• Posted February 27, 2023

Could a Common Sweetener Raise Heart Risks?

An artificial sweetener commonly used in processed foods could be increasing people's risk of heart attack and stroke, a new study argues.

Erythritol is a natural sugar alcohol found in many vegetables and fruit. Even the human body produces small amounts of erythritol.

But higher levels of the sweetener added to processed foods might increase people's risk of blood clots, researchers reported Feb. 27 in the journal Nature Medicine.

People who had large amounts of erythritol in their blood were up to twice as likely to suffer a heart attack or stroke compared to those with the least amounts, the researchers found.

"I think there's plenty of data here to argue that we should be reading our labels and avoiding erythritol, particularly if you're at risk for cardiovascular disease,"said senior researcher Dr. Stanley Hazen, chair of cardiovascular and metabolic sciences at the Cleveland Clinic's Lerner Research Institute.

But other experts expressed skepticism, saying more study is required before erythritol can be considered potentially harmful.

"At this point, I think that using small amounts of this, whether it should be in some power bar that you eat or you use a granulated form to put it in your coffee or tea or to have occasionally on your oatmeal, I just don't think it's a worrisome thing at this point in time,"said Dr. Karen Aspry, chair of the American College of Cardiology's Nutrition and Lifestyle Workgroup. "But I do think more study is warranted."

The Calorie Control Council, a trade association, noted that erythritol has been commercially produced for more than 30 years and is used as an industrial sweetener in more than 50 countries.

"The safety of erythritol as a food ingredient under conditions of its intended use is substantiated by a number of human and animal safety studies, including short- and long-term feeding, multi-generation reproduction and teratology [congenital abnormalities] studies,"the Calorie Control Council said in a statement.

Erythritol is about 70% as sweet as sugar and is produced commercially by fermenting corn. It's found in many keto foods and zero-sugar foods, Hazen said, and is an ingredient in Splenda Naturals Stevia sweetener and Truvia. Heartland Food Products Group, which makes the Splenda product, did not reply to a request for comment on the study.

"It's literally one of the fastest growing artificial sweeteners in processed foods,"Hazen said. "We make it ourselves in our body, but at an amount that is a thousand to a million-fold less than what it is when we ingest it in an artificially sweetened product that has it."

Sweetener tied to clot risk

For this study, Hazen and his team first evaluated 1,157 patients undergoing heart health assessments, and found that blood levels of erythritol were associated with a person's three-year risk of suffering a heart attack or stroke.

"We were not looking to study artificial sweeteners at all. We were looking to find chemicals in the blood in patients that identify who was at risk for a future heart attack, stroke or dying in the next three years,"Hazen said. "And then this compound in the blood that predicted the future development of a heart attack, stroke or death ended up being erythritol."

The investigators followed that up with another study of 2,149 Americans and 833 Europeans, which found that Americans with the highest circulating levels of erythritol were 80% more likely to have a heart attack or stroke, while Europeans with heavy erythritol levels were 2.2 times more likely.

The research team then went to the lab to see why erythritol might have this effect.

They found in lab tests that erythritol appears to make platelets more hyper-responsive, Hazen said.

"It's like giving a stimulus to cause the platelets to clot,"Hazen said. "Instead of only producing 10% of the effect, you get the whole 100% of the effect."

The lab tests and subsequent animal studies also showed a dose-dependent effect, Hazen added.

"As you go even higher in erythritol levels, the risk for clotting increases even more, so there's reason to be concerned about ingesting high amounts of this stuff,"Hazen said.

Hazen and his team also conducted a small-scale study in eight healthy volunteers, who were asked to consume 30 grams of erythritol dissolved in water. The researchers found that enough erythritol remained in the participants' blood to potentially increase clotting risk for two to three days.

"I think any exposure actually is worrisome,"Hazen said. "We chose 30 grams because it was at the upper end of what is actually reported that some people are ingesting. If you look at some keto foods, 30 grams is within one portion size."

However, other experts and the Calorie Control Council noted that this sort of study cannot establish a cause-and-effect link between erythritol and risk of heart attack or stroke.

Other dietary risk factors may play a part

The Calorie Control Council noted that the researchers did not evaluate the patients' overall diets, so their study couldn't assess other dietary risk factors. The study also didn't distinguish between a person's natural erythritol levels and the levels that occurred as a result of what they ate.

Experts also noted the potential for "reverse causation"-- in other words, people with heart problems might be more interested in eating foods with erythritol to lose weight, and that could cause the additive to look harmful even if it isn't.

"For the most part, the populations that they were studying were patients with high risk of cardiovascular disease, and we know that often when people have a particular disease state, they may make dietary changes,"said Maya Vadiveloo. She is an associate professor of nutrition and food sciences at the University of Rhode Island and a member of the American Heart Association's nutrition committee.

"And so in some ways this may reflect those dietary changes among people with high cardiovascular disease risk," Vadiveloo added.

Aspry agreed, and also questioned whether erythritol really remains in a person's bloodstream as long as the researchers found in their small follow-up study.

"Other studies showed that most of this compound is excreted in the urine -- 90% of a 20-gram dose is recovered in the urine within 24 hours,"said Aspry, director of the Lipid and Prevention Program at the Brown University Lifespan Cardiovascular Institute, in Providence, R.I. "So I think the point that this stays around for a long time was a little bit discordant with this other finding."

Vadiveloo also noted that erythritol is used in processed foods, which typically contain many other ingredients that aren't heart-healthy.

"Just because something is low in sugar doesn't necessarily mean that it should be consumed at any level. We already encourage people to limit their intake of highly processed foods,"she noted.

"In this country, in the mid-20th century, processed foods flooded the market, and we've never really kind of gotten away from it,"Aspry said. "And I think that's hopefully going to shift in the next 20 years when people start to realize that you need to be actually going back to basics. And I think the food industry is going to try to move in that direction,"she added.

"But for now, would I be afraid to use small amounts of this sweetener? Absolutely not,"Aspry said.

More information

The Mayo Clinic has more on artificial sweeteners.

SOURCES: Stanley Hazen, MD, PhD, chair, cardiovascular and metabolic sciences, Cleveland Clinic's Lerner Research Institute, Ohio; Karen Aspry, MD, director, lipid and prevention program, Brown University's Lifespan Cardiovascular Institute, Providence, R.I.; Maya Vadiveloo, PhD, RD, associate professor, nutrition and food sciences, University of Rhode Island, Kingston, R.I.; Calorie Control Council, statement; Nature Medicine, Feb. 27, 2023