The mechanism of action proposed centres on a by-product of aspartame breakdown known as phenylalanine.
This substance is thought to inhibit intestinal alkaline phosphatase (IAP), an enzyme that plays a preventative role in the onset of metabolic conditions such as type 2 diabetes and cardiovascular disease.
Researchers from the Massachusetts General Hospital (MGH) gathered four groups of mice. Two groups were placed on a normal diet, with one drinking water with aspartame, and the other drinking just water.
Similarly, the other two groups were placed on a high-fat diet, one group drinking aspartame-infused water, the other with ordinary drinking water. This regimen continued for 18 weeks.
The team found that mice in the normal diet group that drank water containing aspartame consumed an amount equivalent to an adult human's drinking about three and a half cans of diet soda daily. However, there was very little weight difference between the two groups.
Mice in the high-fat diet group, who drank water containing aspartame, consumed an amount equivalent to around two cans. This group also gained more weight than those on the same diet that received plain water.
“Our findings regarding aspartame's inhibition of IAP may help explain why the use of aspartame is counterproductive," said lead author, Dr Richard Hodin, 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."
Further investigations revealed that the mice ingesting aspartame in both diet groups had higher blood sugar levels.
The team thought this to be a sign of glucose intolerance.
Levels of the inflammatory protein TNF-alpha in the blood were also raised compared to mice fed the same diets without aspartame,
Raised TNF-alpha protein levels have previously been seen in individuals with metabolic syndrome.
Responding to these findings, the British Soft Drinks Association (BSDA) director general Gavin Partington said the claims were "being made by a study conducted on mice and run contrary to the overwhelming body of scientific evidence."
“Decades of scientific research, including human clinical trials, show that low-calorie sweeteners, such as those in diet drinks, have been found to help consumers manage their calorie intake when part of an overall healthy diet.”
Source: Applied Physiology, Nutrition, and Metabolism
Published online ahead of print, doi: 10.1139/apnm-2016-0346
“Inhibition of the gut enzyme intestinal alkaline phosphatase may explain how aspartame promotes glucose intolerance and obesity in mice.”
Authors: Richard Hodin et al.