No evidence that low calorie sweeteners could cause or increase the risk of cardiovascular disease

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ISA statement in response to the study by Mossavar-Rahmani et al.

Current evidence, including recent reviews commissioned by the World Health Organisation (WHO), indicates that there is no evidence that low calorie sweeteners could cause or increase the risk of cardiovascular disease1,2, contrary to what the study published in Stroke suggests3.

Indeed, the paper by Mossavar-Rahmani et al, based on data analysis from the Women’s Health Initiative, which is an observational study and not a clinical trial, does not examine any plausible mechanism to explain a link between low calorie sweetened beverage consumption and coronary heart disease or stroke. It is known that observational studies present certain limitations, including the possibility of reverse causality and of residual confounding factors that might affect the reported associations as well as self-misreporting of intake data. In this paper, low calorie beverage consumption was estimated based on a single, self-reported and not validated method of dietary intake assessment, measured at only one point of time. Therefore, as the authors acknowledge, it could be the case that consumption patterns may have changed over time before the health incidents occurred.

Additionally, women who reported higher consumption of low calorie beverages were more likely to be obese, past smokers, hypertensive, with poorer diet quality and higher overall energy intake, and thus more likely to have (undetected) diabetes, showing that there could be other unmeasured factors to confound the relationship between low calorie beverages and heart disease. “Indeed, there is a drastic fall in the hazard ratios (HRs) after allowance for covariates. This indicates that more precise and valid adjustment for confounding would likely imply further decrease of the association. In addition, there was no trend in risk with dose.”, added Dr. Carlo La Vecchia, Professor of Epidemiology at the University of Milan, Italy.

In a published letter to the Editor by Pyrogianni and La Vecchia4, the authors pointed to severe limitations of this study including selection bias, reverse causation and, mainly, residual confounding, which may partly or largely explain the reported associations. They also emphasised that the current evidence supports no plausible mechanism of how low calorie sweetened beverages could increase the risk of stroke, coronary heart disease, or other cardiovascular disease in humans. They further pointed to data from both observational studies and randomised controlled trials, which indicate that low calorie sweeteners do not negatively affect risk factors linked to cardiovascular disease, including blood pressure, blood lipids levels, glycemia, or body weight.

Finally, it is important to highlight that, before being approved for use on the market, low calorie sweeteners are thoroughly tested and regulatory bodies around the world have consistently confirmed their safety and the lack of any negative health effect.

  1. Lohner, S., Toews, I., & Meerpohl, J. J. (2017). Health outcomes of non-nutritive sweeteners: analysis of the research landscape. Nutr J 2017; 16(1): 55
  2. Toews I, Lohner S, Ku?llenberg de Gaudry D, Sommer H, Meerpohl JJ. Association between intake of non-sugar sweeteners and health outcomes: systematic review and meta-analyses of randomised and non-randomised controlled trials and observational studies. BMJ 2019;364:k4718
  3. Mossavar-Rahmani Y, Kamensky V, Manson JE, et al. Artificially Sweetened Beverages and Stroke, Coronary Heart Disease, and All-Cause Mortality in the Women’s Health Initiative. Stroke 2019;50:00-00. DOI:10.1161/STROKEAHA.118.023100
  4. Pyrogianni V and La Vecchia C. Letter by Pyrogianni and La Vecchia Regarding Article, “Artificially Sweetened Beverages and Stroke, Coronary Heart Disease, and All-Cause Mortality in the Women’s Health Initiative”. Stroke 2019; 50(6): e169