You are probably aware that individuals with PWS have a slightly elevated risk for thrombosis (blood clot formation), with 8.4% of respondents aged 30-61 years reporting a history of one or more in our 2018-2022 survey, compared to <1% in the non-PWS population. So you may have been concerned to hear the mainstream media reporting on a recent publication from the Cleveland Clinic associating the popular sweetener erythritol with thrombosis formation.
Many of us have used artificial sweeteners in efforts to reduce glucose and calorie intake for ourselves and our loved ones, and erythritol (a.k.a. stevia, truvia, monk fruit) has been skyrocketing in popularity due to its natural origins, poor metabolism, and resilience to loss of sweetness when exposed to heat (e.g. baking) like aspartame. Moreover, you may have seen earlier studies that suggested health benefits of erythritol, including antioxidant potential and improvement in endothelial function in diabetes models. These studies have not been invalidated. However, with any new chemical it can take time as well as innovation to recognize the effects of regular use. This underscores the importance of using artificial ingredients in moderation.
First, it’s important to note that the new Cleveland Clinic study does not conclude that erythritol causes major adverse cardiovascular events (death, myocardial infarction, and stroke), nor even that having used it increases one’s likelihood of experiencing such an event. It is very difficult to determine causation in longitudinal medical outcome data, and a brief review of the approach used will help to explain why.
The authors here did not set out to investigate health effects of erythritol – they had three-year-old blood samples and associated medical records from patients “undergoing cardiac catheterization or have had a heart catheterization within one year, coming in for outpatient appointments, or have scheduled cardiac CT scans or CT scans performed within one year of scheduled blood draw”, so they thought it could be useful to see if any metabolites were more common in the blood of those patients who ultimately experienced a cardiovascular event. Studies like this have been done before, but the technology to identify metabolites is ever-improving (indeed the authors actually developed a new technique to distinguish erythritol from threitol in this type of analysis), so it is a great idea to redo this sort of thing every few years. Yes, these patients all already had very high cardiovascular risks – about 75% already had high blood pressure and heart disease, and about 25% had diabetes – so there is nothing associating erythritol use with cardiovascular events in other (e.g. healthy) populations. Also, the blood samples were singular and from the beginning of the three-year monitoring period. The authors determined that elevated erythritol can be detected in blood for two days after consumption, so the blood tests analyzed only reveal if the patients consumed erythritol within those two days – it cannot be known if any patient continued using erythritol regularly for the following years.
Nevertheless, despite these caveats, those patients with the highest levels of erythritol did proceed to have three times more major adverse cardiovascular events in the following three years. It would be unwise to assume that those patients continued consuming erythritol regularly, but these results seem to justify monitoring the erythritol factor in future studies.
What might be the mechanism by which erythritol in blood increases risk of cardiovascular events? To determine if thrombosis was affected, the Cleveland Clinic researchers exposed blood, platelet-rich plasma, and isolated platelets to concentrations of erythritol equal to what was measured in the patient blood described above, along with compounds known to promote blood clotting. In all of these cases, erythritol made platelets more sensitive, i.e. less stimulation was required to make clotting happen. It’s important to note that erythritol didn’t directly cause clotting, but enhanced it in situations where clotting would have otherwise occurred. This was also validated in mice, where erythritol-fed mice bled less following injury. While that almost sounds good, it could heighten risks in individuals already prone to unwanted clot formation, i.e. PWS. For that reason, while additional studies proceed, it is likely wise to minimize intake of erythritol by the highest-risk individuals.
Note that erythritol may appear as ‘sugar alcohols’ on nutrition labels and may be present even in food products that claim ‘no artificial sweeteners’ on the label, since technically erythritol is a naturally occurring compound (but is present at much, much lower levels in natural foods). Keto friendly treats that you buy at the grocery store often include erythritol, so reading labels carefully is necessary to understand whether this sweetener is used. In keeping with current recommendations from PWS clinicians, FPWR continues to recommend a diet focused on variety, freshness, and balance. Please consider reviewing this presentation on Optimal Nutrition for People with PWS from Registered Dietitian Melanie Silverman.