If you’re taking a multivitamin to help you live longer, a new study by researchers at the National Cancer Institute may prompt you to reconsider.

After analyzing health and nutrition data from nearly 400,000 Americans, the researchers found that people who took multivitamins had a small but significantly greater risk of premature death than people who eschewed the supplements.

The findings, reported Wednesday in the journal JAMA Network Open, may seem baffling. Americans aren’t known for having the most balanced diets, and swallowing a pill to fill in our nutrition gaps is often touted as a sensible insurance policy.

Besides, vitamins are essential. It would stand to reason that the more you take, the better.

But like so many things regarding our health, the science is not so straightforward.

As recently as 2022, the experts on the U.S. Preventive Services Task Force conducted a thorough review of the medical literature regarding the potential for multivitamins to help prevent cardiovascular disease and cancer. They concluded there was not enough reliable evidence to make a recommendation one way or the other.

Two things make it difficult to assess the value of multivitamins.

On the one hand, there’s the “healthy user effect.” This describes the fact that people who take multivitamins tend to do a lot of beneficial things, including eating fruits and vegetables, getting regular exercise and abstaining from smoking. When assessing the relationship between multivitamin use and longevity, these habits could make the pills or liquids seem more beneficial than they actually are.

On the other hand, there’s the “sick user effect.” People who are diagnosed with a chronic disease often respond by adding a multivitamin to their daily regimen. In real-world studies, this links the supplements to poorer health and tends to make them seem less helpful than they truly are.

To help fill the gaps left by prior research, a team led by epidemiologist Erikka Loftfield collected data from three large studies that tracked participants over decades — the National Institutes of Health-AARP Diet and Health Study; the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial and the Agricultural Health Study. Anyone who had a chronic condition when they enrolled was excluded from the team’s analysis.

A total of 390,124 people across the three studies shared information about their multivitamin use, and half of them were at least 61½ years old when they began being tracked. By the time the study period came to an end — December 2019 or December 2020, depending on which cohort they were in — 164,762 of them had died, including roughly 50,000 deaths from cancer and 35,000 deaths from heart disease.

There were some clear differences between those who took multivitamins and those who didn’t. For example, 49% of the people who took a multivitamin every day were women, compared with 39% of those who never took them. In addition, 42% of those with a daily multivitamin habit had gone to college, compared with 38% of those who hadn’t.

The health habits of vitamin users and nonusers were different as well. People who took multivitamins every day were less likely to smoke, more likely to exercise, had higher scores for diet quality and lower ones for body mass index, and were more likely to take individual vitamin and mineral supplements.

After accounting for those and other differences, the researchers calculated that the people who eschewed all multivitamins had the lowest risk of death during the first 12 years they were tracked. Compared to them, the mortality rate was 4% higher for those who took multivitamins daily and 9% higher for those who took them less often.

Younger vitamin users had the highest risk. Among those who joined one of the studies before their 55th birthday, the mortality rate for those who took the supplements every day was 15% higher than for those who didn’t take them at all.

Loftfield and her team also compared the mortality risks during the following 15 years. Over that longer time horizon, there were no statistically significant differences between the three groups.

That may not be welcome news to the roughly 1 in 3 Americans who take a multivitamin at least once a month — and who do so despite the fact that researchers have been saying for years that vitamin supplements do not live up to their healthful reputation.

“Multiple vitamins overpromise and they underdeliver,” said Dr. Neal D. Barnard, president of the Physicians Committee for Responsible Medicine. “They took on this undeserved reputation as being an essential aspect of a healthy lifestyle.”

Barnard and two of his colleagues from PCRM explained how this came to be in a commentary that accompanies the study.

The importance of individual nutrients began to become apparent centuries ago, they wrote. For example, lime juice was found to cure sailors with scurvy long before anyone realized the juice was a delivery vehicle for vitamin C. Similarly, doctors were preventing beriberi by replacing white rice with brown rice before they understood that the polishing process removed the grain’s outer layers, which are rich in thiamine.

Multivitamins divorced from foods became a commercial product in the 1940s, and Americans now spend $8 billion per year on the supplements.

There are some cases where vitamin pills can be helpful, Barnard and his colleagues wrote. People with age-related macular degeneration may slow the disease’s progression by taking a cocktail of beta carotene, zinc, and vitamins C and E. Multivitamin use by older adults has been linked with better memory and cognitive function. And people who’ve had bariatric surgery are advised to take multivitamins to make up for the fact that their bodies are no longer able to extract as many nutrients from food.

But those benefits don’t extend to staving off death. Indeed, taking the pills may backfire.

Multivitamins containing calcium and zinc can impede the body’s ability to absorb antibiotics. Multivitamins with vitamin K can counteract the blood-thinning benefits of warfarin, a drug taken by millions of Americans to prevent dangerous blood clots. The iron in multivitamins can result in hemochromatosis, which puts patients at risk for cardiovascular disease, liver failure and Alzheimer’s, among other problems.

“There’s a pretty big downside to all this,” said Barnard, who is also an adjunct professor at the George Washington University School of Medicine and Health Science. “They’re not just benign.”

In most cases, if you want vitamins to help you, you’d be much better off getting them directly from food, Loftfield said. Barnard agreed.

“Taking a vitamin completely out of its context and ramping up the dosage to a formulation that nature never really saw is not necessarily a good idea,” he said. “Mortality is decreased by dietary patterns, not by pills.”