No supplement has been shown in large trials to extend human lifespan. A few have solid trial evidence for one narrow job, and many popular ones have none. Prevention recently asked experts whether longevity supplements work, and the trial record backs the cautious answer. Here is what the largest studies found, and what to do with it.
Vitamin D and omega-3: big trials, flat results
The VITAL trial gave 25,871 adults (men 50 and older, women 55 and older) vitamin D3 at 2,000 IU a day, fish-oil omega-3s at 1 gram a day, or placebo, and followed them for a median of 5.3 years. It is a randomized controlled trial, the design best able to separate a supplement’s effect from chance. Vitamin D did not lower the rate of invasive cancer (hazard ratio 0.96) or major cardiovascular events (0.97) compared with placebo.[1] Omega-3s did not lower major cardiovascular events (0.92) or cancer (1.03) either.[2]
One result did stand out: heart attacks were less common in the omega-3 group (0.72). That was a secondary outcome, so treat it as a lead for future trials, not a finding to build a routine on.[2] Deaths from any cause did not differ significantly between groups for either supplement.
Creatine: the best case for a narrow job
Creatine has the clearest result in the longevity-adjacent aisle, and it is about muscle, not lifespan. A pooled analysis of 22 randomized trials (721 adults, average ages 57 to 70) compared creatine with placebo during resistance training two to three days a week. The creatine groups gained about 1.4 kg more lean tissue, and a bit more chest-press and leg-press strength.[3] The strength gains were small, and every person in these trials was also lifting. Creatine here is a booster for training, not a replacement for it.
NAD+ boosters: a lab number is not an outcome
Nicotinamide riboside (NR) and similar products are sold to raise levels of NAD+, a molecule your cells use to make energy. A six-week randomized crossover trial in healthy middle-aged and older adults found NR was well tolerated and did stimulate NAD+ metabolism.[4] That is a surrogate marker: the number moved. The trial did not show that anyone felt, functioned or lived better. Its authors pointed to blood pressure and arterial stiffness as questions for larger future trials.[4]
Multivitamins and antioxidant pills: no longevity signal
Two large looks found no edge. A US cohort study followed 390,124 adults for up to 27 years and found daily multivitamin use was not associated with lower all-cause mortality; if anything, the first half of follow-up showed slightly higher mortality (hazard ratio 1.04), and the second half showed no difference.[5] That design shows association, not cause, but it is a lot of people over a long time.
A Cochrane systematic review of 78 randomized trials (296,707 participants) tested antioxidant supplements: beta-carotene, vitamins A, C and E, and selenium. Across all trials, mortality did not differ meaningfully (relative risk 1.02, 95% CI 0.98 to 1.05). In the 56 trials with the lowest risk of bias, mortality was slightly higher with antioxidant supplements (1.04), and beta-carotene and vitamin E carried that signal. Vitamin C and selenium showed no significant effect.[6]
How to use this
The honest frame is healthspan: more years of feeling and functioning well. Daily habits are the better-supported lever. If you still want to take something, these steps keep it grounded.
- Name the job first. “Longevity” is not a job. “Support strength gains while I lift” is one, and creatine fits it. Skip anything you can’t tie to a specific, measurable goal.
- Check the dose against the trial. If the evidence came from 2,000 IU of vitamin D3 or 1 gram of omega-3s, a product with a very different amount is untested in that way.
- Test before you add. Ask your clinician whether a blood test makes sense before you take vitamin D or anything else for a suspected shortfall.
- Add one thing at a time. A “longevity stack” taken all at once makes it impossible to tell what is doing what, or what caused a side effect.
- Bring the bottles to your pharmacist. Tell your clinician about every supplement you take, especially if you use blood thinners or other prescriptions, and don’t start, stop or change a medication on your own.
Put the money you would spend on a stack toward the better-supported basics first: lifting regularly, sleeping consistently and eating plenty of plants and protein. Supplements come after that, if at all.
References
[1] Manson JE, Cook NR, Lee IM, Christen W, Bassuk SS, Mora S, et al. Vitamin D Supplements and Prevention of Cancer and Cardiovascular Disease. N Engl J Med, 2019;380(1):33-44. Population: 25,871 US men 50+ and women 55+, randomized to vitamin D3 2,000 IU/day or placebo (2×2 factorial with omega-3), median follow-up 5.3 years. DOI: https://doi.org/10.1056/NEJMoa1809944. Finding as used: vitamin D was not associated with a lower risk of invasive cancer (HR 0.96, 95% CI 0.88-1.06) or major cardiovascular events (HR 0.97, 95% CI 0.85-1.12) versus placebo; death from any cause HR 0.99 (95% CI 0.87-1.12). ↑︎
[2] Manson JE, Cook NR, Lee IM, Christen W, Bassuk SS, Mora S, et al. Marine n-3 Fatty Acids and Prevention of Cardiovascular Disease and Cancer. N Engl J Med, 2019;380(1):23-32. Population: same VITAL cohort of 25,871 adults, randomized to marine n-3 fatty acids 1 g/day or placebo, median follow-up 5.3 years. DOI: https://doi.org/10.1056/NEJMoa1811403. Finding as used: major cardiovascular events HR 0.92 (95% CI 0.80-1.06) and invasive cancer HR 1.03 (95% CI 0.93-1.13), neither significant; total myocardial infarction HR 0.72 (95% CI 0.59-0.90) as a key secondary end point; death from any cause HR 1.02 (95% CI 0.90-1.15). ↑︎
[3] Chilibeck PD, Kaviani M, Candow DG, Zello GA. Effect of creatine supplementation during resistance training on lean tissue mass and muscular strength in older adults: a meta-analysis. Open Access J Sports Med, 2017;8:213-226. Population: 22 randomized trials, 721 men and women, mean age 57-70, resistance training 2-3 days/week for 7-52 weeks. DOI: https://doi.org/10.2147/OAJSM.S123529. Finding as used: creatine produced greater gains in lean tissue mass (mean difference 1.37 kg, 95% CI 0.97-1.76), chest press strength (SMD 0.35) and leg press strength (SMD 0.24) than placebo. ↑︎
[4] Martens CR, Denman BA, Mazzo MR, Armstrong ML, Reisdorph N, McQueen MB, et al. Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults. Nat Commun, 2018;9:1286. Population: healthy middle-aged and older adults in a 2 x 6-week randomized, double-blind, placebo-controlled crossover trial. DOI: https://doi.org/10.1038/s41467-018-03421-7. Finding as used: NR was well tolerated and stimulated NAD+ metabolism; the authors suggest future trials assess blood pressure and arterial stiffness. ↑︎
[5] Loftfield E, O’Connell CP, Abnet CC, Graubard BI, Liao LM, Beane Freeman LE, et al. Multivitamin Use and Mortality Risk in 3 Prospective US Cohorts. JAMA Netw Open, 2024;7(6):e2418729. Population: 390,124 adults without a history of cancer or other chronic disease (NIH-AARP, PLCO, Agricultural Health Study), follow-up up to 27 years, 164,762 deaths. DOI: https://doi.org/10.1001/jamanetworkopen.2024.18729. Finding as used: multivitamin use was not associated with lower all-cause mortality (multivariable-adjusted HR 1.04, 95% CI 1.02-1.07 in the first half of follow-up; 1.04, 95% CI 0.99-1.08 in the second). ↑︎
[6] Bjelakovic G, Nikolova D, Gluud LL, Simonetti RG, Gluud C. Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases. Cochrane Database Syst Rev, 2012;(3):CD007176. Population: 78 randomized trials, 296,707 participants, mean age 63. DOI: https://doi.org/10.1002/14651858.CD007176.pub2. Finding as used: overall RR 1.02 (95% CI 0.98-1.05, random-effects); in 56 low-risk-of-bias trials RR 1.04 (95% CI 1.01-1.07); beta-carotene RR 1.05 (1.01-1.09) and vitamin E RR 1.03 (1.00-1.05) increased mortality in low-bias trials; vitamin C and selenium did not significantly affect mortality. ↑︎
Kurt Greiner
Kurt is a digital strategist and IT professional blending emerging technology with practical application to help businesses and individuals streamline their digital presence. His current work focuses on the intersection of intentional living and technological resilience, exploring how individuals can leverage modern tools to navigate the second half of life with purpose.
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