Neotame and gut microbiota: in-vitro experiment cannot draw definitive conclusions on real life effects

ISA statement in response to new in vitro study by Shil et al.

Brussels, 25th April 2024: The International Sweeteners Associations (ISA) highlights the limitations of the new in-vitro study by Shil et al that tested the effects of neotame on isolated cells and bacteria outside of the human body and concluded that neotame could lead to metabolic and inflammatory diseases such as irritable bowel disease, sepsis or insulin resistance.1 Such cell experiments cannot reproduce the whole, complex, interactive system of the human body.

In vitro testing conditions may cause reactions that would not be seen with real-life exposure conditions in humans. For example, individual cells were exposed to neotame for 24 hours in these experiments whereas transit time in the human intestine is approximately 5 hours, meaning that the epithelium and gut microbiota would never be exposed in the human body to sustained sweetener for as long as was studied by Shil et al. This indicates that this study design cannot be predictive of what would happen in real life use of a sweetener.

It is well established that neotame is rapidly metabolized, completely eliminated, and does not appear to accumulate in the body. It is a low/no calorie sweeteners that is between 7000 and 13,000 times sweeter than sucrose. Therefore, only a tiny amount of this sweetener is needed to sweeten foods and it is highly unlikely that the amounts of neotame used in foods or drinks and consumed in human relevant levels would have any negative impact on the human gut microbiota.2

All approved low/no calorie sweeteners, including neotame, are safe at current exposure levels and play an important role in providing consumers choice with sweet-tasting options with low or no calories.


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  1. Shil A, Ladeira Faria LM, Walker CA, Chichger H. The artificial sweetener neotame negatively regulates the intestinal epithelium directly through T1R3-signaling and indirectly through pathogenic changes to model gut bacteria, Front. Nutr., 2024 Apr 24;11.
  2. Ruiz-Ojeda FJ, Plaza-Díaz J, Sáez-Lara MJ, Gil A. Effects of Sweeteners on the Gut Microbiota: A Review of Experimental Studies and Clinical Trials. Adv Nutr. 2019 Jan 1;10(suppl_1):S31-S48. doi: 10.1093/advances/nmy037