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Splenda may damage gut bacteria, boost weight gain: study

By Stephen Daniells , 25-Sep-2008
Last updated the 29-Sep-2008 at 15:29 GMT

Consumption of the sweetener Splenda at doses within the US FDA’s Acceptable Daily Intake may suppress beneficial bacteria in the gut, and cause weight gain, says a new rat study.

According to findings published in the peer-reviewed Journal of Toxicology and Environmental Health, Part A, a 12-week feeding study with the sweetener also affected the expression of certain enzymes known to interfere with the absorption of nutrients and pharmaceuticals.

The study, performed by researchers from Duke University in North Carolina and co-sponsored by the Sugar Association, may raise questions about the safety profile of the sweetener, reported to be used as an ingredient in over 4,000 products worldwide.

McNeil Nutritionals, the company behind Splenda, was quick to dismiss the study and draw attention to a number of other studies supporting the safety of the sweetener. The company questioned the methodology and the conclusions drawn by the researchers. Emphasis was also placed on the involvement of the Sugar Association as partial sponsor of the study.

Study methodology

The Duke University researchers separated 50 male Sprague-Dawley rats into five equal groups. One group was administered only water with its diet, thereby acting as the control group, while the other four groups had the diet supplemented with different doses of Splenda in water. The doses used were 100, 300, 500, and 1,000 mg of Splenda per kg of body weight per day, equivalent to sucralose doses of 1.1, 3.3, 5.5, and 11 mg per kg per day.

“These dosage levels were selected because they span the range of values below and above the accepted daily intake (ADI) for sucralose of 5 mg/kg/d established by the U.S. Food and Drug Administration (FDA),” wrote the researchers, led by Professor Mohammed Abou-Donia.

Moreover, Professor Abou-Donia told FoodNavigator.com that the study was performed with rats because they are the animal of choice for such studies. “The studies that were submitted for the approval of Splenda to the FDA were mostly performed in rats,” he said. “The Acceptable Daily Limit (ADI) approved by the FDA, was based on studies in rats.”

The study protocol was approved by the Duke University Institutional Animal Care and Use Committee (IACUC).

After 12 weeks, half of the animals in each group were sacrificed and the cytochrome P-450 (CYP) metabolism system and membrane efflux transporter P-glycoprotein (P-gp) were measured. Both P-gp and CYP are known to impact on the bioavailability of orally consumed compounds, such as drugs and nutrients.

The remaining animals spent a further 12 weeks without any Splenda in the diet.

Results

Professor Abou-Donia and his co-workers report that, at the end of the initial 12 weeks, significant reductions in the levels of so-called beneficial bacteria were observed. Specifically, the numbers of total anaerobes was decreased by 50 per cent, relative to the control animals, while bifidobacteria, lactobacilli, and Bacteroides were reduced by 37, 39, and 67.5 per cent respectively.

The body weight of the animals in all the groups increased, but significant increases were observed in animals receiving Splenda, said the researchers. Control animals experienced an increase in body weight of 93 per cent over the 12 weeks. Body weight increases in the 100, 300, 500, and 1,000 mg of Splenda per kg per day groups were 104, 101, 102, and 88.5 per cent, respectively.

“The lack of a dose-response effect of Splenda on body weight is likely due to the combined elevation of both intestinal P-gp and CYP that affected the bioavailability of Splenda,” stated the researchers. “At the higher concentrations, less Splenda was absorbed due to the increase in the expression of both P-gp and CYP proteins.”

Concerning P-gp and types of CYP, expression of P-gp increased by 2.43- fold, CYP3A4 by 2.51-fold, and CYP2D1 by 3.49-fold, over the course of the 12 weeks.

Low beneficial bacteria levels, and elevated P-gp and CYP levels were maintained after the 12 week recovery period, said the researchers.

“Evidence indicates that a 12 week administration of Splenda exerted numerous adverse effects, including a reduction in beneficial faecal microflora, an increased faecal pH, and enhanced expression levels of P-gp, CYP3A4, and CYP2D1, which are known to limit the bioavailability of orally administered drugs,” concluded the researchers.

Both industry and academia has responded to the results of the study. To read this reaction, click here .

Source: Journal of Toxicology and Environmental Health, Part A
Volume 71, Issue 21, Pages 1415-1429
“'Splenda Alters Gut Microflora and Increases Intestinal P-Glycoprotein and Cytochrome P-450 in Male Rats”
Authors: M.B. Abou-Donia, E.M. El-Masry, A.A. Abdel-Rahman, R.E. McLendon, S.S. Schiffman
URL: http://dx.doi.org/10.1080/15287390802328630

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