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The findings, published May 28 in the Journal of the American College of Cardiology, largely confirm what's already known: Supplements may be popular, but in most cases, there is no evidence they protect against heart disease.
However, experts said, it's not clear whether the same benefit would be seen in countries where folic acid is added to grain products, and people generally have sufficient levels of the B vitamin. It's found in leafy green vegetables, fruits, dried beans, peas and nuts.
The bottom line? Eat a healthy diet and do not rely on supplements, said Dr. David Jenkins, who led the review.
"There are big health benefits from a mostly plant-based diet," said Jenkins, a professor of nutritional sciences at the University of Toronto. "In my opinion, that's the way to go."
Dr. Andrew Freeman, a cardiologist who was not involved in the research, agreed.
"If you eat a healthy diet rich in plant foods, you're likely to get all the nutrients you need without supplements," said Freeman, who is a member of the American College of Cardiology's Prevention of Cardiovascular Disease Section Leadership Council.
"Taking all those supplements," he added, "really just makes your pee very expensive."
The latest version of the U.S. dietary guidelines recommends three diet patterns for protecting cardiovascular health: the traditional Mediterranean diet; a vegetarian diet; and the so-called "healthy American" diet, which is low in red meat and heavy on fruits and vegetables.
What all three have in common, Jenkins said, is an emphasis on plant foods and limits on things such as red meat and sugar: That means plenty of fiber-rich grains, fruits and vegetables, legumes and nuts, fish (in the non-vegetarian diets) and "good" unsaturated fats from sources like olive oil.
Meanwhile, trials have uncovered potential risks with some other supplements. Across 21 trials of antioxidant mixtures, participants actually showed a slightly higher risk of dying during the study period. The same was true across several trials testing the B vitamin niacin, Jenkins' team found.
On the flip side, there is evidence that folic acid supplements might help lower stroke risk.
That finding came from a 2015 trial in China where the supplements curbed stroke risk among middle-aged and older adults by about 20 percent, according to the review.
The study was done, however, in a place without folic acid supplementation in the food supply. If people already have adequate amounts in their diet, Freeman said, supplements might not help.
In general, Freeman noted, research into the disease-preventing abilities of supplements has been disappointing. It often starts with studies showing that people who eat certain foods, or certain nutrients, have a lower risk of a given disease. But then when supplements of that nutrient are tested, they show no benefit.
"Basically, when we isolate the nutrient from the matrix of the food, we don't do it justice," Freeman said.
So the key message is to eat whole foods. But, Freeman stressed, "don't just add vegetables to your cheeseburger. Replace the junk with plant-based foods."
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SOURCES: David Jenkins, M.D., Ph.D., D.Sc., professor of nutritional sciences, University of Toronto, Ontario, Canada; Andrew Freeman, M.D., cardiologist, National Jewish Health, Denver, and member, Prevention of Cardiovascular Disease Section Leadership Council, American College of Cardiology; May 29, 2018, Journal of the American College of Cardiology, online