NAD+

Why scientists study it

• It sets the pace of energy production through glycolysis and the TCA cycle, and the balance of NAD+ to NADH drops with age as mitochondria work less well.
• Sirtuins (SIRT1, SIRT3, SIRT6) and PARP DNA-repair enzymes use up NAD+ each time they act, so gene control and DNA upkeep depend on how much is on hand.
• Studies compare two precursors, NMN (one step from NAD+) and NR (two steps, more human trials), and point to rising CD38 with age-linked inflammation as a main cause of falling NAD+.

Three studies to know

2016 · Cell Metabolism

Camacho-Pereira and colleagues named CD38 as the main cause of the drop in NAD+ with age. Normal mice aged 32 months had about half the NAD+ of young mice. Mice of the same age without CD38 showed no drop. The rise in CD38 was tied to chronic low-grade inflammation. Read the paper

2021 · Science

Yoshino and colleagues ran a 10-week randomized, placebo-controlled trial in postmenopausal women with prediabetes. On 250 mg of NMN a day, insulin-stimulated glucose disposal went up, measured by hyperinsulinemic-euglycemic clamp. AKT and mTOR signaling in skeletal muscle rose too. Whole-blood NAD+ showed no detectable change. Read the paper

2018 · Nature Communications

Martens and colleagues gave healthy adults aged 55 to 79 a daily 1000 mg of nicotinamide riboside for six weeks in a crossover trial. Blood NAD+ rose by about 60%. Secondary endpoints gave early signs of lower systolic blood pressure and less stiffness in the aorta. Read the paper

Safety and legal status

• The evidence is truly mixed. Animal healthspan data are extensive. Human randomized trials of NMN and NR, usually 6 to 12 weeks long with 20 to 80 people, show higher blood NAD+ and some better markers. No trial has measured human lifespan, and there is no long-term safety data.
• NAD+ is a large, charged molecule that is poorly absorbed by mouth, so most research uses precursors (NMN, NR) or gives it into a vein or muscle. A theoretical worry that it could feed fast-dividing cancer cells has not been settled by clinical data.
• No NAD+ precursor is approved as a treatment by the FDA, the EMA or the MHRA. The regulatory status of NMN is disputed in some places. It is not on the World Anti-Doping Agency’s Prohibited List at present. For laboratory research and in vitro use only.