Daily multivitamins improved the brain function of seniors in a trial — but plenty of questions remain

While pharma companies struggle to show that cutting-edge therapies can treat, prevent, or slow Alzheimer’s disease and other forms of dementia, a new study suggests that a far simpler and cheaper tool could improve cognition in seniors: daily multivitamins.

Researchers found that adults 65 and older who took the common multivitamin Centrum Silver over the course of a three-year study showed more improvement on scores of overall cognition and memory than participants who took a placebo. Those benefits seemed to be greatest among those who had a history of cardiovascular disease. In contrast, daily consumption of cocoa extract didn’t show significant benefit, despite positive findings from previous studies.

A team led by scientists out of Wake Forest University’s medical school published the findings on Wednesday in Alzheimer’s & Dementia, the journal of the Alzheimer’s Association.

It’s the kind of result that is bound to raise both hopes and eyebrows. Centrum Silver is sold practically everywhere — you’ve doubtless seen bottles in your local Walmart, CVS, or Rite Aid. But nutrition science has a long and fraught history that has been marred by poorly designed studies from charlatans looking to peddle supposed panaceas.

The new findings, however, come from a randomized, placebo-controlled trial, which is the kind of study researchers consider the gold standard of evidence that an intervention is helpful. And this is the first time that such a study has shown that multivitamins can improve cognition in older adults.

Still, the report leaves many questions unanswered. The vast majority of study participants were white, so it’s unclear whether these findings translate to other racial and ethnic groups. Researchers also don’t know which of the vitamins and minerals in Centrum Silver are responsible for the cognition-boosting effects. And Jeff Kaye, director of Oregon Health & Science University’s aging and Alzheimer’s center, wonders whether the benefits seen in the trial will translate into real-world benefits.

“You could score a point better when you take the test a year later, and it’s statistically significant,” said Kaye, who was not part of the study. “But does that translate into anything meaningful in a person’s life?”

There’s a clear need for new ways to tackle dementia. Alzheimer’s is the sixth leading cause of death for adults and affects more than 6 million people in the U.S., according to the nonprofit Alzheimer’s Association, which projects the figure could reach 13 million by 2050. And there have been some notable setbacks in the search for new therapies lately. Earlier this summer, Swiss pharma giant Roche announced that its experimental antibody treatment crenezumab failed to prevent or even slow cognitive decline in a Phase 2 study of people with a mutation that guarantees they’ll develop Alzheimer’s.

There’s sporadic and conflicting evidence for nutritional ways to boost cognitive health and ward off dementia. Some studies have suggested that unprocessed cocoa might improve brain function through flavonoids, a class of organic compounds capable of traveling from the bloodstream into the brain. And there’s a smattering of small and mostly observational reports that various vitamins and minerals might do the same.

To look at these effects in a more rigorous way, researchers ran a clinical trial of about 2,200 seniors who did not already have significant cognitive impairment. Participants were randomly assigned to one of four study groups. One group received a daily dose of cocoa extract and Centrum Silver; one group received placebos for both interventions; another group received the multivitamin and a placebo instead of cocoa extract; and the final group got cocoa extract with a placebo instead of a multivitamin.

The use of a placebo and randomization helps researchers rule out other factors that could affect the results — for instance, the possibility that the people who regularly take multivitamins are healthier to begin with. And, notably, Haleon, the health care company that produces Centrum Silver, did not fund this study or shape its design. The firm did provide bottles of Centrum Silver to the researchers, but it didn’t know the trial results until the research team submitted the paper.

Participants received over-the-phone cognitive assessments at the trial’s outset and every year for three years. This was a so-called pragmatic trial, meaning that volunteers participated via mail and over the phone but didn’t have to travel to a research site. It’s a setup that’s meant to make research more accessible, though the study wasn’t racially diverse — nearly 90% of participants were white.

The trial’s main endpoint was how overall cognition changed over the three-year period in those who’d taken cocoa extract versus a placebo. But researchers didn’t see any difference there. Instead, multivitamin use, a secondary endpoint of the trial, led to a statistically significant increase in a cognitive score that averages several different tests of memory, focus, and other cognitive abilities.

Participants who got a daily placebo typically improved, too, with higher scores one and two years after starting the study than at the outset. But that’s a well-known phenomenon with these kinds of cognitive tests, says Laura Baker, the study’s first author.

“Their scores are actually improving, but it’s not because they’re getting smarter. It’s because they’re more familiar with the test,” she said.

The key thing, Baker adds, is to compare that rise in scores of people in the placebo group with those who are on a multivitamin. Two years into the study, cognitive scores leveled out for both groups, but remained higher among those on vitamins through year three.

The effect of multivitamins was more pronounced among participants with a history of heart disease. In this group, cognitive scores actually decreased among those on placebo over time, while they rose among participants on the multivitamins.

To understand how much multivitamins might be slowing the effects of aging, researchers looked at how cognitive scores varied by age at the study’s outset and at how those on Centrum Silver fared over time. Based on those calculations, they infer that multivitamins might have slowed aging’s effects by 60%. But even the study’s authors admit that this rough calculation, tucked away in the report’s discussion section, is imprecise and speculative.

Baker and her colleagues are now trying to understand how this all works and, importantly, if their findings are reproducible. They’re planning to conduct another trial in a larger and more diverse group of older adults. That study will include a mix of blood biomarkers, brain imaging, and in-depth studies of the microbiome to better understand the biological changes multivitamins might be triggering.

There’s plenty of work to be done, she says, and researchers certainly aren’t ready to issue any sweeping recommendations to the public. Neither is the Alzheimer’s Association, says Heather Snyder, the group’s vice president of medical relations.

“There are multiple pieces of that puzzle that throughout life may be contributing to that risk in later life,” she said. “This is a piece of that puzzle. But it is a complex puzzle.”

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