Low-calorie sweeteners cause only limited metabolic effects in mice

Abstract

There are widespread concerns that low-calorie sweeteners (LCSs) cause metabolic derangement. These concerns stem in part from prior studies linking LCS consumption to impaired glucose tolerance in humans and rodents. Here, we examined this linkage in mice. In experiment 1, we provided mice with chow, water, and an LCS-sweetened solution (saccharin, sucralose, or acesulfame K) for 28 days and measured glucose tolerance and body weight across the exposure period. Exposure to the LCS solutions did not impair glucose tolerance or alter weight gain. In experiment 2, we provided mice with chow, water, and a solution containing saccharin, glucose, or a mixture of both for 28 days, and tested for metabolic changes. Exposure to the saccharin solution increased the insulinemic response of mice to the glucose challenge, and exposure to the saccharin + glucose solution increased the rate of glucose uptake during the glucose challenge. However, neither of these test solutions altered glucose tolerance, insulin sensitivity, plasma triglycerides, or percent body fat. In contrast, exposure to the glucose solution increased glucose tolerance, early insulin response, insulin sensitivity, and percent body fat. We conclude that whereas the LCS-containing solutions induced a few metabolic changes, they were modest compared with those induced by the glucose solution.

The Impact of Artificial Sweeteners on Body Weight Control and Glucose Homeostasis

“…Consistently, modulation of the gut microbiota was found in other rodent studies upon saccharin consumption, as a minor fraction of saccharin is not absorbed and will concentrate in the colon (96,127). Besides saccharin, sucralose was consistently found to affect microbiota in mice as it accumulates in the colon (85,88,96). However, contradictory results regarding the effect of acesulfame-K on gut microbiota composition have also been found in rodents (85,86).…”

“…specifically, one study that used the ADI-dosage for human consumption (15 mg/kg/day) showed no effect on body weight in mice after 8 weeks of acesulfame-K consumption, while another study shows an increase in body weight by exceeding the ADI more than 2-fold (37.5 mg/kg/day) after 4 weeks in mice (85,86). Furthermore, saccharin consumption was found to increase body weight in mice compared to water, sucrose or glucose, whereas other studies in rodents have shown reduced or unchanged body weight compared to mice receiving water, glucose, fructose or sucrose (87)(88)(89)(90)(91)(92)(93)(94). However, the absorption of saccharin is lower in rodents compared to humans due to a relative higher stomach pH in rodents (92).…”

“…Notably, contradictory results from rodent studies for the effect on body weight exist only for acesulfame-K and saccharin, which are largely or entirely absorbed in their intact form, thereby being able to reach the peripheral tissues. Consistently, rodent and human studies found no effect of sucralose on body weight as only a small amount is absorbed in its intact form, thereby reaching the microbiota in a larger amount compared to acesulfame-K and saccharin (37,38,85,88,96). As artificial sweeteners have different metabolic fates, differences in physiological effects affecting energy balance and adiposity should be elucidated.…”

“…Moreover, human data on the effect of saccharin on body weight is scarce with only one study showing no significant effects on body weight after 12 weeks of saccharin consumption compared to sucrose in overweight and obese individuals (36). Moreover, sucralose consumption has been reported to have no effect on body weight in mice compared to water, and in human studies compared to placebo (calcium carbonate) or control (no-intervention) (37,38,85,88,96). Notably, contradictory results from rodent studies for the effect on body weight exist only for acesulfame-K and saccharin, which are largely or entirely absorbed in their intact form, thereby being able to reach the peripheral tissues.…”

High-dose saccharin supplementation does not induce gut microbiota changes or glucose intolerance in healthy humans and mice

“…However, it is noticeable that, among these numerous studies, there is no reproducible microbiota signature even for commonly studied NCAS, such as sucralose [ 49 , 51 , 52 , 87 ]. The consequences of these microbiota alterations on glucose tolerance were not assessed in these reports, except for one that found no effect on glucose tolerance (OGTT) after 6 weeks of sucralose supplementation in ileitis-prone SAMP mice [ 52 ] that is consistent with other independent reports which showed that consumption of NCAS, such as sucralose or aceK, has either a minor [ 82 ], or no effect [ 81 ] on glucose tolerance.…”