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.

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.

Vendor notes

NAD+ for research use is stocked by some UK peptide suppliers as a lyophilised powder. NR and NMN are widely available from supplement retailers. Verify COAs for purity and identity when sourcing research-grade NAD+.

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