Scientific Reference

NAD+ (Nicotinamide Adenine Dinucleotide)

Evidence profile: Controlled human evidence

NAD+, nicotinamide adenine dinucleotide, is a non-peptide coenzyme formed from two nucleotides joined through their phosphate groups. One nucleotide carries adenine and the other nicotinamide, a form of vitamin B3, and the molecule occurs in every living cell. Cells can make it from tryptophan or nicotinic acid, but mammalian cells rely mostly on a salvage pathway that recycles nicotinamide, with the enzyme NAMPT setting its pace. Identified in yeast extracts more than a century ago, it has long been central to enzymology; recent work, mostly in rodents and cell culture, concerns its roles in signalling and how its levels change with age and metabolic state. Human data on exogenous NAD+ remain limited.

Mechanism of Action

NAD+ accepts a hydride ion to become NADH, and the NAD+/NADH pair carries electrons from glycolysis and mitochondrial dehydrogenases to complex I of the respiratory chain. Beyond this redox role, three enzyme families consume NAD+ as a substrate: the sirtuins, which remove acetyl and other acyl groups from proteins; the poly(ADP-ribose) polymerases (PARPs), which are activated by DNA strand breaks; and CD38 and related enzymes, which generate signalling molecules such as cyclic ADP-ribose. NAD+ outside cells is generally thought to be broken down by cell-surface enzymes into smaller precursors before cells take it up, so the fate of exogenous NAD+ is itself a research question.

Molecular Information

  • Type: Coenzyme (dinucleotide)
  • Molecular weight: 663.4 g/mol
  • Molecular formula: C21H27N7O14P2
  • CAS: 53-84-9

Published Research

  • Nicotinamide adenine dinucleotide metabolism and arterial stiffness after long-term nicotinamide mononucleotide supplementation: a randomized, double-blind, placebo-controlled trial

    Katayoshi T et al. · Scientific reports · 2023 · Clinical

    PMID 36797393 — View on PubMed
  • Safety and Metabolism of Long-term Administration of NIAGEN (Nicotinamide Riboside Chloride) in a Randomized, Double-Blind, Placebo-controlled Clinical Trial of Healthy Overweight Adults

    Conze D et al. · Scientific reports · 2019 · Clinical

    PMID 31278280 — View on PubMed
  • Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD(+) in healthy middle-aged and older adults

    Martens CR et al. · Nature communications · 2018 · Clinical

    PMID 29599478 — View on PubMed
  • NAD⁺ supplementation for anti-aging and wellness: A PRISMA-guided systematic review of preclinical and clinical evidence

    Gallagher C et al. · Ageing research reviews · 2026 · Review

    PMID 41655607 — View on PubMed
  • Supplementation with NAD+ Precursors for Treating Alzheimer's Disease: A Metabolic Approach

    Alghamdi M et al. · Journal of Alzheimer's disease : JAD · 2024 · Review

    PMID 39422945 — View on PubMed