Low calorie sweeteners and gut microbiome: no effect confirmed in humans

Posted: 05 July 2018

Science news from the 36th Symposium on Diabetes and Nutrition in Croatia


  • Low calorie sweetener-induced effects on gut microbiome are not confirmed in humans. Outcomes of animal studies testing low calorie sweeteners in very high amounts cannot be translated to effects in humans.
  • Clinical trials confirm no adverse effects of low calorie sweeteners on glucose tolerance and insulin sensitivity in humans.
  • Recent systematic reviews and meta-analyses of clinical trials show that low calorie sweeteners do not affect post-prandial glycaemia and thus can be used in diabetes management without raising blood glucose levels.

In a highly interesting session entitled “Low calorie sweeteners and microbiome: Implications for diabetes”, organised in the context of the 36th Symposium on Nutrition and Diabetes by the Diabetes and Nutrition Study Group (DNSG) of the European Association for the Study of Diabetes (EASD), four internationally renowned experts presented the latest evidence and discussed the effect of low calorie sweeteners on gut microbiota, glucose control and tolerance, insulin resistance and overall on diabetes management.

Low calorie sweeteners, microbiome and glucose tolerance

Dr Allison Sylvetsky, George Washington University, USA, and Dr John Sievenpiper, University of Toronto, Canada, presented latest evidence around low calorie sweeteners and gut microbiota in a debate which ended up in consensus that current evidence in humans does not confirm effects of low calorie sweeteners on the microbiome and that findings of animal studies should not be translated to human effects.

The question that needs to be addressed primarily is not whether low calorie sweeteners induce glucose intolerance through changes in the microbiome but rather if they do induce glucose intolerance at all, Dr Sievenpiper emphasised. In fact, current evidence suggests otherwise: that low calorie sweeteners have no adverse effect on glucose tolerance. Dr Sievenpiper concluded that systematic reviews and meta-analyses of higher quality evidence show modest improvements in body weight with the use of low calorie sweeteners compared to sugar, and no effect on glycaemia or cardiometabolic risk factors, when compared to water.

Dr Sylvetsky noted that alterations in gut microbiota are observed in rodent studies using high doses of low calorie sweeteners, close to, or higher than the Acceptable Daily Intake (ADI), and that such effects on gut microbiota have not been confirmed in humans. In fact, very few studies have assessed effects of low calorie sweeteners on gut microbiota in humans, with those available being mainly observational studies and only one human intervention study published which had severe limitations and limited applicability (Suez et al, 2014). She concluded that future well-designed studies should examine potential effects in the context of human realistic consumption levels (Sylvetsky et al, 2018).

In the panel discussion that followed, the speakers agreed that studies investigating effects of the diet in general on the gut microbiota are challenging, as any compound that reaches the colon has the potential to alter the microbiome without though knowing the clinical significance of any changes observed in the microbiome. Furthermore, since the human diet is diverse and complex, and people don’t eat individual foods and drinks but a variety of them, it is difficult to study the effects of single nutrients, ingredients or foods.

Impact of low calorie sweeteners on glucose control and diabetes management

In a presentation looking at the latest evidence around the role of low calorie sweeteners in diabetes, Prof Anne Raben, University of Copenhagen, Denmark, concluded that current evidence as examined in a recent systematic review and meta-analysis strongly support that low calorie sweeteners do not affect post-prandial glycaemia (Nichol et al, 2018). This is also recognised by the European Food Safety Authority (EFSA) and by diabetes and nutrition associations in the US (American Diabetes Association, 2018; Franz et al. Academy of Nutrition and Dietetics, 2017) and the UK (Dyson et al. Diabetes UK, 2018). Furthermore, Prof Raben presented new data showing no different effect of diet beverages containing low calorie sweeteners on insulin resistance compared to water (Engel et al, 2017).

A recent systematic review and meta-analysis of 29 randomised controlled trials (RCTs) by Nichol et al. (2018) concluded that low calorie sweeteners do not increase nor affect blood glucose levels after consumption (post-prandial glucose levels). The study also found that the glycaemic impact of sweetener consumption did not differ by type of low calorie sweetener. The authors conclude that this absence of glycaemic impact of low calorie sweeteners’ consumption makes these a potentially useful dietary aid for people with diabetes or on a weight loss diet.

Low calorie sweeteners may also help consumers control cravings

Addressing sweetness and the psychological determinants influencing the consumption of low calorie sweeteners, Prof Jason Halford, University of Liverpool, UK, highlighted that body weight concerns, restrained eating patterns and positive beliefs about low calorie sweeteners’ palatability and effectiveness are key determinants of consumption of low calorie sweetened beverages. Indeed, frequent consumers of diet beverages turn to them in their effort to combine successful weight control and pleasurable eating. Recent data show that consumers may actually use low calorie sweetened drinks as a successful strategy to control food intake when in a state of craving, as their consumption helps them to control cravings without increasing sweet foods intake. Prof Halford emphasised the fact that dieting is already difficult for most people, so allowing individuals to use different strategies including the consumption of low calorie sweetened foods or drinks that help them control cravings may facilitate and increase compliance to the weight loss effort.

Take-home messages

Consumers get really confused with the multiple and diverse messages they receive from media and scientists, all experts agreed. It is a critical need to translate findings of research into the context of realistic human consumption and to understand the clinically relevant effects in humans. With regard to effects on glucose control and tolerance, current evidence supports the replacement of sugar with low calorie sweeteners.


  1. American Diabetes Association. 4. Lifestyle management: Standards of Medical Care in Diabetes – 2018. Diabetes Care 2018;41(Suppl. 1):S38–S50
  2. Dyson PA., et al. Diabetes UK Position Statements. Diabetes UK evidence-based nutrition guidelines for the prevention and management of diabetes. Diabet Med. 2018;35:541-547
  3. EFSA. Scientific opinion on the substantiation of health claims related to intense sweeteners. EFSA Journal 2011, 9(6), 2229. Available at: http://onlinelibrary.wiley.com/doi/10.2903/j.efsa.2011.2229/epdf
  1. Engel S, Tholstrup T, Bruun JM, Astrup A, Richelsen B, Raben A. Effect of high milk and sugar-sweetened and non-caloric soft drink intake on insulin sensitivity after 6 months in overweight and obese adults: a randomized controlled trial. Eur J Clin Nutr 2018;72:358-366
  2. Franz MJ., et al. Academy of Nutrition and Dietetics Nutrition Practice Guideline for Type 1 and Type 2 Diabetes in Adults: Systematic Review of Evidence for Medical Nutrition Therapy Effectiveness and Recommendations for Integration into the Nutrition Care Process. Journal of the Academy of Nutrition and Dietetics 2017;117(10):1659 – 1679
  3. Nichol AD, Holle MJ and An R. Glycemic impact of non-nutritive sweeteners: a systematic review and meta-analysis of randomized controlled trials. Eur J Clin Nutr 2018;72:796-804
  4. Suez, J. et al. Artificial sweeteners induce glucose intoler-ance by altering the gut microbiota. Nature 2014; 514: 181–186
  5. Sylvetsky AC and Rother KI. Nonnutritive Sweeteners in Weight Management and Chronic Disease: A Review. Obesity 2018;26:635-640