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People who consume higher-than-normal quantities of erythritol, a popular sugar substitute sold under a variety of brand names, are at greater risk of having a heart attack or stroke, according to a study in Nature Medicine.

The risk of heart disease can last for years after consuming erythritol. This is concerning because “the very people who are being targeted for foods that contain erythritol” — those with diabetes, obesity, or a history of cardiovascular diseases — “are the same people who already are at increased risk for cardiovascular events,” according to one of the study’s authors.

Stanley Hazen, M.D., Ph.D., a cardiologist at the Cleveland Clinic, led the study, which consisted of four experiments.

The first two experiments considered associations between erythritol blood levels and cardiovascular events. The third experiment found erythritol caused blood platelets to become stickier. And the fourth found ingesting erythritol raised blood levels to concerning levels for over two days.

Breaking down the study

Among 1,157 patients undergoing heart-health exams, those whose blood contained non-sugar sweeteners and their breakdown products were more likely to have a heart attack or stroke during a three-year follow-up period.

Researchers identified several artificial sweeteners in the patients’ blood, but erythritol seemed to have the strongest connection with heart attack and death.

Because the sweeteners are related chemically and several were present, researchers initially could not be sure that erythritol was to blame.

They began a second investigation among 2,149 U.S. and 833 European subjects undergoing heart tests. This time, they analyzed blood in a way that allowed them to detect only erythritol and its effects.

After categorizing subjects into four groups of increasing blood erythritol levels, those in the highest-level group were more than three times as likely to have a heart attack or stroke during the following three years.

In both the U.S. and European study groups, the highest erythritol blood levels were found in patients with the most serious heart conditions and those who went on to suffer a serious cardiac event during the study.

The risk for heart attack or stroke in the highest-level group, compared with the lowest-level group, increased by 164% for the U.S. subjects and 348% for the European subjects.

Results did not change when investigators factored in sex or existing cardiovascular risk factors like obesity or smoking.

This led Hazen to conclude that erythritol was “independently associated” with death, heart attack and stroke — meaning that consuming it is risky regardless of a person’s health status or risk factors.

In a third experiment, researchers found that adding erythritol to blood samples made platelets stickier, which could lead to increased clotting and higher heart attack and stroke risk.

Finally, investigators were interested in seeing if erythritol reached unhealthy blood levels after ingestion of a drink containing 30 grams of the sweetener — a dose typically found in one diet drink or serving of diet ice cream.

Baseline levels started low, increased a thousandfold just 30 minutes after consuming the drink, and remained elevated for more than two days. Levels surpassed thresholds established earlier in this study linked to platelet changes and a higher risk of heart problems.

The dangers of sugar alcohols

People use sugar substitutes to replace natural sweeteners like sucrose (table sugar) or fructose (the main sugar in fruit) in order to reduce or eliminate calories in drinks, snacks and other foods.

Many sugar replacements, like aspartame, saccharin and sucralose, are not found in nature but are produced in chemical plants.

Stevia is sometimes grouped with artificial sweeteners but is a natural (albeit processed) product chemically related to table sugar.

Erythritol, another natural sweetener commonly found in commercial baked goods, drinks, candies, snacks and sweetener packets, belongs to the “sugar alcohol” family, which includes mannitol, sorbitol, xylitol, lactitol, isomalt and maltitol.

Sugar alcohols have long been considered safer than artificial sweeteners but recent data, including the Hazen study, suggest otherwise.

Erythritol occurs naturally but sparingly in melons, pears, grapes and in fermented foods like cheese and soy sauce. Red blood cells also naturally make very low levels of erythritol.

Erythritol is most often manufactured from corn sugar (dextrose), typically derived from genetically modified organism (GMO) cornstarch, but can also be made from wheat, maize or potatoes.

Because it is not metabolized and contains less than 6% of sugar’s calories, erythritol’s caloric contribution to foods is minimal despite being only 70% as sweet as sugar. And since it does not feed bacteria as well as sugar, erythritol does not promote dental cavities.

Some Americans consume 30 grams (a bit more than an ounce) of erythritol per day, which is a thousand times greater than what they would consume through natural foods plus the body’s own production.

U.S. and European Union regulators designate sugar substitutes as generally safe and recommend them for individuals with metabolic diseases like Type 2 diabetes and obesity.

However studies increasingly link artificial sweeteners to the very diseases sugar substitutes are meant to improve, such as weight gain, insulin resistance, Type 2 diabetes, heart disease and all-cause mortality.

Long-term safety studies on sugar substitutes, even for older sweeteners like sucralose and aspartame, are lacking.

Study strengths and weaknesses

This was a prospective, observational study, meaning investigators first observed the hypothetical cause (erythritol consumption) and looked for effects (heart attack and stroke) occurring afterward.

Establishing a potential causal relationship was therefore easier than retrospective studies, which look first at an effect and then at some exposure or event in the past that might have been the cause.

Yet on this note, Hazen was cautious: “By design, these studies can only show association and not causation.”

As the authors noted, their investigation tested subjects’ erythritol levels just once, but measuring levels at several time points may have provided better predictive value. As all subjects were undergoing testing for heart issues, the study subjects were already sicker on average than people in the general population.