Low calorie sweeteners and gut bacteria: No adverse effects at doses relevant to human use

Key remarks from two new review studies on low calorie sweeteners and gut microbiota

Highlights:

• Current studies establish no evidence of adverse effect of low calorie sweeteners on the gut microbiota at doses relevant to human use
• Dietary changes unrelated to low calorie sweeteners’ consumption are likely the major determinants of change in gut microbiota composition, confirming the viewpoint supported by all the major international food safety and health regulatory authorities that low calorie sweeteners are safe at currently approved levels
• Future human research should be carefully designed to study dietary effects at realistic consumption levels and to account for factors known to affect the microbiome, such as changes in diet composition or body weight, to avoid confounding effects

The role that the trillions of microorganisms living in our gastrointestinal tract, collectively referred to as gut microbiota or microbiome, can play in affecting human health is an area of extensive research, especially since accumulating evidence has linked the microbiota to obesity and to chronic diseases like diabetes. At the same time, scientific interest has increased around the role of diet, which is a known significant factor in shaping the microbiome. Thus, when in 2014 a study supporting that some low calorie sweeteners might affect the gut microbiota was published by Suez et al., it raised high scientific interest and big media headlines despite existing evidence from metabolism and safety studies showing no clinically relevant effect of low calorie sweeteners on gut microbiota.

As the debate around the topic of low calorie sweeteners’ impact on the gut microbiota continues, two recently published reviews of the scientific literature examined the available evidence from animal and human studies aiming to provide a clear answer based on the totality of the current data (Lobach et al, 2019; Ruiz-Ojeda et al, 2019). The key points and main conclusions, supporting that current studies establish no evidence of health effects of low calorie sweeteners via impact on the gut microbiota at doses relevant to human use, are discussed in the current ISA article.

Background: What is the gut microbiota and how does diet affect its profile?

The trillions of symbiotic microorganisms present in the human body, the majority of which are located within the gastrointestinal tract, are collectively referred to as the microbiota or microbiome. There are more than 1000 species of bacteria that have been identified in total, with Firmicutes and Bacteroidetes being the most predominant. However, the relative proportions of these species can vary enormously between individuals (Rowland et al, 2018).

The type and quantity of foods we consume every day can largely affect the gut microbiota. Our habitual diet as well as short- and long-term dietary changes have been found to influence the composition, diversity and functionality of the gut microbiota (Lobach et al, 2019). In fact, temporary microbial shifts due to dietary changes can occur even within 24 hours (David et al, 2014). There are hypotheses that particular nutrients and food ingredients may affect the microbiome profile and/or function and that certain types of changes in the diet could translate into increased risk of certain health outcomes, however, in general, the meaningfulness of most changes is still unclear.

No clinically relevant effect of low calorie sweeteners on gut microbiota, according to new review studies

Identifying a total of 17 publications investigating the administration of low calorie sweeteners to animals (14 studies) or humans (3 studies) and effects on the gut microbiota, the study by Lobach et al. represents an in-depth review of the literature of published in vivo animal and human studies. The authors conclude that “the sum of the data provides clear evidence that changes in the diet unrelated to low calorie sweeteners’ consumption are likely the major determinants of change in gut microbiota numbers and phyla [species], confirming the viewpoint supported by all the major international food safety and health regulatory authorities that low calorie sweeteners are safe at currently approved levels.” (Lobach et al., 2019).

A second review by Ruiz-Odeja et al. (2019) discusses the evidence from 18 animal and human studies examining the effects of low calorie sweeteners and polyols on the composition of gut microbiota. The authors note that current studies, primarily animal experiments, have shown some effect of high doses of saccharin and sucralose on the composition of the gut microbiota, but the clinical relevance of these findings in humans is not clear. The authors note that more human studies are needed to clarify these preliminary observations. The authors also state that research to date shows that sucralose is safe and generally note that all approved sweeteners critically evaluated by the FDA, EFSA, and Codex Alimentarius are considered safe. As noted in the Lobach et al. 2019 review, critical study design problems in most of the animal studies referenced as putative evidence of effects, make it impossible to reliably translate findings from these studies to humans. Moreover, available research does not support a reasonable mechanism by which approved low calorie sweeteners could exert a clinically meaningful effect on health by interaction with the gut microbiota. For example, long-term studies in animals at doses far in excess of those that would be consumed by people show sucralose to be safe, indicating no adverse effect on gut microbiota health or function, and research shows that sucralose is not an energy source for, nor otherwise metabolized by, gut microflora.

Key remarks and findings from the recently published review papers include:

• • Current studies establish no clear evidence of any adverse effect of low calorie sweeteners on the gut microbiota at doses relevant to human use.

• • Normal dietary changes, that have no relationship to low calorie sweeteners, are likely the main reason for changes in the gut microbiota profile and such changes are likely happening every day.
    • Studies of possible effects of low calorie sweeteners must consider this in interpreting changes found.
  • The reports of correlated effects stem mainly from animal studies where doses tested are beyond the possible expected intakes of humans, and where significant study design issues existed that make conclusions of effects questionable.
    • Extrapolation of the effect of one sweetener on the gut microflora to all low calorie sweeteners is also not appropriate, on the basis of well-documented differences in their chemistry, their metabolism in the body, and the amount of low calorie sweeteners or their metabolites that reach the gut microflora.
  • There are large differences between the gut microbiome profile in laboratory animals and people, so translating data from animal studies that test effects of extremely high doses of low calorie sweeteners is very suspect.
  • Results of metabolism and safety studies show no evidence of a likely mechanism for a clinically relevant effect on gut microbiota.
• International food safety and health regulatory authorities consistently confirm that low calorie sweeteners are safe at currently approved levels. This includes evaluation of gut function and overall health.
• Future research should include well-designed and controlled trials with appropriated doses in the context of human realistic cnsumption levels and adequate subject sizes to evaluate the potential impact of low calorie sweeteners on the gut microbiota (Ruiz-Ojeda et al., 2019). Careful control of other factors known to affect the gut microflora, such as changes in food consumption and diet composition, are also necessary to avoid confounding effects.