Non-nutritive Sweeteners

Abstract

Five non-nutritive sweeteners (NNS) are currently approved for use in the United States as food additives by the Food and Drug Administration (FDA): acesulfame-K, aspartame, neotame, saccharin, and sucralose; stevia glycosides (principally rebaudioside A) are also permitted for use based on a GRAS (generally recognized as safe) petition submitted to the FDA. The daily intake of each NNS by children and adults in the United States is well below the acceptable daily intake (ADI) set by the FDA. The ADI is the amount that can be consumed daily for life without health or safety concern. The FDA approval process for new food additives (including GRAS) includes the generation and submission of extensive safety databases in animals and humans. Nutritive and NNS initiate sweet taste in the mouth by binding to the same sweet-taste receptor, located on the cell membrane of taste bud cells. The oral sweet-taste receptor consists of two membrane-associated proteins coupled to an intracellular G-protein. The variety of molecules that taste sweet (nutritive and non-nutritive) bind to different parts of these membrane proteins. The same sweet-taste receptor is also found on enteroendocrine cells of the small intestine. Both nutritive and NNS bind to these receptors and can cause the release of hormones involved in glucose homeostasis. The sweet-taste receptor is also found on pancreatic, insulin-secreting beta cells, and while not mediating glucose-induced insulin secretion, can promote insulin secretion in vitro in the presence of high (non-physiologic) concentrations of NNS. Unlike nutritive sweeteners (NS), the ingestion of NNS by fasting humans does not elevate plasma concentrations of the hormones secreted by enteroendocrine or pancreatic beta cells. NNS ingestion may enhance some of these responses to NS when both are ingested together, but the effects thus far reported are not consistent among studies. The body of epidemiologic evidence exploring for associations between NNS use and body weight gain is not convincing; moreover, epidemiologic studies cannot prove causality. Active intervention studies in which NNS are covertly substituted for NS in the diet for extended periods of time (e.g., up to 18 months in children) show that NNS do not cause weight gain or obesity.