In groundbreaking new research, experts at the International Agency for Research on Cancer (IARC) have raised a cautious red flag about the artificial sweetener, aspartame, and its link to liver cancer, but stress that evidence is “limited”.

IARC’s Dr Mary Schubauer-Berigan described the artificial sweetener as “possibly carcinogenic to humans” based on “limited evidence” of links to a liver cancer called hepatocellular carcinoma. She spoke at an embargoed media briefing on Wednesday, just before the release of the new IARC report, early Friday morning.

But in light of the dearth of evidence, the World Health Organization (WHO) will not changed its guideline on aspartame consumption, the agency said in an assessment of exposure risks. The WHO guideline, set in 1981, holds that it is safe for most people to consume up to 40 milligrams of aspartame daily per kilogram of body weight. 

In the WHO risk assessment, issued simultaneously, the WHO and Food and Agriculture Organization’s Joint Expert Committee on Food Additives (JECFA) concluded that there was “no convincing evidence from experimental animal or human data that aspartame has adverse effects after ingestion”, said Dr Francesco Branca, the WHO’s Director of Nutrition and Food Safety. He also spoke at the Wednesday media briefing just ahead of the release of the IARC and WHO reports Friday.  

IARC assesses potentially carcinogenic substances, WHO determines safe levels of exposure

While IARC assesses carcinogenic hazards, as such, JECFA looks at what levels of actual exposure to the hazard are really dangerous.

“It is very important to note that this was a hazard identification and not a risk assessment,” said Schubauer-Berigan, who heads the monograph programme at IARC, a Lyon, France-based research institution affiliated with the WHO.

“A hazard identification aims to identify the specific properties of the agent and its potential to cause harm,” she added.

IARC has four classifications: 1. causes cancer; 2A. probably causes cancer; 2B. possibly causes cancer and 3. unclassifiable as a cancer risk. It has given aspartame a “2B” classification.  

Advice for consumers

Even so, WHO has already recommended that people should be moving away from sweetened drinks – whether sweetened with sugar or artificial ingredients, Branca said.

“If consumers are faced with the decision of whether to take cola with sweeteners or one with sugar I think there should be a third option, which is to drink water instead,” said Branca.

He pointed to a recent WHO guideline that showed artificial sweeteners may also be associated with an increased risk of type 2 diabetes and cardiovascular diseases, as well as not protecting against excess weight gain.

Common sodas contain between 200 and 300 mg of aspartame, meaning that an adult would need to consume between nine and 14 cans daily to exceed the WHO recommended threshold of 40mg/kg, “which is quite a large amount”, added Branca. 

“So definitely, WHO is not recommending that producers or authorities withdraw products from the market, but considering that there are some concerns identified by some studies… certainly advising the consumers to limit the consumption of sweeteners,” he added.

Moderation and switching to naturally sweet food such as fruit is important because “the consumption of products containing sweeteners has increased and the use of sweeteners, including aspartame has increased to try and respond to consumers’ demand to reduce free sugars”, said Branca. 

“This is particularly important for young children who will be exposed early enough to a taste adjustment,” said Branca.

Call to scientists to do more research

In discussing IARC’s assessment,  Schubauer-Berigan said that “the findings of limited evidence of carcinogenicity in humans and animals, and of limited mechanistic evidence on how carcinogenicity may occur, underscore the need for more research to refine our understanding on whether consumption of aspartame poses a carcinogenic hazard”. 

“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,” she added.

IARC had used studies in the US and Europe

Branca agreed, adding that some of the evidence missing included epidemiological studies looking at human outcomes over a longer period, and better mechanistic studies to understand how aspartame could actually affect insulin balance or the risk of inducing cancer.

“We’ve in a sense, raised a flag here, indicating that we need to clarify much more the situation,” said Branca.

Dr Federica Madia, IARC’s senior toxicologist,  said that while aspartame’s key components were almost completely hydrolysed during digestion, there was consistent evidence of oxidative stress, some evidence that it increased insulin levels, and suggestions of impact on “chronic inflammation and increase angiogenesis”.

“The evidence is still limited, but it is there where we would like to go through and investigate more,” said Madia.

Dr Moez Sanaa, WHO’s Head of Standards and Scientific Advice on Food and Nutrition Unit, said: “We need better studies with longer follow-up and repeated dietary questionnaires in existing cohorts. We need randomized controlled trials, including studies of mechanistic pathways relevant to insulin regulation, metabolic syndrome and diabetes, particularly as related to carcinogenicity.”

Aspartame’s links to other health conditions

Aspartame has been linked to a wide range of other serious health conditions aside from cancer. A July roundup by the US-based public health group, Right to Know, cites peer-reviewed studies around the sweetener’s links to cardiovascular disease, Alzheimer’s seizures, stroke and dementia, along with a range of head, stomach and mood disorders, and even weight gain. 

Branca said that JECFA had only found associations with type 2 diabetes and cerebrovascular disease and that these findings were in observational studies and “difficult to interpret”.

Research published last week looking at aspartame’s possible links to Parkinson’s disease found “multiple studies demonstrated decreased brain dopamine, decreased brain norepinephrine, increased oxidative stress, increased lipid peroxidation, and decreased memory function in rodents after (aspartame) use”. 

However, Branca said this study had been published too late for IARC or JECFA to consider.

“We have not clearly identified a potential mechanism of action. Potentially insulin sensitivity could be a pathway but we need to have more demonstrations about that,” said Branca.

Evaluations by the US Food and Drug Administration (FDA), and the European Food Safety Authority have so far rebuffed claims that there is significant evidence of health risks. The FDA states that aspartame is “safe for the general population under certain conditions of use.

Image Credits: Coca Cola, Regular Toxicology and Pharmacology /Elsevier, James Hall/Twitter .