Long-Term Saccharin Consumption and Increased Risk of Obesity, Diabetes, Hepatic Dysfunction, and Renal Impairment in Rats

Abstract

Background and objectives: This study evaluated the effect of chronic consumption of saccharin on important physiological and biochemical parameters in rats. Materials and Methods: Male Wistar rats were used in this study and were divided into four groups: A control group and three experimental groups (groups 1, 2, and 3) were treated with different doses of saccharin at 2.5, 5, and 10 mg/kg, respectively. Each experimental group received sodium saccharin once per day for 120 days while the control group was treated with distilled water only. In addition to the evaluation of body weight, blood samples [total protein, albumin, glucose, lipid profile, alanine transaminase (ALT), aspartate transaminase (AST), lactate dehydrogenase (LDH), creatinine, and uric acid] and urine (isoprostane) were collected in zero time, and after 60 and 120 days for biochemical evaluation. Liver (catalase activity) and brain (8-hydroxy-2’-deoxyguanosine, 8-OHdG) tissues were collected at time zero and after 120 days. Results: The data showed that saccharin at 5 mg/kg increased body weight of treated rats after 60 (59%) and 120 (67%) days of treatment. Increased concentration of serum glucose was observed after treatment with saccharin at 5 (75% and 62%) and 10 mg/kg (43% and 40%) following 60 and 120 days, respectively. The concentration of albumin decreased after treatment with saccharin at 2.5 (34% and 36%), 5 (39% and 34%), and 10 mg/kg (15% and 21%) after 60 and 120 days of treatment, respectively. The activity of LDH and uric acid increased proportionally with dosage levels and consumption period. There was an increased concentration of creatinine after treatment with saccharin at 2.5 (125% and 68%), 5 (114% and 45%), and 10 mg/kg (26% and 31%) following 60 and 120 days, respectively. Catalase activity and 8-OHdG increased by 51% and 49%, respectively, following 120 days of treatment with saccharin at 2.5 mg/kg. Elevation in the concentration of isoprostane was observed after treatment with saccharin at all doses. Conclusions: The administration of saccharin throughout the treatment period was correlated with impaired kidney and liver function. Both hyperglycemic and obesity-inducing side effects were observed. There was an increased oxidative status of the liver, as well as exposure to increased oxidative stress demonstrated through the increased levels of isoprostane, uric acid, 8-OHdG, and activity of catalase. Therefore, it is suggested that saccharin is unsafe to be included in the diet.

The Impact of Artificial Sweeteners on Body Weight Control and Glucose Homeostasis

“…specifically, one study that used the ADI-dosage for human consumption (15 mg/kg/day) showed no effect on body weight in mice after 8 weeks of acesulfame-K consumption, while another study shows an increase in body weight by exceeding the ADI more than 2-fold (37.5 mg/kg/day) after 4 weeks in mice (85,86). Furthermore, saccharin consumption was found to increase body weight in mice compared to water, sucrose or glucose, whereas other studies in rodents have shown reduced or unchanged body weight compared to mice receiving water, glucose, fructose or sucrose (87)(88)(89)(90)(91)(92)(93)(94). However, the absorption of saccharin is lower in rodents compared to humans due to a relative higher stomach pH in rodents (92).…”

“…Furthermore, saccharin consumption was found to increase body weight in mice compared to water, sucrose or glucose, whereas other studies in rodents have shown reduced or unchanged body weight compared to mice receiving water, glucose, fructose or sucrose ( 87 – 94 ). However, the absorption of saccharin is lower in rodents compared to humans due to a relative higher stomach pH in rodents ( 92 ). Furthermore, differences in perception of sweetness for individual artificial sweeteners exist between different rodent species and strains ( 95 ).…”

Neuroendocrine and Metabolic Effects of Low-Calorie and Non-Calorie Sweeteners

“…An increased body weight was noted in rats after 60 and 120 days of 5 mg/kg saccharin treatment. Authors also observed an increase in glucose, uric acid and creatinine levels, as well as in oxidative status in the liver of saccharin-treated rats, suggesting that saccharin may impair glucose homeostasis, induce obesity and lead to impairments in kidney and liver function (140). The World Health Organization and the EU Scientific Committee for Food declared saccharine as safe up to the approved daily intake doses (5 mg/kg body weight) (53).…”

“…However, very high saccharin concentrations were tested in animal models, if compared to the doses commonly ingested by humans (139). With regard to metabolic parameters, a recent study evaluated the administration of saccharin (at different doses, namely: 2.5, 5, and 10 mg/kg) in male Wistar rats (140). An increased body weight was noted in rats after 60 and 120 days of 5 mg/kg saccharin treatment.…”

Analytical Methods for Determination of Non-Nutritive Sweeteners in Foodstuffs

“…Chi et al [8] reported neotame effect on the gut microbiome, and it concluded that neotame induces adverse effects on gut microbiota. The risk of obesity and diabetes also increased due to long-term saccharin consumption [9]. Some regulatory authorities deal with food control around the globe, such as Joint FAO/WHO Expert Committee on Food Additives (JECFA), Codex Alimentarius Commission (CAC), Food and Drug Administration (FDA) from the United States, Food Standards Australia New Zealand (FSANZ), and National Agency of Drug and Food Control (NADFC) of the Republic of Indonesia have determined the Acceptable Daily Intake (ADI) value and maximum amount for high-intensity sweeteners in foodstuffs (Table 1).…”