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

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Two sugar substitutes, also known as non-nutritive sweeteners, can disrupt the function of a protein that plays an important role in liver detoxification and the metabolism of certain drugs, including blood pressure and antidepressants, according to a new study.

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

“With approximately 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 statement.


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

The non-nutritive sweeteners acesulfame potassium and sucralose were analyzed using liver cell 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 shelves in 2018 and contain the artificial sweetener acesulfame potassium or “Ace-K,” which is a high-intensity sweetener that’s 200 times sweeter than sugar. Ace-K is often used in diet sodas, alcohol, table-top sweeteners, dairy products, jelly, desserts, pastries, toothpastes, and mouthwashes.
(Photo by Cindy Ord/Getty Images for NYCWFF)

Researchers found that acesulfame potassium and sucralose inhibited the activity of a protein in the body called P-glycoprotein (PGP). According to health experts, PGP pumps many foreign substances out of cells and is part of a group of transporters that help cleanse the body of drugs, toxins, 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, PhD, who leads the research team, in the release. “To our knowledge, we are the first group to decipher the molecular mechanism by which non-nutritive sweeteners impact liver detoxification.”

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

Splenda, a popular tabletop sweetener, is a sucralose product. Sucralose is a calorie-free 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 sweeteners stimulate transport activity and likely bind to PGP. This competes with and inhibits the transport of other substrates such as xenobiotics, drugs and their metabolites, short-chain lipids and bile acids, the statement said. According to a presentation by Danner, this potentially leaves other PGP substrates such as certain drugs trapped in the cells, which can lead to liver toxicity.


In the event that an individual is taking blood pressure medications, antidepressants and antibiotics, which are medications that rely on PGP as the primary detox transporter, this could be problematic, the researchers said in the statement.

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

Nonnutritive sweeteners (NSNs) consumed in the diet enter the liver from the bloodstream. The 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 drugs trapped in the cells, potentially leading to liver toxicity.

The researchers recommended that the results be confirmed by 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 investigate potential interactions and determine safe consumption levels for at-risk groups,” Danner said in the statement and added, “It may also be important to include specific amounts of non-nutritive sweeteners on food labels so people can better track their intake.”


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

The researchers plan to continue their research on both sweeteners using more complex drug transport models and also plan to study mixtures of these sweeteners, as this is typically how they are found in food products.

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