NAD+ (nicotinamide adenine dinucleotide) is one of the most important molecules in the human body. It takes part in more than 500 enzymatic reactions — from energy production in mitochondria, through DNA repair, to circadian rhythm regulation. And there is one serious problem: its level drops dramatically with age.
How much NAD+ do we lose with age?
The data is concerning. Research indicates that NAD+ levels may fall by as much as 80% compared with early adulthood. In skeletal muscle — one of the best-studied tissues — researchers at Maastricht University confirmed in living human measurements that older adults have significantly lower NAD+ levels than younger ones, at comparable physical activity levels.
Importantly, the same team found that athletic seniors — older people who train regularly — had NAD+ levels comparable to young adults. This suggests the age-related decline is not entirely inevitable.
Why does NAD+ decline?
The mechanisms are complex but well documented. 1. Increased PARP activity — DNA damage accumulates with age, and PARP-family repair enzymes consume enormous amounts of NAD+. 2. Increased CD38 activity — this NAD+-degrading enzyme becomes more active in tissues over time. 3. Reduced production — the activity of NAD+ biosynthesis pathways (including the kynurenine pathway) declines with age. 4. Inflammation — the chronic low-grade inflammation typical of aging (inflammaging) both consumes NAD+ and inhibits its production.
What does science say about NAD+ precursor supplementation?
A review published in Nature Metabolism in 2025 summarises results from over a dozen clinical trials using NAD+ precursors in humans. Supplementation consistently and safely raises blood NAD+ levels. A 2024 study in 65–75-year-olds showed that 12 weeks of NMN supplementation (250 mg/day) significantly shortened 4-metre walking time and improved sleep quality versus placebo. One study reported reductions in LDL cholesterol, body weight, and diastolic blood pressure with NMN supplementation.
The Nature Metabolism authors also note that evidence for effects of NAD+ supplementation on age-related disease remains limited, and larger, long-term trials are needed.
Practical takeaways
Science is clear on several points: NAD+ declines with age, physical activity slows that decline, and precursor supplementation safely raises blood NAD+. Does that translate into better health? The research is promising, but the field is young.
If you are considering supplementation, keep a few rules in mind: 8–12 weeks of consistent use is the minimum needed to judge effects; physical activity works synergistically with NAD+ supplementation; consult a doctor if you take medication or have a medical condition.
Dietary supplements are not medicines and do not replace a varied diet. This article is educational and does not constitute medical advice.
