WHO declares aspartame sweetener ‘possibly carcinogenic’ to humans

The World Health Organization (WHO) considers the sweetener aspartame, present in low-calorie soft drinks, candy, and even medicines, to be “possibly carcinogenic” to humans. The International Agency for Research on Cancer (IARC), the WHO body responsible for identifying the carcinogenic potential of substances, has concluded, after studying the available scientific evidence, that this sweetener may have the potential to cause cancer in the population. It does, however, classify it as level 2B, which is the second-to-last category in its hazard identification pyramid: this means that the evidence is very limited and, although safety is not a concern at the doses commonly taken, potential harmful effects have been described. However, the Joint FAO/WHO Expert Committee on Food Additives (JECFA), which is in charge of basing these risks on the population and establishing an acceptable daily intake (ADI), has also evaluated the available evidence and has decided to maintain the existing acceptable daily intake recommendation of 40 milligrams per kilogram (2.2 pounds) of body weight per day.

Aspartame, which is up to 200 times sweeter than sugar, is in thousands of products. It is used as a tabletop sweetener or to sweeten low-calorie soft drinks, chewing gum, jellies, breakfast cereals, yogurts, ice cream, toothpaste, and in some pharmaceuticals. JECFA evaluated the safety of this substance in 1981 and established the maximum recommended consumption at 40 milligrams per kilogram of body weight per day: below that amount, consuming this substance was safe. Now, however, and “given the availability of new research results,” explained the IARC, a committee of 25 independent experts has for the first time evaluated the potential of aspartame to cause cancer. JECFA, for its part, has also reanalyzed the studies to assess the risks and, if necessary, refine the recommended daily intake. A portion of these reviews was published in the journal The Lancet Oncology on Friday.

The results of the new IARC scientific review conclude that aspartame is “possibly carcinogenic” to humans. That is, a level 2B on the agency’s rating scale. According to the IARC scale, this means that there is limited, but not conclusive, evidence of cancer in humans, or there is convincing evidence of cancer in experimental animals, but not both. Or it may also be that only the evidence on aspartame’s mechanisms of action in causing cancer is robust. In this case, the IARC found that the evidence was limited in all three study streams (humans, experimental animals and mechanism evidence), but did see indications that raised a warning flag.

“This classification reflects the strength of the scientific evidence on whether an agent can cause cancer in humans, but it does not reflect the risk of developing cancer from a given exposure,” Mary Schubauer-Berigan, head of IARC’s Monographs Program, said during the press conference. Aspartame is not, in fact, the only food additive analyzed by the IARC: it has already studied more than 70, including saccharin and cyclamate, both classified at level 3, the last level of the classification, which indicates that there is no evidence that they are carcinogenic.

Aspartame is at the same level as lead or gasoline engine exhaust fumes. That is, the scientific evidence on their potential to cause cancer is similar, but that does not imply that the risk is the same. This classification does not indicate the degree of risk of developing cancer at a given exposure. “The cancer risk (at typical exposure levels) associated with two agents classified in the same IARC Group can be very different,” warns the WHO body. Thus, tobacco and processed meat, for example, are at the highest level of the scale — they are “carcinogenic” — but the real risk of habitual exposure is not the same.

Schubauer-Berigan specified that, in the analysis on aspartame, an association between the consumption of beverages with artificial sweeteners and a type of liver cancer was detected in three studies with cohorts from the United States and Europe. However, she pointed out, “despite the consistently positive results in these three studies, the working group concluded that chance, bias, and contradiction could not be ruled out with reasonable confidence and therefore concluded that the evidence was limited.” In experiments with animals, the experts found that there was an increased incidence of tumors in mice and rats, but they also ended up considering that there was “limited” evidence due to doubts about the design of the studies and the interpretation of the data. The IARC also considered that the mechanistic evidence (whether the agent exhibited key features of carcinogens) was limited, although there was some evidence pointing to aspartame inducing oxidative stress or chronic inflammation.

More research

The head of IARC’s Monographic Programmes said that, rather than a direct statement that aspartame carries known cancer risks, this scientific review and the classification of aspartame as a possible carcinogen can serve “as a call to the research community to try to clarify and better understand the carcinogenic hazard that may or may not be posed by the consumption of aspartame.”

As a matter of fact, the weak scientific evidence on the relationship between aspartame and cancer has led JECFA to keep its recommendations unchanged, said Francesco Branca, director of WHO’s Department of Nutrition and Food Safety: “The main conclusion was that there was no convincing evidence for and from experimental or human data that aspartame had adverse effects after intake within the limits set by the previous committee, which is 40 milligrams per kilogram of body weight.” Branca argued that analysis of genotoxicity studies — the ability of a substance to cause DNA damage — in vitro and in vivo yielded conflicting results. “It was not possible to demonstrate any genotoxic effect. Nor was it possible to obtain any consistent or convincing evidence from animal studies,” he said.

The JECFA committee also evaluated randomized trials and epidemiological studies to examine the association between aspartame and health effects, such as cancer or diabetes, and found statistically significant increases for hepatocellular, breast, and some hematological cancers in cohort studies consuming aspartame. However, he added, “a consistent association” between sweetener consumption and a specific type of tumor could not be demonstrated, and there were limitations in the studies, such as the way in which exposure to this sweetener was estimated.

Moderate consumption

In practice, little has changed. Beyond the warning flag to monitor its consumption and strengthen research on this sweetener, the results of the WHO reviews, Branca pointed out, “do not indicate that the consumption of products containing sweeteners automatically has an impact on health.” Within the maximum intake threshold established by JECFA, consumption is “acceptable” with “no appreciable effects” on health, but experts recommend controlling the use of these sweeteners. “We are not advising companies to recall products nor are we recommending consumers to stop consuming altogether. We just advise a bit of moderation,” Branca summarized. The WHO senior official insisted that the maximum recommendation of 40 milligrams per kilogram of weight per day is a high ceiling and gave an example: if an adult weighs 70 kilograms, his maximum acceptable intake is about 2,800 milligrams of aspartame per day; and if the presence of this sweetener in a common soft drink is between 200 or 300 milligrams per day, this means consuming between nine and 14 cans of soft drinks per day to exceed the acceptable threshold (assuming no other food source is ingested).

For a start, Branca said, there is no problem for occasional consumers of aspartame products. “Unless we have more robust data to recommend a reduction in acceptable daily intake, we are confident or comfortable that the occasional level of exposure, which is far from the acceptable daily intake, is safe or does not produce an appreciable health risk. The problem is for large consumers,” warned the expert, who focused on the increase in the consumption of artificial sweeteners as sugar substitutes and their use, especially among children.

We are not advising companies to recall products nor are we recommending consumers to stop consuming altogether. We just advise a little moderation.”

Francesco Branca, Director of WHO’s Department of Nutrition and Food Security

Branca urged food manufacturers to avoid excessive use of sugar and salt and stated that sweeteners are probably “not the way to go either.” To the general public, he threw out another piece of advice, “If consumers are faced with the decision to drink a cola with sweeteners or one with sugar, I think a third option should be considered, which is to drink water instead and limit consumption of sweetened products altogether.”

The external experts that were consulted, for their part, also call for caution in the interpretation of the WHO decision. “All of this can be scary and can be misinterpreted. But if JECFA does not modify the acceptable daily intake, the evidence is very low,” Carmen Vidal, professor of Nutrition and Bromatology at the University of Barcelona laments. The expert fears a repeat of the controversy raised in 2015 by the same WHO body when it also listed red meat as a possible carcinogen: “I am concerned about the alarm that will be generated unnecessarily.”

Vidal insists on the need to distinguish between risk and hazard — ultraviolet light is a hazard, but risk depends on exposure and protection — and warns that observational and association studies often have “many contradictory variables” that make it difficult to find a strong link between agent and disease. Ramon Estruch, head of the Cardiovascular Risk, Nutrition and Aging research group at Hospital Clínic-Idibaps, agrees: “The main problem with these types of additives is that the relationship between them and health is difficult to measure in some respects.” The researcher, coordinator of the Predimed study on the Mediterranean diet on health, gives an example: “At the cardiovascular level, on the fact that it could have an effect on diabetes, mortality, and that it is not useful for weight loss, it seems that the evidence is solid. But in cancer it is more complicated because the factors that induce cancer are more complex and the time that passes between exposure and the appearance of the event is very long and makes it difficult to draw conclusions.”

The fewer additives, the better

The physician maintains that any food or supplement, such as aspartame, is within a broader dietary pattern and it is “very difficult” to isolate the effect of a single element and attribute cancer to the action of a particular dietary supplement. “The recommendation in health, in any case, is with all such additives, the fewer the better. And if it can be zero, then zero. The general recommendation is to follow a Mediterranean diet and there is no room for any type of additives,” he recommends. Estruch suggests, however, that the WHO review is positive “to alert companies to change the composition of products or reduce the amount of sweetener”: “I think [the decision] is good to improve the quality of products,” he says.

The amount ingested, in any case, is always key. And as long as it is below the threshold recommended by health authorities, “it is safe” insists Vidal. Aspartame may be present in some drugs, but the amounts are far from the maximum recommended daily intake, explains Miguel Villaronga, a hospital pharmacist at Sant Joan de Déu in Barcelona: “In pharmacy, aspartame is a notifiable excipient. It is a sweetener used in the formulation of drugs. When the drug is very bitter, for instance, and you want to make it more palatable.” Villaronga is the author of a list of drugs containing aspartame, a compendium aimed at patients suffering from phenylketonuria, a rare hereditary disorder that causes phenylalanine, an amino acid found in aspartame, to accumulate in the body. For this group of people, exposure to this sweetener can have health consequences, but for the general population, the amounts present in these drugs are tiny: for example, a 100-milligram chewable tablet of Viagra contains only 8.6 milligrams of aspartame, biodramine chewing gum contains three milligrams and a sachet of ibuprofen contains about 30 milligrams.

In Europe, the European Food Safety Authority (EFSA) will have the final say on any regulatory changes affecting manufacturers or consumers. This institution is responsible for regulating the conditions of the products ingested by the consumer and can set new ceilings on food and beverage formulas. In a 2013 review, EFSA experts concluded that “aspartame did not represent a safety concern at current estimates of aspartame exposure or at the acceptable daily intake of 40 milligrams per kilogram of body weight per day.” They only made an exception for persons suffering from phenylketonuria, for whom this acceptable daily intake was “not applicable, as they require strict compliance with a low-phenylalanine diet,” they clarified.

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