Table 3.
Summary of animal studies evaluating early-life non-nutritive sweetener (NNS) exposure and obesity-related outcomes.
| Study, Year | Animal Model | NNS Type | NNS Dose, Route (Exposure) * to Dams | Timing of NNS Exposure | Outcomes Measured | NNS Effects in Offspring |
|---|---|---|---|---|---|---|
| Prenatal Exposure only | ||||||
| von Poser Toigo et al., 2015 [53] | Wistar rats | Aspartame or Saccharin | Aspartame: 2 g/L in water ad libitum (343 mg/kg/day) ** or Saccharin: 1.35 g/L in water ad libitum (232 mg/kg/day) ** | 30 days pre-conception until birth | Body weight, metabolic profile, feeding behavior, anxiety | Increased weight gain, serum cholesterol and triglycerides, intake of sweet foods with aspartame exposure (stronger effects in males); increased weight gain with saccharin exposure (males only) |
| Prenatal Exposure, Continued through Lactation and Post-weaning | ||||||
| Soffritti et al., 2010 [54] | Swiss mice | Aspartame | 0–32,000 ppm in feed ad libitum (0–3903 mg/kg/day) |
12th day gestation to natural death or 130 weeks of age | Neoplastic lesions, body weight (as a covariate) | No difference in body weight between consumption groups |
| Collison et al., 2012 [55] | C57BL/6J mice | Aspartame | 0.25 g/L in water ad libitum (55 mg/kg/day) |
3 weeks pre-conception to 17 weeks of age | Fasting blood glucose, insulin, lipid profile, body weight, % weight gain, visceral fat | Increased weight gain (males only), decreased insulin sensitivity; elevated fasting glucose levels (females only) |
| Collison et al., 2012 [56] | C57BL/6J mice | Aspartame | 0.25 g/L in water ad libitum (55 mg/kg/day) |
3 weeks pre-conception to 20 weeks of age | Glucose and insulin homeostasis, body weight, adiposity | Increased body weight and fasting blood glucose; decreased insulin sensitivity |
| Exposure through Lactation only | ||||||
| Parlee et al. 2014 [57] | C57BL/6J mice | Saccharin | 3% Saccharin (30 g/L) in water ad libitum (280 μM in serum of pups) |
Birth to 21 days | Weight, body composition by NMR, adipocyte size and number, serum insulin concentration, glucose tolerance test | Decreased body weight (females only), increased lean and decreased fat mass (males only), increased small and decreased large adipocytes, improved glucose tolerance |
| Cardoso et al. 2016 [58] | Wistar rats | Sorbitol | Exact amount required to achieve target dose, diluted in 2 mL water (0.15 to 150 mg/kg/day) |
Birth to 14 days | Weight gain, serum proteins, cholesterol, glucose, liver enzymes | Increased weight gain and total serum cholesterol with low dose; liver toxicity, lower serum glucose and triglycerides with high dose |
Studies sorted by year of publication. Abbreviations: NMR, nuclear magnetic resonance; NNS, non-nutritive sweetener. * For comparison, the US FDA acceptable daily intakes for humans are 50 mg/kg/day for aspartame and 15 mg/kg/day for saccharin [59]. ** Exposure not reported by authors; estimated from reported dose, approximate consumption and body weight. Bold text indicates main direction of association between NNS exposure and obesity-related outcomes.