Sugar substitutes may interfere with liver’s ability to detoxify, researchers say

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Two sugar substitutes, also known as non-nutritive sweeteners, may disrupt the function of a protein that plays an important role in detoxifying the liver and the metabolizing certain drugs, including blood pressure medications and antidepressants, a new study suggested. 

These sweeteners are commonly used in foods and even some medications to give a sweet taste while providing an alternative to table sugar with few or no calories, according to nutrition experts. 

“With an estimated 40% of Americans regularly consuming non-nutritive sweeteners, it’s important to understand how they affect the body,” Laura Danner, a doctoral student at the Medical College of Wisconsin said in the release.

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Danner, who presented the new research at the American Society for Biochemistry and Molecular Biology annual meeting this week in Philadelphia, also said in the release, “In fact, many people don’t realize that these sweeteners are found in light or zero-sugar versions of yogurts and snack foods and even in non-food products like liquid medicines and certain cosmetics.” 

Non-nutritive sweeteners, acesulfame potassium and sucralose, were analyzed while using liver cells and cell-free assays, which allow the study of cellular processes such as transport, the authors explained in the release. 

These Diet Coke flavors hit the shelves in 2018 and contain the artificial sweetener acesulfame potassium or "Ace-K," which is a high-intensity sweetener that is 200 times sweeter than sugar. Ace-K is often used in diet sodas, alcohol, tabletop sweeteners, dairy products, jelly, deserts, baked goods, and toothpaste and mouthwash. 

These Diet Coke flavors hit the shelves in 2018 and contain the artificial sweetener acesulfame potassium or "Ace-K," which is a high-intensity sweetener that is 200 times sweeter than sugar. Ace-K is often used in diet sodas, alcohol, tabletop sweeteners, dairy products, jelly, deserts, baked goods, and toothpaste and mouthwash. 
(Photo by Cindy Ord/Getty Images for NYCWFF)

The investigators found that acesulfame potassium and sucralose inhibited the activity of a protein in the body called P-glycoprotein (PGP). PGP pumps many foreign substances out of cells, according to health experts, and is part of a group of transporters that help cleanse the body of drugs, toxins, and drug metabolites. 

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

Splenda, a popular tabletop sweetener, is a sucralose based product. Sucralose is a zero calorie artificial sweetener that can potentially lead to diabetes, increased risk of Crohn's disease, and weight gain.

Splenda, a popular tabletop sweetener, is a sucralose based product. Sucralose is a zero calorie artificial sweetener that can potentially lead to diabetes, increased risk of Crohn’s disease, and weight gain.
(Photo by Smith Collection/Gado/Getty Images)

According to the team’s work, the study also showed that the sweeteners stimulate transport activity and likely bind to PGP. This causes a competition with and inhibits the transport of other substrates such as xenobiotics, drugs and their metabolites, short-chain lipids and bile acids, the release stated. According to a presentation by Danner, this potentially leaves other PGP substrates such as certain medications left trapped in cells, possibly leading to liver toxicity.

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In a case where an individual takes blood pressure medications, antidepressants and antibiotics, which are medications that rely on PGP as a primary detoxification transporter, this could be problematic, the researchers said in the release. 

Non-nutritive sweeteners (NNS) consumed in the diet enter the liver from the blood circulation. Researchers found that in liver cells, the detoxifying transporter p-glycoprotein (PGP) exports NNS preferentially to several known substrate compounds. In a physiological context, this could leave other PGP substrates such as certain medications trapped in cells, potentially leading to liver toxicity.

Non-nutritive sweeteners (NNS) consumed in the diet enter the liver from the blood circulation. Researchers found that in liver cells, the detoxifying transporter p-glycoprotein (PGP) exports NNS preferentially to several known substrate compounds. In a physiological context, this could leave other PGP substrates such as certain medications trapped in cells, potentially leading to liver toxicity.
(CREDIT: LAURA DANNER, MEDICAL COLLEGE OF WISCONSIN. CREATED WITH BIORENDER.COM)

The researchers did recommend that the findings be further confirmed through preclinical and clinical studies, since their study is preliminary. 

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

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The researchers noted in the release that PGP also plays a role with maintaining the blood-brain barrier and therefore it is important to explore how inhibition of this protein may interfere with the function of cells in other organs besides the liver. 

The researchers plan on conducting further research on the two sweeteners using more complex models of drug transport and also plan on studying mixes of these sweeteners, since that is typically how they are found in food products.

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