Low-calorie sweetener linked to heart attack, stroke, study finds


A sugar substitute called erythritol — used to bulk add or sweeten stevia, monk fruit, and reduced-sugar keto products — has been linked to blood clotting, stroke, heart attack and death, according to a new study.

“The degree of risk was not modest,” said lead author Dr. Stanley Hazen, director of the Center for Cardiovascular Diagnostics and Prevention at the Cleveland Clinic Lerner Research Institute.

People with existing risk factors for heart disease, such as diabetes, were twice as likely to have a heart attack or stroke if they had the highest levels of erythritol in their blood, according to the study published Monday in the journal Nature Medicine.

“If your blood level of erythritol was in the top 25% compared to the bottom 25%, there was about a two-fold higher risk of heart attack and stroke. It’s on par with the strongest cardiac risk factors, such as diabetes,” Hazen said.

Additional laboratory and animal research presented in the paper revealed that erythritol appeared to cause platelets to clot more quickly. Clots can break off and travel to the heart, causing a heart attack, or to the brain, causing a stroke.

“This certainly sounds like an alarm,” said Dr. Andrew Freeman, director of cardiovascular prevention and wellness at National Jewish Health, a hospital in Denver, Colorado, who was not involved in the study.

“There appears to be a clotting risk with the use of erythritol,” Freeman said. “Obviously more research is needed, but with an abundance of caution, it may make sense to limit erythritol in your diet for now.”

In response to the study, the Calorie Control Council, an industry association, told CNN that “the results of this study contradict decades of scientific research showing that low-calorie sweeteners such as erythritol are safe, as evidenced by global regulatory approvals for their use. of it. in foods and beverages,” Robert Rankin, executive director of the council, said in an email.

The results “should not be extrapolated to the general population, as the intervention participants were already at increased risk for cardiovascular events,” Rankin said.

The European Association of Polyol Producers declined to comment, saying it had not yet reviewed the study.

Like sorbitol and xylitol, erythritol is a sugar alcohol — a carbohydrate found naturally in many fruits and vegetables. It has about 70% of the sweetness of sugar and is considered low in calories according to experts.

Artificially manufactured in large quantities, erythritol has no lingering aftertaste, does not cause blood sugar spikes, and has a less laxative effect than some other sugar alcohols.

“Erythritol looks like sugar, it tastes like sugar, and you can bake with it,” says Hazen, who also directs the Cleveland Clinic’s Center for Microbiome and Human Health.

“It has become the darling of the food industry, an extremely popular addition to keto and other low-carb products and foods marketed to people with diabetes,” he added. “Some of the diabetes-labeled foods we looked at contained more erythritol than any other weight item.”

Erythritol is also the largest ingredient by weight in many “natural” stevia and monk fruit products, Hazen said. Since stevia and monk fruit are about 200 to 400 times sweeter than sugar, only a small amount is needed in each product. The bulk of the product is erythritol, which adds the sugary crystalline appearance and texture that consumers expect.

The discovery of the link between erythritol and cardiovascular problems was purely accidental, Hazen said: “We never expected this. We weren’t even looking for it.”

Hazen’s research had a simple goal: to find unknown chemicals or compounds in a person’s blood that could predict their risk of heart attack, stroke or death in the next three years. To do this, the team began analyzing 1,157 blood samples from people at risk for heart disease between 2004 and 2011.

“We found this substance that seemed to play a big role, but we didn’t know what it was,” Hazen said. “Then we found out it was erythritol, a sweetener.”

The human body naturally produces erythritol, but in very small amounts that would not account for the measured levels, Hazen said.

To confirm the findings, Hazen’s team tested another batch of blood samples from more than 2,100 patients in the United States and another 833 samples collected by colleagues in Europe through 2018. About three-quarters of participants in all three populations had coronary disease or high blood counts. busy and about a fifth had diabetes, Hazen said. More than half were male and between 60 and 70 years old.

In all three populations, researchers found that higher levels of erythritol were associated with a greater risk of heart attack, stroke or death within three years.

But why? To find out, researchers conducted further animal and lab tests and found that erythritol “caused enhanced thrombosis,” or clotting in the blood, Hazen said.

Clotting is necessary in the human body, otherwise we would bleed to death from cuts and injuries. The same process also takes place internally all the time.

“Our blood vessels are always under pressure and we’re leaking, and platelets are constantly filling up these gaps,” Hazen said.

However, the size of the clot made by platelets depends on the size of the trigger that stimulates the cells, he explained. For example, if the trigger is only 10%, you will only get 10% of a clot.

“But what we see with erythritol is that the platelets become super sensitive — just 10% of the stimulant produces 90 to 100% of a clot formation,” Hazen said.

“For people who are at risk for clotting, heart attack and stroke — such as people with existing heart disease or people with diabetes — I think there’s enough data here to say steer clear of erythritol until more studies are done,” Hazen said.

Oliver Jones, a chemistry professor at RMIT University in Victoria, Australia, who was not involved in the study, noted that the study had revealed only association, not causation.

“As the authors themselves note, they found an association between erythritol and clotting risk, not definitive evidence that such an association exists,” Jones said in a statement.

“Any possible (and as yet unproven) risks of excessive erythritol should also be weighed against the very real health risks of excessive glucose consumption,” Jones said.

In a final part of the study, eight healthy volunteers drank a drink containing 30 grams of erythritol, the amount many people in the U.S. consume, Hazen said, according to the National Health and Nutrition Examination Survey, which surveys the U.S. diet each year.

Blood tests over the next three days monitored erythritol levels and clotting risk.

“Thirty grams was enough to raise blood levels of erythritol a thousandfold,” Hazen said. “It remained above the threshold needed to activate and increase clotting risk for the next two to three days.”

How much is 30 grams of erythritol exactly? The equivalent of eating a pint of keto ice cream, Hazen said.

“If you look at nutrition labels on many keto ice creams, you’ll see ‘reduce sugar’ or ‘sugar alcohol,’ which are terms for erythritol. You’ll find that a typical pint contains anywhere from 26 to 45 grams,” he said.

“My co-author and I have been going to grocery stores and looking at labels,” Hazen said. “He found a ‘confectionery’ marketed to people with diabetes that contained about 75 grams of erythritol.”

There is no set “accepted daily intake” or ADI, established by the European Food Safety Authority or the US Food and Drug Administration, that erythritol considers generally recognized as safe (GRAS).

“Science needs to take a deeper dive into erythritol and hurry, because this substance is now widely available. If it’s harmful, we need to know,” said Freeman of National Jewish Health.

Hazen agreed: “I don’t normally get on a pedestal to raise the alarm,” he said. “But this is something I think we need to look at carefully.”

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