Give and Take: Artificial Sweeteners and Cardiometabolic Health

Researchers from Cleveland Clinic looking for new links to cardiovascular disease found that high levels of erythritol in the blood contributed to a higher risk of stroke and heart attack. Could they have inadvertently uncovered a new pathway to heart disease?

Sugar Substitutes: More Flavor Less Guilt?

It is no surprise that demand for and consumption of artificial sweeteners have increased in the last few decades, as the cardiometabolic dangers of sugar consumption are expounded. Studies show that a diet high in sugar is associated with the development of cardiorenal metabolic diseases such as obesity, type 2 diabetes, and cardiovascular disease.

The Coronary Artery Risk Development in Young Adults (CARDIA) study demonstrated that the consumption of sugar-sweetened beverages was associated with several cardiometabolic outcomes – high waist circumference, high levels of low-density lipoprotein cholesterol, high triglycerides, and hypertension. The American Heart Association (AHA) endorses lowering sugar intake, recommending no more than six teaspoons of sugar per day for women, and no more than nine teaspoons of sugar per day for men.

Health agencies seem to agree with swapping out sugar for substitutes; there are six low-calorie sweeteners approved for use as food additives in the U.S. and Europe. But, is all the flavor of sugar with a fraction of the calories too good to be true?

Findings on the Effects of Erythritol

A study published in Nature Medicine draws attention to the effects erythritol, a sugar alcohol containing only about 6% of the calories found in an equal amount of sugar. Erythritol is created when a type of yeast ferments glucose from corn or wheat starch. It was approved as a food additive by the U.S. Food and Drug Administration in 2001. One benefit of erythritol, other than being low-calorie, is that it’s not metabolized by oral bacteria and therefore doesn’t contribute to tooth decay, unlike sugar.

Citing data that suggest a connection between the sweetener and adverse cardiovascular events that include abnormal clotting, stroke, and heart attack. Of the 4,000 people included in the study’s dataset, those who had high levels of erythritol in their blood were more likely to suffer a major cardiac event within three years than those with lower levels.

But, lead author and Cardiometabolic Health Congress faculty member Stanley L. Hazen, MD, PhD, said that his team didn’t set out to study erythritol.

“Our original intent was to see if we could find compounds in blood whose levels predict the future development of heart attack, stroke or death." When looking at the data, the very top-ranking compound … was erythritol.”

Stanley L. Hazen, MD, PhD

Senior author, Dr. Hazen, is chairman of the Department of Cardiovascular & Metabolic Sciences in Lerner Research Institute and co-section head of Preventive Cardiology at Cleveland Clinic. He is also a past Cardiometabolic Health Congress keynote speaker who lectured on gut microbes as a therapeutic target in cardiometabolic diseases at the 12th Annual Cardiometabolic Health Congress in Boston in 2017.

Study Details

Hazen and colleagues used mass spectrometry to study 1,157 patients undergoing cardiac risk assessment. Based on three years of outcome data, they found that circulating levels of multiple polyol sweeteners — particularly erythritol — were connected with elevated risk of adverse cardiovascular events.

They noted that “when participants consumed an artificially sweetened beverage with an amount of erythritol found in many processed foods, markedly elevated levels in the blood are observed for days – levels well above those observed to enhance clotting risks.”

These observations were confirmed by independent studies in the U.S. (n = 2,149) and Europe (n = 833).

"[These findings are] of concern given that the very subjects for whom artificial sweeteners are marketed (patients with diabetes, obesity, history of CVD and impaired kidney function) are those typically at higher risk for future CVD events.”

Further Investigation

To follow up on the initial observational findings, Dr. Hazen and colleagues then exposed blood, platelets and plasma samples directly to erythritol in the lab setting, which showed the same clotting risk. The amount of erythritol was “completely within the range of what we’re seeing in the [blood] circulation of patients, and the effect is quite rapid. Just being in the presence of erythritol for minutes was all that was necessary to change platelet function and make them more prone to clot,” said Dr. Hazen.

Also notable was that the confirmed results were seen in healthy volunteers with no known cardiovascular disease. Raising erythritol levels in the blood “was more than sufficient to induce a prothrombotic state and enhance clot formation even in the platelets from healthy volunteers,” Dr. Hazen said.

Conclusion and Reccomendations

The present study contributes to existing differences in opinion regarding the use of artificial sweeteners among both clinicians and patients in the cardiometabolic health realm. Joanne Slavin, Ph.D., RD, a professor of food science and nutrition at the University of Minnesota noted that the people who consume high amounts of artificial sweeteners may already be at risk for cardiovascular issues. If they have conditions like diabetes or obesity, they may be using artificial sweeteners to try to cut back on sugar, she said. Dr. Priya M. Freaney, a cardiologist at Northwestern University, suggests that those with heart disease and already at risk for heart attacks or strokes may want to avoid large amounts of artificial sweeteners.

One thing experts do seem to agree on is that the results of the study underline the need for more research, and that individuals and their providers must approach their nutrition and lifestyle needs together. The authors of the study recommend talking to your doctor or a certified dietician to learn more about healthy food choices and for personalized recommendations.

The study's authors noted 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.”

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