Do multivitamins do anything? The long trials, in plain terms

Less than the shelf space suggests. In four trials covering 48,859 people, a daily multivitamin lowered new cancers by between 0.2 and 1.2 cases in every hundred people, and changed nothing about heart disease or death.¹ The memory finding everyone quotes comes from one trial program.²

Who these trials enrolled

A multivitamin trial is really a cancer and heart-disease trial. The review that anchors this post collected 84 studies with 739,803 participants.¹ Everyone in them was an adult with no heart disease, no cancer and no known vitamin or mineral shortfall.¹ What the researchers counted was deaths, heart attacks and strokes, new cancers and serious harm.¹

That entry rule settles much of the answer in advance. The trials did not enroll anybody short of a nutrient. They enrolled the well-fed person hedging a bet, which is exactly who buys the tablets. A third or more of the US population takes one every day.⁷

The cancer result, and its actual size

Within that population, one thing moved. Multivitamin takers developed fewer cancers of any kind, at 0.93 times the odds of everyone else, or about 7% lower.¹ Lung cancer fell further in relative terms, to 0.75.¹

Relative numbers flatter small effects, so the absolute one matters more. In the trials large enough to measure it, the gap between takers and non-takers was 0.2 to 1.2 cases of cancer per hundred people, and 0.2 per hundred for lung cancer.¹ That is the number to hold onto. It is real in the data, small enough to be invisible inside any one life, and the reviewers attached important limitations to it.¹

Everything else in that review was flat. Vitamin D showed no link with death across 27 trials with 117,082 participants, nor with heart disease or cancer.¹ Vitamin E showed no link with any of the three.¹ An earlier review of 12 long-term studies and 3 trials in generally healthy adults found the same shape of answer, with no clear pattern by country, sex, smoking or how often people took their tablet.⁷

Where the large effects were: people whose diets were poor

The one setting where supplements of this kind produced big effects was a bad diet. A 2006 review for a US National Institutes of Health conference found five trials that tested whether they worked.⁶

In a poorly nourished Chinese population, beta-carotene, alpha-tocopherol and selenium together cut stomach cancer cases, stomach cancer deaths and overall cancer deaths by 13% to 21%.⁶ Adding retinol and zinc cut stroke deaths by 29%.⁶ In a French trial, a mix of vitamin C, vitamin E, beta-carotene, selenium and zinc cut the cancer rate by 31% in men, and not at all in women.⁶ Multivitamins did nothing for heart disease or cataracts, and the reviewers judged the evidence insufficient either way.⁶

The benefit tracks the deficit. A Scottish trial makes the point from the other end. It gave 910 men and women aged 65 and over either a daily tablet of 11 vitamins and 5 minerals or a dummy pill, for 12 months.⁵ The tablet carried between 50% and 210% of the UK reference intake for each nutrient.⁵ Across the whole group, neither immediate memory nor verbal fluency changed.⁵

Two groups had been singled out before the trial began: people aged 75 and over, and people at higher risk of a shortfall. Their verbal fluency scores ran 2.8 and 2.5 units higher on the tablet, with ranges wide enough to include no effect at all.⁵ Weak evidence, pointing at the same people as everything else here.

The memory results are three windows on one study

The newest and most-quoted findings come from COSMOS, a trial of cocoa extract and a daily multivitamin in 21,442 US adults aged 60 and over, with three cognitive studies run inside it.²

The first tested 2,262 participants by telephone once a year for three years.³ The multivitamin group scored higher on the overall thinking measure, by 0.07 of a standard deviation, and the gain was larger in people with a history of heart disease, at 0.14 against 0.06.³ Cocoa extract did nothing for cognition.³

The second tested 3,562 older adults through an online battery, using a supermarket multivitamin, and set word-list recall as the outcome to beat.⁴ That group recalled more at one year and across three years of follow-up, with no effect on object recognition or executive function.⁴ The researchers put the memory advantage at the equivalent of 3.1 years of age-related memory change.⁴

The third brought 573 participants in for detailed testing in person over two years.² Here the overall thinking gap of 0.06 standard units fell short of significance, while memory for events reached it at 0.12.² Combining all three studies gave 0.07 standard units for overall thinking and 0.06 for memory, which the researchers translated as roughly two years less cognitive aging.²

Two years sounds like a great deal. Two things shrink it. These effects are a few hundredths of a standard deviation on their own scale, which is why they have to be converted into years to sound like anything. And all three came out of one trial, one product and one narrow slice of people: mean age 73, and 89% of them non-Hispanic White.³ The researchers asked for confirmation in a more diverse group themselves.³

The harms belong to single ingredients

Nothing here pins a harm on the multivitamin as a product. The harms attach to single ingredients at high doses.

Beta carotene, alone or with vitamin A, was linked to more lung cancer, at 1.20 times the odds, across four trials with 94,830 participants.¹ In people already at high risk of lung cancer it was also linked to more heart-disease deaths, at 1.10.¹ Thinner evidence ties vitamin A to hip fracture, vitamin E to bleeding strokes, and vitamin C and calcium to kidney stones.¹

The multivitamin itself came out clean twice. The review of 12 studies and 3 trials found no rise in death, cancer or heart disease among takers, and the conference review found no consistent adverse effects.⁷⁶

Where that leaves the hedge

The hedge-your-bets case says a multivitamin is cheap insurance against a diet with gaps. The trials answer a narrower question. In adults with no known shortfall, a daily tablet does not prevent heart disease or death, may prevent a small number of cancers, and in one trial program lifted memory scores in older adults by a small margin.¹²

The groups with the strongest signals are the ones the big prevention trials excluded or barely sampled: the poorly nourished, the over-75s at risk of a shortfall, and older adults who already have heart disease.⁶⁵³

What remains unknown

Whether the COSMOS memory result survives outside COSMOS, with a different product and a broader group of people, is untested.³ Whether the cancer reduction holds is the reviewers' own caveat, and they called the multivitamin evidence limited in important ways.¹ Nobody has run a modern prevention trial built around people with measured low intakes, which is the one group where the older trials found effects worth the name.⁶