Differential Effects of Chronic Low Calorie Sweetener Consumption on Body Weight, Glycemia, and Ingestive Behavior

Low calorie sweeteners (LCS) provide sweetness with little to no energy. Each sweetener has a unique chemical structure that possesses unique sensory and functional characteristics. While LCS are generally considered in aggregate, these unique chemical structures have potential implications for sensory, metabolic, and behavioral differences that may impact body weight and glycemia. Therefore, two, twelve-week experiments were conducted to determine the effect of chronic LCS consumption on body weight, glycemia, and ingestive behaviors. The first experiment investigated the differential effects of four LCS (saccharin, aspartame, rebaudioside A, and sucralose) and sucrose consumed for twelve weeks on body weight, glycemia, and ingestive behaviors among healthy adults with overweight or obesity (body mass index (BMI) between 25 and 40 kg/m2). In a parallel-arm design, 154 participants were randomly assigned to consume 1.25 to 1.75L of beverage sweetened with 1 of the 5 sweeteners daily for 12 weeks. Body weight was measured every two weeks; energy intake, energy expenditure, and appetite were assessed every 4 weeks; and glucose tolerance was measured at baseline and week 12. Every four weeks, participants completed 24-hour urine collections to determine study compliance via PABA excretion. Sucrose and saccharin consumption led to increased body weight across the 12-week intervention (Δ weight = +1.85 and +1.18kg, p ≤ 0.02) and did not differ from each other. While there was no significant change in body weight with consumption of the other LCS treatments compared to baseline, changes in weight in comparison to the sucrose treatment (sucrose – LCS) were significantly different for aspartame, rebA, and sucralose after 12 weeks (weight difference = 1.13, 1.25, 2.63kg, respectively; p ≤ 0.03). In addition, change in body weight at week 12 was significantly lower between sucralose and all other LCS (weight difference ≥ - 1.37 kg, p=0.008). The second experiment investigated the effect of daily aspartame ingestion on glycemia, body weight, and appetite. One hundred lean (BMI between 18 and 25 kg/m2) adults were randomly assigned to consume 0, 350, or 1050 mg aspartame/day for twelve weeks in a parallel-arm design. This experiment followed a similar protocol but measured body weight and blood pressure weekly and contained a 240-min glucose-tolerance test (OGTT) with measurements of selected hormones at baseline and week 12. Participants also collected 24-h urine samples every four weeks. There were no group differences for glucose, insulin, resting leptin, glucagon-like peptide 1, or gastric inhibitory peptide at baseline or week 12. There also were no effects of aspartame ingestion on appetite, body weight, or body composition. These trials demonstrate that all LCS contribute negligible energy but should not be aggregated because of their differing effects on body weight. Sucrose and saccharin consumption significantly increased body weight compared to aspartame, rebA, and sucralose. This differential change in body weight among LCS indicates individual LCS likely exert different physiological responses beyond the contribution of sweetness with negligible energy. Saccharin, rebA, sucralose, and aspartame (ingested at three doses) for twelve weeks had no effect on glycemia. These data do not support the view that LCS are problematic for the management of glycemia. If substantiated through additional testing, findings from this trial have implications for consumers, food industry, clinicians, and policy makers. Some LCS may not hold the anticipated beneficial effects on body weight (e.g., saccharin) and positive effects of one LCS (sucralose) may be attenuated if combined with select other LCS. Going forward it will be important to consider each LCS as a distinct entity with respect to its potential health effects.