A randomized controlled trial contrasting the effects of 4 low-calorie sweeteners and sucrose on body weight in adults with overweight or obesity

Am J Clin Nutr. 2019 May 1;109(5):1288-1301. doi: 10.1093/ajcn/nqy381.


Background: Low-calorie sweeteners (LCSs) provide sweetness with little or no energy. However, each LCS's unique chemical structure has potential to elicit different sensory, physiological, and behavioral responses that affect body weight.

Objective: The purpose of this trial was to compare the effects of consumption of 4 LCSs and sucrose on body weight, ingestive behaviors, and glucose tolerance over a 12-wk intervention in adults (18-60 y old) with overweight or obesity (body mass index 25-40 kg/m2).

Methods: In a parallel-arm design, 154 participants were randomly assigned to consume 1.25-1.75 L of beverage sweetened with sucrose (n = 39), aspartame (n = 30), saccharin (n = 29), sucralose (n = 28), or rebaudioside A (rebA) (n = 28) daily for 12 wk. The beverages contained 400-560 kcal/d (sucrose treatments) or <5 kcal/d (LCS treatments). Anthropometric indexes, energy intake, energy expenditure, appetite, and glucose tolerance were measured at baseline. Body weight was measured every 2 wk with energy intake, expenditure, and appetite assessed every 4 wk. Twenty-four-hour urine collections were completed every 4 wk to determine study compliance via para-aminobenzoic acid excretion.

Results: Of the participants enrolled in the trial, 123 completed the 12-wk intervention. Sucrose and saccharin consumption led to increased body weight across the 12-wk intervention (Δweight = +1.85 ± 0.36 kg and +1.18 ± 0.36 kg, respectively; P ≤ 0.02) and did not differ from each other. There was no significant change in body weight with consumption of the other LCS treatments compared with baseline, but change in body weight for sucralose was negative and significantly lower compared with all other LCSs at week 12 (weight difference ≥ 1.37 ± 0.52 kg, P ≤ 0.008). Energy intake decreased with sucralose consumption (P = 0.02) and ingestive frequency was lower for sucralose than for saccharin (P = 0.045). Glucose tolerance was not significantly affected by any of the sweetener treatments.

Conclusions: Sucrose and saccharin consumption significantly increase body weight compared with aspartame, rebA, and sucralose, whereas weight change was directionally negative and lower for sucralose compared with saccharin, aspartame, and rebA consumption. LCSs should be categorized as distinct entities because of their differing effects on body weight. This trial was registered at clinicaltrials.gov as NCT02928653.

Keywords: appetite; energy intake; glycemia; ingestive behavior; low-calorie sweeteners; obesity; overweight; sweetness.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Aspartame / pharmacology
  • Beverages
  • Body Mass Index*
  • Body Weight
  • Diet*
  • Dietary Sucrose / pharmacology*
  • Diterpenes, Kaurane / pharmacology
  • Energy Intake
  • Feeding Behavior*
  • Female
  • Humans
  • Male
  • Non-Nutritive Sweeteners / pharmacology*
  • Obesity* / metabolism
  • Overweight / metabolism
  • Saccharin / pharmacology
  • Stevia
  • Sucrose / analogs & derivatives
  • Sucrose / pharmacology
  • Sweetening Agents / pharmacology
  • Weight Gain / drug effects*
  • Young Adult


  • Dietary Sucrose
  • Diterpenes, Kaurane
  • Non-Nutritive Sweeteners
  • Sweetening Agents
  • Sucrose
  • trichlorosucrose
  • rebaudioside A
  • Saccharin
  • Aspartame

Associated data

  • ClinicalTrials.gov/NCT02928653