Low/no calorie sweeteners and cardiometabolic health: Where does the evidence stand?

Science news from the 7th Annual Dubai International Nutrition Congress (DINC) 2021


  • To assess the benefits of low/no calorie sweeteners, research should examine their impact in the context of their intended purpose of use, that is when used as sugar substitutes and, thus, to help achieve calorie reduction.
  • Analyses of the collective data examining the substitution of sugary drinks with beverages containing low/no calorie sweeteners show benefits in weight outcomes and cardiometabolic risk factors.
  • Emerging research also indicates potential benefits in liver fat reduction, when low calorie sweetened alternatives are used in place of sugar-sweetened beverages.


The 7th Annual Dubai International Nutrition Congress (DINC) 2021, held on 4-6 November 2021, provided a platform for nutrition experts in Middle East countries and beyond to discuss the recent advances and guidelines in the field of nutrition aiming to facilitate evidence-based practice and policy in the region. As the topic of sugar and sweeteners is always important in this context, a talk on low/ no calorie sweeteners and cardiometabolic health was part of the scientific programme of the congress. Dr. John Sievenpiper, MD, PhD, FRCPC, University of Toronto, Canada, explained why there is conflicting reporting on the role of low/no calorie sweeteners in the diet and presented data from new studies examining the health impact of substituting sugar sweetened beverages with low calorie sweetened alternatives.

Public health authorities and organisations globally, including the World Health Organization (WHO), recommend a reduction of excess sugars intake for all population groups. This recommendation has led to a heightened scientific interest in sugar substitutes options such as low/no calorie sweeteners. At the same time, conflicting reporting in science and in media about sweeteners’ impact on health has raised questions among consumers about their beneficial role in substituting sugar in the diet. The varied interpretation of the current literature by different scientific experts has fuelled confusion which needs to be addressed by carefully designed research.

How to accurately assess and interpret current evidence

To evaluate the potential benefits of low/no calorie sweeteners, the research hypothesis should be clear and aim to examine their intended purpose of use, i.e. to reduce calories by substituting excess sugars intake. When the comparison is made with placebo or water, and thus without caloric displacement, no beneficial (or adverse) effect should be expected. It is, therefore, important to clarify in the study hypothesis what sweeteners are compared to.

Similarly, systematic reviews and meta-analyses that pool together caloric (e.g. sugar) and non-caloric comparators (e.g. water) do not examine a clear hypothesis and therefore yield mixing results which are difficult to interpret.1 Low/no calorie sweeteners do not bear magic properties, and their benefits depend on the level of caloric displacement achieved through sugar (and hence calorie) reduction in the diet.

Analysing the collective evidence from human studies

Outcomes of two meta-analyses, aiming to bridge the evidence gap about the impact of substituting sugar-sweetened beverages with low/no calorie sweetened beverages, were presented at the Congress.

A network meta-analysis of 14 randomised controlled trials (RCTs) found that with the intended substitution of sugar with sweeteners, i.e. when caloric reduction is achieved, there was a benefit in body weight and body fat decrease, as well as cardiometabolic benefits such as a reduction in liver fat. When the comparison was made with water, low/no calorie sweetened drinks had a neutral effect. The advantage of network meta-analyses is that this form of analysis leverages all available direct, i.e. sweeteners vs sugar, and indirect comparisons, i.e. water vs sugar and water vs sweeteners.2

Another meta-analysis of 12 prospective cohort studies showed that the substitution of sugary drinks with low/no calorie sweetened beverages is associated with reductions in body weight, waist circumference, coronary heart disease incidence, cardiovascular disease mortality, and of all-cause mortality. While providing lower quality of evidence due to the observational nature of the included studies, these results are in agreement with meta-analyses of RCTs indicating a benefit of this substitution and no evidence of adverse effects.3

Emerging research on low/no calorie sweeteners’ role in metabolic health

Currently, there are several ongoing studies examining the impact of low/no calorie sweeteners on cardiometabolic health. Also, new clinical studies looking at the impact of sweeteners on the human gut microbiota are under way, including a trial led by Dr Sievenpiper, called “Strategies To OPpose SUGARS with Non-nutritive sweeteners Or Water trial”.4 This is a crossover RCT studying the effect of replacing sugary drinks with low/no calorie sweetened beverages or water on glucose tolerance, gut microbiome diversity, and other cardiometabolic outcomes, over 4-weeks in individuals at risk/ with overweight or obesity. Preliminary data in a sub-set of 32 participants looking specifically at liver fat, showed that substituting sugar-sweetened beverages with low/no calorie sweetened drinks or water reduces liver fat, confirming the intended benefit of this substitution.

Take home message

In his talk, Dr Sievenpiper concluded that, in order to understand if and under which conditions the use of low/no calorie sweeteners could have potential cardiometabolic benefits, we should look at the collective evidence evaluating the intended purpose of low/no calorie sweeteners’ use. Although there are concerns that sweeteners may not have the intended benefits, current evidence supports the assertion that the intended substitution of sugar calories with low/no calorie sweeteners can help improve body weight control and associated cardiometabolic risk factors.

  1. Sievenpiper JL, Khan TA, Ha V, Viguiliouk E, Auyeung R. The importance of study design in the assessment of nonnutritive sweeteners and cardiometabolic health. CMAJ. 2017; 189: E1424–E1425.
  2. McGlynn et al, submitted. Network Meta-analyses of Artificially Sweetened Beverages and Cardiometabolic Risk. ClinicalTrials.gov Identifier: NCT02879500
  3. Lee et al, under review. Meta-analysis of Low-calorie Sweetened Beverages and Cardiometabolic Outcomes. ClinicalTrials.gov Identifier: NCT04245826
  4. Sievenpiper J. Strategies To OPpose SUGARS with Non-nutritive sweeteners Or Water trial. ClinicalTrials.gov Identifier: NCT03543644