Washington: Artificial sweeteners, known as sugar alcohols, are common replacements for table sugar in low-calorie, low-carbohydrate, “zero sugar” and “keto” products but a recent study has found their use is associated with an increased chance of cardiovascular events.

Erythritol, one of the most popular sugar alcohols, is the subject of new findings released by Cleveland Clinic.

Elevated blood erythritol levels are associated with an increased chance of cardiovascular events, like heart attack or stroke, according to the study published in Nature Medicine.

The research, led by Stanley Hazen, MD, PhD, supports launching further investigation and clinical trials to determine the effects of polyols, a group of sugar alcohols including erythritol, on patients long term.

“Sweeteners like erythritol, because they appear naturally, had minimal requirements to pass through the regulatory process, but there needs to be more in-depth research into long term effects,” says Dr. Hazen, chairman for the Department of Cardiovascular & Metabolic Sciences, and co-section head of Preventive Cardiology. “Cardiovascular disease builds over time, and heart disease is the leading cause of death globally. We need to make sure the foods we eat aren’t hidden contributors.”

Erythritol associated with blood clots

Erythritol is about 70% as sweet as sugar and is produced through fermenting corn. The sweetener also has a similar flavor profile, “mouthfeel” and texture to table sugar – aspects that influenced rapid adoption in processed foods. Because humans don’t have the enzymes to breakdown sugar alcohols like erythritol, it isn’t metabolized by the body.

Instead, it goes into the bloodstream and leaves the body mainly through urine.

"Sugar-free" products containing erythritol are often recommended for people who have obesity, diabetes or metabolic syndrome and are looking for options to help manage their sugar or calorie intake. People with these conditions also are at higher risks for adverse cardiovascular events like heart attack and stroke.

Products containing erythritol are often recommended for people who have obesity, diabetes and metabolic syndrome and are looking for options to help manage their sugar or calorie intake.

People with these conditions also are at higher risks for adverse cardiovascular events like heart attack, stroke and death.

Dr. Hazen’s lab focuses on identifying environmental and genetic factors that contribute to residual cardiovascular disease risk, moving beyond traditional risk indicators like high blood pressure, diabetes or high cholesterol.

His team studies molecules in the blood that can predict who is at risk for experiencing cardiovascular events in the future.

This particular study investigated the association between higher circulating levels of erythritol in patients who experienced major adverse cardiac events (MACE), including non-fatal heart attack, stroke or death. The first author is Marco Witkowski, MD, a cardiologist and graduate student in Dr. Hazen’s lab.

After confirming an association between blood erythritol levels and incident MACE risks in studies of over 4,000 subjects in both the US and Europe, researchers examined the effects of adding erythritol to either whole blood or isolated platelets – cell fragments that clump together to stop bleeding and contribute to blood clots that cause stroke and heart attack.

Erythritol made platelets easier to activate and form a clot, with the study showing increased clot formation in models of arterial injury.

Setting the stage for future study

Measuring sugar alcohols is difficult and labeling requirements are minimal and often do not list individual compounds, Dr. Hazen says. He added, because erythritol is “Generally Recognized As Safe (GRAS)” by the FDA, that means there is no requirement for long-term safety studies.

One of the reasons to investigate erythritol’s cardiovascular effects is how much people consume. Because erythritol is less sweet than other artificial options, manufacturers tend to add much more of it. Erythritol is also at times added to other sweeteners and is referred to as a “bulking” sweetener because it adds weight and volume to foods similar to sugar.

Research on how many grams of artificial sweeteners people consume per day, and observing the results, can shape dietary recommendations. Our bodies create low amounts of erythritol naturally, so any additional consumption can stack up, Dr. Hazen says.

“Our studies show that when healthy volunteers consumed an artificially sweetened beverage with an amount of erythritol observed in many processed foods, markedly elevated levels in the blood are observed for days – levels well above those observed to enhance clotting risks,“ Dr. Hazen says. “The question is whether it's safe for some of us to be consuming this much erythritol – and for an extended period of time.”