Long-Term Saccharin Consumption: Effects on Insulin Resistance and Metabolic Parameters in Rats

Background. Saccharin is widely used as a non-caloric sweetener, yet its long-term metabolic safety at permissible daily doses remains controversial. Objective. To evaluate the effects of 60-day oral saccharin administration at 5 mg/kg/day on carbohydrate, protein, lipid and mineral metabolism, liver enzymes, body weight and insulin resistance indices in rats using baseline values as internal controls. Methods. Adult rats received saccharin (5 mg/kg/day, orally) for 60 days. Metabolic, hepatic, lipid and mineral parameters, together with insulin-based (HOMA-IR, FIRI, QUICKI, Caro) and non–insulin-based (TG/HDL-C, TGI, MI) insulin resistance indices and body weight, were assessed at baseline (pre-treatment), day 30 and day 60. Each animal’s baseline served as its own control, and changes over time were analyzed statistically (p<0.05). Results. Saccharin induced progressive hyperglycemia (glucose +53.4% at day 30 and +80.5% at day 60 vs baseline) with parallel increases in glycosylated hemoglobin (+64.7% and +82.4%, respectively) and insulin (+40.8% at day 30, remaining +23.2% at day 60). Albumin and total protein decreased by 33.2% and 19.3%, while ALT activity rose by about 70% over baseline. Total cholesterol and HDL declined (−15.2% and −25.8%, respectively), accompanied by a 50.4% rise in atherogenicity coefficient. Serum sodium, potassium and calcium fell by 15.8%, 42.9% and 31.2%, respectively. Body weight increased by 52.8%, and insulin resistance indices markedly worsened (HOMA-IR and FIRI ≈+120%, MI up to +252.2%), whereas QUICKI decreased by about 9%. Conclusion. Even at the acceptable daily intake level, chronic saccharin administration produced significant baselinerelative disturbances in glucose homeostasis, protein and lipid metabolism, liver enzyme activity, mineral balance and insulin sensitivity in rats, indicating a substantial metabolic risk profile.

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