Could This Zero-Calorie Sweetener Increase Your Risk of Heart Attack and Stroke?

Erythritol, a popular zero-calorie sweetener used in many low-carb and low-calorie foods, has been linked to an increased risk of heart attack and stroke, new research suggests. It’s led some experts to urge people to cut back on the amount of sugar substitutes they consume.

The study, published last week in the journal Nature Medicine, looked at circulating levels of erythritol in blood samples of over 4,000 people, and found that those with the highest levels had the greatest risk of a major adverse cardiac event over a period of three years.

“We followed subjects over time and monitored who developed non-fatal heart attack, non-fatal stroke, or died,” senior study author Stanley Hazen, MD, PhD, a specialist in preventative cardiovascular medicine at Cleveland Clinic, told Health. “The erythritol predicted increased risks for myocardial infarction, stroke, or death in all subsets examined.” 

Though more research is needed, the news has the potential to majorly impact the production of erythritol-sweetened foods, which are often recommended for people with diabetes and obesity—and could eventually lead to new dietary guidance around erythritol for people with cardiovascular disease risk.

Here’s what to know, and what experts recommend if the artificial sweetener is part of your daily diet.

Although erythritol was first identified in 1852, it has only become mainstream in the American food supply in recent years, adding sweetness to newer-to-market beverages, oatmeals, baked goods, and more.

Because it contains almost no calories or carbohydrates, the alt-sweetener has been touted as a saving grace for people on diabetic, ketogenic, or low-calorie eating plans. “Unlike table sugar, it has not been found to raise blood glucose or insulin levels,” Erin Palinski-Wade, RD, CDCES, author of 2 Day Diabetes Diet, told Health.

Erythritol, which is processed through fermenting corn, is not as sweet as cane sugar, but many people find it an acceptable alternative. “It has 70% of the sweetness of table sugar, but without any aftertaste that can come with some artificial sweeteners,” Palinski-Wade said. “Because of its similar volume and sweetness level, erythritol makes an easy substitute for table sugar in recipes.”

Besides these benefits, erythritol has been considered a superior alternative sweetener for its limited side effects. Because the body cannot metabolize erythritol very well, it gets absorbed into the bloodstream and excreted through urine.

“Because of this, it causes little GI discomfort, unlike many other sugar alcohols that can cause gas and bloating in large amounts,” Palinski-Wade said.

Humans also naturally create erythritol in low levels, and when paired with dietary erythritol, the compound can accumulate in the body. “Erythritol is made in everyone’s cells, just like cholesterol,” Dr. Hazen said. “Like cholesterol, we see that erythritol is a risk marker for heart disease.”

Though alternative sweeteners like erythritol are common in the American food supply, they’re difficult to measure, and don’t have specific labeling requirements on products. Ultimately, erythritol is regarded as Generally Recognized As Safe (GRAS) by the FDA, which suggests that long-term safety studies aren’t required.

To start, Dr. Hazen and his colleagues first focused on erythritol levels in over 4,000 human blood samples from 2004–2011, which were taken from both Americans and Europeans.

In the first group of about 1,100 people who were undergoing cardiac risk assessments, researchers looked at erythritol levels in blood test results. The more erythritol in a person’s blood stream, the higher their chances of suffering a major cardiac event—like a heart attack or stroke—during a three-year period.

Based on those results, researchers looked at additional groups—about 2,150 people in the U.S. and more than 800 people in the U.K.—and found similar results. “In our validation cohorts, the top quartile of blood erythritol was approximately twice as likely to develop a MACE during three years of follow-up, compared to subjects in the bottom quartile,” Marco Witkowski, MD, the study’s first author, told Health.

After confirming higher levels of erythritol circulating in the blood led to an increased risk of cardiovascular events, researchers sought to explore whether erythritol had any impact on platelet function, or the mechanism through which blood clots. In both human whole blood, and blood from mice, added erythritol induced platelet activity and increased blood clotting.

“Adding erythritol to blood from healthy volunteers quickly changes the platelet function, making them more prone to clot,” Dr. Hazen said. He noted that blood clots can block the arteries leading to the heart or brain—which can then cause heart attack or stroke—thus explaining the likely connection between erythritol and major cardiac events.

Finally, researchers were curious to know how large quantities of erythritol—like those found in “zero-calorie” or “keto” foods and beverages—affect circulating levels of erythritol in the blood shortly after exposure.

After giving a group of eight people erythritol-sweetened drinks made with 30g of erythritol (a similar amount to what would be in a pint of keto ice cream), researchers observed extremely elevated levels in the blood that remained elevated for over two days.

All told, the new research suggests a very clear link between erythritol, blood clotting, and cardiovascular risk—and experts are pushing for more studies to investigate dietary erythritol and its effects on health.

The new research may seem alarming—especially if you knowingly consume erythritol regularly—but it’s important to note that it only demonstrated an association between erythritol and cardiovascular disease risk, not causation. Researchers also said that follow-up studies are necessary to confirm the findings in a larger population.

“The additional finding that enhanced platelet reactivity and aggregation was noted in individuals with higher circulating erythritol levels points to a plausible mechanism of action, but this does not prove causation,” Elizabeth Klodas, MD, FACC, board-certified cardiologist, founder of the Preventive Cardiology Clinic near Minneapolis, and founder of Step One Foods, told Health.

Palinski-Wade also pointed out that the study did not specifically examine dietary consumption of erythritol, and that its subjects were already at risk of adverse cardiovascular events.

But Dr. Witkowski, a cardiologist and graduate student in Dr. Hazen’s lab, believes his team’s research warrants caution around eating erythritol in foods. “Our studies show that, at high levels such as those in the keto foods sweetened with erythritol, when ingested, erythritol in the blood goes up 1,000-fold, and remains well above thresholds linked to heightened clotting risks for days,” he said.

If you have risk factors for cardiovascular disease and erythritol has been part of your diet up until now, you may want to bring it up with your healthcare provider—but there aren’t necessarily steps to take to remedy past consumption. “There is no ‘antidote’ to erythritol and you can’t un-eat what you’ve eaten in the past,” Dr. Klodas said.

As for whether to continue to eat foods with erythritol—especially if you have risk factors for cardiovascular disease, but even if you don’t—experts recommend reducing your intake.

“Whether you have heart disease risk factors or are otherwise healthy, the more productive action to take would be to try and reduce exposure to erythritol, and probably other sugar alcohols as well, going forward,” Dr. Klodas said.

As with most things, moderation is key when it comes to alternative sweeteners. “When it comes to added sweetener, the best practice is to keep intake of all added sweeteners, both caloric and non caloric, in moderation,” Palinski-Wade said. “If you have a high risk of cardiovascular disease, consult your physician and registered dietitian to see what may be the best recommendation for you.”