [ ] i increase. Although the uptake of NAM and NA certainly occurs in intact cells (48,53), the exact underlying mechanisms are not known. Regarding extracellular NMN, it is still not clear how it enhances the intracellular NAD ϩ content, thereby improving metabolism in diet-and age-induced type 2 diabetes in mice (54).…”

Antidepressants may lead to a decrease in niacin and NAD in patients with poor dietary intake

“…Niacin (nicotinamide and nicotinic acid) is abundant in fish, eggs, dairy products and in some vegetables [1]. Although meat is considered poor in niacin it contains NAD and NADP that are cleaved by mucosal enzymes and by nicotinamidase in the GIT to form nicotinamide and nicotinic acid, respectively, which are then absorbed into the circulation [1].…”

“…Nicotinic acid, however, must react with 5-phosphoribosyl-1-pyrophosphate to form the nicotinic acid mononucleotide, which then condenses with ATP to form the nicotinic acid analogue of NAD, which is subsequently converted to NAD by a reaction with glutamine and ATP [1,14,15]. Although niacin is generally described as a vitamin, niacin and NAD can also be synthesized in the body.…”

“…The term niacin is the generic name for the two compounds nicotinic acid and nicotinamide, the major dietary precursors for two important coenzymes, nicotinamide adenine dinucleotide (NAD) and its phosphorylated form, NADP [1,2]. Niacin is biosynthetically converted to NAD, an acceptor of hydride equivalents, to form the reduced nucleotide NADH.…”

Basic leucine zipper transcription factor, ATF-like (BATF) regulates epigenetically and energetically effector CD8 T-cell differentiation via Sirt1 expression

“…Sirt1 is a NAD + -dependent histone deacetylase (21,22). NAD + is the cosubstrate of Sirt1 and acts as a coenzyme in redox reactions where it continuously cycles between NAD + and NADH forms to produce ATP without being consumed (23,24). EL4/BATF cells showed increased levels of cellular NAD + , but not NADH, relative to EL4 cells (Fig.…”