Effects of Unsweetened Preloads and Preloads Sweetened with Caloric or Low-/No-Calorie Sweeteners on Subsequent Energy Intakes: A Systematic Review and Meta-Analysis of Controlled Human Intervention Studies

Abstract

Effects of isocaloric (sweetness differences but constant calories) preloads and isosweet (caloric differences but constant sweetness) preloads, as well as preloads that were neither isosweet nor isocaloric (sweetness and caloric differences) on subsequent ad libitum meal and total (preload + ad libitum) energy intakes were investigated. Thirty-five crossover studies were eligible for inclusion, representing 116 comparisons (41, isocaloric; 41, isosweet; and 34, neither isosweet nor isocaloric). References of existing reviews and literature from 4 databases were searched. The calculated raw mean differences in ad libitum and total energy intakes were pooled in meta-analyses using a random-effects model and the inverse of the variance as the weighting factor. Energy intakes at an ad libitum meal were significantly lower for low-/no-calorie sweetener (LNCS)–sweetened compared with unsweetened preloads in the isocaloric comparison (−55.5 kcal; 95% CI: −82.9, −28.0 kcal; P < 0.001); however, the difference in energy intake was not significant in additional sensitivity analyses (i.e., removal of comparisons where the matrix was a capsule and when xylitol was the LNCS). For the isosweet comparison, although the pooled energy intake at the ad libitum meal was significantly greater with the LNCS-sweetened preload compared with the caloric sweetener (CS)–sweetened preload (58.5 kcal; 95% CI: 35.4, 81.7 kcal; P < 0.001), the pattern was reversed when total energy intake was considered (−132.4 kcal; 95% CI: −163.2, −101.6 kcal; P < 0.001), explained by only partial compensation from the CS-sweetened preload. The results were similar when assessing ad libitum and total energy intakes when unsweetened compared with CS-sweetened preloads were consumed. Unsweetened or LNCS-sweetened preloads appear to have similar effects on intakes when compared with one another or with CS-sweetened preloads. These findings suggest that LNCS-sweetened foods and beverages are viable alternatives to CS-sweetened foods and beverages to manage short-term energy intake.

Oral Erythritol Reduces Energy Intake during a Subsequent ad libitum Test Meal: A Randomized, Controlled, Crossover Trial in Healthy Humans

“…Artificial LCS are frequently used in foods and beverages. In a recent meta-analysis, which included several human studies, Lee et al [ 33 ] analyzed the effects of unsweetened preloads and preloads sweetened with either LCS or caloric sugars on subsequent energy intake. The total energy intake after unsweetened preloads or after preloads sweetened with LCS followed by an ad libitum test meal was lower compared to preloads sweetened with caloric sugars.…”

“…The authors conclude that the caloric differences of the preloads rather than differences in sweetness account for the results. The preloads with caloric sugars possibly resulted in a satiation effect during the ad libitum test meal [ 33 , 34 ]. The meta-analysis included studies with different designs: (1) various LCS were included, including artificial and bulk LCS and caloric sugars, and (2) the test meal composition and the time between preload and test meal were variable.…”

“…These studies highlight a notable difference between the artificial LCS sucralose and the natural bulk sweetener erythritol. Artificial LCS and water were not able to induce satiation and reduce energy intake during ad libitum test meals [ 33 ]. Erythritol, on the other hand, seems to induce a satiation effect comparable to that of sucrose as shown by Overduin et al [ 27 ] and indicated in the present study.…”

Is There an Academic Bias against Low-Energy Sweeteners?

“…Given this extensive literature on mechanisms, one might expect that there is an equally large and convincing body of evidence demonstrating the adverse effects of LES on humans, prompting the need for mechanistic understanding and explanations. Yet, every recent systematic review (SR) and meta-analysis of randomised controlled trials (RCTs) in humans—from acute studies of appetite and glycaemic responses through longer-term studies with anthropometric and glycaemic control endpoints—finds neutral or beneficial effects of LES, and almost no indications of adverse effects on these outcomes [ 2 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 ]. Thus, the stream of papers offering a multitude of mechanisms for the adverse effects of LES exists within the context of a wall of empirical evidence that fails to find any adverse effects to be explained.…”

“…These narratives can only be constructed on a foundation of a narrow selection of basic research and prior opinion, “confirmed” by uncritical reference to observational associations and mechanistic studies, further supplemented by speculation and assumptions. Meta-analyses using data from tens of human trials consistently show that exposure to LES reduces total energy intake vs. caloric sweeteners, and generally has neutral effects on total energy intakes relative to unsweetened (mainly water) controls [ 10 , 11 , 15 , 16 ]. Similarly, systematic reviews from a large body of human trials show that LES on their own or together with nutrient loads have no significant effect on subsequent glycaemic or insulinaemic responses [ 9 , 14 , 17 ].…”