Aspartame: the litmus test for the FSA and EFSA
22nd May 2006
Erik Millstone, Professor of Science Policy at the University of Sussex, warns that recent research into the artificial sweetener aspartame is being ignored by food regulators.
Aspartame (often called by its brand name Nutrasweet) has not only been one of the most controversial food additives in the history of the industry, it has also been one of the most profitable.
In autumn 2005 the controversy intensified with the publication of the results of a long-term feeding study of aspartame conducted by the Ramazzini Foundation in Italy, indicating that aspartame caused a dose-related and statistically significant increase in the incidence of several types of tumour.1 The significance of these results can only be appreciated if they are seen against the bizarre context of the aspartame saga.
In the early 1970s, when the company seeking to market aspartame (G D Searle – and its subcontractor) was testing it for safety and/or toxicity, serious failings occurred in the conduct of those tests.
There is, for example, evidence of rats dying during the course of the experiment, but instead of being dissected in a search for evidence that the test compound might have been responsible, they were discarded and replaced with other rats.
The test material was not accurately characterised, and was not always properly mixed with the feed, so that some of the animals ate the basic diet but avoided the lumps of test compound. Serious shortcomings occurred in all 15 of the pivotal chronic (i.e. long-term) toxicology studies. Instead of acknowledging the mistakes and starting again, Searle submitted the data from the flawed studies.
The errors were revealed by the diligent efforts of an heroic scientist, Adrian Gross at the US Food and Drug Administration (FDA).
So much of Searle's scientific evidence was flawed, including that on two drug products Flagyl and Aldactone, that the Chief Lawyer at the Food and Drug Administration wrote in April 1976 to the Federal Attorney (FA) in Chicago (Searle's HQ was in Illinois) instructing him to convene a Grand Jury to indict, then prosecute Searle.
Shortly thereafter, the Chicago FA was invited to join the law firm Sidley & Austin that represented Searle. He accepted and the Searle legal process was suspended until a new FA came into post. He too was invited to join Sidley & Austin, and the process was delayed again. This continued until the Statute of Limitations expired, so no effective legal action was taken.
Public pressure from scientists and campaigners forced the FDA to experiment with what was called a Public Board of Inquiry (PBoI) to adjudicate on at least some of the facts concerning the possibility that aspartame might cause brain cancer. The inquiry concluded in 1980 that it was not satisfied that aspartame was acceptably safe, and that judgement was endorsed by at least five senior FDA toxicologists.
Despite this, aspartame was licensed in the US by the new head of the FDA, under the incoming Reagan Administration, who shortly thereafter left the FDA and went to work for Nutrasweet's PR company. The sweetener was approved in the UK on the advice of the Committee on Toxicity, whose chairman had his laboratory indirectly funded by Searle, and was approved in Europe and by the World Health Organisation with the involvement of scientists with undeclared commercial links to Nutrasweet.
After products containing aspartame reached the market, some consumers began reporting that they felt acute adverse effects. No-one knows the frequency with which such problems occur, but I estimate between 1% and 10% of consumers experience some adverse effects after ingesting aspartame.
The most common symptoms are severe headaches and blurred vision, while, thankfully, epileptic-type seizures are rare. That evidence has repeatedly been dismissed officially as ‘anecdotal’, although the sufferers often report that occasionally symptoms recur. And when they do, they discover that inadvertently they had consumed aspartame.
In 1996 John Olney of Washington University St Louis, a noble veteran of the aspartame debate, published a paper reporting evidence that the introduction of aspartame had been responsible for an abrupt increase in the incidence of a particularly aggressive type of brain tumour, called glioblastomas, in the US.2
His argument was reinforced by evidence that the tumour type had also been conspicuous in one of the previous, though flawed, animal studies and by biochemical evidence indicating a mechanism through which aspartame could exert a carcinogenic effect. Predictably, the FDA and the US food industry discounted his analysis.
In the UK and Europe it was officially discounted because similar patterns had not emerged in the data, but that is probably because the age-profile of people consuming artificially sweetened products differs between the US and this side of the Atlantic. In the UK and continental Europe, artificially sweetened products are predominantly consumed by younger people rather than by ‘senior citizens’, and it was the latter group that Olney argued were especially at risk.
I and others have repeatedly called for a repetition of the pivotal chronic toxicity tests on aspartame by independent scientists. Morando Soffritti and his colleagues at the Ramazzini Foundation in Italy have not just repeated the flawed tests, using the protocol preferred by the chemical industry. They have substantially improved upon it.
The Italian study, published in 2005, did not use 400 rats, they used 900. Instead of testing the compound at three dose levels (plus a control group) they tested it at five dose levels (plus controls). Instead of killing the rats before they reached the ends of their average natural lives, the rats lived longer so that long-term effects could be studied. In these and many other ways, the Ramazzini study was more thorough, sensitive, reliable and relevant to human exposure than those conducted in accordance with conventional protocols.
The safety of aspartame is officially 'under review'. Provisional comments from the Food Standards Agency (FSA), its Committee on Carcinogenicity and the European Food Safety Authority (EFSA) have emphasised possible reasons for discounting the results of the Ramazzini study, which had indicated that aspartame causes statistically significant increases in the incidence of several types of cancers, as if they were a 'false positive', while they remained blind to the evidence that all the previous studies on which they have been relying are almost certainly false negatives.
Aspartame represents a powerful litmus test for both the FSA and for the EFSA, but current indications suggest that they are likely to fail the test. Both the FSA and EFSA were created to end the subordination of food safety policy-making to industrial and commercial concerns, and instead to put consumers first and to do so in a transparent and accountable fashion.
In the meantime, the chair of EFSA's expert advisory committee is a paid consultant to the International Life Sciences Institute, which is a pseudo-scientific front organisation for the major food and chemical companies. If, despite the evidence from Soffritti et al, and all the earlier evidence of the inadequacies of all the previous studies, aspartame remains on the market, consumers will know that the FSA and EFSA are failures and that more radical reforms will be necessary.
1 M Soffritti et al, 'Aspartame induces lymphomas and leukaemias in rats', European Journal of Oncology, vol. 10, No 2, pp. 107-116, 2005 www.ramazzini.it/fondazione/docs/AspartameGEO2005.pdf; M Soffritti et al, 'First experimental demonstration of the multipotenial carcinogenic effects of aspartame administered in the feed to Sprague-Dawley rats' Environmental Health Perspectives, 2005, Vol. 114, No. 3, March 2006 pp. 379-385 available at www.ehponline.org/docs/2006/114-3/toc.html
2 Olney J. W. et al, 'Increasing brain tumor rates: is there a link to aspartame?', Journal of Neuropathology and Experimental Neurology, Vol. 55, No 11, November 1996
Latest news on aspartame
On 5 May 2006, EFSA announced the findings of its review of the Ramazzini cancer study, concluding it considers aspartame to be ‘safe’.
EFSA acknowledged improvements in design of the scientific study. However, it questioned the link between a slight increase in incidence of cancers (lymphomas and leukemias) in treated rats, saying that they felt this was attributable to a high background incidence of inflammatory changes in the lung in both treated and untreated rats, and associated with high doses of a number of different types of chemicals tested on animals.
However, as Erik Millstone points out, an anomaly remains that rats fed no aspartame did suffer with lung inflammations, but they did not get cancer. EFSA did not address this point.
For EFSA’s response, visit: www.efsa.eu.int/press_room/media_events/1460_en.html