Sweeteners · Metabolic & Cardiometabolic · Gut & Microbiome
saccharin worsens glucose tolerance
Part of: • saccharin
📅 Last reviewed: 2026-07-15 ⓘ
Evidence ladder
How far up the ladder this claim has climbed. A high consensus on a low rung means "consistent so far," not "proven in people."
Top evidence so far: Human trials (RCT / n-of-1)
How the studies fall
What the evidence shows
Saccharin is the sweetener with the strongest microbiome-mediated glucose-intolerance signal: it was the lead compound in both Suez 2014 (mice + humans) and the Suez 2022 human RCT, where it impaired glycemic responses in susceptible individuals by altering the gut microbiome.
The evidence (10)
| Source | Grade | Stance | Quality | Finding |
|---|---|---|---|---|
| Del Pozo S, Gómez-Martínez S, Díaz LE, Nova E, Urrialde R, Marcos A 2022 · Nutrients | observational | mixed | low | Review: current evidence indicates saccharin (with sucralose) can influence gut-microbiota composition. |
| Kalin K, Rådholm K, Olsson L, Tremaroli V, Woodward M, Wennberg M, Bäckhed F, Rolandsson O 2026 · Journal of the Endocrine Society | observational | contradicts | low | 14 overweight non-diabetic adults, 5mg/kg/day saccharin x3mo: no change in clamp-measured insulin sensitivity (ΔM -0.1, P=.85); no change in gut microbiota composition/richness. |
| Suez et al. 2022 · Cell | RCT | supports | high | Human RCT: saccharin impaired glycemic responses via microbiome changes in responsive individuals (lead compound). |
| Conz A, Salmona M, Diomede L 2023 · Nutrients | observational | mixed | low | NNS–microbiota review: effects real but heterogeneous and personalized. |
| Pacheco-Sánchez B, Melgar-Locatelli S, López-Merchán R, Benítez-Marín MJ, Blasco-Alonso M, González-Mesa E, Tovar R, Rubio P, Suárez J, Sanjuan C, de Fonseca FR, Alén F, de Ceglia M, Rivera P 2025 · Biology of sex differences | animal | supports | low | Gestational 0.1% saccharin in rats disrupted offspring glucose homeostasis and insulin/GLP-1 signaling in gut-brain axis, sex-dependent effects through adolescence. |
| Ruiz-Ojeda FJ, Plaza-Díaz J, Sáez-Lara MJ, Gil A 2019 · Adv Nutr | observational | mixed | low | Review: saccharin among the few sweeteners that measurably change human gut microbiota. |
| Gauthier E, Milagro FI, Navas-Carretero S 2024 · Nutrition | observational | supports | moderate | Human-trial review: saccharin (with sucralose) changed microbiota/glucose tolerance. |
| Suez J, Korem T, Zeevi D, Zilberman-Schapira G, Thaiss CA, Maza O, Israeli D, Zmora N, Gilad S, Weinberger A, Kuperman Y, Harmelin A, Kolodkin-Gal I, Shapiro H, Halpern Z, Segal E, Elinav E 2014 · Nature | animal | supports | moderate | Nature: saccharin was the primary non-caloric sweetener inducing glucose intolerance via gut-microbiota changes (mice + human arm). |
| Al-Ishaq RK, Kubatka P, Büsselberg D 2023 · Nutrients | observational | mixed | low | Sweeteners–microbiome review: saccharin among agents altering microbiota, clinical relevance debated. |
| Rathaus M, Azem L, Livne R, Ron S, Ron I, Hadar R, Efroni G, Amir A, Braun T, Haberman Y, Tirosh A 2024 · Mol Metab | animal | contradicts | moderate | Long-term NNS study: saccharin metabolic effects context-dependent. |
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