KUALA LUMPUR, July 14 – The World Health Organization (WHO) has kept its stance on aspartame unchanged, after the latest safety review of the artificial sweetener found only limited evidence linking it to cancer.
The International Agency for Research on Cancer (IARC), the WHO’s cancer agency, recently reviewed all published evidence on aspartame’s potential carcinogenic effects and classified the sweetener as “possibly carcinogenic to humans”.
But while three studies showed a link between the consumption of artificially sweetened beverages – a good proxy for aspartame exposure – and hepatocellular carcinoma, a type of liver cancer, the evidence was limited, according to the IARC.
There was also limited mechanistic evidence that aspartame exhibits key carcinogen characteristics, such as the induction of oxidative stress, chronic inflammation, and the modification of cell proliferation, cell death, or nutrient supply.
A separate WHO and Food and Agriculture Organization (FAO) committee, the Joint Expert Committee on Food Additives (JECFA), has also updated its risk assessment on aspartame, reaffirming the acceptable daily intake of 40 mg/kg body weight.
According to the findings by JECFA’s panel, there is no compelling evidence, based on experimental or human data, to suggest adverse effects of aspartame within the established limits set by the previous committee.
JECFA’s evaluation covered in vitro and in vivo genotoxicity studies, which yielded conflicting results, making it difficult to establish any general toxic effects.
Similarly, animal studies failed to provide consistent or convincing evidence. JECFA reviewed 12 animal studies, the majority of which yielded negative results. Studies reporting positive results had limitations in their design and data interpretation.
While epidemiological studies in humans identified certain associations with cancer and Type 2 diabetes, JECFA said that these observations were primarily based on long-term observational and large cohort studies.
Observational studies, including long-term studies and large cohorts, have certain limitations in that they cannot establish a cause-and-effect relationship with certainty, as they rely on observation rather than controlled experiments.
“The conclusion, again, was reaffirming the acceptable daily intake of aspartame,” said Dr Francesco Branca, director at WHO’s Department of Nutrition and Food Safety, at a virtual WHO media briefing last Wednesday.
Aspartame is a widely used sweetener found in various beverages like Coke Zero Sugar, Diet Coke, Sprite Zero, Pepsi Zero Sugar, and Mountain Dew Zero Sugar. It is also present in chewing gum, cough drops, toothpastes, and other products.
In the United States, the US Food and Drug Administration (FDA) has conducted multiple reviews of aspartame and has determined it to be safe for the general population.
In anticipation of the WHO analysis, the FDA recently updated its website with information regarding aspartame and other sweeteners, saying it continues to monitor the latest science and levels of consumer exposure to sweeteners. The FDA also calls aspartame “one of the most studied food additives in the human food supply.”
What It Means For Consumers
During WHO’s press conference Wednesday, Dr Branca said that the WHO is not recommending the withdrawal of products containing aspartame from the market. However, due to certain concerns identified by some studies, albeit inconsistently and without sufficient clarity, the WHO advises consumers to limit their consumption of sweeteners.
Dr Branca highlighted that the current acceptable daily intake for aspartame is “pretty large”.
“An acceptable daily intake of 40 milligrams per kilogram for bodyweight, and if you consider an average adult of about 60-70 kilos, translates to 2,800 milligrams per day of aspartame.
“If we look at, for example, the content of aspartame in common sodas, which is between 200 and 300 milligrams per day, that means consuming between nine and 14 cans of sodas,” Dr Branca explained. “You can see this is quite a large amount.”
“So, definitely, we’re not advising companies to withdraw products nor we are advising consumers to stop consuming altogether. We are just advising for a bit of moderation.”
Dr Branca highlighted a surge in the consumption of sweetener-laden products over the years as a response to consumers’ growing preference for reduced sugar content, leading to an upswing in the usage of sweeteners like aspartame.
What Prompted The Assessments
Dr Mary Schubauer-Berigan, acting head of the IARC Monographs programme, explained that the IARC was given advice by a group of experts in 2019 to evaluate the potential carcinogenic hazard of aspartame, with high priority.
“This was on the basis of new evidence that was emerging, both from animal cancer bioassays and from studies of human cancer given the long latency that has occurred.
“IARC is often called the WHO’s encyclopaedia of carcinogens, and in our long 50-year history, we’ve evaluated more than 70 food additives, including other artificial sweeteners. So it’s not at all unusual for us to be recommended to evaluate these agents,” said Dr Schubauer-Berigan.
Meanwhile, the WHO has a responsibility to be thorough in looking at all potential harms, including harmful compounds or processes, that may lead to cancer initiation or progression, Dr Branca said. “There is a societal concern that our organisation needs to respond to.”
JECFA’s review was requested by the Codex Alimentarius Commission, which develops and adopts food standards that serve as a reference for international food trade.
“What we have done is actually to try and combine these two assessments in a way that allows us to make the best use of their respective mandates and expertise.
“We have adjusted the procedure to avoid, for example, the situation where these two groups were not considering the same pool of data, or when one expert was not informed about the other’s work. We have made it work this way so that the process becomes complementary rather than duplicative.
“This approach allows us to look at the issue from different perspectives and consider various routes of ingestion when examining cancer. In JECFA, we focus on dietary intake and not just the cancer effect but also other cancer effects.
“By bringing together two organisations, we purposely designed the time to be consecutive, so that we could avoid giving conflicting messages and that’s why we’ve been careful in trying to avoid incomplete information from being disseminated to the public. We want to be very transparent and very clear about what these results mean,” Dr Branca said.
Recommendations For Future Research
Dr Moez Sanaa, unit head for WHO’s Standards and Scientific Advice on Food and Nutrition, said one key gap is the lack of time. “We see when we look at the in-depth analysis of the current data, we see some associations that occur when we have a longer period of time.”
Dr Schubauer-Berigan acknowledged that most of the observational epidemiology studies that were done for cancer were either conducted in Europe, although they have broad diversity across European countries with different lifestyles and income levels, or in the US.
“It’s definitely true that a more diverse set of studies across the globe would be needed to understand fully whether there was a carcinogenic hazard from aspartame consumption.”
She highlighted that one of the key limitations of the existing studies is that most of them measured artificially sweetened beverage consumption only at a single time point, with the exception of a few studies.
“All three of the studies that I mentioned for liver cancer only collected data at a single time point. From an epidemiological perspective, the working group concluded that the most likely impact of that limitation is it would tend to lead to exposure misclassification that would be randomly distributed across the entire cohort. And this tends to cause bias towards a null value.
“They didn’t feel that this limitation was really impeding their ability to understand what the findings were. However, it means that the studies currently do not have very good sensitivity to detect effects. And so one of the research gaps is to have better quality exposure assessment, particularly for individual artificial sweeteners,” Dr Schubauer-Berigan said.
“At the same time, it would be helpful to have more mechanistic studies in consumers of these products, these sweeteners, to understand more than mechanistic pathways.
“I think that some of those studies are already in the initial phases, or in conception stage right now, but I think the global community could undertake more and better research to understand these non-traditional pathways to carcinogenesis other than genotoxicity, which is sort of classic mechanism of carcinogenesis,” she added.