Safety of low calorie sweeteners confirmed by global scientific and regulatory authorities

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ISA statement in response to new study by Mullee et al.

Brussels, 4th September 2019: Responding to the new study by Mullee et al. regarding the consumption of sugar- and low and no calorie-sweetened soft drinks,1 the International Sweeteners Association (ISA) points to the observational nature of this study, which, as also acknowledged by the authors, cannot prove any cause and effect relationship. Furthermore, in line with the overwhelming body of scientific evidence available, the safety of all approved low calorie sweeteners has been repeatedly and consistently confirmed by regulatory authorities around the world.2,3,4

At a time when obesity and non-communicable diseases including diabetes remain major global health challenges, and public health authorities are encouraging food manufacturers to replace sugar and reduce calories as part of their reformulation goals, it is critical that the public is provided with reliable science-based information regarding the safety and the utility of low calorie sweeteners, which is supported by food safety authorities and health organisations worldwide.

Regarding this new study by Mullee et al., it is crucial to highlight that observational studies, by their nature, do not and cannot prove cause and effect. Extreme caution must therefore be applied when considering results of this type of studies, as selection bias, residual confounding and reverse causation may affect the observed associations.5,6 Indeed, the authors of this study themselves recognise that: “Given the observational design of the study, it is not possible to establish causality between soft drink consumption and mortality, and we recognize that the observed associations may be biased because of residual confounding.” Furthermore, there is no evidence that low calorie sweetener consumption would increase the risk of circulatory diseases in humans. On the contrary, data from clinical studies show that low calorie sweeteners do not negatively affect known risk factors such as blood pressure, blood lipids levels, glycemia, or body weight.7,8

From a statistical analysis perspective, it is interesting to note also that baseline characteristics data from this study show that subjects drinking 2 or more diet drinks per day had higher BMI, were less educated and more frequently smokers. While those variables were adjusted for in the analysis, residual confounding is possible and likely, and this may well have implications, particularly for the association found for vascular disease. Frequently, consumers of 2 or more soft drinks per day had a number of poorer socioeconomic indicators and lifestyle habits, and this, partly or largely, accounts for the apparent associations.

It is also worth highlighting a series of further limitations of this study, which include the use of baseline data – where exposure assessment (measure of intake) was collected only once (between 1992 and 2000), and this has been associated to events up to 20 years later; and the fact that the use of intake data collected varied by country. Indeed, these limitations may produce inconsistent and biased associations between diet drinks and mortality or cardiometabolic outcomes.9 Actually, studies that have used repeated measures to assess changes in intakes of low calorie sweetened beverages have found no, or attenuated, link between their consumption and disease risk, following adjustment for adiposity.10,11,12

In addition, studies that have used substitution analyses that model the intended replacement of sugar-sweetened beverages (SSB) with low calorie sweetened beverages (LCSB) have shown that, for example, replacing 1 serving/day of SSB with 1 serving/day of LCSB was associated with a 4% lower risk of total mortality, 5% lower risk of cardiovascular disease mortality, and 4% lower risk of cancer mortality.11This specific type of analysis can somewhat overcome methodological limitations and provide more consistent, robust, and biologically plausible associations.9 Importantly, the findings by Malik et al. indeed suggests that replacing SSB with low calorie sweetened beverages may bring health benefits.

Used in foods, beverages and tabletop sweeteners, low calorie sweeteners can 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. Low calorie sweeteners are also non-cariogenic, which means that they do not contribute to tooth decay.

  1. Mullee et al. Association Between Soft Drink Consumption and Mortality in 10 European Countries. JAMA Intern Med. 2019 Sep 3; doi:10.1001/jamainternmed.2019.2478
  5. Sievenpiper JL, Khan TA, Ha V, Viguiliouk E, Auyeung R. The importance of study design in the assessment of non-nutritive sweeteners and cardiometabolic health. A letter in response to Azad et al study in CMAJ. CMAJ?November 20, 2017?189?(46)?E1424-E1425
  6. 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
  7. Johnson RK, Lichtenstein AH, Anderson CAM, et al. Low-Calorie Sweetened Beverages and Cardiometabolic Health: A Science Advisory From the American Heart Association. Circulation 2018; 138:e126–e140. DOI: 10.1161/CIR.0000000000000569
  8. Toews I, Lohner S, de Gaudry DK, Sommer J, 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;?363:?k4718
  9. Khan TS, Malik V, Sievenpiper J. Letter by Khan et al Regarding Article, “Artificially Sweetened Beverages and Stroke, Coronary Heart Disease, and All-Cause Mortality in the Women’s Health Initiative”. Stroke 2019; 50(6): e167-e168
  10. Pan A, Malik VS, Schulze MB, Manson JE, Willett WC, Hu FB. Plain water intake and risk of type 2 diabetes in young and middle-aged women. Am J Clin Nutr. 2012;95:1454–1460. doi: 10.3945/ajcn.111.032698
  11. Malik et al. Long-Term Consumption of Sugar-Sweetened and Artificially Sweetened Beverages and Risk of Mortality in US Adults. Circulation. 2019 April 30;139(18):2113–2123. DOI: 10.1161/CIRCULATIONAHA.118.037401
  12. Hinkle SN, Rawal S, Bjerregaard AA, Halldorsson TI, Li M, Hey SH, et al. A prospective study of artificially sweetened beverage intake and cardiometabolic health among women at high risk. AJCN 2019 Jun 7. pii: nqz094. doi: 10.1093/ajcn/nqz094. [Epub ahead of print]