PhotoStudies have found that the sugar substitute aspartame -- sold under the brand names NutraSweet and Equal -- isn't as helpful in losing weight as one might think, and now researchers at Massachusetts General Hospital have found a possible explanation.

In their report published online in Applied Physiology, Nutrition and Metabolism, the researchers show how an aspartame breakdown product called phenylalanine interferes with the action of an enzyme previously shown to prevent metabolic syndrome, the symptoms associated with type 2 diabetes and cardiovascular disease.

They also found that mice receiving aspartame in their drinking water gained more weight and developed other symptoms of metabolic syndrome than animals fed similar diets that lacked aspartame.

Gut enzyme

"Sugar substitutes like aspartame are designed to promote weight loss and decrease the incidence of metabolic syndrome, but a number of clinical and epidemiologic studies have suggested that these products don't work very well and may actually make things worse," says Richard Hodin, MD, of the MGH Department of Surgery, the study's senior author.

"We found that aspartame blocks a gut enzyme called intestinal alkaline phosphatase (IAP) that we previously showed can prevent obesity, diabetes and metabolic syndrome; so we think that aspartame might not work because, even as it is substituting for sugar, it blocks the beneficial aspects of IAP."

Hodin and colleagues have been working on the issue for quite awhile. In 2013, they published a study that found that feeding IAP to mice kept on a high-fat diet could prevent the development of metabolic syndrome and reduce symptoms in animals that already had the condition.

Phenylalanine is known to inhibit the action of IAP, and the fact that it is produced when aspartame is digested led the researchers to investigate whether that could explain aspartame's lack of a weight-loss effect.

IAP is primarily produced in the small intestine, and the researchers found that injecting an aspartame solution into segments of the small intestines of mice significantly reduced the enzyme's activity. In contrast, IAP activity remained unchanged in bowel segments injected with a saline solution.

"People do not really understand why these artificial sweeteners don't work. There has been some evidence that they actually can make you more hungry and may be associated with increased calorie consumption. Our findings regarding aspartame's inhibition of IAP may help explain why the use of aspartame is counterproductive," says Hodin, who is a professor of Surgery at Harvard Medical School.

"While we can't rule out other contributing mechanisms, our experiments clearly show that aspartame blocks IAP activity, independent of other effects," he said. 


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