Research has linked a commonly used product, erythritol, with greater risk of cardiovascular problems.
Currently, there are no long-term clinical trials examining the safety of most sweeteners, although some studies have suggested that several of them may be linked to weight gain, cardiovascular disease and type 2 diabetes.
Erythritol is commonly used, and although naturally present in small amounts in fruits and vegetables, it is often added to processed foods in 1 000 times higher quantities, reports Medical News Today.
And although some studies show it may have antioxidant effects in animal models of diabetes, others show it may be linked to increased weight gain in college students, and to the onset of type 2 diabetes.
Further study of the effects of erythritol on cardiometabolic risk could inform healthful dietary practices, said a research team who found that erythritol consumption increases cardiovascular risk, including risk of a heart attack or stroke, thrombosis (blood clotting), and death related to a cardiovascular event.
They first analysed blood samples from 1 157 participants, and found multiple compounds linked to cardiovascular risk. However, erythritol had some of the strongest links to the risk of cardiovascular events.
Next, they analysed blood samples from 2 149 participants from the US and from 833 European participants. Plasma levels of erythritol were higher among participants with cardiovascular disease.
They also found that participants in the US and European cohorts with the highest 25 percentile erythritol blood levels were 2.5 and 4.5 times more likely to have a cardiovascular event than those in the lowest 25 percentile.
Each micromole increase in erythritol levels was linked to a 21% and 16% increase in cardiovascular event risk in US and European cohorts, respectively.
Next, the researchers set out to see how erythritol impacted blood clotting. Through multiple tests, they found that increased erythritol levels indicated higher rates of clot formation and increased thrombosis potential.
Last, they examined the effects of consuming a snack or drink containing 30g of erythritol in eight participants.
While erythritol levels were low at baseline, they remained 1 000-fold higher for hours after ingestion.
“It is important that further safety studies are conducted to examine the long-term effects of artificial sweeteners in general, and erythritol specifically, on risks for heart attack and stroke, particularly in people at higher risk for cardiovascular disease,” said senior author Dr Stanley Hazen, chairman of the Department of Cardiovascular and Metabolic Sciences in Lerner Research Institute and co-section head of Preventive Cardiology at Cleveland Clinic.
Dr John Alan Galat, a cardiac surgeon with Novant Health in Charlotte, not involved in the study, said: “This makes a convincing argument that one of the more common sugar substitutes – erythritol – may very well increase the risk for heart attack and stroke.(The authors nevertheless) concede that much more investigation needs to be done. The important question is whether the benefits of reduced sugar and caloric intake outweigh the risk of consuming products with these sugar substitutes.”
Cardiovascular risk
Dr Rigved Tadwalkar, a board-certified cardiologist at Providence Saint John’s Health Centre in Santa Monica, who was not involved in the study, said erythritol facilitates mechanisms needed for platelet aggregation and thrombosis, which are both key for developing heart attack or stroke.
“As cardiovascular disease is a process that is more complex than platelet aggregation alone, it is possible that erythritol causes other pathophysiologic changes on the molecular level to increase the risk for a cardiovascular event. Complicating matters, it appears that consuming erythritol-sweetened foods increases plasma erythritol levels for days, potentially prolonging cardiovascular effects.”
He further cautioned that although “(a)djustments were made in this study for traditional risk factors that are known to be implicated in cardiovascular disease, including age, smoking status, blood pressure, and cholesterol levels (…) it is possible that unmeasured confounders may be present, such as diet, which could have affected the results.”
Dr Yu-Ming Ni, a cardiologist of non-invasive cardiology at MemorialCare Heart and Vascular Institute at Orange Coast Medical Centre in Fountain Valley, not involved in the study, said “(w)e cannot say for certain that erythritol is the cause for increased heart disease unless this finding can be replicated in larger studies.”
“Until then, it is unclear whether it is necessary to stop all consumption of artificial sweeteners,” said Ni.
“I often advise my patients to eat food as naturally as possible, as that reduces (the) risk of exposure to potentially harmful chemicals like artificial sweeteners, and to consider sugar substitutes if it serves as a means to help overweight people with weight loss, since overall weight loss has clearer evidence for health improvements.”
Study details
The artificial sweetener erythritol and cardiovascular event risk
Marco Witkowski, Ina Nemet, Hassan Alamri, Jennifer Wilcox, Nilaksh Gupta, Nisreen Nimer, Arash Haghikia, Xinmin S. Li, Yuping Wu, Prasenjit Prasad Saha, Ilja Demuth, Maximilian König, Elisabeth Steinhagen-Thiessen, Tomas Cajka, Oliver Fiehn, Ulf Landmesser, W. H. Wilson Tang & Stanley L. Hazen
Published in Nature Medicine on 27 February 2023
Abstract
Artificial sweeteners are widely used sugar substitutes, but little is known about their long-term effects on cardiometabolic disease risks. Here we examined the commonly used sugar substitute erythritol and atherothrombotic disease risk.
In initial untargeted metabolomics studies in patients undergoing cardiac risk assessment (n = 1,157; discovery cohort, NCT00590200), circulating levels of multiple polyol sweeteners, especially erythritol, were associated with incident (3 year) risk for major adverse cardiovascular events (MACE; includes death or nonfatal myocardial infarction or stroke).
Subsequent targeted metabolomics analyses in independent US (n = 2,149, NCT00590200) and European (n = 833, DRKS00020915) validation cohorts of stable patients undergoing elective cardiac evaluation confirmed this association (fourth versus first quartile adjusted hazard ratio (95% confidence interval), 1.80 (1.18–2.77) and 2.21 (1.20–4.07), respectively).
At physiological levels, erythritol enhanced platelet reactivity in vitro and thrombosis formation in vivo.
Finally, in a prospective pilot intervention study (NCT04731363), erythritol ingestion in healthy volunteers (n = 8) induced marked and sustained (>2 d) increases in plasma erythritol levels well above thresholds associated with heightened platelet reactivity and thrombosis potential in in vitro and in vivo studies.
Our findings reveal that erythritol is both associated with incident MACE risk and fosters enhanced thrombosis. Studies assessing the long-term safety of erythritol are warranted.
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