'Go natural': Common zero-calorie artificial sweetener increases risk for cardiac events

A popular artificial sweetener, erythritol, was linked to worsened risks for heart attack and stroke, according to new research published in Nature Medicine.

Stanley L. Hazen, MD, PhD, chairman for the department of cardiovascular and metabolic sciences in Lerner Research Institute and co-section head of preventive cardiology at the Cleveland Clinic, told Healio that erythritol is a molecule that bodies naturally produce, “but also more recently, in the last decade, it has become one of those used in artificial foods and also zero-sugar foods.”

Hazen and his colleagues originally sought to identify what new pathways may be linked to heart disease because of residual cardiovascular risk. They were not looking to study artificial sweeteners and “have no skin in this game,” he said.

But when they found that erythritol was the top new pathway linked to heart disease, it set off some alarms and they looked deeper.

“We know if we treat cholesterol, diabetes, obesity, blood pressure and all of the traditional risk factors, the majority of events still continue to happen. We still have at least 50% of the heart attacks and strokes happening,” he said. “In this unbiased approach, this is what percolated up as being the top new pathway that we discovered.”

The unbiased approach was mass spectrometry, Hazen said. In initial untargeted metabolomics studies among patients undergoing cardiac risk assessment, the researchers found that circulating levels of multiple polyol sweeteners — particularly erythritol — were connected with incident risk for major adverse cardiovascular events (MACE).

These results were then replicated in a large cohort in the United States and again in a large European cohort. Compared with patients in the lowest quartile of erythritol levels, those in the highest quartile had adjusted HRs of 1.8 (95% CI, 1.18-2.77) in the U.S. cohort and 2.21 (95% CI, 1.2-4.07) in the European cohort.

The researchers additionally took blood from volunteers without CVD or diabetes to see how erythritol levels would impact other populations.

Hazen and colleagues ultimately found that, after erythritol consumption, “a prolonged period of potentially heightened thrombotic risk may occur,” which is concerning, they wrote, given that the people who are usually the targets of artificial sweetener marketing — those with obesity, diabetes or who have a history of CVD — are the same patients who are typically at risk for future CVD events.

“Trying to do some benefit by reducing our calories or reducing our sugar instead may inadvertently be causing some harm with regard to heart disease risk,” Hazen said.

He noted that high erythritol levels predicted an increased cardiovascular risk not only in those with CVD or diabetes, but also among those without.

“We also took whole blood from healthy volunteers with no known diabetes, no known cardiac disease, and showed that when we raised erythritol levels in the blood and added it to the platelets at levels that were seen in healthy volunteers who drank an artificially sweetened drink with erythritol that that was more than sufficient to induce a pro-thrombotic state and enhance clot formation even in the platelets from healthy volunteers,” he said.

Therefore, Hazen said, “the concern with erythritol is something that should be thought of not just in people at risk, but also people who are middle-aged and may or may not have cardiac disease or diabetes.”

“At the present time, I’m advising my patients to avoid erythritol,” Hazen said. “While it may be okay and potentially beneficial from a glucose or a weight-reduction standpoint ... it does not appear to be okay in terms of avoiding a long-term risk for heart attack or stroke. I think that the prudent thing, the cautionary thing, to advise people is to avoid erythritol at the present time and go natural.”

Hazen also said he recommends food shopping in the produce section rather than buying highly processed, artificial products.

“I realize people are trying to choose a healthy alternative, but we didn't know this a year ago,” he said. “Now that we do, I think that we should probably reassess how prudent it is to use it until further studies are done.”

Future studies, Hazen said, “really need to drill down on this pathway” between erythritol and risk for CVD.

“Someday, once we have a better understanding of how this is linked to enhanced CVD risk, it may be something we can intervene on and help reduce heart attack stroke and death risk in patients,” Hazen said. “That's our long-term goal.”

In the meantime, the researchers wrote that their findings “highlight the need to establish reporting requirements, safety profiles and margins of daily intake amounts given that broad consumption continues to increase” and that “public policy decisions need to be evidence-based and better informed.”