The Safety of Artificial Sweeteners and their Use in Pharmaceuticals
Artificial sweeteners are sugar substitutes that add sweetness to foods and beverages without the extra calories found in sugar. These additives are used to help patients with diabetes avoid hyperglycemia and assist people in losing weight or avoiding weight gain by providing a replacement to higher calorie sugar sweetened foods. Artificial sweeteners can be found in many sugar free beverages, candies and gum, as well as pharmaceutical products. Although artificial sweeteners are often recommended over the sugar sweetened alternatives in weight loss and diabetes prevention, the use of such products are not without risk. Studies have been conducted to assess artificial sweeteners involvement in contributing to cancer, genotoxicity and diabetes. To provide optimal health care to patients, it is imperative to know the implications involved with these risks. Pharmaceutical products formulated for oral and peroral administration have been sweetened by both artificial and natural sweeteners, and the utilization of artificial sweeteners has been deemed more beneficial than its natural counterpart. As health care professionals, it is our job to counsel patients on the benefits of artificial sweeteners over natural sweeteners along with the importance of using artificial sweeteners in moderation. Introduction and Background Information on Artificial Sweeteners Currently there are five artificial sweeteners approved by the U.S. Food and Drug Administration (FDA) including sucralose, aspartame, saccharin, stevia and acesulfame potassium (acesulfame) These compounds are regulated by the FDA as food additives and were evaluated for safety before being made available for public consumption (Table 1).1Artificial sweeteners are currently the gold standard as additives in food and beverages consumed by those with type II diabetes mellitus and those who either want to lose weight or avoid weight gain.2 Artificial sweeteners help diabetics avoid hyperglycemia and maintain a more consistent blood sugar level. Artificial sweeteners add little to no calories to achieve the equivalent sucrose sweetness within their food and beverage formulations, which makes artificial sweeteners a viable choice for those limiting their daily caloric intake.1 By limiting both sugar intake and overall calories consumed, the risk of developing diabetes and obesity decreases.3 However, artificial sweetener consumption has been linked to an increased cancer incidence, with both genotoxic and carcinogenic properties in studies conducted in lab rats. Subsequently, when more stringent safety studies were performed, an increase in cancer incidence was not observed in human subjects. However, long term studies have not been conducted to assess the overall effect artificial sweeteners have in humans after consumption over a lifetime.4 Toxicity Testing A study done in 2002, at the Center of Advanced Study, Cell and Chromosome Research, Department of Botany at the University of Calcutta, in conjunction with the Department of Internal Medicine at the University of Kentucky, studied the genotoxicity of the artificial sweeteners aspartame, acesulfame and saccharin. Genotoxicity was evaluated according to how much damage was sustained to the DNA when exposed to external factors. The study population included mice that were fed increasing dosages of one sweetener, and their bone marrow tissue was analyzed for genotoxicity. From the test performed in this study it was concluded that each of the three sweeteners induced DNA damage in the mouse bone marrow cell. This study concluded that it is impossible to assess the long term effects of artificial sweetener use, but use should be limited based on the genotoxic effects found within the study.6 A bioassay evaluation of aspartame carcinogenicity in Sprague Dawley rats was conducted by the Cesare MaltoniCancer Research Center of the European Ramazzini Foundation. Aspartame was added to the rat's normal feed at the concentrations of 100,000; 50,000; 10,000; 2,000; 400; 80 and from the control group 0 ppm. These concentrations were calibrated to parallel the human consumption of 5,000; 2,500; 500; 100; 20; 4 or 0 mg/kg, respectively, each day. Aspartame was added to the feed when the rats were 8 weeks old until natural death, upon which an extensive autopsy was conducted. Both the male and female population showed a significant increase in the incidence of malignant tumors with (p: 0.05) for males and (p 0.01) as compared to controls. The study concluded that with aspartame consumption, the risk of malignant tumor development increased within the rat subjects. These findings show more research is necessary to adequately assess aspartame carcinogenicity with long term consumption in the human population.7 Sucrose versus Artificial Sweeteners A prospective cohort study examined the association of artificially and sugar sweetened beverages in the development of type II diabetes.a The study included 51,529 men ages 40 to 75 years who were recruited to form a Health Professionals Follow Up Study. The study consisted of questionnaires mailed every other year to assess health status and lifestyle factors. After excluding the men who did not respond to the survey and those with type II diabetes, cardiovascular disease and cancer, a 131 item semiquantitative food frequency 38 THE PHARMACY AND WELLNESS REVIEW February 2014 Volume 5, Issue 1 T*h*e *Sa**ety o*f*A*rt*ifi *1c*ia*l*S*w*e*et*e*ne* r*s*a*n*d*th*e*ir* U* s*e*in_. P.ha* r*m*a*c*eu* ti "c.a*ls Preventative1Vledicine Table 1. Overview of FDA Approved Artificial Sweeteners 1,2,3,s Artificial Brand Sweetness Compared Physical Food Sweetener Name to Sugar Characteristics Additive