Researchers discover how sugar substitutes disrupt liver detoxification

The results of a new study suggest that two sugar substitutes disrupt the function of a protein that plays a vital role in liver detoxification and the metabolism of certain drugs. These sugar substitutes, also called non-nutritive sweeteners, provide a sweet taste with little or no calories.

“With about 40% of Americans regularly consuming non-nutritive sweeteners, it’s important to understand how they affect the body,” said Laura Danner, a doctoral candidate at the Medical College of Wisconsin. “In fact, many people don’t realize that these sweeteners are found in light or sugar-free versions of yogurts and snacks and even in non-food items like liquid medications and some cosmetics. »

Danner will present the new research at the annual meeting of the American Society for Biochemistry and Molecular Biology at the Experimental Biology (EB) 2022 meeting, taking place April 2-5 in Philadelphia.

In their new work, the researchers studied the non-nutritive sweeteners acesulfame potassium and sucralose using liver cell and cell-free assays, which allow the study of cellular processes such as transport.

They found that acesulfame potassium and sucralose inhibited the activity of P-glycoprotein (PGP), also known as multi-drug resistance protein 1 (MDR1). PGP is part of a family of transporters that work together to cleanse the body of toxins, drugs, and drug metabolites.

“We observed that sweeteners impacted PGP activity in liver cells at concentrations expected from consumption of common foods and beverages, well below the maximum limits recommended by the FDA,” said Stephanie Olivier. Van Stichelen, Ph.D., who leads the research team. “To our knowledge, we are the first group to decipher the molecular mechanism by which non-nutritive sweeteners impact liver detoxification. »

The experiments also showed that sweeteners stimulate transport activity and probably bind to PGP, and thus compete with and inhibit the transport of other substrates such as xenobiotics, drugs and their metabolites, short chain lipids and bile acids.

Although the researchers caution that the study is preliminary and needs to be confirmed in preclinical and clinical studies, the results suggest that non-nutritive sweeteners could be problematic for people taking medications that use PGP as their primary detox carrier. These include certain antidepressants, antibiotics, and blood pressure medications.

“If future studies confirm that non-nutritive sweeteners impair the body’s detoxification process, it would be essential to investigate potential interactions and determine safe consumption levels for at-risk groups,” Danner said. “It might also be important to include specific amounts of non-nutritive sweeteners on food labels so people can better track their intake. »

Although the United States Food and Drug Administration recommends that non-nutritive sweeteners remain below an acceptable daily intake amount – the amount included in approximately 35 diet sodas for acesulfame potassium or eight diet sodas for sucralose per day – food manufacturers are only required to list these as ingredients. They do not have to indicate the amount of non-nutritive sweetener used in the product.

Next, the researchers plan to use more complex drug transport models to determine the extent to which acesulfame potassium and sucralose might interfere with drug detoxification and metabolism. They are also studying blends of these sweeteners, which would be more representative of how they end up in food products.

The researchers point out that because PGP is expressed on exchange surfaces throughout the body and plays an important role in maintaining systems such as the blood-brain barrier, it will also be important to study how inhibition of PGP could interfere with the normal function of cells in other organs. .


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