Supplement Safety & Quality
Longevity Supplements: What Has Evidence in Humans?
Most supplements lack evidence of longer life. Vitamin D has a narrow mortality signal after 75; other findings concern memory, strength or disease risk.
A longevity supplement shelf can hold a multivitamin, vitamin D, fish oil, creatine, an NAD+ product and a few ingredients you may never have heard of, all promising some version of a longer life. It’s a lot of optimism per square foot. At Humanic Blue, the question is which longevity supplements have evidence in humans—and what kind of evidence that actually is—so we pulled the trials and read them alongside you.
Start with the headline. Human trials have not established that taking supplements generally adds years to life. There is a narrow survival finding: the Endocrine Society cites a very small reduction in deaths with vitamin D in adults 75 and older. Fewer deaths during study follow-up matters, but it does not tell us how many extra years people live or establish the same benefit for other ages. Other supplements have human evidence for narrower outcomes. Correcting a real deficiency, such as vitamin B12 in people who absorb it poorly, is established care. Multivitamins trimmed cancer slightly in one large trial and nudged memory scores in another, but didn’t lower death rates. Vitamin D and fish oil didn’t lower cancer or major heart events in a big US trial. Creatine adds a little strength when paired with training. And the US Preventive Services Task Force recommends against beta-carotene and vitamin E supplements for preventing heart disease or cancer.
In This Article
- Four kinds of evidence, from firmest to thinnest
- Fixing a deficiency is the most solid ground
- Big trials found little effect on cancer, heart disease or death
- Multivitamin users in long studies weren’t less likely to die
- The newer “longevity” products mostly move lab markers
- What the FDA does and doesn’t check
- The trials, numbers and disclosures behind all of this
Key Takeaways
- A change in death rates during a trial is evidence about survival, but does not tell us how many extra years people live. Multivitamin trials here found no significant drop in death rates.
- A handful of supplements have randomized-trial evidence for specific, narrower outcomes: cancer rates, memory scores, strength or a lab marker.
- The Endocrine Society suggests vitamin D for adults 75 and older, citing a very small drop in deaths.
- The US Preventive Services Task Force recommends against beta-carotene and vitamin E supplements for preventing heart disease or cancer.
- The FDA doesn’t approve supplements before they’re sold or routinely test what’s in them.
First, the ladder
Supplement evidence comes in four rungs: an established medical use or deficiency, then randomized human trials, then observational studies, then mechanism and animal work. Each rung answers a different question.
A randomized trial can show that a supplement caused a change. An observational study can only show that the change and the supplement travel together, and people who take supplements often differ from those who don’t in ways that affect health. A mouse study can suggest a mechanism but says nothing yet about people.
“Evidence in humans” also needs an outcome attached. Raising a blood level, changing an epigenetic clock score, improving a memory test and preventing death are four different results. Only the last one is directly about living longer.
Rung one: what counts as an established use?
This rung stands on the most solid ground, and it’s also the least glamorous. Fixing an absorption problem doesn’t make for much of an ad. Supplements here correct a shortfall or serve a defined medical purpose.
Vitamin B12. The National Institute on Aging, part of the NIH, notes that “While older adults need just as much vitamin B12 as other adults, some have trouble absorbing the vitamin naturally found in food.” For those people, it says, a doctor may recommend fortified foods or a B12 supplement.
Vitamin D after 75. The Endocrine Society’s 2024 clinical practice guideline suggests vitamin D without testing first for adults 75 and older, “because of the potential to lower the risk of mortality.” The Mayo Clinic review behind the guideline rated that as a very small drop in deaths, backed by high-certainty evidence. For healthy adults under 75, the same guideline suggests against doses above the recommended daily intake to lower disease risk. The guideline’s wording
Rung two: randomized trials with health outcomes
This is where most of the famous names land. Several big trials have tested supplements against placebo for years, and the evidence review for the independent US Preventive Services Task Force concluded that vitamins and minerals provide “little to no benefit in preventing cancer, CVD, and death,” with a possible small exception for multivitamins and cancer.
Multivitamins pull in two directions. In the Physicians’ Health Study II, Brigham and Women’s Hospital and Harvard Medical School researchers gave about 14,600 male doctors aged 50 and older a daily multivitamin or a placebo for about 11 years. The multivitamin group had about 8% fewer cancers, but deaths from cancer didn’t differ significantly. Pfizer supplied the multivitamin, Centrum Silver, and BASF Corporation provided part of the funding, according to the paper.
The later COSMOS trial, from the same Harvard-affiliated hospital, gave about 21,400 older US adults a daily multivitamin or a placebo for a median of about three and a half years. The authors concluded that it “did not significantly reduce the incidence of total cancer among older men and women.” It didn’t significantly change heart disease or deaths from any cause either. The multivitamin in COSMOS was Centrum Silver, supplied by Pfizer Consumer Healthcare, according to the trial paper.
The cognitive signal came later. A 2024 analysis led by Chirag Vyas of Massachusetts General Hospital combined COSMOS-Mind and COSMOS-Clinic for overall thinking; its memory analysis also included COSMOS-Web. The team wrote that the benefit to overall thinking was equivalent to about two years less cognitive aging. That’s a test-score result, not a result about lifespan.
Vitamin D and fish oil. The VITAL trial, also run from Brigham and Women’s Hospital, gave nearly 26,000 US adults 2,000 IU of vitamin D a day or a placebo for a median of about five years. The authors reported that vitamin D didn’t lower the incidence of invasive cancer or cardiovascular events compared with placebo. The same trial’s fish-oil arm didn’t lower major heart events or cancer either, and a 2020 Cochrane review of 86 trials found omega-3 supplements made little or no difference to deaths from any cause. Omega-3s have their own article, Do Omega-3 Supplements Help You Live Longer?, which covers VITAL and the one prescription form that did reduce events in a high-risk group.
Creatine. Creatine is covered in Does Creatine Help You Live Longer? In short, a 2026 pooled analysis of 11 trials in adults 60 and older found that creatine added a small strength gain to resistance training, with moderate certainty. Its effects on muscle mass and everyday physical function weren’t statistically significant.
The Task Force’s evidence review behind all this covered 84 studies and nearly 740,000 people. Its 2022 recommendation found the evidence insufficient to weigh the benefits and harms of multivitamins and of most single or paired nutrients. Every trial’s numbers, side by side
Rung three: can observational evidence show a longer life?
Observational studies can follow far more people for far longer than trials. They are also where the healthy-user problem lives.
One recent study tackled the multivitamin question directly. National Cancer Institute researchers led by Erikka Loftfield followed about 390,000 US adults from three long-running studies for up to 27 years. Daily multivitamin users were more likely to be college educated and less likely to smoke, which are the kinds of differences that can make a supplement look protective.
After the researchers accounted for those differences, multivitamin use “was not associated with a mortality benefit.” In the first half of follow-up, users actually had a slightly higher risk of dying, about 4%. The authors reported no conflicts of interest.
A null result from an observational study doesn’t prove harm or rule out an effect in some subgroup. It does mean that a look at nearly 400,000 people found no sign that daily multivitamin users were less likely to die. The study details
What would help separate a supplement effect from differences between people who take it and those who do not?
Rung four: markers, mechanisms and animals
This is the rung where the packaging tends to get more exciting than the data. It holds most of what’s sold specifically as a “longevity supplement.” NAD+ precursors—ingredients the body uses to make NAD+, a molecule involved in cellular energy—along with spermidine, urolithin A, taurine and similar products typically rest on animal studies, lab mechanisms and small human trials of blood markers. Each gets its own evidence review in this series.
NAD+ precursors show the pattern. In a 2018 trial at the University of Colorado Boulder, healthy middle-aged and older adults took nicotinamide riboside (NR) and a placebo for six weeks each, in random order. NR was well tolerated and raised NAD+ levels. The investigators cautioned that the dose they tested “exceeds the label-recommended dose and should be considered investigational.” ChromaDex, which sells NR under the name NIAGEN, provided the study pills and partial funding, according to the paper; the authors declared no competing interests.
That’s a clear case of a supplement moving a marker in humans. It is not evidence of a health outcome.
Epigenetic clocks sit on this rung too. They’re tests that estimate “biological age” from chemical tags on DNA. In a later analysis of the DO-HEALTH trial, led by Heike Bischoff-Ferrari of the University of Zurich, Swiss adults aged 70 and older who took 1 gram of omega-3 a day for three years aged more slowly on three clocks; on two of them, the difference came to roughly three to four months. The authors called it “a small protective effect of omega-3 treatment on slowing biological aging.” Co-author Steve Horvath was working for Altos Labs at the time and founded a nonprofit that licenses epigenetic-clock patents, according to the paper’s competing-interests statement. The main trial had European Commission funding along with support from several companies.
A 2026 COSMOS analysis of older adults found a daily multivitamin modestly slowed two clocks over two years; the authors called the effects “statistically significant but small.” Pfizer Consumer Healthcare (now Haleon) and Mars Edge donated the study pills, according to the paper. A slower clock is a biomarker change. No one has yet shown that it translates into longer life. How the marker studies worked
Which step is still missing between a promising mechanism and a demonstrated human benefit?
What doesn’t the supplement label tell you?
In the United States, “FDA does not have the authority to approve dietary supplements before they are marketed,” according to the agency’s dietary supplement Q&A. Firms generally don’t have to show FDA the evidence behind a product’s safety before selling it. The FDA also doesn’t decide how much of an ingredient goes into a serving; the manufacturer does. And the agency says it doesn’t routinely analyze what’s inside supplements.
The National Institute on Aging puts the risk plainly in its guide for older adults: supplements “can also have unwanted side effects, such as unsafe prescription drug interactions. They could also not work at all.”
More isn’t automatically safer. The Task Force’s evidence review found beta-carotene “is associated with increased risk of lung cancer and other harmful outcomes in persons at high risk of lung cancer.” The Task Force recommends against it, and against vitamin E, for preventing heart disease or cancer. The FDA rules and the harm data
What’s Interesting
The only trial-based mortality signal in this roundup doesn’t come from a longevity product. It comes from plain vitamin D in people over 75, and even there the Endocrine Society’s review describes the effect as very small. The products marketed most directly at aging tend to sit lower on the evidence ladder, mostly because they’re newer and the long trials haven’t been run.
Meanwhile the multivitamin, one of the most-studied supplements on the shelf, has now given careful answers to five different questions: cancer, heart disease, memory, death rates and a clock score. Less tidy than a label, but a lot more honest about what living longer research can and can’t settle.
Those answers also come from specific groups. Physicians’ Health Study II enrolled male physicians aged 50 and older, COSMOS enrolled older US adults, VITAL enrolled US adults, and the Endocrine Society’s vitamin D signal applies only to people 75 and older. Someone younger, someone outside those groups or someone with a documented deficiency may sit in a different place on the ladder.
What This Means in Practice
- Different reasons mean different evidence. Correcting a documented deficiency, following a clinician’s recommendation and pursuing a specific trial-tested outcome are different uses from taking something “for longevity.”
- Bring the full list to appointments. The NIA flags drug interactions as a real risk. A pharmacist can check them.
- Ask about age-specific guidance. The Endocrine Society’s vitamin D guidance differs for people 75 and older, and absorption of B12 can change with age.
- Read the outcome, not the headline. When a product cites a study, check whether it measured a blood level, a clock score, a function test or a health event.
A primary care clinician or registered dietitian can assess whether a deficiency exists, and a pharmacist can review interactions. The individual supplement reviews in this series, starting with creatine and omega-3s, go deeper on each ingredient.
Bottom Line
The human evidence on supplements for living longer is thinner than the shelf suggests. The Endocrine Society reports a very small reduction in deaths with vitamin D in adults 75 and older. That narrow finding concerns mortality during follow-up; it does not establish how many extra years people live or a general lifespan benefit from supplements. Other evidence concerns specific outcomes: B12 when absorption is poor, a multivitamin for some cancer and memory measures, and creatine for strength with training. The US Preventive Services Task Force recommends against beta-carotene and vitamin E supplements for preventing heart disease or cancer. The open question is whether the newer products built specifically around aging will ever show a health outcome in people rather than a change on a lab report. Until then, your clinician and pharmacist are the right people to review what you take.
A NOTE FROM LONGEVITY365
We read research, consult expert perspectives and work to make complicated health information easier to understand. What you’re reading here reflects how we’ve interpreted and organized that information. It is educational content—not personal medical advice, diagnosis or treatment guidance.
We’re not perfect, and neither is the available research. Evidence changes, new studies emerge and what’s appropriate for one person may not be appropriate for another.
Use this article as a starting point for your own research and conversations with qualified professionals. Always talk with your doctor or another trusted healthcare professional before making decisions that could affect your health, particularly if you take medications, are receiving treatment, have existing health conditions, are pregnant or have other circumstances that could affect what’s appropriate for you.
Reader Questions
A few questions to carry into the comments or your next conversation. Please leave out identifying or personal medical details.
- 01What would you want to know before putting "Longevity Supplements: What Has Evidence in Humans" into the same conversation as sleep, food, movement, and medical care?
- 02Which evidence boundary stood out most: lifespan, function, symptoms, biomarkers, dose, safety, or who was actually studied?
- 03What question would help keep a supplement conversation grounded instead of turning it into a shopping list?
Extra Insights & Sources
The trial sizes, statistics, full quotes and disclosures behind the story, for anyone who wants to check the math. In the statistics below, a hazard ratio (HR) compares how quickly events occur during follow-up; a risk ratio (RR) compares the likelihood of an event over a stated period; and an odds ratio (OR) compares the odds of an event, the ratio of events to nonevents. For all three, 1 means no difference, but they are not interchangeable measures or personal probabilities. A 95% confidence interval (CI) describes uncertainty around an estimate under the statistical model. A P value describes how compatible the data are with a no-effect model, not the probability that a benefit is real. Standard deviation (SD) describes the spread of test scores; SD units express differences on that scale, not percentage improvements. The symbol g is a standardized measure of effect size. For score or clock differences, 0 rather than 1 means no difference. These are group comparisons, not individual predictions.
What We Know
- A general lifespan-extension benefit from supplements has not been established. The narrow vitamin D mortality signal below concerns fewer deaths during follow-up, not measured extra years of life. Unknown for a general lifespan benefit.
- Large randomized trials of multivitamins, vitamin D and omega-3s in general adult populations mostly found little or no effect on cancer, cardiovascular events and mortality, with a small cancer-incidence reduction for multivitamins in older male physicians. Supported.
- Vitamin D in adults 75 and older shows a very small mortality reduction, according to the Endocrine Society’s review. Supported, narrow population.
- Beta-carotene and vitamin E are recommended against for preventing heart disease or cancer. Established.
What We Don’t Know
- Whether any NAD+ precursor, spermidine, urolithin A or similar product changes a health outcome in people. The human trials so far mostly measure markers. Preliminary.
- Whether the COSMOS cognition signal holds up in other populations and over longer follow-up. Promising.
- Whether slowing an epigenetic clock by a few months means anything for how long people live. Unknown.
- How closely a given product matches its label, since FDA doesn’t review supplements before sale or routinely analyze their contents.
The established uses in detail
Vitamin B12. The National Institute on Aging’s guide (content reviewed April 23, 2021) says: “While older adults need just as much vitamin B12 as other adults, some have trouble absorbing the vitamin naturally found in food. If you have this problem, your doctor may recommend that you eat foods like fortified cereals with this vitamin added, or take a B12 supplement.”
Vitamin D. The Endocrine Society’s 2024 guideline, led by Marie Demay of Massachusetts General Hospital, defines empiric supplementation as vitamin D intake above the Dietary Reference Intakes, taken without testing blood levels first. The panel suggests it for adults 75 and older “because of the potential to lower the risk of mortality,” in the wording of the Society’s guideline page. For healthy adults younger than 75, it suggests against empiric supplementation above the current DRI to lower disease risk. It also suggests against routine vitamin D blood testing. The supporting systematic review from the Mayo Clinic Evidence-Based Practice Center, led by Vishal Paresh Shah, reported a very small drop in deaths among adults older than 75, backed by high-certainty evidence.
The randomized trials in detail
Physicians’ Health Study II (JAMA, 2012). 14,641 male US physicians aged 50 and older (mean age 64.3) were randomly assigned to a daily multivitamin or placebo, with a median follow-up of 11.2 years. Total cancer incidence was 17.0 versus 18.3 events per 1,000 person-years (HR 0.92; 95% CI 0.86–0.998; P=.04). Cancer mortality did not differ significantly (4.9 versus 5.6 per 1,000 person-years; HR 0.88; 95% CI 0.77–1.01). The authors concluded that daily multivitamin supplementation “modestly but significantly reduced the risk of total cancer.” Disclosure: the trial was funded by NIH grants and an investigator-initiated grant from BASF Corporation; study agents and packaging came from BASF and Pfizer (formerly Wyeth, American Home Products and Lederle), and packaging from DSM Nutritional Products. The paper states that the sponsors had no role in design, analysis or the manuscript.
COSMOS multivitamin trial (American Journal of Clinical Nutrition, 2022). 21,442 US adults (women 65 and older, men 60 and older) were randomly assigned to a daily multivitamin or placebo, with a median follow-up of 3.6 years. Invasive cancer: 518 versus 535 cases (HR 0.97; 95% CI 0.86–1.09). Cardiovascular disease: 429 versus 437 (HR 0.98). All-cause mortality: HR 0.93 (95% CI 0.81–1.08), not significant. The trial did report a lower rate of lung cancer with the multivitamin (HR 0.62; 95% CI 0.42–0.92), a secondary outcome. Disclosure: Centrum Silver was supplied by Pfizer Consumer Healthcare (later part of GSK Consumer Healthcare, now Haleon); Mars Edge supplied the cocoa extract and an investigator-initiated grant. Lead author Howard Sesso and JoAnn Manson reported those grants, and Sesso reported grants from Pure Encapsulations and Pfizer Inc. and lecture honoraria from groups including the Council for Responsible Nutrition. The paper says neither company had input on design, analysis or the manuscript.
COSMOS cognition (American Journal of Clinical Nutrition, 2024). Vyas and colleagues used nonoverlapping samples from three COSMOS substudies (COSMOS-Clinic, 573 people; COSMOS-Mind, 2,158; COSMOS-Web, 2,472). Global cognition, or overall thinking, combined COSMOS-Mind and COSMOS-Clinic; episodic memory, memory for events and experiences, drew from all three. The multivitamin improved global cognition (mean difference 0.07 SD units; 95% CI 0.03–0.11) and episodic memory (0.06 SD units). The authors put the effect on global cognition as equivalent to about two years less cognitive aging. The same Mars Edge and Pfizer (now Haleon) pill support applies; several authors reported research support from Mars Edge.
VITAL, vitamin D arm (NEJM, 2019). 25,871 US adults (men 50 and older, women 55 and older) took 2,000 IU of vitamin D3 a day or placebo, with a median follow-up of 5.3 years. Invasive cancer: HR 0.96 (95% CI 0.88–1.06). Major cardiovascular events: HR 0.97 (0.85–1.12). Death from any cause: HR 0.99 (0.87–1.12). JoAnn Manson’s disclosure in the Physicians’ Health Study II paper notes help with VITAL study pills and packaging from Pronova BioPharma and Pharmavite.
VITAL, omega-3 arm (NEJM, 2019). 1 gram a day of marine omega-3 fatty acids versus placebo: major cardiovascular events HR 0.92 (95% CI 0.80–1.06); invasive cancer HR 1.03 (0.93–1.13); death from any cause HR 1.02 (0.90–1.15). Total heart attacks, a secondary outcome, were lower (HR 0.72; 0.59–0.90).
Cochrane omega-3 review (2020). Asmaa Abdelhamid and colleagues at the University of East Anglia pooled 86 randomized trials with 162,796 participants, mostly of capsules. They found that increasing long-chain omega-3s had little or no effect on all-cause mortality (RR 0.97; 95% CI 0.93–1.01; high-certainty evidence) and on cardiovascular events (RR 0.96; high certainty). The authors reported no known conflicts.
Creatine. A 2026 three-level meta-analysis in Frontiers in Nutrition (Lingzi Yao and colleagues, Guangzhou Maritime University) pooled 11 trials in adults 60 and older comparing creatine plus resistance training with training alone. Strength improved (g = 0.31; 95% CI 0.18–0.45; moderate certainty); muscle mass (g = 0.35; −0.09 to 0.78; low certainty) and physical function (g = 0.47; −0.08 to 1.03; very low certainty) did not change significantly. The authors declared no commercial conflicts. An earlier 2024 review led by Thomas Davies at Queen Mary University of London pooled 33 trials (1,076 participants) in older adults and adults with chronic disease and found an average lean-mass gain of 1.08 kg, with the certainty of the evidence rated low or very low because of a high risk of bias in the trials.
USPSTF evidence review and recommendation (2022). The evidence review, led by Elizabeth O’Connor for the Agency for Healthcare Research and Quality, included 84 studies (739,803 people). Pooled multivitamin trials showed a possible reduction in any cancer (OR 0.93; 95% CI 0.87–0.99; 4 trials), with important limitations. Vitamin D with or without calcium showed no association with all-cause mortality (OR 0.96; 27 trials). The review concluded: “Vitamin and mineral supplementation provides little to no benefit in preventing cancer, CVD, and death, with the exception of a possible small benefit for cancer incidence with multivitamin use.” The June 21, 2022 recommendation gives beta-carotene and vitamin E a D grade (recommend against) and gives multivitamins and single or paired nutrients an I statement (insufficient evidence).
| Supplement | Key trial or review | What it found | Evidence label |
|---|---|---|---|
| Multivitamin | Physicians’ Health Study II, 14,641 male physicians aged 50+, about 11 years | 8% lower total cancer incidence (HR 0.92); no significant effect on cancer death | Supported (cancer incidence, men) |
| Multivitamin | COSMOS, 21,442 older US adults, median 3.6 years | No significant effect on total invasive cancer, cardiovascular disease or all-cause mortality | Supported (null) |
| Multivitamin | COSMOS cognition substudies, pooled | Global cognition benefit equivalent to about 2 years less cognitive aging | Promising |
| Vitamin D (2,000 IU/day) | VITAL, 25,871 US adults, median 5.3 years | No lower incidence of invasive cancer or major cardiovascular events | Supported (null) |
| Omega-3 (fish oil) | VITAL; Cochrane 2020 review | Little or no effect on overall mortality or main cardiovascular outcome in routine use | Supported (null for general population) |
| Creatine | 2026 meta-analysis, 11 trials, adults 60+ with resistance training | Small added strength; muscle mass and function not significant | Supported (strength, not lifespan) |
| Beta-carotene, vitamin E | USPSTF 2022 review | Recommended against for heart disease and cancer prevention | Established (harm or no benefit) |
The multivitamin cohort in detail
Loftfield et al. (JAMA Network Open, 2024). Erikka Loftfield and colleagues in the National Cancer Institute’s Division of Cancer Epidemiology and Genetics pooled 390,124 adults without cancer or other chronic disease at baseline from the NIH-AARP Diet and Health Study, the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial and the Agricultural Health Study, with follow-up of up to 27 years; 164,762 died. Among daily users, 42.0% were college educated versus 37.9% of nonusers, and 11.0% were current smokers versus 13.0%. Multivitamin use was not associated with lower all-cause mortality in the first half of follow-up (multivariable-adjusted HR 1.04; 95% CI 1.02–1.07) or the second half (HR 1.04; 0.99–1.08). The authors concluded that “MV use was not associated with a mortality benefit.” Conflict-of-interest disclosures: none reported.
The marker studies in detail
Nicotinamide riboside (Nature Communications, 2018). Christopher Martens, Douglas Seals and colleagues at the University of Colorado Boulder ran a 2 × 6-week randomized, double-blind, placebo-controlled crossover trial in 30 healthy middle-aged and older adults, using 500 mg of NR twice a day. The full statement on dose: “although NR is presently available as a dietary supplement under the trade name NIAGEN® (ChromaDex, Inc.), the dose tested in the present study exceeds the label-recommended dose and should be considered investigational until further work can be performed to confirm the safety and efficacy of higher doses for use by the general population.” Acknowledgments: “Study pills, NR standards for metabolite analyses and partial funding support were provided by ChromaDex, Inc.” Competing interests: “The authors declare no competing interests.”
DO-HEALTH clocks (Nature Aging, 2025). A post hoc analysis of 777 Swiss participants in the three-year DO-HEALTH trial tested vitamin D (2,000 IU a day), omega-3 (1 g a day) and a home exercise program on four DNA-methylation clocks. Omega-3 alone slowed PhenoAge, GrimAge2 and DunedinPACE. The reductions in PhenoAge and GrimAge2 came to 2.9–3.8 months over three years; the DunedinPACE effect was about a 1% slower pace of aging. The Swiss subgroup was healthier and more active than the full trial population. Competing interests: “S.H. is a founder of the nonprofit Epigenetic Clock Development Foundation, which has licensed several patents for epigenetic clocks (including for GrimAge) from his former employer, UC Regents. Further, S.H. works for Altos Labs, Cambridge, UK.” Funding: the European Commission’s Seventh Framework Program, the University of Zurich, and companies listed as DNP (printed in the paper only as that abbreviation), Roche, NESTEC, Pfizer and Streuli; the paper states the funders had no role in the study or manuscript.
COSMOS clocks (Nature Medicine, 2026). Sidong Li, with senior author Howard Sesso and colleagues, measured five DNA-methylation clocks in 958 COSMOS participants over two years. Compared with placebo, the multivitamin slowed yearly change by 0.113 years on PCGrimAge (95% CI −0.205 to −0.020) and 0.214 years on PCPhenoAge (−0.410 to −0.019). The positive figures describe the amount of slowing. The treatment-minus-placebo estimates were −0.113 and −0.214 years: a negative difference means the clock increased less in the multivitamin group, which explains the negative confidence intervals. These are changes in clock estimates, not extra years of life. The effect on PCGrimAge was larger in people with faster biological aging at baseline. Cocoa extract had no effect. Competing interests include Mars Edge and Pfizer Consumer Healthcare (now Haleon) grants for pill donations; additional grants to Sesso from FOXO Technologies, Pure Encapsulations, Haleon and others; and a co-author formerly employed by FOXO Technologies, which provided in-kind donations to generate and preprocess the DNA methylation data.
The FDA rules and the harm data
The FDA’s Q&A explains that under the Dietary Supplement Health and Education Act, “a firm does not have to provide FDA with the evidence it relies on to substantiate safety before or after it markets its products.” The exception is a new dietary ingredient, which requires a safety notification at least 75 days before sale. On serving size, the agency says there are “no laws or regulations that limit the serving size of a dietary supplement or the amount of a dietary ingredient that can be in a serving of a dietary supplement,” and “This decision is made by the manufacturer and does not require FDA approval.” Asked whether it routinely analyzes supplement contents, the FDA answers: “No.” (Page content current as of August 27, 2026.)
In the USPSTF evidence review, beta-carotene with or without vitamin A was associated with higher cardiovascular mortality (OR 1.10; 95% CI 1.02–1.19; 5 trials) and lung cancer (OR 1.20; 1.01–1.42; 4 trials). The review found “clear evidence that vitamin E (with or without vitamin C or selenium) offers no benefit” for all-cause mortality, cardiovascular events or cancer.
Sources
- Demay MB, et al. Vitamin D for the Prevention of Disease: An Endocrine Society Clinical Practice Guideline, Journal of Clinical Endocrinology & Metabolism, 2024: PubMed 38828931
- Endocrine Society: Vitamin D for the Prevention of Disease (guideline page with the full recommendation list)
- Shah VP, et al. Systematic review supporting the Endocrine Society vitamin D guideline, Journal of Clinical Endocrinology & Metabolism, 2024: PubMed 38828942
- National Institute on Aging: Dietary Supplements for Older Adults
- Gaziano JM, et al. Physicians’ Health Study II, JAMA, 2012: PubMed 23162860
- Sesso HD, et al. COSMOS multivitamin trial, American Journal of Clinical Nutrition, 2022: PubMed 35294969; full text PMC9170475
- Vyas CM, et al. COSMOS cognition meta-analysis, American Journal of Clinical Nutrition, 2024: PubMed 38244989
- Manson JE, et al. VITAL vitamin D, New England Journal of Medicine, 2019: PubMed 30415629
- Manson JE, et al. VITAL omega-3, New England Journal of Medicine, 2019: PubMed 30415637
- Abdelhamid AS, et al. Omega-3 fatty acids for cardiovascular disease, Cochrane Database of Systematic Reviews, 2020: PubMed 32114706
- Yao L, et al. Creatine plus resistance training in older adults, Frontiers in Nutrition, 2026: PubMed 42712402
- Davies TW, et al. Creatine for physical function, Journal of Parenteral and Enteral Nutrition, 2024: PubMed 38417175
- O’Connor EA, et al. USPSTF systematic evidence review, Agency for Healthcare Research and Quality: PubMed 35767665
- US Preventive Services Task Force: Vitamin, Mineral, and Multivitamin Supplementation to Prevent Cardiovascular Disease and Cancer, 2022
- Loftfield E, et al. Multivitamin use and mortality in 3 US cohorts, JAMA Network Open, 2024: PubMed 38922615
- Martens CR, et al. Nicotinamide riboside trial, Nature Communications, 2018: PubMed 29599478; full text PMC5876407
- Bischoff-Ferrari HA, et al. DO-HEALTH epigenetic clocks, Nature Aging, 2025: PubMed 39900648
- Li S, et al. COSMOS epigenetic clocks, Nature Medicine, 2026: PubMed 41803341
- US Food and Drug Administration: Questions and Answers on Dietary Supplements
Related product and service comparisons
These companion comparisons add exact label, formulation and certification examples alongside the broader human-evidence discussion. They distinguish company claims and quality checks from evidence of health outcomes.
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