When a division of the World Health Organization (called the International Agency for Research on Cancer or IARC) issued a declaration on the safety of aspartame, the media took notice. 

The artificial sweetener is widely used in the U.S. and throughout the world. IARC’s Monograph 134, which will share the much-anticipated details on its findings, is still in press and no release date has been provided. Although, according to IARC standard protocol, this should be in about nine months.

The recent declarations that aspartame is ‘possibly carcinogenic’ and not helpful in weight loss caused quite a stir. While some criticism from food and beverage companies was to be expected, these claims also contradict those of food regulatory agencies in Europe, Japan, and the U.S., some of which have spoken out and shared concerns about the IARC’s process.

The FDA’s statement on aspartame, which was released the same day as IARC’s statement, had concerns about the quality of the studies used by IARC to reach its conclusion. According to the agency, “FDA scientists reviewed the scientific information included in IARC’s review in 2021 when it was first made available, and identified significant shortcomings in the studies on which IARC relied.”

Additional questions surround the issue, putting the credibility of IARC into question: 

• What were the methods used by IARC to reach these conclusions about aspartame? 

• Why were the findings released many months before the monograph, not allowing scientists outside of IARC’s working group to see their complete methods, as WHO recommends in its own framework? 

• Why has IARC put consumers, who are not food additive experts, in a position to fear cancer from ingesting aspartame during the many years it was classified as safe, while health care providers have insufficient information to council them? 

This last question is particularly upsetting for individuals with liver cancers, who are wondering if their use of diet drinks and other artificially sweetened foods in the name of sugar avoidance caused their cancer. 

What is currently available to the public is a short summary of IARC’s findings on the alleged carcinogenicity of aspartame (as well as two additional substances it was reviewing) in a July 2023 article in The Lancet. No mention is made of peer review. 

The recent article mentions only six studies on aspartame, even though IARC reported reviewing 1,300 papers. It offers no explanation of the process or criteria used to choose the studies it decided to include in its analysis. And while we should, in theory, be able to get a general description of what guides IARC’s evaluation process from the Preamble to IARC Monographs, a deep dive into the preamble document raises more questions than it answers.

Here is what we learn from the short summary article in The Lancet: 

The IARC Working Group concluded that for cancer in humans, there was limited evidence that aspartame causes hepatocellular carcinoma (aka. liver cancer), officially given a label of “2B” or “possibly carcinogenic.” The group found the evidence for other cancers inadequate.

Of the human studies it mentioned, only one looked at aspartame consumed from all sources in the individuals they were following. The others looked at artificial sweeteners more broadly, where aspartame was one of a number that were consumed. The IARC felt that “artificial sweeteners” was a good enough proxy for aspartame in epidemiological studies, although they did not share their scientific reasoning beyond stating that the studies were conducted in countries where aspartame is predominantly used in artificial sweeteners. This degree of extrapolation is problematic. 

There are differences among artificial sweeteners that need to be accounted for, and it would be difficult to determine what dosages might inform outcomes in such a study (in addition to the limitations already presented by studies that rely on self-reporting).

The one study that looked at aspartame specifically was a large French prospective cohort study which found an increased risk for breast cancer, obesity-related cancers, and overall cancer risk, but these have not been confirmed in additional studies. This type of observational study looks at two groups of similar individuals over longer periods of time. 

IARC further identified three cohort studies (one in 10 European countries and two in the U.S) that did find an increased risk for liver cancer associated with artificially sweetened beverage consumption. IARC concluded that all three were good studies, but could not rule out chance, bias, or confounding as being responsible for the results. 

The Lancet article says that IARC considered several (although it did not give a number) animal studies across a range of species, including mice, rats, dogs, and hamsters, as well as European Food Safety Authority reports of negative findings based on oral exposure. The article qualifies that many of these studies took place before Good Laboratory Practices (GLP) guidelines were in place and may have had some limitations. 

The IARC Working Group found no increase in liver tumors in three well-conducted GLP mouse studies, but claimed that these mouse models may not have been sensitive enough to detect a carcinogenic effect (again, no scientific explanation as to why). The only studies that showed an increase in risk for liver cancer after aspartame was fed to the mice were from the Ramazzini Institute. These have been discredited by many groups. 

IARC found the mechanistic evidence “limited” for key characteristics of carcinogens. In animal studies it induced oxidative stress in several tissues including liver, chronic inflammation, and angiogenesis (in a few studies), as well as some positive findings for genotoxicity. However, most experts think these findings need to be explored further.

Overall, IARC declared there is “limited” evidence for increased cancer risk after aspartame oral exposure. A minority of the group disagreed and wanted its classification changed from 2B to 2A (“probably causes cancer”), but they were overruled.

The Expert Committee on Food Additives of WHO found no reason to change its position that aspartame is safe when consumed in the recommended amounts. So far, most other national and international groups including the U.S. FDA, Health Canada, and the European Food Safety Authority, maintain that aspartame consumption, in the recommended amounts, is safe.

This brings us back to why our questions surrounding the IARC process are so critical to answer. Because of its global stature, citizens who are not trained in toxicology and risk analysis—along with governments and health policy experts in countries that do not have enough resources to conduct their own analyses—pay close attention to IARC study findings. 

But these audiences are at a loss as to how to interpret the findings when they are announced with so much media fanfare, and so little substance around the details. 

How is IARC achieving its mission of “cancer research for cancer prevention” by raising alarms on aspartame without sharing its process and methods with the broader community to allow for better scrutiny and understanding?

The Center for Truth in Science will be exploring this further in the coming months.