WHO Plans to Classify an Artificial Sweetener as a Possible Carcinogen

A Debate About Artificial Sweetener Safety: Aspartame and Cancer

Artificial sweeteners, used widely around the world, bring continuing debates about health and safety. These substances replace sugar in various foods and drinks to reduce calories and offer safer alternatives for people with diabetes. However, research in recent years has raised concerns about their possible adverse effects on human health. This is particularly true of aspartame, which is expected to be classified for the first time as “a possible carcinogen” by the International Agency for Research on Cancer (IARC), part of the World Health Organization (WHO), one of the world’s leading health organizations.

A Surprising WHO Announcement: “Aspartame May Be Carcinogenic”

According to a Reuters report, aspartame—used in many products, from Coca-Cola’s diet colas to Mars’s Extra chewing gum and some Snapple drinks—will be listed in July as “possibly carcinogenic to humans” by the International Agency for Research on Cancer (IARC), the World Health Organization’s (WHO) cancer research arm.

The term “possible carcinogen” means that a substance may cause cancer, but the relationship has not been fully established. This classification is generally used when there is limited evidence that the substance causes cancer in humans, or sufficient evidence of cancer in animal experiments. However, it is not considered definitive proof that the substance will cause cancer in humans.

By contrast, when a substance is classified as a “definite carcinogen,” there is strong and conclusive scientific evidence that cancer occurs in humans after exposure to it. This classification generally rests on evidence from numerous epidemiological studies (the branch of science examining disease patterns in human populations). When these studies show a strong association between a particular substance and a particular cancer type, the substance is generally classified as a “definite carcinogen.”

According to this new development, aspartame will be placed in the Group 2A carcinogen category.

IARC’s assessment aims to determine whether something is a potential hazard based on all published evidence. It does not consider how much of a product someone can consume. Advice for individuals comes from JECFA, a separate WHO expert committee on food additives (the Joint WHO and Food and Agriculture Organization Expert Committee on Food Additives), and national regulators.

However, similar IARC assessments of other substances in the past have raised consumer concerns about using them, led to lawsuits and forced manufacturers to reformulate recipes and switch to alternatives. This has prompted criticism that IARC’s assessments can be confusing for the public.

WHO and the Evaluation of Aspartame

JECFA, WHO’s committee on food additives, is also reviewing aspartame use this year. Its meeting began in late June, and it plans to announce its decision on 14 July, the same day IARC makes its decision public.

Since 1981, JECFA has stated that aspartame can be safely consumed within acceptable daily limits. For example, a 60 kg adult would need to drink between 12 and 36 cans of diet cola every day—depending on the amount of aspartame—to be at risk. This view has been widely shared, including by national regulators in the United States and Europe.

Debates and Next Steps

IARC’s decisions can have a major impact. In 2015, its committee decided that glyphosate was “probably carcinogenic.” Years later, companies were still feeling the effects, even though other bodies, such as the European Food Safety Authority (EFSA), disputed the decision.

However, IARC’s decisions have also been criticized for creating unnecessary alarm about substances or circumstances that are difficult to avoid. It has four classification levels: carcinogenic (Group 1), probably carcinogenic (Group 2A), possibly carcinogenic (Group 2B) and not classifiable (Group 3). The levels are based on the strength of the evidence rather than how dangerous a substance is.

Aspartame has been studied intensively in recent years. An observational study of 100 thousand adults in France last year found a slightly higher cancer risk among people consuming larger amounts of artificial sweeteners, including aspartame.

Listing aspartame as a possible carcinogen is intended to encourage further research. However, it will reignite debate about IARC’s role and the safety of sweeteners more broadly.

Aspartame has been authorized for use worldwide by regulators that reviewed all available evidence, and major food and beverage manufacturers have defended its use for decades. IARC said it evaluated 1300 studies in its June review.

Recent recipe changes by soft-drink giant Pepsico illustrate the industry’s struggle to balance taste preferences and health concerns. Pepsico removed aspartame from its fizzy drinks in 2015, brought it back a year later, but removed it again in 2020.

Sources close to IARC said that listing aspartame as a possible carcinogen was intended to encourage more research, helping agencies, consumers and manufacturers draw firmer conclusions.

However, this report will probably once again ignite debate about IARC’s role and sweetener safety more generally.

Last month, WHO issued guidelines advising consumers against using non-sugar sweeteners for weight control. The guidelines caused a stir in the food industry, which argued that these products can help consumers reduce the amount of sugar in their diets.

What Is Aspartame’s Possible Mechanism of Carcinogenic Action?

A number of studies on aspartame’s carcinogenic effects have suggested that this artificial sweetener could contribute to cancer development. When consumed, aspartame is known to be hydrolyzed and absorbed in the gastrointestinal (GI) tract. This process releases methanol, aspartic acid and phenylalanine.

Methanol metabolism begins in the liver, where it is first oxidized to formaldehyde and then to formic acid. In addition to the damage caused directly by methanol in the liver, formaldehyde is directly toxic to liver cells and has carcinogenic properties.

Many studies have investigated aspartame’s carcinogenic potential. For example, one study found that early-life exposure to aspartame increased the risk of developing cancer later in rat offspring.

A number of studies in living organisms and tissue cultures have shown that aspartame may have a role in cancer development. Their results suggested that its safety for human consumption should be reassessed by regulatory bodies such as IARC. These findings also support the generally small number of human studies.

In a French population-based study, researchers reported an association between aspartame consumption and increased cancer risk. These individuals were found to be at particularly high risk of breast cancer and obesity-related cancers (colorectal, stomach, liver, oral, pharyngeal, laryngeal, esophageal, ovarian, endometrial and prostate cancers).

These findings support aspartame’s distinctive effect on certain cancer risks. Although it did not appear to affect the risk of developing pancreatic cancer, men who consumed aspartame were observed to have a higher risk of developing non-Hodgkin lymphoma and multiple myeloma.