Longevity Interventions: What Human Evidence Exists

The short version

"Do longevity supplements work?" is really many questions. The strongest human evidence is for everyday habits, especially physical activity. For most supplements and experimental drugs marketed for longevity, human evidence on living longer or staying healthier is limited, early or absent. Evidence labels used: established, promising but limited, mixed, insufficient evidence, evidence of harm, preclinical (cells/animals only). Education only; this page does not recommend products or amounts.

Human evidence

Physical activity: strongest signal. A 2023 meta-analysis of 94 cohorts (over 30 million participants) found higher activity was linked to lower risk of death and heart disease. At about the level of 150 minutes a week of moderate-to-vigorous aerobic activity, relative risk of all-cause death was 0.69 versus no activity, with smaller added benefit beyond that. [1] These are observational studies, so they show association, not proof of cause, but the pattern is consistent. The National Institute on Aging also names regular exercise, healthy eating, enough sleep, limited alcohol and regular health care as steps within reach. [2] Label: established as a health habit. Details are on Nutrition, Exercise, Sleep and Prevention and Healthy Aging.

Calorie restriction: promising but limited. In the CALERIE trial, 218 non-obese adults aged 21 to 51 were randomized to aim for 25% calorie restriction or usual eating for two years. They achieved about 12% restriction, kept off about 10% of weight, and had improved cardiometabolic risk factors without harm to quality of life. [3] That is a change in risk markers, not proof of longer life. Trials have not followed people long enough to test lifespan; the authors of a later analysis said a conclusive test needs long follow-up on disease and death. [4] Ask a clinician before restricting calories, especially if you take medicines or have a health condition.

Antioxidant vitamins: no benefit, possible harm. A meta-analysis of 68 randomized trials (232,606 participants) found no significant effect of antioxidant supplements on death overall. In the 47 lower-bias trials, supplements slightly increased mortality (relative risk 1.05), and beta carotene, vitamin A and vitamin E may increase mortality; vitamin C and selenium showed no significant effect. [5] Label: evidence of harm for those specific supplements in that analysis. (This is a 2007 analysis, so newer trials are not included.) See Supplements for Healthy Aging and Reading Supplement Labels.

NAD+ precursors (NMN, nicotinamide riboside): promising but limited. A 2023 review found these supplements were safe and tolerable in the studies done and raised NAD+ levels, but said clinical evidence that raising NAD+ improves physiological function is unclear, with small studies and varied designs. [6] Details: NAD+, NMN and Nicotinamide Riboside.

What the reviews say about "anti-aging medicines"

A 2024 review of eight drugs and natural compounds tested in people (metformin, NAD+ precursors, GLP-1 drugs, TORC1 inhibitors, spermidine, senolytics, probiotics, anti-inflammatories) described multiple trials underway, focused on age-linked diseases, and called the hope that they slow aging an expectation, not a result. [7] A 2025 JAMA review said that whether reducing senescent cells gives health benefits in humans remains unclear. [8] Prescription candidates are covered at Experimental Longevity Compounds.

Summary table

Safety and next steps

Supplements can interact with medicines and vary in quality: see medication interactions and talking with a health professional. To judge claims, read Longevity Research Limitations and Safety.