The cancer-research arm of the World Health Organisation (WHO) has classified the low-calorie sweetener aspartame as ‘possibly carcinogenic’.

The International Agency for Research on Cancer (IARC) in Lyon, France, said its decision, announced on 14 July, was based on limited evidence for liver cancer in studies on people and rodents.

However, the Joint FAO/WHO Expert Committee on Food Additives (JECFA) said that recommended daily limits for consumption of the sweetener, found in thousands of food and drink products, would not change.

“There was no convincing evidence from experimental or human data that aspartame has adverse effects after ingestion, within the limits established by the previous committee,” said Francesco Branca, director of the WHO’s Department of Nutrition and Food Safety, at a press conference on 12 July in Geneva, Switzerland.

The new classification “shouldn’t really be taken as a direct statement that indicates that there is a known cancer hazard from consuming aspartame”, said Mary Schubauer-Berigan, acting head of the IARC Monographs program, at the press conference. “This is really more of a call to the research community to try to better clarify and understand the carcinogenic hazard that may or may not be posed by aspartame consumption.”

Other substances classed as ‘possibly carcinogenic’ include extracts of aloe vera, traditional Asian pickled vegetables, some vehicle fuels and some chemicals used in dry cleaning, carpentry and printing. The IARC has also classified red meat as ‘probably carcinogenic’ and processed meat as ‘carcinogenic’.

Sweet science
Aspartame is 200 times sweeter than sugar and is used in more than 6,000 products worldwide, including diet drinks, chewing gum, toothpaste and chewable vitamins. The US Food and Drug Administration (FDA) approved it as a sweetener in 1974 and, in 1981, the JECFA established an acceptable daily intake (ADI) of 40 milligrams per kilogram of body weight. For a typical adult, this translates to about 2,800 milligrams per day — equivalent to 9–14 cans of diet soft drinks.

The artificial sweetener has been the subject of several controversies over the past four decades.

In 2019, an advisory group to the IARC recommended a high-priority assessment of a range of substances, including aspartame, on the basis of emerging scientific evidence. The IARC’s evidence for a link between aspartame and liver cancer comes from three studies that examined the consumption of artificially sweetened beverages.

One of these, published online in 2014, followed 477,206 participants in 10 European countries for more than 11 years and showed that the consumption of sweetened soft drinks, including those containing aspartame, was associated with increased risk of a type of liver cancer called hepatocellular carcinoma. A 2022 US-based study showed that consumption of artificially sweetened drinks was associated with liver cancer in people with diabetes. The third study, involving 934,777 people in the US from 1982 to 2016, found a higher risk of pancreatic cancer in men and women consuming artificially sweetened beverages

Another study found that among 102,865 adults in France, people who consumed higher amounts of aspartame had an increased risk of breast cancer and obesity-related cancers.

In the body, the sweetener breaks down into three metabolites: phenylalanine, aspartic acid and methanol. “These three molecules are also found from the ingestion of other food or drink products,” says Branca. This makes it impossible to detect aspartame in blood testing. “That’s a limitation of our capacity to understand its effects.”

Other health effects of aspartame
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.  

Behavioural disorders
Various neurological effects have been attributed to aspartame exposure, some of which include neurological and behavioural 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 behavioural changes. These microbiome alterations also increase the release of corticosterone and adrenocorticotropic hormone (ACTH).