The article in Reuters suggests that aspartame is set to be declared a possible carcinogen by the International Agency for Research on Cancer (IARC), the World Health Organization’s (WHO) cancer research arm.
Prof Amy Berrington, Professor of Clinical Cancer Epidemiology at The Institute of Cancer Research, London, said:
“The IARC monograph program has a rigorous process for assessing whether a chemical can cause cancer, known as hazard identification. They convene world experts and review of all the relevant evidence using a systematic process to determine if chemicals are possibly, probably or definitely carcinogenic. IARC recommendations indicate that a compound has the potential to cause cancer, but they do not tell us whether they are likely to cause cancer when consumed in a realistic quantity – this is the job of the JEFCA.
“Given the wide use of aspartame, it’s important that any new data is rigorously assessed. I am pleased that the IARC have carried out their first review of the evidence. It is critical that we wait for these official reports from IARC and JECFA before commenting on the findings or implications.”
Prof Andy Smith, visiting worker, MRC Toxicology Unit, University of Leicester, said:
“The question of whether aspartame possesses carcinogenicity potential relevant for humans has been debated many times. It was explored exhaustively by EFSA in 2013 with reassuring conclusions as to its safety for consumers at levels used in food products. It is important for consumers that before new concerns are raised the IARC and JECFA opinions are published and critically reviewed by toxicology and risk assessment experts. IARC conclusions are not always in alignment with the wider scientific community.”
FSA (Food Standards Agency) Deputy Chief Scientific Adviser, Rick Mumford, said:
“Our view is that the safety of this sweetener has been evaluated by various Scientific Committees and it is considered safe at current permitted use levels.
“The IARC report has not yet been published and, when it is, it will be examined by the Joint FAO/WHO Expert Committee on Food Additives (JECFA), who will put together a risk assessment by the end of July. We will closely study JECFA’s report and decide whether any further actions are needed.”
Prof Gunter Kuhnle, Professor of Nutrition and Food Science, University of Reading, said:
“The media report does not provide any further information on the data used by IARC, so it is impossible to comment on the outcome. However, it is important to note that IARC investigate whether a compound can cause cancer at all – because this can help regulators and the public to deal with the risk. Whether a compound causes cancer depends on many factors, in particular the dose or exposure: sunshine for example is classed as carcinogenic by IARC – and the link between sunshine and skin cancer is well established – but we can manage the risk by reducing exposure and using sunscreen. A classification as “carcinogenic” by IARC therefore can have different consequences: bacon and smoking are in the same category of “carcinogenic to humans”, but the risk associated is very different.
“The ”possibly carcinogenic to humans” category, which aspartame is allegedly classed into, is a very large category which includes things such as aloe vera extract and bracken fern, but also diesel fuel and HIV. Aspartame has been investigated by various regulators – including IARCs sister WHO-agency, JECFA – and they found that a consumption of up to 40 mg/kg BW per day (2.4 g/d for a 70 kg adult) does not cause any adverse effects. New evidence will of course be reviewed by regulators and that might result in a change of guidelines depending on the evidence, but it is premature to second guess these decisions and create unnecessary concern.”
Prof Sir Colin Berry, Emeritus Professor of Pathology, Queen Mary University of London, said:
“We need to wait to see the detail of the IARC evaluation before being able to assess what this means and what evidence they have looked at. Aspartame has been repeatedly reviewed in the past and the epidemiology has not been convincing in terms of robust evidence of harms.”
Prof Oliver Jones, Professor of Chemistry at RMIT University in Melbourne, Australia, said:
“We really need to wait and see the full IARC evaluation before we can make any firm conclusions. Without that we are really shooting in the dark. We don’t know what the terms of the assessment were, or what criteria they used to rule evidence in or out.
“What we can say is that IARC generally reviews the existing scientific literature on a particular substance or process, then weighs the evidence as to the likelihood said substance or process may be able to cause cancer under certain conditions or exposure. In this case the IARC are apparently going to list aspartame as a ‘possible carcinogen’ (the same as it previously classified eating red meat and using mobile phones), which means there is some evidence that it can cause cancer in humans but at present it is far from conclusive. But we really can’t be sure of anything until a formal announcement is made.
“It is also important to note that just because something may possibly cause cancer does not mean that it automatically does if you are exposed to it. The dose makes the poison.
“For example we know UV light in sunlight causes cancer, that’s why we put on sunscreen at the beach – but we don’t put on sunscreen when we go outside in winter even though we are still exposed to sunlight, why? Because the dose is lower in winter.
“Similarly we know that smoking causes cancer but that doesn’t mean that I will get cancer if one day I happen to breath in some second hand smoke.
“Like other food additives Aspartame had to undergo robust safety evaluation before it was approved for use in food. It is the world’s most widely used artificial sweetener and current evidence is that it is safe at current levels of consumption.”
Prof Tom Sanders, Professor emeritus of Nutrition and Dietetics, King’s College London, said:
“Aspartame has been in use as an intense sweetener for more than thirty years in the UK. It is typically used as a concentration of up to 500 mg/litre but usually less as it is used in blends with acesulfame K. However, there have been reports from the Ramazzini Institute claiming that rats fed very large amounts of aspartame developed more tumours. However, the fidelity of the data was questioned by the European Food Safety Authority.
“Other more recent animal studies in the USA have failed to show any evidence of carcinogenicity and the US Food and Drug Administration continues to maintain that aspartame is safe to use.
“Aspartame consists of two amino acids joined together (phenylalanine – an essential amino acid, aspartic acid) which is esterified to a methyl group. On digestion, phenylalanine and aspartic acid are released and small amount of methanol are produced. Methanol is potentially carcinogenic because it converted to formic acid via formaldehyde, which can damage DNA. However, the amounts of methanol released following the consumption of aspartame containing beverages is exceedingly low about 50 mg in a litre at the most, which is about three times lower than the amount of methanol in fruit juices such as orange juice (Committee of Toxicology https://cot.food.gov.uk/sites/default/files/cot/cotstatementmethanol201102revjuly.pdf), and levels of methanol in wine can be as high as 250 mg/litre.
“As far as I am aware there is no evidence from human prospective studies linking aspartame use to cancer (Haighton et al; 2019; Fulgori & Drenowski 2022) and regulatory authorities have extensively reviewed the toxicological data and given aspartame a clean bill of health.”
Fulgoni, V.L., III; Drewnowski, A. No Association between Low-Calorie Sweetener (LCS) Use and Overall Cancer Risk in the Nationally Representative Database in the US: Analyses of NHANES 1988–2018 Data and 2019 Public-Use Linked Mortality Files. Nutrients 2022, 14, 4957. https://doi.org/10.3390/nu14234957
Haighton L, Roberts A, Jonaitis T, Lynch B. Evaluation of aspartame cancer epidemiology studies based on quality appraisal criteria. Regul Toxicol Pharmacol. 2019 Apr;103:352-362. doi: 10.1016/j.yrtph.2019.01.033. Epub 2019 Feb 2. PMID: 30716379.
Prof Kevin McConway, Emeritus Professor of Applied Statistics, Open University, said:
“Obviously the Reuters story does not tell us for certain what the relevant UN/WHO agency, IARC, is going to announce about aspartame. IARC have already said (as Reuters report) that they are going to announce their findings about aspartame on 14 July. The fact that there will be an announcement does not tell us in itself that IARC are going to say that aspartame might be carcinogenic. They review many substances, and exposures, to see whether they are carcinogenic to humans, and by no means do they label all of them as carcinogenic. We really should wait until 14 July to see what IARC actually say.
“But even if Reuters’ sources are good and IARC are indeed going to say that aspartame is in their category of being “possibly carcinogenic to humans”, I don’t think that will be the most important announcement about aspartame from a UN agency that day. For reasons I’ll explain, an IARC categorisation of being possibly carcinogenic does not mean that a substance actually presents a risk to humans in normal circumstances, despite what the wording appears to say. The UN body that does have the job of assessing the risk from food additives, including aspartame, is JECFA, the Joint FAO/WHO Expert Committee on Food Additives. IARC have never considered aspartame before. JECFA have, and back in 1981 they established an acceptable daily intake of aspartame, of 40 milligrams per kilogram of body weight per day. To consume over that limit would require a very large daily consumption of diet Coke or similar drinks. On 14 July, JECFA may change that risk assessment, or they may not. Reuters’ sources don’t appear to have given any information about that. So really we do have to wait.
“In short, the IARC categorisation won’t tell us anything about the actual level of risk from aspartame, because that’s not what IARC categorisations mean. The JEFCA categorisation is intended to tell us something useful about the risk, but so far we don’t know what it will say.
“Why isn’t the IARC categorisation helpful in assessing whether aspartame presents a health risk, even if the Reuters story is correct about what IARC will announce? It’s because those IARC categorisations indicate whether something presents a hazard. This means that the IARC experts do not assess whether, in practice, a substance or exposure presents a cancer risk to people. Instead they assess whether it would ever be capable of presenting a risk, under any circumstances, even if the only harmful circumstances are really, really unlikely to occur. IARC leave it to others to assess the actual risk that a substance presents to the public.
“As an example of the distinction between a hazard and a risk, consider the possibility that a meteorite might fall from the sky and kill a human. Obviously meteorites do definitely present a hazard to humans. They fall to earth regularly, at very high speeds, and often weighing a substantial amount. But in fact only one person has ever been hit by a meteorite in recorded history, and though she did suffer a painful bruise, the encounter was definitely not fatal. So the risk to humans from meteorites is very tiny indeed, despite the fact that meteorites definitely present a hazard to human health.
“This distinction has caused endless confusion in relation to IARC assessments over the years. This wasn’t helped by the fact that the series or IARC publications that presented their evaluations was called “IARC Monographs on the Evaluation of Carcinogenic Risks to Humans” right up to 2019, even though it never assessed actual risks. IARC have, however, now changed the name to “IARC Monographs on the Identification of Carcinogenic Hazards to Humans”, which at least describes what they actually do. And at least, this time, there will be a risk assessment published by JEFCA, at the same time as the IARC assessment.
“IARC now make it very clear what they are aiming to do in their assessments. For instance they produce an infographic, at https://www.iarc.who.int/wp-content/uploads/2023/06/IARC_MONO_classification_2023_updated.png, showing the four categories they use (unhelpfully labelled 1, 2A, 2B and 3). A substance or exposure is classified according to the strength of evidence that it can potentially cause cancer in humans, that is, that it presents a cancer hazard. So for something in group 1, “carcinogenic to humans” like tobacco smoking, the experts consider that there is sufficient evidence it could cause cancer in humans. The next group down in strength of evidence, group 2A, “probably carcinogenic to humans”, includes things like emissions from high-temperature frying or working night shifts. The evidence is weaker than for group 1, so the experts aren’t entirely confident that these exposures could ever be carcinogenic, though they could well be carcinogenic.
“But the group where aspartame will go, according to Reuters’ sources, is one further down on the strength of evidence scale. Group 2B, “possibly carcinogenic to humans”, is used where the evidence of potential carcinogenicity in humans is ‘limited’, and the evidence in experimental animals is ‘less than sufficient’, in the IARC’s words. So there could remain considerable doubt that something in this group could ever, under any circumstances, cause cancer in humans. There is a group below that, group 3, “not classifiable as to its carcinogenicity in humans” where the evidence of a hazard is so weak that the IARC experts don’t regard it as at all adequate, so the evidence for a group 2B exposure is a bit stronger than that, but could still be really pretty weak.
“To date, IARC have classified 1,042 different substances and exposures into these four groups. (See https://monographs.iarc.who.int/agents-classified-by-the-iarc/.) Almost half of them (500) are in Group 3, so there isn’t any substantial evidence of carcinogenic hazard. But there are 322 in group 2B, where aspartame will be put if Reuters are right, where there is some evidence that they could cause cancers under some possible circumstances, but the evidence for that is fairly weak. The great majority of the 322 are chemical compounds that most people will never have heard of and (in many cases) will never encounter. But there are better-known exposures, like extracts from whole Aloe vera leaves, traditional Asian pickled vegetables, and some exposures to substances that people working in dry cleaning, printing, or hairdressing might encounter. I emphasise again, though, that the evidence that these things could cause cancer is not very strong (or they would have been put in group 1 or 2A), and that the IARC grouping has nothing directly to do with the actual risk arising from these exposures.”
Comment sent out by our colleagues at SMC Spain:
Rafael Urrialde de Andrés, professor at the Faculty of Biological Sciences of the Complutense University of Madrid and at the Faculty of Pharmacy of the San Pablo-CEU University, and member of the Board of Directors of the Spanish Society of Nutrition, says:
“We have to wait until 14 July and see how it determines the assessment and in which group it encompasses it. From then on, the Food Safety Agencies and Authorities will have to determine whether to re-evaluate, ban it or maintain authorisation and under what conditions, whether to continue with the same Acceptable Daily Intake or lower it and to what extent it is lowered.
“Aspartame is present in many types of foods and beverages, although in warm countries, due to taste deviations caused by high temperatures, it is used in lower concentrations and in combination with other sweeteners than, for example, in central and northern Europe.”
Here are the IARC categories: https://monographs.iarc.who.int/wp-content/uploads/2018/07/QA_ENG.pdf
Prof Amy Berrington: “Professor Amy Berrington was vice-chair of the 2020 IARC monograph priorities meeting.”
Prof Andy Smith: “The author is independent and has no financial interest.”
Prof Gunter Kuhnle: “No conflicts of interest.”
Prof Sir Colin Berry: “I have consulted for a number of pharmaceutical and agrochemical companies including Monsanto, Syngenta, BASF and so on. Never worked on aspartame.”
Prof Oliver Jones: “I have no conflicts of interest to declare here.”
Prof Tom Sanders: “I was a consultant on NutraSweet and aspartame fifteen years ago.”
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.”
Rafael Urrialde de Andrés: “From 1986 to 1992 I worked at the Faculty of Biological Sciences in the Chair of Plant Physiology as a collaborator and developing the work of my doctoral thesis. In 1991-1992 I worked as a Scientific Collaborator in the Plant Freezing Unit at the Cold Institute of the Spanish National Research Council (Consejo Superior de Investigaciones Científicas). From 1992 to 2000 I worked in a Consumers’ Association, in the Spanish Consumers’ Union and in the Revista de Consumo Ciudadano (edited by 5 consumer associations), where I was the Director of Food and Health and the Technical Director, respectively. From 2000 to 2006 I worked at Puleva as Director of Food Safety and Health. From 2006 to 2020 at Coca-Cola Iberia as Deputy Director of Scientific and Regulatory Affairs and later as Director of Nutrition and Health. Since 2020 I am Professor in different Faculties of different Universities: Faculty of Biology of the UCM, Faculty of Pharmacy of the USP CEU, Faculty of Nursing of the University of Valladolid and I collaborate in different masters in food, applied plant biology and food safety of the Faculty of Veterinary Medicine of the UCM, of the Faculties of the Campus of Health Sciences of the University of Barcelona, of the Faculty of Pharmacy of the University of Seville and of the Faculty of Pharmacy of the University of Granada. I am a Full Academician of the Royal European Academy of Doctors-RAED and member of its Governing Board and Honorary Academician of the Spanish Academy of Nutrition and Dietetics, President of the Scientific Committee of the Spanish Society of Sports Medicine and Member of the Board of Directors of the Spanish Society of Nutrition-SEÑ. I am also a member or partner of several scientific societies: Spanish Society of Food Safety-SESAL, Spanish Society of Community Nutrition-SENC, Spanish Academy of Nutrition and Dietetics-AEND, Spanish Society of Nutrition-SEÑ, Spanish Society of Sports Medicine and member of the Board of Trustees of the Spanish Nutrition Foundation-FEN. Since March 2020, I have no conflict of interest because I have no contractual relationship of any kind with any food company, neither in the food processing or distribution sector, nor with any pharmaceutical company. I have only collaborated with Consumer Associations and Scientific Societies or I am a member of the Scientific Advisory Committee in some information platforms.”
For all other experts, no reply to our request for DOIs was received.