Published by the New York Times July 8, 2019
By Anahad O’Connor
Some supplements may actually be harmful for cardiovascular health.
Millions of Americans use dietary supplements and a variety of diets to protect their heart health. But a large new analysis found that there was strikingly little proof from rigorous studies that supplements and some widely recommended diets have the power to prevent heart disease.
The new research, published in the Annals of Internal Medicine, reviewed data from hundreds of clinical trials involving almost a million people and found that only a few of 16 popular supplements and just one of the eight diets evaluated had any noticeable effect on cardiovascular outcomes.
Folic acid, reduced salt diets and omega-3 fatty acids, the kind found in fish oil, showed some benefits. But the evidence was fairly weak. And at least one showed evidence of harm: Taking calcium with vitamin D increased the risk of stroke, possibly because it increases blood clotting and hardening of the arteries.
The findings are likely to elicit controversy and continued debate. But the researchers said one clear message from their analysis was that the more than half of Americans who use dietary supplements should be wary of claims that multivitamins and other supplements will improve their heart health.
“People who are taking these supplements for the sake of improving their cardiovascular health are wasting their money,” said Dr. Safi U. Khan, an assistant professor at West Virginia University School of Medicine and the lead author of the new study.
The findings regarding supplements dovetail with the conclusions of a report by the United States Preventive Services Task Force, an influential group of health experts that reviewed vitamin and mineral supplements in 2013 and found little proof that they promote cardiovascular health. “This has been shown very consistently,” Dr. Khan said.
The new study was exhaustive. The authors examined 24 supplements and diets by analyzing data from 277 trials of cardiovascular prevention involving a total of 992,000 people. To get conclusive answers, they selected only randomized controlled trials, in which people are randomly assigned to various interventions for a set period of time and which are considered the “gold standard” for testing treatments. Weaker data from observational studies, which can show only correlations and not cause and effect, were excluded.
Ultimately the researchers found a surprising lack of tangible benefits for almost everything they looked at, both supplements and diets.
Among the supplements that showed no evidence of cardiovascular protection were vitamins A, B, C, D and E, as well as beta-carotene, calcium, iron, antioxidants and multivitamins. While two supplements were found to have some benefit, folic acid and omega-3 fatty acids, there were important caveats.
Taking folic acid was found to lower the risk of stroke. But the finding was largely driven by research from China, where deficiencies of the vitamin are common. The researchers said it was not clear that people who take folic acid in America, where foods are fortified with it, will get the same benefit.
Fish oil, one of the most popular supplements in America, is widely used for its omega-3 fatty acids, which are anti-inflammatory. A recent clinical trial found that high-risk patients who took very large doses of Vascepa, a purified form of omega-3 that is available by prescription only, had a reduction in cardiovascular events. Another study found that supplementing with fish oil could benefit people who eat very little seafood. But the majority of trials involving fish oil have been disappointing. Dr. Khan and his colleagues concluded that there was only weak evidence at best that taking fish oil could prevent heart disease.
“This just reinforces that the supplement story is so shaky,” said Dr. Eric Topol, a cardiologist and the founder of the Scripps Research Translational Institute, who wrote an editorial accompanying the new review. “Not only is there the potential for harm, but there’s also no hard evidence for good.”
When Dr. Khan and his co-authors looked at various diets recommended for cardiovascular prevention, they found a similar lack of solid evidence.
That was certainly the case for low-fat diets, which health authorities have recommended for decades as a way to lower cholesterol and heart disease risk. Dr. Khan and his colleagues found that the most rigorous randomized trials provided no evidence that eating less fat, including saturated fat, had an impact on mortality or cardiovascular outcomes. Low-fat diets have largely fallen out of favor among health authorities in recent years, though the federal government’s dietary guidelines still encourage people to limit their intake of foods rich in saturated fat, such as butter, meat and cheese.
One diet that remains highly touted by health authorities is the Mediterranean diet, with its abundance of whole grains, beans, nuts, fruits and vegetables and olive oil. While clinical trials have found that it reduces cardiovascular risk, some of the major ones have been flawed, and experts who have scrutinized the evidence for the diet have urged caution.
One of the largest and most publicized Mediterranean diet trials, called Predimed and published in 2013, found that it reduced heart attacks and strokes. But last year it was retracted because of methodological problems. The Predimed authors published a new analysis of their data, claiming their conclusions had not changed. But other Mediterranean diet trials have been embroiled in similar controversies. After analyzing data from all the relevant trials, Dr. Khan and his colleagues found that “the totality of evidence did not favor the Mediterranean diet for cardiovascular outcomes.”
“It’s not favorable or harmful,” he added. “It’s just a neutral diet from a cardiovascular perspective.”
The one dietary intervention that seemed to have the most support from randomized trials was lowering salt intake, though the researchers graded the evidence only as having “moderate certainty.” And there was nuance. Low-salt diets reduced mortality from all causes only in people with normal blood pressure. Among people with hypertension, lowering salt intake reduced deaths from heart disease but not from other causes.
Dr. Topol said that in his own clinic he sees a wide range of responses to salt intake. Some people are very sensitive to salt: A small increase in salty foods can have a pronounced effect on their blood pressure. But others can eat salt-laden meals and their blood pressure will hardly budge.
Dr. Topol said he finds diet studies hard to interpret because they rarely take into account the unique way that different people can have markedly different responses to dietary changes, whether it is cutting back on salt or avoiding fat or carbohydrates.
“The problem we have here is that all these studies essentially treat all people as one,” he said. “I think that all these things are going to turn out to be quite heterogeneous. Maybe salt restriction really is beneficial for some, but we haven’t defined the people yet that would drive that.”