WHO to declare artificial sweetener aspartame as possible carcinogen

By Benedette Cuffari, M.Sc.Jun 29 2023Reviewed by Susha Cheriyedath, M.Sc.

The International Agency for Research on Cancer (IARC), which is the cancer arm of the World Health Organization (WHO), recently indicated that aspartame will likely be declared a “possible carcinogen to humans.”

Image Credit: Iryna Imago / Shutterstock.com

What is aspartame?

After several decades of research on artificial sweeteners (ASW) to reduce obesity and diabetes rates, aspartame was discovered in 1965 and eventually brought to market in 1981. Aspartame is between 150-200 times sweeter than sugar and, as a result, does not increase the caloric value of food and drink products.

According to the United States Food and Drug Administration (FDA), the acceptable daily intake (ADI) for aspartame is 50 mg/kg, whereas European regulatory bodies recommend an ADI of 40 mg/kg for aspartame for both adults and children. Throughout the world, aspartame can be found in over 6,000 products, including food and beverages, cough drops, and some toothpaste, thus indicating the ubiquitous nature of this chemical in many everyday items.

Although most food and drink products with aspartame are advertised as ‘healthy’ or ‘diet’ alternatives to sugar-sweetened products, the ability of these products to reduce the risk of diabetes or obesity has never been confirmed. Instead, some evidence suggests that the flavor of both sugar- and artificially sweetened-beverages increases hunger sensations and, as a result, causes weight gain.

Does aspartame cause cancer?

After consuming aspartame, this chemical is hydrolyzed and absorbed in the gastrointestinal (GI) tract. This process leads to the release of methanol, aspartic acid, and phenylalanine.

The metabolism of methanol begins in the liver, where it is first oxidized to formaldehyde then again to formic acid. In addition to the direct damage methanol causes to the liver, formaldehyde is also directly toxic to liver cells and associated with cancer-causing properties.

Several studies have investigated the carcinogenic potential of aspartame. For example, one study in rats found that aspartame exposure early in life increased the risk that rat pups subsequently developed cancer.

The vast number of in vivo and in vitro studies indicating a potential role of aspartame in the development of cancer have led many regulatory agencies, like IARC, to reconsider the safety of aspartame for human consumption. Likewise, the results from these studies have also supported human studies, which are largely scarce.

In a recent French population-based study, researchers reported an increased risk of cancer associated with aspartame consumption. These individuals were found to be at a particularly high risk for breast cancer and obesity-related cancers including colorectal, stomach, liver, mouth, pharynx, larynx, esophageal, ovarian, endometrial, and prostate cancers.

These findings support the unique influence of aspartame on specific cancer risks. Whereas aspartame does not appear to influence the risk of developing pancreatic cancer, men who consume aspartame appear to be at a greater risk of developing non-Hodgkin’s lymphoma and multiple myeloma.

Other health effects of aspartame

The anticipated IARC ruling will likely raise concerns among consumers about their consumption of aspartame products. Thus, in addition to mitigating their risk of developing cancers by reducing or eliminating their consumption of aspartame products, consumers will also be protected against the various other potential health effects of aspartame.

Teratogenicity

During pregnancy, it is crucial for mothers to consume a healthy diet to ensure the proper development of the fetus, as well as the overall health of the mother. Previous studies have demonstrated that ASW consumption during pregnancy may increase the risk of preterm delivery and allergic diseases in the fetus.

Many in vivo studies have also reported a wide range of teratogenic effects associated with aspartame consumption during pregnancy, some of which include adverse glucose and insulin tolerance, altered intestinal microbiota composition, greater weight gain, as well as an increased risk of type 2 diabetes, cardiovascular diseases, nonalcoholic fatty liver disease, and hormone-related cancers in the infant.  

Behavioral disorders

Various neurological effects have been attributed to aspartame exposure, some of which include neurological and behavioral disorders, as well as certain neuropsychiatric reactions including headache, convulsions, and depression. These effects are largely attributed to the metabolism of aspartame, which leads to the production of phenylalanine, aspartic acid, and methanol, all of which can cross the blood brain barrier (BBB) and directly interact with neurotransmitters.

In addition to the direct effects of aspartame on the central nervous system (CNS), its interactions with the gut microbiota may also contribute to long-term behavioral changes. These microbiome alterations also increase the release of corticosterone and adrenocorticotropic hormone (ACTH).