Non-nutritive sweeteners in food-drug interactions: An overview of current evidence

Food-drug interactions occur when the presence of foods interferes with the absorption, distribution, metabolism, or excretion of pharmaceuticals. Specific compounds within foods, like certain phytochemicals from grapefruit, have been known to precipitate food-drug interactions for decades, leading to guidance from physicians and pharmacists about patients' dietary restrictions while taking certain drugs. Although approved by the Food and Drug Administration, high-intensity non-nutritive sweeteners (NNS) share qualities with drugs that suggest the potential for similar interactions. In this minireview, we have reviewed 5 of the most popular NNS, including saccharin, aspartame, acesulfame potassium, sucralose, and stevia, and detail their drug-like qualities, regulatory status, pharmacokinetics, and primary research articles containing evidence of NNS interacting with drug absorption, distribution, metabolism, and excretion. Although studies varied widely in concentration ranges for NNS, model systems, and methods, all NNS included in this review were found to have known interactions with mediators of absorption, distribution, metabolism, and excretion from studies conducted after their Food and Drug Administration approval or generally recognized as safe designation. We have highlighted essential gaps in the literature and recommend the scientific community actively research NNS as food additives that may interact with drugs. SIGNIFICANCE STATEMENT: Food-drug interactions are a growing concern in Western societies where polypharmacy and ultraprocessed foods and beverages are increasingly common. High-intensity non-nutritive sweeteners bear structural similarities to pharmaceuticals, and evidence suggests they interact with mediators of drug pharmacokinetics. This minireview highlights the interactions uncovered thus far and serves as a call to action for the scientific community to establish rigorous, consistent testing that will enable updated safety guidelines for consumers.