Low and No Calorie Sweeteners and the Gut Microbiota: A Scientific Review

— Neva Cochran, MS, RDN, LD

Posted: January 23, 2019

The launch of the Human Microbiome Project by the National Institutes of Health in 2007 dramatically increased interest in the human gut microbiota, also called the microbiome. Consumers, health professionals and scientists want to know more about the relationship of the microbiome to our health and how foods and beverages we consume may have an influence. And over the last five years, the potential impact of low and no calorie sweeteners (LNCS) on the microbiome has been a subject of debate. A new comprehensive review, “Assessing the in vivo data on low/no-calorie sweeteners and the gut microbiota,” published in the journal, Food and Chemical Toxicology1, is the basis of the following summary of the science on this issue.

Microbiota Defined

The human microbiome is composed of trillions of microorganisms with the majority located in the gastrointestinal tract. The gut microbiome is created at birth, rapidly develops over the first three years and continues to change and adapt throughout our lives. Over 1000 species of microorganisms have been identified in the microbiome, but about 160 are present in the gut of any one individual. The microbiota plays a key role in human digestion and metabolism by contributing enzymes not produced by the body to help break down polysaccharides and polyphenols and synthesize vitamins.

Diet and Microbiome

Both long-term observational studies of population groups and short-term human intervention studies have shown that diet can affect gut microbial content. Poorly digested food components like fiber help regulate the microbiome, acting as substrates for microbial fermentation in the colon. Higher fiber intakes have been linked to increased fecal levels of certain bacteria. Higher protein and fat intake is associated with greater amounts of others,thus plant-based vs. animal-based diets can result in different gut microbiome.

Overall, studies suggest that dietary changes can modify the composition and function of the microbiome. Because there are important differences among individuals in the response of gut microbiomes to diet, researchers caution that it is difficult to generalize about the influence of specific dietary components. In interventional studies to assess the effects of different ingredients added to the diet in small amounts, the subjects’ usual diets should be determined and the intervention diets carefully controlled.

Low and No Calorie Sweeteners and the Microbiome

Concern about the effect of LNCS on the gut microbiome was prompted by a 2014 study by Israeli researchers2. The study concluded that consuming LNCS changes the composition and function of the gut microbiome, leading to an increased risk of glucose intolerance. But an expert review questioned the conclusions of the study based on limitations in the experimental design and the analysis and reporting of the data.

The authors of the new Food and Chemical Toxicology article1 reviewed 17 relevant primary research articles that investigated the effect of LNCS intake on the gut microbiome. The majority of these were animal studies, primarily with rodents. Only three were conducted with humans. A table in the paper provides a detailed summary of the studies.

There were limitations and confounding factors common in most of the studies including lack of proper control groups, use of LNCS doses in the animal studies that were far greater than the equivalent current acceptable daily intakes (ADIs) for humans and the lack of relevance in applying results of animal studies to humans. Most of the bacteria present in mice do not exist in the human gut.

Of the three human trials, none accounted for habitual dietary intake. Therefore, any changes found in the gut microbiome were not necessarily due to the LNCS itself but could be related to dietary differences between the LNCS and non-LNCS groups.

In addition, the chemical structures and metabolism of LNCS preclude any effect they could have on the human microbiome. Aspartame is a methyl ester of a dipeptide that is rapidly hydrolyzed into two amino acids and methanol, which are absorbed in the small intestine. So neither aspartame nor its metabolites ever reach the colon for direct interaction with the microbiome.

Although most of the sucralose consumed is not absorbed it is also not digested, so it is not a substrate for gut microbiome. Saccharin and acesulfame K are not metabolized in the small intestine but are rapidly absorbed and excreted unchanged in the urine. So these LNCS do not come in contact with the colon microbiome to have any effect.

Steviol glycosides, including stevioside and rebaudioside A, pass unabsorbed through the GI tract and enter the colon intact. In the colon, the microbiome removes the sugar portion attached to the steviol backbone and use it for energy. But as total daily intake of steviol glycosides is very low it should not have a significant influence on the microbiome. The steviol backbone that remains after the sugar is removed is not a substrate for the intestinal microbiome and is absorbed from the colon virtually intact. While the gut microbiome actively acts on steviol glycosides, recent research showed that steviol glycosides, at levels comparable to the ADI, did not affect the gut microbiome.

Finally, because LNCS are so intensely sweet, the milligram amounts consumed will always be low and well below the levels necessary to produce a significant impact on the gut microbiome.

Conclusions and Applications for Practice

The authors of the review paper conclude that studies of LNCS to date do not establish any clear evidence of any adverse effect on the gut microbiome in amounts relevant to human use. They also assert that studies evaluating the relationship between food additive and ingredient consumption and the microbiome need to be conducted in animals or humans at relevant intakes and be carefully controlled to account for the confounding factors, including the habitual diet. Safety has been well-documented over decades for acesulfame K, aspartame, saccharin, sucralose, and steviol glycosides, indicating that these low or no-calorie sweeteners as a group, or individually, do not pose any safety concerns at their currently approved levels. Therefore, nutrition and health professionals can feel confident in recommending LNCS to patients, clients and consumers as an option for sweetening foods and beverages without the addition of sugar or calories.

  1. Lobach AR, Roberts A, Rowland IR. Assessing the in vivo data on low/no-calorie sweeteners and the gut microbiota. Food Chem Toxicol. 2019;124(December 2018):385-399. doi:10.1016/j.fct.2018.12.005
  2. Suez J, Korem T, Zeevi D, et al. Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Nature. 2014;514(7521):181-186. doi:10.1038/nature13793


Neva Cochran, MS, RDN, LD is a registered dietitian nutritionist based in Dallas. She serves as a nutrition communications consultant to a variety of food and nutrition organizations, including the Calorie Control Council. She is passionate about promoting fact-based food and nutrition information to help people enjoy nutritious eating. Follow her on Twitter @NevaRDLD and check out her blog at www.NevaCochranRD.com.

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