Erythritol is a 4-carbon sugar alcohol (a polyol) that is commonly used as a sugar substitute. It exists naturally in low amounts in fruits and vegetables(1). The daily intake of erythritol in the U.S. population is estimated to reach up to 30g per day(2).
After consumption, erythritol is poorly metabolized and mostly excreted in the urine.
Therefore, erythritol is characterized as both a ‘zero-calorie’ or ‘non-nutritive’ sweetener and a ‘natural’ sweetener, leading to its rapid rise in popularity and predicted doubling in market share within the sweetener sector in the next 5 years(3).
A recent headline “Zero-calorie sweetener linked to heart attack and stroke, study finds” of a CNN article that was published made quite a stir in the media and amongst scientist and doctors(4).
The articles first paragraph below set the stage and caused many people to make conclusions without understanding the full extent and limitations of this study.
“A sugar replacement called erythritol – used to add bulk or sweeten stevia, monkfruit and keto reduced-sugar products – has been linked to blood clotting, stroke, heart attack and death, according to a new study.”
There was a very important caveat and response from the Calorie Control Council’s executive director in the article that stated “the results of this study are contrary to decades of scientific research showing reduced-calorie sweeteners like erythritol are safe, as evidenced by global regulatory permissions for their use in foods and beverages,”
He also stated that results: “should not be extrapolated to the general population, as the participants in the intervention were already at increased risk for cardiovascular events.”
The above-mentioned CNN article was written based on a recent peer-reviewed article published in Nature Medicine(5).
These researchers quantitatively examined the relationship between plasma levels of erythritol and incident death, myocardial infarction and stroke in distinct US and European validation cohorts.
Initially, this research utilized an untargeted metabolomics approach as a discovery platform to identify circulating metabolites associated with incident coronary vascular disease event risk. The qualitive results suggested that multiple polyols in general, and erythritol specifically, are associated, not causative with incident coronary vascular disease risks.
Across both US and European validation cohorts, it was confirmed that circulating levels of erythritol were associated with incident adverse cardiovascular event risk independent of traditional coronary vascular disease risk factors(5).
Patients in the observational cohorts show a high prevalence of coronary vascular disease and traditional risk factors, therefore the translatability of these findings to the general population needs to be determined.
These people were very sick and high-risk individuals as described in the paper(5):
There is an opportunity for reverse causality in this situation. There is a possibility that people with these disease profiles produce more erythritol as part of metabolic dysfunction. In fact, it’s been show in people with obesity, type 2 disease, and cardiovascular disease the pentose phosphate pathway is more activated and produces more substrate(6).
Clinical observational studies, by design, can only show association or correlation and not causation.
Vascular disease and thrombosis are multifactorial phenotypes. Thus, the association of circulating erythritol levels with incident coronary vascular disease event risks and enhanced thrombosis formation in preclinical models may consequently involve factors beyond platelet responsiveness.
It is important to note that this study did not assess dietary erythritol intake in these participants. They looked at erythritol as a metabolite in the blood. At no point did they look at their dietary intake of erythritol.
Research also suggest high blood sugar levels and oxidative stress can raise erythritol levels(7).
I think the claims made in this paper are drastically overblown based on what was done in the paper. The cohort of participants in this study have high levels of erythritol because they are very sick and therefore, endogenously produce more erythritol as evidenced by the more activated pentose phosphate pathway.
The study design was appropriate to answer the question “Does erythritol in the blood correlate with cardiac events and mortality” but it was not appropriate to make the claim that erythritol consumption somehow leads to heart disease and death.
We cannot rule out that erythritol may potentially have an effect but this study does not provide conclusive evidence that consuming dietary erythritol leads to heart attack and stroke.
References:
1. Mitchell, H., Sweeteners and Sugar Alternatives in Food Technology. 2006: Blackwell Publishing.
2. Administration., F.a.D., GRAS notice (GRN) No. 789. 2018.
3. Reports, R., Global erythritol market research report 2020. . 2020.
4. Sandee LaMotte, C. Zero-calorie sweetener linked to heart attack and stroke, study finds. 2023.
5. Witkowski, M., et al., The artificial sweetener erythritol and cardiovascular event risk. Nat Med, 2023.
6. Gupte, S.A., Targeting the Pentose Phosphate Pathway in Syndrome X-related Cardiovascular Complications. Drug Dev Res, 2010. 71(3): p. 161-167.
7. Peiro, C., et al., Erratum to: Inflammation, glucose, and vascular cell damage: the role of the pentose phosphate pathway. Cardiovasc Diabetol, 2017. 16(1): p. 25.
