No plausible mechanism to explain a potential association between diet drinks consumption and stroke or dementia

Posted: 21 Apr 2017

ISA statement in response to Pase et al. observational study and AHA Press Release

Having reviewed this paper by Pase et al.1, the International Sweeteners Association (ISA) highlights that this is yet another observational study providing no convincing evidence and no plausible mechanism for a causal relationship between diet drinks’ consumption and health indices, in this case stroke and dementia.

The findings of that study, in fact, are based only on a small group of 97 cases of incident stroke and 81 cases of dementia out of a total of 2888 participants aged over 45 and 1484 participants over 60 who were included in the analysis for incident stroke and dementia, respectively. Given such small numbers, consumption of low-calorie sweetened beverages could be divided into 3 levels only, i.e. non users, occasional (less than daily) and regular users (one or more beverage per day). The latter category included 519 subjects only. This translates into less than two dozen cases of stroke or dementia among regular low-calorie sweetened beverage users. In addition, there was no convincing trend in risk, i.e. the hazard ratio of ischemic stroke was already about 2-fold elevated among occasional low-calorie sweetened beverage users.

Furthermore, commenting on the findings of the study, Professor Carlo La Vecchia, University of Milan, Italy, notes: “The association between diet drinks and stroke is less strong in the third statistical model, which adjusted for additional cardiometabolic variables that may be associated with an increased risk of stroke. Thus, under-adjustment is possible, i.e. more accurate and/or valid measurement of blood pressure and other covariates may lead to less strong association. With regard to dementia, in the more complete model 3, there is no significant association with diet drinks’ consumption.”

Indeed, when prevalent hypertension, the single most important stroke risk factor, was taken into account in the statistical analysis, the association between diet drinks and incident all-stroke was already attenuated. Similarly, the magnitude of the association of diet drinks with dementia decreased further when the authors considered the influence of diabetes as a potential confounding factor. Lastly, another limitation of this study is the method used for dietary intake data (self-reported food frequency questionnaire (FFQ)), which may be subject to recall bias, thus introducing error into the estimated models, as acknowledged by the authors.

While the findings in Pase et al. publication are only observational, there is an established and strong bank of scientific evidence from clinical studies demonstrating that low calorie sweeteners and diet drinks containing them can be a useful tool in sugar and energy reduction, when used in place of sugar.

At a time when obesity (a major risk factor for cardiovascular diseases including stroke) and diabetes rates (a known risk factor for dementia) continue to increase worldwide, it would be unfortunate and dangerous from a public health perspective if people were to be discouraged from using low calorie sweeteners as a safe and effective means of reducing and maintaining their weight2, as well as of managing blood glucose levels3.


  1. Pase MP et al. Sugar- and artificially-sweetened beverages and the risks of incident stroke and dementia: A prospective cohort study. Stroke, 2017.
  2. Rogers PJ, Hogenkamp PS, de Graaf K, et al. Does low-energy sweetener consumption affect energy intake and body weight? A systematic review, including meta-analyses, of the evidence from human and animal studies. Int J Obes 2016; 40(3): 381-94
  3. American Diabetes Association 2017 Standards of Medical Care in Diabetes: 4. Lifestyle management. Diabetes Care 2017 Jan; 40(Supplement 1): S33-S43