One type of artificial sweetener may increase heart attack risk, preliminary study says

The sweetener erythritol, which is becoming increasingly popular in snack bars and low-sugar ice cream substitutes, may increase the risk of heart attacks and strokes, according to a paper published Monday in the journal Nature Medicine.

Outside experts who reviewed the findings emphasized that more evidence is needed, with some raising concerns that the results of the study could be due to other factors that make it appear the sweetener causes risks when it does not.

Experts differed as to how consumers should react. Some said individuals who were at risk of heart attacks should avoid erythritol completely as a precaution. Others worried that switching to products with added sugar, which has well-established negative health effects, could have more serious consequences.

Several emphasized that consumers should eat whole foods like fruits and vegetables and not packaged items whenever possible.

The research, conducted by scientists at the Cleveland Clinic in Ohio, is actually a collection of several studies conducted in order to try and establish whether erythritol, a sugar alcohol that tastes sweet but is not digested by the body as sugar, poses risks.

At first, the researchers were looking in blood samples from 1,157 volunteers whose health records were available to try to find chemical compounds that might indicate people were at higher risk of heart attacks and strokes. Such research might help shed light on what causes cardiovascular disease, the leading cause of death in the U.S., aside from known factors like high blood pressure and elevated cholesterol.

But Stanley Hazen, the chair of the department of cardiovascular and metabolic sciences at the Cleveland Clinic’s Lerner Research Institute and the paper’s senior author, said that the compound that was most associated with risk was a surprise: erythritol.

The researchers confirmed the result in two other separate cohorts of patients: a 2,149-person group in the U.S. and an 859-person group in Europe. They found similar risks, with the highest levels of erythritol doubling the risk of heart attacks, strokes, and cardiac procedures compared to the lowest levels.

Then Hazen’s group conducted other studies that showed that erythritol seemed to cause clotting of blood in laboratory experiments, and that the compound appeared to increase the risk of clotting in certain genetically engineered mice. Heart attacks and strokes generally begin as clots in blood vessels.

After that, researchers gave eight volunteers 30 grams of erythritol in a drink, about the amount that might be found in a pint of low-sugar ice cream. They found that blood levels of the compound persisted.

“This is not something we found in just a few people,” said Hazen. “This was a very strong signal.” Both the human observational studies and the studies of human platelets, which are involved in clotting, and in animal models all seem to suggest that higher erythritol levels indicate higher risk of clotting.

“So I think certainly people who are at risk for cardiovascular disease, middle-aged, have known coronary disease or have diabetes, have other cardiac risk factors, with the understanding of being cautious, they should avoid, I think products, that have this on the label,” Hazen said.

Some outside researchers praised the paper for not only establishing that there might be a risk, but also explaining how it might be that a sugar alcohol could cause that risk.

“What these investigators have done is go a very long way in helping us infer cause and effect from the issues they found in the initial fishing expectation,” said David Juurlink, a drug safety expert at Sunnybrook Hospital in Toronto. “They’ve pushed a lot of buttons.”

The paper, he said, is only a first step. “Obviously it warrants replication,” Juurlink said. “If it was me I would think twice in terms of consuming erythritol.”

Scott Simon, a professor of biomedical engineering at the University of California, Davis, said that he thought that the study certainly provided grounds for more research. He suggested that the next step would be to follow two groups of patients, one that ingested erythritol and one that didn’t, and measure the platelet activity in their blood plasma to see if the volunteers who ingested erythritol had blood that was more likely to clot. The next step after that would to see if the increased clotting was correlated with heart attacks and strokes.

But other researchers in nutrition saw significant reasons to doubt the results. One issue, raised by both Karen Aspry, an associate professor of medicine at Brown University, and Deirdre Tobias, a nutrition and obesity epidemiologist at Brigham and Women’s Hospital, is that conditions that cause heart disease might also cause high levels of erythritol in the blood.

Hazen said that the first cohorts he was examining included samples from before erythritol was widely available. The molecule is made by the body in concentrations far lower than those that occur when it is ingested. So more studies may be needed to establish whether it does cause blood to clot.

Aspry, who chairs the American College of Cardiology’s nutrition and lifestyle working group, said that she thought that comparisons of erythritol should have been done with sucrose, the chemical component in table sugar, not a relative of glucose, as they were, and that she would want to see much more about the compound’s effect on other cardiovascular risks, such as cholesterol levels, not just clotting. She also noted that past studies of the function of blood vessel walls, which would normally line up with studies of platelet function, had shown a benefit.

She said it’s best for people to get their sweets from fruits, but was skeptical that eating an energy bar or other low-sugar product would pose a significant risk. “If you’re a diabetic and you have a choice between eating sugar and eating this, I would put my bets on this,” she said.

Kimber Stanhope, a research nutritional biologist at UC Davis, said that a previous review of data on erythritol had identified it as a strong candidate as a sugar alternative. She said she had also used it herself in making cherry pies for Christmas.

She also raised the concern that levels of erythritol created by the body might indicate risk because the compound may be produced in states that increase cardiovascular risk. She said that the new information in the study was the animal and in vitro data, and that she thought larger studies needed to be conducted in order to fully understand erythritol’s risks and benefits.

The evidence on sugar, she said, is “overwhelmingly negative.” She said she would still use erythritol in cooking and would not use sugar. But Stanhope also said that there was a need for further studies — and that it was not clear who would fund them.

“We have work to do on every single one of the artificial sweeteners,” Stanhope said. “It’s ridiculous how understudied they are.”