Daily multivitamins for years: what the large randomized trials found

The question usually arrives in a practical form: can you take vitamins all year round, and for how long? Behind it sits a bigger one — does a daily multivitamin, taken for years, actually change anything that matters: cancer, heart attacks, memory, how long you live?

That question has been tested directly. Several large randomized trials gave people a daily multivitamin or a placebo and followed them for years. Their answers are more specific — and narrower — than either the label or the sceptics suggest.

This material is for information only and does not replace a consultation with a doctor.

What exactly was tested?

"Multivitamin" here means a standard daily tablet with roughly the recommended amounts of many vitamins and minerals. That is a different thing from high-dose single nutrients, and the difference matters: some single nutrients at high doses have done harm in trials (more on that below).

The largest long-term test is the Physicians' Health Study II: 14,641 male US physicians aged 50 and older (mean age 64.3), randomized from 1997 to a daily multivitamin or placebo, with a median follow-up of 11.2 years. The same men were also randomized to vitamin E, vitamin C, and beta-carotene; the multivitamin figures below are the multivitamin-versus-placebo comparison inside that factorial trial. A second programme, COSMOS, randomized 21,442 US adults — women aged 65 and older and men aged 60 and older — with several cognitive substudies. Both used ordinary commercial multivitamins.

Did it change the risk of cancer?

In the Physicians' Health Study II, total cancer was slightly less frequent with the multivitamin: 17.0 versus 18.3 cases per 1,000 person-years, a hazard ratio of 0.92 (95% CI 0.86–0.998). The upper limit of that interval almost touches 1 — the result is real in statistical terms but small. There was no significant effect on prostate or colorectal cancer, or on cancer deaths (HR 0.88, 95% CI 0.77–1.01).

Two caveats belong next to that number. The participants were male doctors — a well-nourished, highly educated group — and in the next large trial, which included women, the result was not reproduced (see below). And the authors themselves called the effect modest.

The second large trial did not repeat it. In COSMOS, 21,442 US adults (women aged 65 and older, men aged 60 and older, free of major cardiovascular disease and recently diagnosed cancer) took a daily multivitamin or placebo for a median of 3.6 years. Invasive cancer occurred in 518 versus 535 people — a hazard ratio of 0.97 (95% CI 0.86–1.09), no significant difference. Among its many secondary outcomes, lung cancer was less frequent (HR 0.62, 95% CI 0.42–0.92) — a single secondary result that needs confirmation rather than a conclusion. That trial was shorter, but it included women.

When the USPSTF evidence review pooled four multivitamin trials (48,859 people), cancer incidence was slightly lower (odds ratio 0.93, 95% CI 0.87–0.99), but the reviewers listed important limitations of that evidence.

And heart attacks and strokes?

No clear difference. In the Physicians' Health Study II, after a median of 11.2 years, major cardiovascular events occurred at the same rate in both arms (HR 1.01, 95% CI 0.91–1.10), and so did heart attacks, strokes and cardiovascular deaths. Total mortality did not differ significantly either (HR 0.94, 95% CI 0.88–1.02). COSMOS, in older women and men over 3.6 years, found the same: cardiovascular events HR 0.98 (95% CI 0.86–1.12), all-cause mortality HR 0.93 (95% CI 0.81–1.08).

What about memory?

Here the trials disagree, and the disagreement is informative.

In the Physicians' Health Study II, 5,947 men aged 65 and older had up to four cognitive assessments by telephone over 12 years. There was no difference between multivitamin and placebo.

COSMOS found something different. In COSMOS-Mind (2,262 adults, mean age 73, 60% women, 89% non-Hispanic white), three years of a daily multivitamin produced a small, statistically significant benefit on a global cognition score (mean difference 0.07 standard units, 95% CI 0.02–0.12). In COSMOS-Web (3,562 older adults, online testing), immediate word recall was better at one year. A pooled analysis of three non-overlapping COSMOS substudies (about 5,200 people) put the effect on global cognition at 0.07 standard units — which the authors estimated as equivalent to about two years of age-related cognitive change.

What these results do not say: the effect is measured in test scores, not in dementia diagnoses or daily independence; the participants were mostly white and well educated; and the follow-up was two to three years. A twelve-year trial in men showed nothing. "A small difference on cognitive tests in older adults over three years" is the honest summary.

Does it help you live longer?

The randomized trials did not show it. Observational data point the same way on benefit. In 390,124 US adults without cancer or other chronic disease at baseline, from three cohorts (NIH-AARP, the PLCO screening trial, and the Agricultural Health Study), followed for up to 27 years, daily multivitamin users did not have lower mortality. The adjusted hazard ratio in the first half of follow-up was 1.04 (95% CI 1.02–1.07), a small association with higher mortality; in the second half it was 1.04 (95% CI 0.99–1.08). This is an association, not a test of the tablet. The authors adjusted for the healthier habits of supplement users and still note that unmeasured differences could remain. Their conclusion was that there was no mortality benefit.

The US Preventive Services Task Force reached the same place in 2022: the evidence is insufficient to judge the balance of benefits and harms of multivitamins for preventing cardiovascular disease or cancer in community-dwelling, non-pregnant adults.

Did high doses of single nutrients cause harm?

The same review drew a firm line elsewhere. Beta-carotene raised the risk of lung cancer in people at high risk of it. In the Finnish ATBC trial (29,133 male smokers aged 50–69), lung cancer incidence was 18% higher with beta-carotene (95% CI 3–36%). In CARET (18,314 smokers, former smokers and asbestos-exposed workers), beta-carotene with vitamin A gave a relative risk of lung cancer of 1.28 (95% CI 1.04–1.57), and the trial was stopped early. The USPSTF recommends against beta-carotene supplements for preventing cardiovascular disease or cancer, because it judges that the harms outweigh the benefits. It also recommends against vitamin E for that purpose on a different basis: moderate certainty of no net benefit, not a lung-cancer increase like the one in the trials above.

The lesson is not that every multivitamin is dangerous. It is that "more of a nutrient" is not automatically neutral, and that the effect depends on who takes it.

So — how long can you take one?

The data answer a narrower question than the one people ask. For a broad-spectrum daily multivitamin, the longest randomized exposure is a median of 11.2 years in older male physicians, and 3.6 years in older women and men (COSMOS). Those papers do not say that no safety difference appeared. In the Physicians' Health Study II there was no significant difference in gastrointestinal symptoms, fatigue, drowsiness, skin discoloration, or migraine. Skin rash was more common with the multivitamin (2,111 vs 1,973 men; HR 1.08, 95% CI 1.01–1.15), and so were nosebleeds (1,216 vs 1,106; HR 1.11, 95% CI 1.02–1.20). Blood in the urine was less common (HR 0.89, 95% CI 0.81–0.97); the cardiovascular report called the bleeding findings inconsistent. In COSMOS the abstract said there were no safety concerns. The results also reported less stomach upset, diarrhea, rash, and easy bruising, and more gastrointestinal bleeding (HR 1.17, 95% CI 1.03–1.32). A third large trial, SU.VI.MAX, followed 13,017 French adults (women aged 35 to 60, men aged 45 to 60) for a median of 7.5 years on a low-dose antioxidant combination (vitamin C, vitamin E, beta-carotene, selenium, and zinc), not a full multivitamin; total cancer was not clearly different overall. A result in one age group and one product is evidence about that group and that product.

"All year round" or "in courses" is not something these trials compared; there are no data that favour breaks or favour continuous use.

There are also situations where a specific nutrient has its own evidence-based indication, independent of the multivitamin question — for example, folic acid for people who are planning or could become pregnant, which the USPSTF recommends with high certainty. That is a decision about one nutrient for a defined group, not about a daily multivitamin for everyone.

What to do with this

• If you are considering a multivitamin to prevent cancer, heart disease, or to live longer, these trials do not give a reason to expect that. The one primary result that cleared the line of no difference was a small reduction in total cancer in older male physicians. The trial that included older women did not repeat that result for total cancer. A lower lung-cancer count in that second trial was one secondary result among many.

• If you already take one, these trials did not find a difference in cancer deaths, heart attacks, strokes, or total deaths that the authors treated as a safety alarm. They did report the symptom differences above, including rash and nosebleeds in the physicians' trial and more gastrointestinal bleeding in COSMOS. High-dose single nutrients are a separate question. Whether to keep taking a tablet is a question for your doctor.

• If a deficiency is suspected (diet, absorption, medication, pregnancy), that is a question for a blood test and a doctor, not for a general tablet. A related question, limited to vitamin D in older adults, is discussed separately: vitamin D after sixty.

The useful conversation with your doctor is not "should I take vitamins?" but "is there a specific deficiency or a specific indication in my case?"

Sources

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• Sesso HD et al. Multivitamins in the prevention of cancer and cardiovascular disease: the COcoa Supplement and Multivitamin Outcomes Study (COSMOS) randomized clinical trial. Am J Clin Nutr. 2022. PMID 35294969

• Grodstein F et al. Long-term multivitamin supplementation and cognitive function in men: a randomized trial. Ann Intern Med. 2013. PMID 24490265

• Baker LD et al. Effects of cocoa extract and a multivitamin on cognitive function: a randomized clinical trial (COSMOS-Mind). Alzheimers Dement. 2023. PMID 36102337

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• Alpha-Tocopherol, Beta Carotene Cancer Prevention Study Group. The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers. N Engl J Med. 1994. PMID 8127329

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• US Preventive Services Task Force. Folic acid supplementation to prevent neural tube defects: reaffirmation recommendation statement. JAMA. 2023. PMID 37526713