A spoon of sugar. Photo: Sharon McCutcheon/Unsplash
- There is no consensus in the expert community on whether aspartame causes cancer in humans.
- The principal stumbling block is that though there is some evidence both for and against the idea, it is of bad quality.
- An oncologist told The Wire Science that connections between dietary interventions and cancer are among the toughest to figure out.
New Delhi: A new commentary based on animal studies has reignited an old controversy over links between the artificial sweetener aspartame and cancer, and calls for a thorough reexamination in the interests of public health.
The commentary, published in the journal Environmental Health by scientists from Boston College, Massachusetts, addresses the scientific wrangle over aspartame – one of the world’s most widely used artificial sweeteners. An estimated 3,000-6,000 metric tonnes are produced worldwide (2019) for use in more than 5,000 foods and beverages, including cereals, chewing gum, yogurt, pharmaceuticals and instant coffee. Its consumers include children and pregnant women as well.
At the heart of the controversy is an animal study by Ramazzini Institute, an independent, not-for-profit laboratory in Bologna, Italy, which reported in 2006 and 2007 that “aspartame causes dose-related increases in malignant tumours in multiple organs in rats and mice.” The study reported increased cancer risk even at low exposure, approaching the acceptable daily intake (ADI). Exposure during pregnancy increased the risk of tumours in the offspring as well.
The Ramazzini study was disputed on grounds of inaccurate diagnosis of tumours, especially of lung tumours that critics said the researchers had confused with patches caused of inflamed tissue due to a Mycoplasma bacterial infection.The European Food Safety Agency also said that the experimental animals had been poorly managed at the Ramazzini Institute, and had other uncontrolled infections as well.
The institute later reevaluated its diagnosis and confirmed the findings in rats, after ruling out Mycoplasma infection.
The Boston College scientists who looked at the second study by the Ramazzini Institute said that the new results “confirm the very worrisome finding that prenatal exposure to aspartame increases cancer risk in rodent offspring. They validate the conclusions of the original RI studies.”
The scientists add that these findings “are of great importance for public health” and appeal to “all national and international public health agencies to urgently reexamine their assessments of aspartame’s health risks – especially the risks of prenatal and early postnatal exposure”. They also call on food agencies to reassess their respective ADI levels for aspartame.
They also said “that an Advisory Group to the International Agency for Research on Cancer has recommended high-priority reevaluation of aspartame’s carcinogenicity to humans.”
According to the scientists’ report, scientists have conducted only two epidemiological studies of aspartame-exposed populations thus far.
The first was in 2006, by a team at the US National Cancer Institute, on a large group of middle-aged Americans. Their results did not reveal any cancer-causing effects. The second study, by researchers at Harvard University, assessed exposure and reported a significantly elevated risk of non-Hodgkin lymphoma in males who consumed one or more servings of soda per day, the report said.
Stand of international agencies
Meanwhile, a spokesperson at the International Agency for Research on Cancer (IARC), a WHO body based in Lyon, France, told The Wire Science a meeting of the independent Advisory Group to Recommend Priorities for the IARC Monographs during 2020-24 had been convened in March 2019.
The IARC Monographs – detailed reports that “identify the preventable causes of human cancer” (source) – hasn’t previously evaluated aspartame. The substance has received a recommendation of high priority (p. 26-27) for evaluation.
“I am not optimistic we will get an answer from human studies anytime soon,” Dr Aju Mathew, an oncologist and haematologist and director of Kerala Cancer Care, an NGO, said. “IARC may rely on animal studies to provide a recommendation. I think it will mirror the methods followed with the cell-phone studies – but the link between this and cancer will be even harder to unravel.”
In 2013, the IARC published its monograph on cancer risk due to cell-phone use, concluding that there was “limited evidence” among both humans and experimental animals “for the carcinogenicity of radiofrequency radiation”. The monograph’s authors – all topical scientists – justified this conclusion writing the “human epidemiological evidence was mixed”: most of the smaller studies were “largely uninformative” while larger studies were potentially biased or contained “several potential sources of misclassification of exposure”.
The American Cancer Society (ACS), which does not determine if something causes cancer but collates and summarises the recommendations of other organisations, has said that “though research into a possible link between aspartame and cancer continues, these agencies agree that studies done so far have not found such a link.”
It pointed out that the US Food and Drug Administration (FDA) has concluded that “the use of aspartame as a general purpose sweetener … is safe”. An article last updated in 2018 on the FDA website states: “FDA scientists have reviewed scientific data regarding the safety of aspartame in food and concluded that it is safe for the general population under certain conditions.”
The ACS page also quotes the European Food Safety Authority (EFSA) saying, “studies don’t suggest an increased risk associated with aspartame consumption for … leukaemia, brain tumours or a variety of cancers, including brain, lymphatic and [blood] cancers.” The corresponding sentence on the EFSA website reads: “Studies do not suggest an increased risk associated with aspartame consumption for pre-term delivery in pregnant women, leukaemia, brain tumours or a variety of cancers, including brain, lymphatic and [blood] cancers.”
An ACS spokesperson said that these statements, by the FDA and the EFSA on its website, reflect the ACS’s stand as well.
The EFSA, which regulates food additives in the European Union, has set the ADI for aspartame at 40 mg per kg of body weight per day. The FDA’s ADI limit is slightly higher – at 50 mg per kg of body weight per day. The FDA has also estimated that “that if all of the added sugar in the diet of an average 60 kg person were replaced by aspartame, it would result in an exposure of about 8 to 9 mg/kg/day.”
There are only scattered studies on the links between artificial sweeteners in general – much less aspartame specifically – and cancers.
A 2020 report in the Journal of Clinical Medicine underscored the significance of artificial sweetener consumption as a potential risk factor for thyroid cancer, and the need for public awareness regarding this association – “if other studies in future report similar findings.”
For a retrospective observational study, researchers enrolled 50 people diagnosed with thyroid cancer and 50 control subjects diagnosed with benign thyroid nodules. The team also had the participants answer a questionnaire that included questions about the total amount and duration of intake of artificial sweeteners.
The team reported higher consumption of artificial sweeteners in the group with thyroid cancer compared to the group with thyroid swelling, suggesting the sweeteners could be a potential risk factor.
A few other studies have also looked into potential links between artificial sweeteners and bladder cancer in men, and to blood and nerve-related cancers in women.
However, their results don’t add up to conclusive evidence. A review of the medical literature, published in 2021 in the journal Nutrients, examined reported findings on a range of possible side-effects of artificial sweeteners, including, obesity, diabetes, autism, nerve degeneration, skin allergies and cancer. It concluded that more research is needed.
As things stand, the uncertainty isn’t surprising. “Dietary interventions and cancer is a tough one to figure out,” Dr Mathew, who is also a faculty member at the University of Kentucky Cancer Center, said. “In fact, the toughest – especially those with only a small, relative risk for cancer, unlike alcohol and liver cancer.”
“So,” he added, “I am concerned about aspartame, because the IARC is going to examine it.”
T.V. Padma is a freelance science journalist.