Low/no calorie sweeteners do not increase the risk of cardiovascular diseases

ISA statement in response to new study by Debras, Chazelas et al.

Brussels, 8th September 2022:  The International Sweeteners Association (ISA) responds to the new study by Debras, Chazelas et al.1 on low/no calorie sweeteners and cardiovascular diseases highlighting that, contrary to claims made in this study, there is no causal evidence that low/no calorie sweeteners could increase the risk of cardiovascular diseases (CVDs).

Indeed, whilst the Debras, Chazelas et al study claim to show an association between low/no calorie sweeteners intake and CVD risk, there is no evidence of a plausible mechanism to support potential effects of low/no calorie sweeteners on cardiometabolic health.2 The safety of all approved low/no calorie sweeteners has been confirmed by food safety bodies worldwide including the Joint Expert Committee on Food Additives of the United Nations Food and Agriculture Organization (FAO) and of the World Health Organization (WHO)3, the European Food Safety Authority (EFSA)4, and the US Food and Drug Administration (FDA).5

Actually, the intake of low/no calorie sweeteners in the NutriNet-Santé cohort was extremely low, even for higher consumers (defined in the study as participants with sweetener intake above the sex specific median among consumers). Importantly, experts have questioned the ability to detect an association between low/no calorie sweeteners at such low levels of intake and any health outcome and stressed that, in such circumstances, confounding factors become more influential.6 By design, observational studies cannot establish a cause-and-effect relationship due to their observational nature and the inability to exclude residual confounding or, importantly, attenuate the effects of reverse causality.7

Contrary to the study by Debras, Chazelas et al, a systematic review and meta-analysis of prospective cohort studies including change and substitutions analyses that mitigate the influence of reverse causality providing more consistent and robust associations found that low/no calorie sweetened beverages are associated with lower risk of coronary heart disease and CVD mortality in the intended substitution for sugar-sweetened beverages.8 These findings are in line with evidence from randomised controlled trials which confirm no adverse effect of low/no calorie sweeteners on cardiometabolic risk factors including blood pressure, lipid levels, blood glucose and body weight, and in fact some benefits when used to replace sugars in the diet.9,10

At a time when non-communicable diseases including diabetes and dental diseases remain major global health challenges, and in light of current public health recommendations to reduce overall sugar intake, low/no calorie sweeteners can be helpful in creating healthier food environments. They provide people with a wide choice of sweet-tasting options with low or no calories, and thus can be a useful tool, when used in place of sugar and as part of a balanced diet, in helping reduce overall sugar and calorie intake, as well as in managing blood glucose levels.11 Low/no calorie sweeteners are also not fermentable by oral bacteria, which means that they do not contribute to tooth demineralisation, which is one of the reasons for tooth decay.12

  1. Debras C, Chazelas E, Sellem L, et al. Artificial sweeteners and risk of cardiovascular diseases: results from the prospective NutriNet-Santé cohort. BMJ 2022;378:e071204.
  2. Pyrogianni V, 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 Jun;50(6):e169
  3. http://www.fao.org/food/food-safety-quality/scientific-advice/jecfa/en/
  4. http://www.efsa.europa.eu/en/topics/topic/sweeteners
  5. https://www.fda.gov/food/food-additives-petitions/high-intensity-sweeteners
  6. Magnuson B. Comments in response to the article by Debras et al “Artificial sweeteners and cancer risk: Results from the NutriNet-Santé population-based cohort study”. Available at: https://journals.plos.org/plosmedicine/article/comment?id=10.1371/annotation/edab6e54-e06a-4e33-ba10-f1a96bc43152
  7. La Vecchia C. Comments in response to the article by Debras et al “Artificial sweeteners and cancer risk: Results from the NutriNet-Santé population-based cohort study”. Available at: https://journals.plos.org/plosmedicine/article/comment?id=10.1371/annotation/e28d577e-cd1c-42eb-85aa-7ea0cf0d5ccd
  8. Lee JJ, Khan TA, McGlynn et al. Relation of Change or Substitution of Low- and No-Calorie Sweetened Beverages With Cardiometabolic Outcomes: A Systematic Review and Meta-analysis of Prospective Cohort Studies. Diabetes Care. 2022 Aug 1;45(8):1917-1930
  9. McGlynn ND, Khan TA, Wang L, et al. Association of Low- and No-Calorie Sweetened Beverages as a Replacement for Sugar-Sweetened Beverages With Body Weight and Cardiometabolic Risk: A Systematic Review and Meta-analysis. JAMA Network Open 2022 Mar 1;5(3):e222092
  10. Rios-Leyvraz M, Montez J (World Health Organization)‎. Health effects of the use of non-sugar sweeteners: a systematic review and meta-analysis. World Health Organization (WHO) 2022. https://apps.who.int/iris/handle/10665/353064. License: CC BY-NC-SA 3.0 IGO
  11. Diabetes UK. The use of low or no calorie sweeteners. Position Statement (Updated December 2018). Available at: https://www.diabetes.org.uk/professionals/position-statements-reports/food-nutrition-lifestyle/use-of-low-or-no-calorie-sweetners
  12. EFSA Scientific opinion on the substantiation of health claims related to intense sweeteners. EFSA 2011 Journal 9(6): 2229, and 9(4): 2076