Nutritional supplements and dietary interventions provide no protection against cardiovascular disease and early death, according to a major new analysis of dozens of studies on the topic, which was published Monday in the Annals of Internal Medicine.

The only possible exceptions were a low-salt diet and two supplements — folate (folic acid) and omega-3 fatty acids (fish oil). But even in those cases, the evidence supporting their benefits was weak.

The study also found — with moderate certainty — that taking vitamin D and calcium supplements together was associated with an increased risk of stroke.

“Do not waste your money on these over-the-counter multivitamins and nutritional supplements, because if you are using them with the belief that they are going to reduce your mortality or improve your cardiovascular health, they don’t,” said Safi Khan, the study’s lead author and an assistant professor at the West Virginia University School of Medicine, in an interview with Bloomberg News.

As background information in the study points out, three in four American adults take some kind of dietary supplement, and the global sales of these products are estimated to reach $300 billion within the next five years.

The use of dietary supplements continues to climb even though their safety remains unclear, with several studies showing that they can cause harm.

The evidence in support (or against) the health claims of various specific dietary interventions — such as cutting back on saturated fat or salt or increasing fish intake — is also ambiguous.

Little or no impact

For their study, Khan and his colleagues conducted a meta-analysis of 277 randomized controlled trials (considered the gold standard of medical research) that looked at the effects of 16 different nutritional supplements and eight dietary interventions on cardiovascular disease and early death from all causes. More than 1 million people took part in these trials.

The analysis found that most of the supplements — including multivitamins, calcium, iron, selenium and vitamins A, B6, C, D and E — had no impact on cardiovascular health or mortality. Taking omega-3 fatty acid supplements was associated with a reduced risk of having a heart attack and taking folic acid supplements was associated with a reduced risk of having a stroke. The evidence in support of those two benefits had a “low certainty,” however.

As an editorial that accompanies the study points out, the findings regarding omega-3 fatty acid supplements are strongly contradicted by several recent randomized controlled trials that failed to find the products had any cardiovascular benefits. “The results of these trials would tend to downgrade the low-certainty rating of omega-3 fatty acid supplements to uncertain at best,” write the editorial’s authors, Drs. Eric Topol and Amitabh Pandey of the Scripps Research Translational Institute in La Jolla, California.

The positive findings regarding folic acid are also problematic, they add, because they are driven primarily by a study conducted in China, where “a folate-rich diet is not routine.”

In the United States, foods are routinely fortified with folic acid, so it’s unlikely that Americans would get the same benefit as the Chinese from taking folic acid supplements.

Additional findings

The meta-analysis found somewhat stronger evidence that supplements containing both calcium and vitamin D were associated with an increased risk of stroke. That finding supports a 2016 study from Johns Hopkins University, which reported that taking calcium supplements (but not eating foods high in calcium) may raise the risk of developing atherosclerosis, a potentially dangerous buildup of plaques in the arteries.

It remains uncertain whether this increased risk is the result of taking the supplements alone or of what Topol and Pandey describe as “oversupplementation” — taking the supplements as part of a Western diet that is already fortified with calcium plus vitamin D. (Dairy products and cereals, for example, are often fortified with one or both of these nutrients.)

The meta-analysis also found no good evidence that eating less fat, including saturated fat — or even following the much-touted (but controversial) Mediterranean diet — had any impact on cardiovascular outcomes or mortality. Of the eight dietary interventions examined in the meta-analysis, only a low-salt diet appeared to influence cardiovascular health. But the evidence in support of that diet was weak.

“Unfortunately, the current study leaves us with the same foggy conditions that we started with,” write Topol and Pandey. “Until these conditions clear, it would be reasonable to hold off on any supplement or dietary modification in all guidelines and recommendations.”

FMI: You’ll find abstracts of the meta-analysis and the accompanying editorial on the website for the Annals of Internal Medicine, but the full papers are behind a paywall.