Some research indicates that even acceptable daily intakes of aspartame, as regulated by the United States Food and Drug Administration (FDA), might make you hungrier and lead to weight gain.
Other studies in rodents have shown that compared with sugar, sweeteners like saccharin and aspartame causes weight gain instead of weight loss.
Reasons why this may happen are not entirely clear, but a team of researchers from the Massachusetts General Hospital decided to investigate why aspartame does not promote weight loss.
Their research - published in the journal Applied Physiology, Nutrition and Metabolism. - suggests one of aspartame's metabolites may play a role.
The researchers were led by Dr. Richard Hodin, from the Massachusetts General Hospital Department of Surgery.
Studying aspartame intake in mice
One of the breakdown products of aspartame is phenylalanine, an inhibitor of a gut enzyme called intestinal alkaline phosphatase (IAP) that has been shown to prevent metabolic syndrome in mice.
Dr. Hodin and team had conducted previous research where they fed IAP to mice that were on a high-fat diet. They found that IAP can prevent the onset of metabolic syndrome, as well as reduce the symptoms in animals that already had the condition.
Based on this known relationship between IAP, phenylalanine, and aspartame, researchers hypothesized that consuming aspartame may promote metabolic syndrome because of its inhibition of phenylalanine.
For the study, researchers added aspartame to diet and regular soda, before measuring IAP activity in mice.
The scientists used four groups of mice. Two groups were put on a normal diet, with one group receiving drinking water with aspartame and the other just plain water. The other two groups were put on a high-fat diet, with one group getting plain water and the other getting water with aspartame.
The normal-diet group that received aspartame consumed the equivalent of 3 ½ cans of diet soda every day. The group that was on a high-fat diet received aspartame in doses the equivalent to almost two cans of diet soda.
The mice were monitored for 18 weeks.
Aspartame does not help with weight loss
Dr. Hodin and team found that IAP activity was reduced when it was added to a drink containing aspartame, but IAP levels remained the same when IAP was added to a drink containing sugar.
Researchers injected aspartame into the mice's small intestines, where IAP is normally produced. They found this reduced IAP levels.
Researchers also injected saline solution in bowel segments, but IAP activity remained the same.
At the end of the 18-week period, there was no significant difference between the weights of the two groups that were fed a regular diet.
However, mice on a high-fat diet that received aspartame gained more weight than mice that did not receive aspartame.
Mice that received the sweetener also had higher blood sugar than those without aspartame.
They also had higher levels of the TNF-alpha inflammatory protein in their blood, which is usually associated with metabolic syndrome.
"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 Dr. Hodin.
Aspartame blocks enzyme that prevents obesity
Inside the human body, aspartame is metabolized and broken down into phenylalanine, aspartic acid, and methanol. Phenylalanine and aspartic acid are amino acids that are naturally present in many protein-containing foods.
However, phenylalanine inhibits the production of IAP.
"We think that aspartame might not work because, even as it is substituting for sugar, it blocks the beneficial aspects of IAP," Dr. Hodin says.
"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."
Dr. Richard Hodin
While the researchers admit that other contributing factors may play a role, Dr. Hodin emphasizes that the findings "clearly show that aspartame blocks IAP activity, independent of other effects."
Inhibition of the gut enzyme intestinal alkaline phosphatase may explain how aspartame promotes glucose intolerance and obesity in mice, Sarah Shireen Gul et al., Applied Physiology, Nutrition and Metabolism, doi: 10.1139/apnm-2016-0346, published online 18 November 2016, abstract.
Massachusetts General Hospital news release, accessed 24 November 2016 via EurekAlert.
American Cancer Society, What is aspartame?, accessed 24 November 2016.
Low intake of aspartame induced weight gain and damage of brain & liver cells in Weanling Syrian hamsters, Magda Ibrahim Hassan, Journal of Food and Nutrition Research, doi: 10.12691/jfnr-4-3-4, published online 2016.
Saccharin and aspartame, compared with sucrose, induce greater weight gain in adult Wistar rats, at similar total caloric intake level, Fernanda de Matos Feijó et al., Appetite, doi: http://dx.doi.org/10.1016/j.appet.2012.10.009, published online 1 January 2013, abstract.