Aspartame May Prevent Weight Loss and Promote Weight Gain by Blocking Intestinal Enzyme's Activity

A team of Massachusetts General Hospital (MGH) investigators has found a possible mechanism explaining why use of the sugar substitute aspartame might not promote weight loss. In their report published online in Applied Physiology, Nutrition and Metabolism, the researchers show how the aspartame breakdown product phenylalanine interferes with the action of an enzyme previously shown to prevent metabolic syndrome – a group of symptoms associated with type 2 diabetes and cardiovascular disease.

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

“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.”

In a 2013 study published in Proceedings of the National Academy of Sciences, Hodin’s team 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 phenylalanine is produced when aspartame is digested led the researchers to investigate whether its inhibitory properties could explain aspartame’s lack of a weight-loss effect.

In a series of experiments the team first found that the activity of IAP was reduced when the enzyme was added to a solution containing an aspartame-sweetened soft drink but remained unchanged if added to a solution with a sugar-sweetened beverage. 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.

Noah Brown