Summary

NAD+ (nicotinamide adenine dinucleotide) is a coenzyme found in all living cells, essential for energy metabolism, DNA repair, and redox reactions. While not technically a peptide, it is widely discussed in peptide and longevity research communities. NAD+ levels decline with age, and this decline is implicated in age-related diseases. Restoration strategies include direct NAD+ supplementation (IV/subcutaneous) and precursor supplementation (NR, NMN). Human clinical trials for precursors show moderate evidence; direct injection evidence is limited. NAD+ is not licensed as a medicine by the MHRA in the UK.

Mechanism

NAD+ functions through three primary mechanisms: (1) Redox metabolism — NAD+/NADH serves as an electron shuttle in glycolysis, the TCA cycle, and oxidative phosphorylation, enabling ATP production. (2) Sirtuin activation — NAD+ is an obligate substrate for sirtuin deacetylases (SIRT1-7), which remove acetyl groups from proteins involved in DNA repair, inflammation control, and mitochondrial biogenesis. Declining NAD+ with age reduces sirtuin activity, impairing these protective pathways. (3) PARP and CD38 signalling — NAD+ is consumed by PARP enzymes (involved in DNA repair) and by CD38 (an NADase enzyme whose expression increases with age and inflammation). The competition for NAD+ among sirtuins, PARPs, and CD38 is thought to be a key driver of age-related NAD+ depletion.

Protocols

In clinical and longevity settings, IV NAD+ is typically administered at 250-1,000 mg over 2-8 hours (slow infusion). Courses of 3-10 consecutive daily infusions are described. In research peptide contexts, 50-100 mg subcutaneously is discussed. NR is dosed at 300-1,000 mg/day orally; NMN at 250-1,000 mg/day orally. These figures are from published literature and community discussion only; NAD+ injection is not licensed in the UK.

Work out the draw →

NAD+ for injection is not licensed by the MHRA and is not a controlled substance. NAD+ precursors (NR, NMN) are sold as food supplements in the UK. Direct NAD+ sold for research purposes falls into the UK grey area — legal for laboratory research but not for human consumption without regulatory authorisation.

References

  1. Trammell SA, Schmidt MS, Weidemann BJ, et al. Nicotinamide riboside is uniquely and orally bioavailable in mice and humans. Nat Commun. 2016;7:12948. doi:10.1038/ncomms12948
  2. Elhassan YS, Kluckova K, Fletcher RS, et al. Nicotinamide Riboside Augments the Aged Human Skeletal Muscle NAD+ Metabolome and Induces Transcriptomic and Anti-inflammatory Signatures. Cell Rep. 2019;28(7):1717-1728. doi:10.1016/j.celrep.2019.07.043
  3. Yoshino M, Yoshino J, Kayser BD, et al. Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women. Science. 2021;372(6547):1224-1229. doi:10.1126/science.abe9985
  4. Tarantini S, Valcarcel-Ares MN, Toth P, et al. Nicotinamide mononucleotide (NMN) supplementation rescues cerebromicrovascular endothelial function and neurovascular coupling responses and improves cognitive function in aged mice. Redox Biol. 2019;24:101192. doi:10.1016/j.redox.2019.101192
  5. Liguori I, Russo G, Curcio F, et al. Oxidative stress, aging, and diseases. Clin Interv Aging. 2018;13:757-772. doi:10.2147/CIA.S158513
  6. Verdin E. NAD+ in aging, metabolism, and neurodegeneration. Science. 2015;350(6265):1208-1213. doi:10.1126/science.aac4854
  7. Strong R, Miller RA, Antebi A, et al. Longer lifespan in male mice treated with a weakly aromatase inhibitor, but not with nicotinamide riboside. Nat Commun. 2022;13(1):4333. doi:10.1038/s41467-022-32069-y