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The summary of findings from the International Agency for Research on Cancer (IARC) evaluation of hazard, and Joint Food and Agriculture Organization/WHO Expert Committee on Food Additives (JECFA) assessment of risk have been published.
Prof Robin May, Chief Scientific Adviser, Food Standards Agency (FSA), said:
“JECFA’s report supports the FSA’s view that aspartame is safe to consume at current permitted use levels.
“While the IARC report finds that evidence of an association between aspartame consumption and cancer in humans is limited, we welcome the WHO’s call for more and better studies to help increase understanding of this potential issue.”
Further information:
Prof Andy Smith, MRC Toxicology Unit, University of Cambridge, said:
“For the first time IARC have evaluated the possibility that aspartame might cause cancer in humans i.e. whether it can be viewed as a cancer hazard. It was classified as possibly carcinogenic (Group 2B) based on limited animal and limited human data. These are not strong opinions. The main animal findings discussed were considered previously by EFSA in 2013 and remain controversial. As with older studies, more recent human investigations are either negative or show apparent weak associations between cancers and aspartame consumption but IARC admit other factors such as lifestyle, diet and underlying health issues cannot be ruled out. In addition, IARC reiterates previous opinions that it is not clear how aspartame could cause cancer since it is fully broken down to natural molecules before absorption. Although the IARC discussions reported seem to focus particularly on liver cancer associated with aspartame in humans, it is important to recognise that in the UK smoking, alcohol intake and a fatty liver can be significant factors for this disease.
“Importantly, the same evidence that IARC considered and their report have been examined by JECFA, the WHO/FAO committee responsible for estimating whether there are any risks or likelihood of cancer developing associated with aspartame consumption. The committee saw no new reasons to change its longstanding recommendation of an acceptable daily intake 0-40 mg per kg of bodyweight without appreciable health risk.
“Overall, the IARC and JECFA reports should not be a source of great concern. They have called for any future animal and human studies to be conducted under strict modern guidelines to encourage both scientific and public confidence. Suggestions for such guidelines have already been published.”
Prof Kevin McConway, Emeritus Professor of Applied Statistics, Open University, said:
“I was asked to write an invited comment for The Lancet Oncology, to be published alongside the summary of the IARC classification. I understand that my comment is available to the media under embargo. I won’t repeat the detailed points from it in my comment here, though my main concerns are mentioned here fairly briefly.
“In the past, there has been widespread misunderstanding of what IARC actually mean by their system of classification of cancer hazards to humans. In recent years, IARC have much improved their explanation of what it all means. But some misunderstanding does still happen, and the public reaction to the leak, two weeks ago, of IARC’s classification of aspartame as “possibly carcinogenic to humans”, did exemplify that to some extent.
“Briefly, the IARC classifications are based on hazard, not risk. That is, the experts advising IARC are asked about the evidence that an agent (for example a chemical substance like aspartame, or an activity like working as a firefighter or doing shift work) could change the chance of cancers in some circumstances. Whether there is a change in risk in circumstances that might actually occur in practice is not part of the IARC’s assessment. In any case, the risk to any particular human or group of humans will depend on their level of exposure to an agent that can cause cancer. Instead, agents are classified by IARC into one of four groups on the basis of the strength of scientific evidence that they are a cancer hazard. The groups are labelled “carcinogenic to humans” (Group 1), “probably carcinogenic to humans” (Group 2A), “possibly carcinogenic to humans” (group 2B), and “not classifiable as to its carcinogenicity to humans” (group 3).
“Of all the agents that IARC have classified over the years, just over a thousand of them, half are currently classified in group 3. Often this will simply because of lack of good evidence, or sometimes because different pieces of evidence point in different directions. But there can be other sets of reasons for allocating an agent to group 3 – basically it includes any agent where IARC did not find enough evidence to conclude even a possibility that it might cause cancer in humans.
“IARC do re-assess agents when enough new evidence emerges, and sometimes they will move an agent between groups as a result. These moves can be in either direction on their strength of evidence scale. Thus IARC classified coffee drinking in group 2B, possibly carcinogenic, when they first classified it in 1990, but in 2016 they reclassified it to group 3, “not classifiable”, in the light of new evidence. Coffee drinking is not in group 3 because of lack of evidence, really, because coffee has been researched endlessly. IARC say that there is in fact evidence suggesting lack of carcinogenicity for several types of cancer in humans, and indeed for a few types of cancer, there is some evidence that coffee drinking reduces rather than increases the chance of cancer. In 1988 they classified diesel engine exhaust as a probable cancer hazard (group 2A), but it was reclassified as a definite cancer hazard (group 1) when they looked again at the evidence in 2012. In this case, the new evidence removed most of the doubt that diesel exhaust was capable of causing cancer in some circumstances. But again, this says nothing about the size of the risk from being exposed to diesel exhaust.
“Another change of classification throws more light in the difference between hazard and risk. The substance 1,1,1-trichloroethane has been considered several times by IARC, and was most recently classified, in 2021, as being probably carcinogenic (Group 2A). That was because more evidence had become available on whether the substance could possibly cause human cancers under any circumstances. Previously it was in Group 3, not classifiable. But in fact any cancer risk to the general population from this chemical will have reduced considerably since the 1990s. Up till then, it was in common use, particularly as a solvent, but in 1989 it was listed in the Montreal Protocol treaty as a substance that can deplete the ozone layer, and its production and use have decreased hugely since then, reducing the risk to the population.
“Aspartame has not previously been classified by IARC, so its classification cannot yet have changed. It is in group 2B, not group 3, but the issue of the lack of good enough evidence does seem to apply to aspartame too. IARC, and JECFA in its assessment (which is based on risk), both comment on the existence of bias, flaws and inconsistencies in the available evidence. More and better evidence will, I hope, become available in the future, and this could well lead one or both organisations to revisit their assessments. But, since that evidence does not yet exist, we can’t say what direction any reassessment might go in. Maybe in future IARC will move aspartame to group 2A, or they may leave it in group 2B – but they could move it to group 3, as happened with coffee, because that is where they classify substances where there is essentially no evidence that they can cause human cancers.
“But for now IARC have put aspartame in group 2, so they are saying it could possibly cause cancer under some circumstances, but that this is far from certain. So it remains perfectly possible that it cannot cause human cancers at all.
“The IARC classification is not based on risk, but exceptionally their classification of aspartame was carried out alongside a re-assessment by JECFA of risks from consuming aspartame as a food or drink additive. This was possible because there does exist an international body, JECFA, charged with assessing risks from food additives, and the fact that both JECFA and IARC come under WHO probably helped in setting up this arrangement. (JECFA reports to the UN’s Food and Agriculture Organization, the FAO, as well as to WHO.) For many, possibly most, of the agents classified by IARC, there is no such international organisation for risk assessment, so it would simply not be possible to publish hazard and risk assessments together.
“However, I do not recall any previous occasion when an IARC cancer hazard assessment was co-ordinated with a risk assessment by another body. That does raise the question of why it was done this time. I don’t know, but perhaps it has something to do with the fact that aspartame has been controversial, particularly in America, since it was first produced. On the website of the FDA, the US federal Food and Drug Administration, at https://www.fda.gov/food/food-additives-petitions/timeline-selected-fda-activities-and-significant-events-addressing-aspartame, is a lengthy list of what has gone on over the years, going back to 1969, and including approvals for different food and drink uses, removals of some approvals under legal challenge, petitions to change things, and so on. The FDA approved the use of aspartame in carbonated beverages back in 1983, with an acceptable daily intake (ADI) of 50mg per kg of bodyweight, somewhat above the JECFA ADI of 40mg/kg bodyweight which was set in 1981 . That has remained the position in the USA ever since, despite more challenges and more re-assessments.
“I realise that there is a risk of public confusion with the simultaneous statements, with IARC saying that there could, possibly, be a cancer hazard from aspartame under some, undefined, circumstances, and JECFA saying that they are not going to change their maximum acceptable daily intake, which is based on risk assessment. But in fact these are not inconsistent, because they are talking about different things. JECFA are not saying that there cannot be any cancer hazard at any consumption level, but only that there’s no convincing evidence of a health risk (from cancer or any other health issues that they considered), as long as daily consumption over a person’s life generally remains under the JECFA ADI of 40mk/kg bodyweight. It remains possible that consumption above that level might increase cancer risk, but since the IARC hazard classification is only that aspartame is a possible cancer hazard, it also remains possible that aspartame does not increase cancer risk even at very high consumption levels. This uncertainty is uncomfortable, perhaps, but it’s not going to go away, at least until more and better research is done.
“In making their re-evaluation of risk, JECFA used new estimates of how much aspartame people do actually consume in their food and drink. So far, they have not published all the details of those new estimates. Presumably more details will be given when they publish the full report on their meeting to reconsider aspartame – we have only a summary so far and the full report will not appear for another six months, as will the full IARC report. But in the summary, JECFA say that high estimates of actual consumption were 20 mg/kg bodyweight for children and 12 mg/kg of bodyweight for adults, which are well below the 40mg/kg ADI. (The reason the actual consumption estimate for children is bigger than for adults is, I assume, simply because children have lower bodyweight than adults, so if an adult and a child drink the same amount of aspartame-containing cola, the child is consuming more per kilogram of bodyweight.)
“Doubtless there are some individuals somewhere who do consume above the ADI. What should they, and anyone else concerned about their aspartame consumption, do? Well, there are other sweeteners, though many of them seem yet not to have been researched to the same extent as aspartame. (I believe the only other sweeteners in common use to have been assessed by IARC are cyclamates, assessed in 1988 and put in the not classifiable group, group 3.) In that context, it’s perhaps worth remembering that there is yet another WHO statement about sweeteners, namely the guideline published this May, “WHO suggests that non-sugar sweeteners not be used as a means of achieving weight control or reducing the risk of noncommunicable diseases”. This applied to a range of sweeteners including aspartame and most others. It isn’t saying that people should go back to drinking sugar-containing drinks instead, and the WHO document about the guideline suggests that public health and similar recommendations should promote water drinking. The guideline relates to the effectiveness of sweeteners for particular uses, not their safety. I should point out that it does not go further than making a suggestion, and that it is a ‘conditional recommendation’ that is, one for which the evidence is not by any means certain (and has been criticised).”
Prof Oliver Jones, Professor of Chemistry, RMIT University, said:
“The IARC has made the assessment that leaked reports over the last few weeks suggested they would and classified aspartame as category 2b, the 2nd lowest level. This means there is insufficient evidence of a link. Other things in this category include mobile phone use, and petrol engine exhaust fumes.
“This is the first time that the IARC has looked at aspartame and seems to have been prompted by a paper that came out in 2022 that mentioned liver cancer. The IARC committee would have reviewed all the available literature when coming to this conclusion, but not done any new research themselves.
“There are two terms we need to understand here. The first is ‘hazard’ which just means a possible harm (even if that harm would be very unlikely to occur), and ‘risk’ which is the likelihood of the harm occurring. Think of it like driving a car. There is definitely a hazard; cars crash, and people get injured, and even die, but the risk of that happening when you drive to the shops or take the kids to school is low, most of us don’t think about it – even though the risk is not zero.
“Now, the IARC only looks at hazard which in this case means they just looked to see if there was any evidence that aspartame might be linked to cancer. They do not make an assessment of how likely the hazard is to occur.
“The Joint FAO/WHO Expert Committee on Food Additives committee has not changed its safety rating on Aspartame which they set at 40mg/kg body weight which for a 70 kg adult would mean drinking roughly 14 cans of Diet Coke a day, over a long period. This is consistent will all the major food safety agencies around the world who regularly conduct their own assessments and all classify aspartame as safe at the levels it is used at.
“We are all exposed to carcinogens every day. Even things that the IARC classifies as class one carcinogens, such as UV light and alcohol, do not cause cancer just because you are exposed to them once. For example, if you get too much sun on the beach in summer you might get sunburn but you’ll recover. If you continually sunbathe with no sun protection then your risk of skin cancer goes up.”
Prof Sir Colin Berry, Emeritus Professor of Pathology, Queen Mary University of London, said:
“Despite a very great deal of scientific evidence from carefully conducted studies, a view is expressed in the IARC classification that appears to be based on a singular pattern of interpretation of animal studies and indifferent epidemiology indicating a possible hazard and failing to identify a risk. It might also be thought that the “mixture” of tumours that are associated with this view are likely to have very different pathogeneses – and that genotoxicity cannot be invoked.”
Prof Sir David Spiegelhalter, Emeritus Professor of Statistics, University of Cambridge, said:
“These IARC reports are getting a bit farcical. In spite of IARC’s conclusion that aspartame was ‘possibly carcinogenic to humans’, which got lots of media attention, another expert committee (JECFA) that actually investigates the magnitude of any risk found “no convincing evidence from experimental animal or human data that aspartame has adverse effects”. As they have said for 40 years, average people are safe to drink up to 14 cans of diet drink a day, which is about an old gallon – about half a large bucketful. And even this ‘acceptable daily intake’ has a large built-in safety factor.”
Prof Paul Pharoah, Professor of Cancer Epidemiology, Cedars-Sinai Medical Center, Los Angeles, said:
“It is somewhat difficult to judge this report as, at this stage all that IARC is publishing only a summary with a brief description of the interpretation of the available evidence by the expert working group, but, the full report with details of all the evidence considered will be published later. In short there is weak epidemiological evidence that aspartame is associated with an increased risk of primary liver cancer (that is cancer that arises in the liver rather than a cancer that started elsewhere and spread to the liver, or secondary liver cancer). This evidence comes from three studies that have reported an association but there is not much evidence to suggest that the association is ‘causal’ (association/correlation does not necessarily mean causation). In addition there was limited evidence that aspartame is carcinogenic in experimental animals, but this evidence was thought to have serious flaws. Finally, aspartame has some chemical properties that might be cancer associated.
“In short the evidence that aspartame causes primary liver cancer, or any other cancer in humans is very weak. This is why it is classified as Group2B. Other examples of classified as Group2B are extract of aloe vera, diesel oil, caffeic acid found in tea and coffee. Group 2B is a very conservative classification in that almost any evidence of carcinogenicity, however flawed will put a chemical in that category or above.
“This is reflected in the view of the Joint FAO/WHO Expert Committee on Food Additives who concluded that there was no convincing evidence from experimental animal or human data that aspartame has adverse effects after ingestion. They noted that aspartame is rapidly metabolised into chemicals found in many common foods. Thus the JECFA had no reason to alter their current recommendation on an acceptable daily intake of aspartame.
“The general public should not be worried about the risk of cancer associated with a chemical classed as Group 2B by IARC.”
Prof Alan Boobis, Emeritus Professor of Toxicology, Imperial College London, said:
“The conclusions of IARC and JECFA on aspartame reflect the respective approaches taken by the two committees. IARC has classified aspartame as 2b, which reflects a lack of confidence that the data from experimental animals or from humans is sufficiently convincing to reach a clear conclusion that aspartame is carcinogenic. But IARC did conclude that any carcinogenicity was most likely through an indirect effect and not through direct interaction with DNA (genotoxicity). JECFA reviewed all of the toxicological effects of aspartame including carcinogenicity and genotoxicity. The weight of evidence did not support any carcinogenic effect and JECFA found no basis to change its previously established acceptable daily intake. Hence, exposure at current levels would not be anticipated to have any detrimental effects.”
Prof Tom Sanders, Professor emeritus of Nutrition and Dietetics, King’s College London, said:
“The new data in the IARC report suggests a possible link between liver cancer and aspartame in some observational studies. There has been a marked increase in liver cancer related to obesity in several Western countries, notably in the USA, that is associated with non-alcoholic fatty liver disease. Type 2 diabetes and obesity are major cause of fatty liver disease. Sugar intake has been previously linked to fatty liver disease as it encourages the synthesis of fat in the liver. There is no evidence that aspartame increases fat accumulation in the liver. People with diabetes or who are obese are more likely to use artificial sweeteners compared with those who are not obese. Consequently, this association while consistent may not be causal.
“IARC noted the evidence is limited because they cannot rule out confounding factors and because the data from animal studies is inconsistent, aspartame was classified 2b – a possible cancer hazard. JECFA, however, does not believe the risks posed by aspartame are anything to be concerned about providing the amounts of aspartame consumed are below the acceptable daily intake, which are unlikely to be exceeded in practice.”
Prof Gunter Kuhnle, Professor of Nutrition and Food Science, University of Reading, said:
“The publication of the IARC and JECFA opinion is very welcome as it ends the speculation about the safety of Aspartame. The two WHO agencies have done what they are supposed to do: IARC has reviewed the data and found some very limited evidence that Aspartame could cause cancer – and based on the same data JECFA has concluded that a consumption up to 40 mg per kg of body weight per day is safe and there is no need to change current recommendations.
“It is unfortunate that leaking some information might have created unnecessary uncertainty and concern as consumers might be rightfully worried if they are told that something that is in many foods could cause cancer. The published opinion puts this into perspective and makes it very clear that there is no cause for concern when consumed at the current amounts. Scientific advisory bodies are often unable to react quickly and respond to an emerging story so it’s good they will now have both the IARC and JECFA assessments to digest and respond to.
“This illustrates also the importance of distinguishing between hazard and risk and highlights the difficulty in communicating hazards: sunlight is a hazard as it can cause cancer, but the risk depends on the amount of sun light and whether we use protection. Likewise, even if Aspartame causes cancer at very high amounts, there is no risk when consuming it at the amounts that are permitted in foods.”
Dr Duane Mellor, Registered Dietitian and Senior Lecturer, Aston Medical School, Aston University, said:
“The findings from the two separate evaluations of aspartame by International Agency for the Research on Cancer (IARC) and the Joint FAO/WHO Expert Committee on Food Additives (JECFA) have carefully considered the research which as explored any association between this non-nutritive sweetener and developing cancer. When considering this type of evaluation it is important to be aware that these documents talk about things being a hazard, which means they could cause harm; and a risk, which looks at the chances of that hazard actually leading to harm.
“Although the press release highlights how common cancers are in general, it and the evaluation focus on a small number of types of cancers and particularly liver cancer, which are relatively rare unless associated with hepatitis, alcohol-related or metabolic liver disease.
“The independent reports both also acknowledge that the evidence is incomplete, as typically to be sure of something being both a hazard and a risk, it needs a clear biological mechanism, good and consistent data from animal models and data from exposure in human studies. With respect to aspartame, the mechanism is not fully clear – it might link to methanol which is produced as it is digested, but that is not fully accepted. The animal data only comes from one group, and although independent of food industry, it has been considered to have some methodological issues. As for the data from studies in humans, it is difficult to see the effect of aspartame over other risk factors and studies of populations have not consistently found the link to the same or similar cancers seen in animal models. With this evidence being unclear, it has led to the IARC classifying aspartame as a possible carcinogen – this means that there might be a link but there is a lack of evidence that it can definitively be linked to an increased cancer risk in humans. With this limited evidence as a possible carcinogen or 2b classification, aspartame sits with things like aloe vera and caffeic acid – a compound commonly found in vegetables and fruit as well as coffee (which are actually associated with a lower risk of cancer).
“With this lack of clear risk, JECFA have concluded that there is no need to change recommendations about intakes of this sweetener – this means that for most people who might have a can or two of diet soft drink there is no change recommended by JECFA.
“Although the press release from WHO suggested anyone consuming between 9-14 cans for an adult would be within the safe limits, when it comes to aspartame intake, to be clear this is not a recommendation to consume, as high intakes of any soft drinks, including diet versions containing sweeteners is likely to lead to less healthy foods being consumed (there is some evidence that there is displacement of healthy food choices in the diet) and other health effects such as dental erosion from the acid many of these products contain.
“So what this does not mean is we should start consuming aspartame or other non-nutritive sweeteners more often, as these reports link to a WHO report published earlier this year which found that there is no clear beneficial link between using non-nutritive sweeteners and improvements in metabolic markers including blood glucose (sugar) or better weight management in people living with higher body weight and obesity. It is the case that for most people water will be the healthiest option, but if a sweetened drink is desired, using non-nutritive sweeteners as a way of reducing sugar intake and ideally sweetened products all together as a ‘stepping stone’ towards a healthy diet would be sensible.”
‘Summary of findings of the evaluation of aspartame at the International Agency for Research on Cancer (IARC) Monographs Programme’s 134th Meeting, 6–13 June 2023 and The JOINT FAO/WHO EXPERT COMMITTEE ON FOOD ADDITIVES (JECFA) 96th meeting, 27 June–6 July 2023’ was published at 23:30 UK time on Thursday 13 July 2023.
Declared interests
Prof Andy Smith: “No commercial or consultancy conflicts of interest.
Member of EFSA Working Group on aspartame 2013.”
Prof Kevin McConway: “I am a Trustee of the SMC and a member of its Advisory Committee. My quote above is in my capacity as an independent professional statistician.”
Prof Oliver Jones: “I have no conflicts of interest to declare.”
Prof Sir Colin Berry: “Have consulted for WHO, Governments, agrochemical and pharmaceutical industries.”
Prof Sir David Spiegelhalter: “None.”
Prof Paul Pharoah: “I have no conflicts of interest to declare.”
Prof Alan Boobis: “I currently chair the Committee on Toxicity (COT) and it is an independent scientific advisory committee providing advice to the Food Standards Agency (FSA). I am a member of a number of advisory committees in the public and private sectors, specifically the International Life Science institute (ILSI), ILSI Europe, The Center for Research on Ingredient Safety at Michigan State University, the Long Range Research Strategy (LRSS) of Cosmetics Europe, Owlstone Medical, The brigid project: Bridging the Gap between Microplastics and Human Health (Plastics Europe), Personal Care Products Council (PCPC) Sunscreen Consortium (all non-remunerated).”
Prof Tom Sanders: “I was a consultant on NutraSweet and aspartame fifteen years ago.”
Prof Gunter Kuhnle: “No conflicts.”
Dr Duane Mellor: “I have previously provided spoken at International Sweetener Association events.”
For all other experts, no reply to our request for DOIs was received.