Do low-calorie sweeteners promote weight gain in rodents?

Low-calorie sweeteners (LCSs) are used globally to increase the palatability of foods and beverages, without the calories of sugar. Recently, however, there have been claims that LCSs promote obesity. Here, I review the literature linking LCS consumption to elevated body weight in rodents. A recent systematic review found when the LCSs were presented in water or chow, only a minority of the studies reported elevated weight gain. In contrast, when the LCSs were presented in yogurt, the majority of the studies reported elevated weight gain. This review focuses on this latter subset of studies, and asks why the combination of LCSs and yogurt promoted weight gain. First, LCSs have been hypothesized to induce metabolic derangement because they uncouple sweet taste and calories. However, the available evidence indicates that the LCS-treated yogurts did not actually taste sweet to rats in the published studies. Without a sweet taste, the concerns about uncoupling sweet taste and calories would not be relevant. Second, in several studies, the LCS-treated yogurt increased weight gain without increasing caloric intake. This indicates that caloric intake alone cannot explain the elevated weight gain. Third, there is evidence that LCSs and yogurt can each alter the gut microbiota of rodents. Given recent work indicating that changes in gut microbiota can modulate body weight, it is possible that the combination of LCS and yogurt alters the gut microbiota in ways that promote weight gain. While this hypothesis remains speculative, it is consistent with the observed rodent data. In human studies, LCSs are usually presented in beverages. Based on the rodent work, it might be worthwhile to evaluate the impact of LCS-treated yogurt in humans.