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NON-NUTRITIVE SWEETENERS (NNS) ARE COMMERCIALLY USED TO ENHANCE PALATABILITY WITHOUT INCREASED SUGAR AND/OR CALORIES IN AN ATTEMPT TO CONTROL BODY WEIGHT AND/OR BLOOD GLUCOSE. RECENTLY, ATHLETES AND FITNESS ENTHUSIASTS ARE CONSUMING MORE NNS; HOWEVER, NOT WITHOUT CONCERN FOR SATIETY, GLUCOSE CONTROL, AND GENERAL PHYSIOLOGICAL ADAPTATIONS. THIS ARTICLE AIMS TO COMPREHENSIVELY EVALUATE THE METABOLIC IMPACTS OF NNS IN CELL CULTURE, ANIMAL MODELS, AND HUMANS, AS WELL AS ESTABLISHING CONSIDERATIONS FOR THOSE SEEKING OPTIMAL PERFORMANCE AND BODY COMPOSITION. APPROXIMATELY 80 ARTICLES WERE IDENTIFIED AND REVIEWED USING 29 SEARCH TERMS. OVERALL, NNS CONSUMPTION HAS THE PROPENSITY TO EITHER AUGMENT OR HINDER EXERCISE ADAPTATION. INTRODUCTION N on-nutritive sweeteners (NNS) are compounds commonly used to commercially enhance the sweetness of foods without significant carbohydrate and/or caloric addition. NNS quite often display sweetness several hundred times greater compared with sucrose (Table 1). Several artificial compounds are approved as food additives in the United States by the FDA, including saccharin, sucralose, aspartame, and acesulfame potassium (Ace-K) (71). In addition, Stevia (Stevia rebaudiana) and its derivatives, stevioside and rebaudioside A, are naturally derived sweeteners that are gaining traction among consumers, but lack the scientific scrutiny and thorough investigation of the more prevalent U.S. sweeteners (19,62). NNS use has targeted demographics seeking to control their weight, glucose levels, or both, since the discovery of saccharin in the late 1800s (19,22). Incorporation of these compounds has developed uncertainty and controversy regarding potential health detriments in human consumption (60). The government has gone to thorough efforts in determining safe levels for human consumption; the adequate daily intake (ADI) is established through rigorous animal testing, and further research has demonstrated little-to-no absorption (depending on the specific compound) (46,69,71). Furthermore, in establishing the ADI, a 100-fold safety factor called the no-observed-adverse-effect-level is used to discern the minimal amount of a specific substance necessary to elicit side effects, ultimately creating a large buffer for interindividual susceptibility to each compound (46,65). Nevertheless, resistance to NNS persists (60). The use of NNS has steadily increased over the past few decades, making their way into a variety of foods and drinks (19). As obesity rates rise in the United States, so does the commercial demand for supposed “weight-loss” products (19). Previously, the most common vehicle for ingestion was beverages such as diet soda and similar formulations (65). However, certain compounds such as sucralose, with its more “sugar-like” taste and chemically resistant nature to heat and processing, has shown utility in baking and other food items (9,30). Individual NNS are also viewed differently by the general population, with aspartame in particular being subject to negativity in the public’s eye (27). The diet food industry has been receptive to consumers desiring a more Address correspondence to Darryn S. Willoughby, [email protected].