ISSN 1662-4009 (online)

ESPE Yearbook of Paediatric Endocrinology (2023) 20 12.13 | DOI: 10.1530/ey.20.12.13

Nat Med. 2023 Mar;29(3):710–718. https://doi.org/10.1038/s41591-023-02223-9


Brief summary: This observational study in three different cohorts found an increased risk for atherothrombotic disease associated with the commonly used sugar substitute erythritol. Untargeted metabolomics (in cohort 1, n=1157) and targeted metabolomics (in cohorts 2 and 3, n=2149 USA and n=833 Europe, respectively) investigations revealed an increased risk for major adverse cardiovascular events (MACE) including death, myocardial infarction and stroke in persons with circulating levels of multiple polyol sweeteners such as erythritol. At physiological levels, erythritol enhanced human platelet reactivity in vitroin a dose-dependent manner; and increased thrombosis formation in a mouse model.

Erythritol is a 4-carbon sugar alcohol which is present in fruits and vegetables in very low amounts. Its sweetness intensity is low and therefore it is often used in high doses as a ‘natural sweetener’. Erythritol is commonly used as an artificial sugar either alone or in combination with other sugar substitutes in many food items. People in USA consume on average about 30 g per day erythritol, which corresponds to the amount of one can of an artificially sweetened drink. Erythritol is not metabolized and is excreted in the urine. The current study shows that after consuming a ‘usual’ amount of erythritol, plasma levels remain elevated for up to 2 days, and these levels were associated with significantly increased risk of thrombosis.

First sugar and now sugar alternatives seem to be a threat to our health. Sugar alternatives have long been recommended to reduce sugar and calorie intake to oppose the obesity epidemic. Especially people at risk for obesity-related metabolic or cardiovascular disorders (e.g. people with diabetes) are still advised to switch to such sugar substitutes. So far, these compounds are generally considered safe by regulatory agencies, but their widespread use shows already traces in our environment (in soil and tap water). Long-term adverse consequences are largely unknown and have not been expected. Only recently studies revealed adverse associations of erythritol (and other sugar replacement compounds) with longer term health related outcomes, such as obesity and diabetes. Studies such as this one by Witkowski et al. are therefore extremely important to inform us on the (new) artificial compounds that we introduce into our food chain with the best intentions, but then turn out quite the contrary.

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