An article published in Nature Medicine on February 27th has drawn a lot of attention. I’m going to try to explain it simply, without taking a stance. Erythritol is a popular artificial sweetener that has become more widely used. Although our bodies produce small amounts of it, and it’s present in small amounts in fruits and vegetables, humans have learned to produce it in large amounts artificially. Erythritol has 70% the sweetness of sugar and doesn’t have a lingering aftertaste like some other sugar substitutes. It also has less of a laxative effect than other sugar alcohols. It’s a popular choice for weight loss and to improve glycemic control for those struggling with type 2 diabetes.
While artificial sweeteners are generally considered safe by the FDA and European Union, there has not been much research into their long-term health effects.
There have been short term animal toxicity studies of erythritol’s safety and reported human clinical studies with ingestion up to 4 weeks. Early animal diabetes model studies implied that erythritol has some benefits. These studies, along with the knowledge that the human body produces erythritol naturally on its own are the reason why erythritol was generally recognized as safe by regulatory agencies.
The authors of this article originally weren’t focused on erythritol. They were trying to find chemicals in blood that could predict a person’s risk for a major cardiovascular event, which includes stroke, heart attack, or death. Between 2004 and 2011, they analyzed blood samples from 1157 people at risk for heart disease. The researchers found that erythritol was among the molecules that were the highest major cardiovascular event risk predictors. To further investigate this association, the researchers took blood samples from 2149 people in the US and 833 people in Europe. Among the three sample groups, over half of the people were male and in their 60s and 70s. Three quarters had coronary disease or high blood pressure. A fifth had diabetes. This study suggests that, in people with EXISTING risk factors for heart disease, levels of erythritol circulating in blood are associated with 3-year risk for major cardiovascular events.
After adjustment for cardiovascular risk factors, the study found that being in the top 25% of erythritol blood levels vs in the bottom 25% was significantly associated with risk of major cardiovascular events in both the US and European groups, and this applied to both males and females. Factoring in coronary artery disease did not substantially change the association of erythritol levels with the incidence of major cardiovascular events.
The authors investigated a potential mechanism behind the association. They decided to look at erythritol’s impact on platelet function in humans, and in live mouse models of arterial injury. While blood clots are important to stop bleeding when you get injured, inappropriately formed blood clots can block blood flow, and they can break off and travel to the heart, where they can cause a heart attack. If they travel to the brain, they can cause a stroke.
While glucose did not have an effect on platelet aggregation, erythritol was found to enhance it in samples of platelet-rich plasma from healthy volunteers. Following exposure to dietary erythritol, the researchers found that it’s possible that a prolonged period of potentially heightened clotting risk may occur. The researchers also looked at how erythritol impacted clotting potential in live mice in a carotid artery injury model. Higher levels of circulating erythritol resulted in a higher rate of clot formation and a decrease in time till blood flow stopped following arterial injury.
Researchers looked at what the physiological range in circulating erythritol levels would be after dietary exposure. They examined erythritol plasma levels in 8 healthy participants after they consumed an erythritol-sweetened drink containing 30 grams. The researchers found that erythritol plasma levels were 1000-fold higher for hours after ingestion and stayed elevated for over 2 days in all participants. These concentrations were well above the thresholds of erythritol observed to cause significant increases in platelet function.
Before making any conclusions from this study, remember subjects of this study were people already at risk for major cardiovascular events. And researchers had ONLY established correlation, not causation! These results should not be extrapolated to the general population. We need further safety studies to examine the long-term effects of artificial sweeteners, and erythritol specifically, especially for patients at increased risk of cardiovascular disease.
We need to do more trials with appropriate follow-up duration and establish reporting requirements, safety profiles and margins of daily intake amount. Especially since artificial sweeteners are marketed towards the population already at a heightened risk for major cardiac events.