Sweet Talking, (Aspartame) The Ecologist, Vol 30, No 4 June 2000 Health Matters: In a recent survey of 166 studies on the effects of the sweetener aspartame on human health, 74 had industry-related funding and 92 were independently funded. Of the industry sponsored articles, 100 per cent attested to aspartame's safety. Of the non-industry sponsored articles, 92 per cent demonstrated some type of adverse reaction. Ed Metcalfe investigates whether the industry's assurances about aspartame are any more than sweeteners themselves. Aspartame is a sugar substitute added to literally thousands of products, most notably diet soft drinks, and known best to the world of diet conscious consumers as NutraSweet. While NutraSweet maintains that its product is entirely safe, independent researchers continue to present evidence of the chemical's neurotoxicity, linking its ingestion with the onset of numerous adverse symptoms including - in particular - headaches seizures (convulsions) and mood disorders. In fact, aspartame had been the focus of controversey long before it was approved for public consumption in l981. Several key tests conducted in the early l970s to establish the safety of the product were heavily critcised by US Food and Drug Administration (FDA) scientists; while a Public Board of Inquiry set up by the FDA to address the question of aspartame's safety actually recommended that aspartame should not be approved until further tests had been done to discount a possible link between aspartame and brain cancer. In spite of these objections, the FDA Commissioner approved aspartame. It is only now, 18 years later, that those further tests on brain tumors are being conducted, not by NutraSweet (not surprisingly), but by independent researchers at King's College London. APPROVAL WITHHELD Aspartame was discovered by accident in l965 by James Schlatter, a chemist working for US pharmaceutical company G D Searle. Following Schlatter's discovery, Searle conducted tests on the safety of aspartame, and in l967 petitioned the FDA for permission to market the chemical as a sweetening agent. In July l974 the FDA gave its approval, only to withdraw it again in December that year. The retraction was caused by controversy within the FDA as to the safety of aspartame and the validity of Searle's tests. In August l974, before aspartame had made it onto the market, consumer interest attorney James Turner and neuroscientist Dr. John Olney of Washington University filed a formal objection to the FDA's approval, stating they believed aspartame could cause brain damage. They cited research carried out by Olney which found that aspartate (one of the constituents of aspartame) destroyed nerve cells in the brains of mice. Furthermore, FDA toxicologist Dr. Adrian Gross had come upon some irregularities in the submitted tests of another Searle product, Flagyl. Searle's unsatisfactory responses to queries concerning Flagyl raised suspicions over the validity of Searle's tests in general. With approval now withheld, Gross and others were appointed to a task force to investigate Searle's studies on a number of products including aspartame. The task force, which reported in March l976, noted that 'Searle has not submitted all the facts of experiments to the FDA, retaining unto itself the unpermitted option of filtering, interpreting, and not submitting information which we would consider material to the safety of the product'. It concluded: 'At the heart of the FDA's regulatory process is its ability to rely upon the integrity of the basic safety data submitted by sponsors of regulated products. Our investigation clearly demonstrates that, (in the case of) the GD Searle Company, we have no basis for such reliance now.' In the light of these findings the FDA singled out three key studies submitted by Searle on the safety of aspartame. It set up a new task force, headed by Jerome Bressler, to investigate these studies and determine whether or not they had been properly conducted. In August l977 the Bressler Report (as it became known) was released. Investigators found significant deviations from acceptable procedures for conducting non-clinical laboratory studies. They discovered, for instance, that a significant proportion of animal tissues from one of the studies had been allowed to decompose before post-mortem examinations could be performed. Original animal pathology sheets and the pathology sheets submitted to the FDA showed marked differences. Animals were recorded as dead and then subsequent records would indicate that the same animal was still alive - almost certain evidence of a mix- up - which tallied with evidence that animals had not been correctly tagged. In one of the studies examining the possible carcinogenicity in rats of a breakdown product of aspartame called diketopiperazine (DKP), investigators could not ascertain what dosage of DKP had been fed to the rats. There was also evidence that the feed in the DKP test had been improperly mixed, allowing the animals to avoid the DKP while eating. In l987 Dr. Jacqueline Verrett, a toxicologist and member of the Bressler Task Force, testified before a US Senate hearing. She described the discrepancies found in the Searle tests of aspartame as, 'serious departures from acceptable toxicological protocols'. 'It is unthinkable', she said, 'that any reputable toxicologist giving a complete objective evaluation of this data resulting from such a study could conclude anything other than that the study was uninterpretable and worthless and should be repeated'. On the crucial question itself: 'It would appear that the safety of aspartame and its breakdown products has still not been satisfactorily determined since many of the flaws cited in these three studies were also present in all of the other studies submitted by Searle'. SWITCHING SIDES Even before the Bressler Report had been released the FDA's Chief Counsel, Richard Merrill, considered there to be enough evidence to bring fraud indictments against Searle. In January l977 Merrill wrote to US Federal Attorney Samuel Skinner requesting that he'convene a Grand Jury investigation into Searle and three of its officers, for their wilful and knowing failure to make reports to the FDA and for concealing material facts and making false statements in reports of animal studies conducted to establish the safety of the food additive aspartame'. Since the studies in question were conducted in the early l970s, it was important that Skinner act quickly to avoid the five year deadline imposed on criminal prosecutions by the US Statute of Limitations. In what can only be described as an interesting twist, Skinner was approached by Searle's lawyers, Sidley and Austin and invited to join their firm. Skinner accepted, leaving the decision on a Grand Jury investigation to await the appointment of his successor. By December l977, despite repeated warnings from Richard Merrill at the FDA, the Statute of Limitations had expired on the aspartame case. TUMOUR RUMOURS In l978, while examining FA files on aspartame animal studies, Dr. John Olney found two studies that revealed an unexpectedly high incidence of malignant brain tumours in aspartame-fed rats. In response to Dr. Olney's concerns, the FDA decided to set up a Public Board of Inquiry (PBOI) to evaluate this brain tumour evidence and reach a final conclusion on the safety of aspartame an issue that had now been dragging on since l974. The study causing most concern was called E33/34. This was a two year study in which 320 rats were fed aspartame and 119 rats were fed a normal diet and used as controls. At the end of the study 12 of the aspartame-fed rats had developed brain tumours while none of the control rats had. This represented a 3.75 per cent incidence of brain tumors in the rats fed aspartame. In order to determine whether or not these were simply naturally occurring brain tumours the PBOI had to ascertain the spontaneous brain tumour rate in laboratory rats. After examining the literature they concluded that the spontaneous brain tumour rate was considerably les - approximately 0.7 per cent. it was clear, therefore, that E33/34 exhibited a worryingly high tumour incidence that could not be discounted. Accordingly, in October l980, the PBOI unanimously recommended that aspartame should not be approved until additional studies were performed to establish whether or not a relationship existed between the ingestion of aspartame and brain tumours. For FDA toxicologist, Dr. Adrian Gross, E33/334 was unambiguous in its significance. In l985, in his testimony before the US Senate, he stated; 'at least one of those studies (E33/34) has established beyond any reasonable doubt that aspartame is capable of inducing brain tumours in experimental animals.' Arthur Hull Hayes, however, the new FDA Commissioner on whom the final approval decision rested, did not share this view. he overruled the PBOI and without any further tests being conducted approved aspartame for use in dry foods in l981 and in beverages in l983. While Hayes left the FDA shortly afterwards to become a paid consultant with Searle's public relations firm Burson-Marsteller, Professor Olney has kept the spotlight on the brain tumour issue, reiterating the PBOI's call for further testing. In l996 a study conducted by Olney and his colleagues from Washington University alleged a link between the widespread use of aspartame and a 10 per cent increase in the incidence of brain tumours in the early l980s in the US. The language used in the paper is cautious, however. The researchers stress the importance of reminding consumers that the evidence presently available is not sufficient to prove that aspartame caused the brain tumour increases. Therefore new studies properly designed to answer this question are urgently needed. SPONSORING SAFETY A new three year study, begun in October l999 at King's College London, should go some way towards resolving this issue. The research team headed by neurochemist Dr. Peter Nunn, will examine whether aspartame could be linked to primary brain tumours as Olney and others have been suggesting. In l985 Searle was bought by US food and chemical giant Monsanto and the NutraSweet Company was made in a separate subsidiary. In response to news of the King's College study, NutraSweet stated: 'There is already an overwhelming amount of scientific evidence which confirms the safety of aspartame'. The brain tumour issue they attribute to 'scare- mongers'. This is typical of the industry's stance since the l970s and mirrors the FDA's frequently repeated description of aspartame as 'the most thoroughly tested additive in history'. Since its approval, however, reports of toxic reactions to aspartame have steadily mounted prompting, in November l987, a US Senate Hearing at which Senator Howard Metzenbaum testified that the FDA had already received close to 4,000 complaints ranging from seizures and headaches to mood alterations. today, US campaigners on aspartame claim that figure represents barely a fraction of those who have suffered from the effects of aspartame toxicity. At present the Internet is awash with accounts of individuals who claim the onset of problems when aspartame is ingested, and their improvement upon the avoidance of aspartame. In the face of this growing pressure both Monsanto and the FDA remain defiant in their defence of aspartame. They dismiss the accusations as anecdotal, not scientifically proven, and fuelled by misinformation posted on the Internet. The response of both NutraSweet and the FDA is to point to an extensive volume of literature attesting to aspartame's safety. The integrity of this literature, however, is not above suspicion. Professor Ralph Walton of Northeastern Ohio University's College of Medicine recently conducted a survey of aspartame studies in peer- reviewed medical literature. Of 166 studies felt to have relevance for questions of human safety, 74 had NutraSweet industry related funding and 92 were independently funded. Of the industry-sponsored articles, 74/74 (100 per cent) attested to aspartame's safety; of the non- industry-sponsored articles, 84/92 (92 per cent) demonstrated some type of adverse reaction. As Walton says, 'the clear split in the literature, with outcome correlated so closely to funding source, is deeply trouble (raising questions) about aspartame's safety and the appropriatedness of industry sponsorship of medical research'. Perhaps the new research currently being conducted will shed further light on the ingredient. One thing seems certain: we do not know everything yet that there is to know about aspartame. For further information on aspartame, and international campaigns against it, see www.dorway.com and www.holisticmed.com/aspartame. Freelance journalist Ed Metcalfe thanks the websites' coordinators Betty Martini and Mark Gold for their invaluable contributions to this article. Further reading 1. Olney, JW, 'Brain damage in infant mice following oral intake of glutamate,aspartate or cysteine', nature l970, 227, pp.609-610. 2. Olney, JW. et al., 'Increasing Brain Tumour Rates: Is there a Link to Aspartame? Journal of Neuropathology and Experimental Neurology, l996 55 (11) pp. 1115-1123. 3. Walton, RG., 'Survey of Aspartame Studies: Correlation of Outcome and Funding Sources' Unpublished study compiled for US TV program 60 Minutes and provided to Ed Metcalfe by the author. 4. Wurtman, RJ.,'Neurological changes following high-dose aspartame with dietary carbohydrates, New Eng J Med, l983, 309 (7), pp. 429-430. 5. Walton, RG, 'Seizure and mania after high intake of aspartame', Psychosomatics, l986, 27, pp218-220. 6. Walton, RG, 'Possible Role of Aspartame in Seizure Induction', In: Wurtman, Walker (eds) Dietary Phenylalanine and Brain Function. Boston: Birkhauser, chp 18. 7. Olney, JW, Excitotix Food Additive', Neurobehav Toxicol Terratol l984, 6, 445-562, Progress in Brain Research, l988, 73, 283-294. 8. Monte,W, 'Aspartame: Methanol and Public Health, J. Appl. Nutr l984, 6:42 -54. 9. Trocho, C., et. al, Formaldehyde derived from dietary aspartame binds to tissue components in vivo', Life Sciences l998, 63 (5): 337 - 49 Other information in article on components listed as: CHEMICAL REACTIONS In seeking to get at the truth of aspartame's safety the interested consumer's beset approach is to listen to the views of independent scientists and researchers. Aspartame is made up of three chemical: phenylalanine, aspartic acid and methanol. Independent researchers have found all three chemicals to have toxic potential linked to adverse clinical events. PHENYLALANINE Phenylalanine is an amino acid normally found in the brain. Ingesting aspartame can significantly increase brain phenylalanine and tyrosine levels and can suppress the usual increase in tryptophan that follows a carbohydrate rich meal. Such neurochemical changes have been postulated as the cause of numerous adverse neurologic and behavioural symptoms including seizures (convulsions), mood disorders and headaches. Reports of aspartame's role in seizure induction are anecdotal though highly persuasive. Walton published an anecdotal case of particular interest in l986. The case involved a 54 year old woman with no known medical difficulties other than a history of depression. without warning she experienced a grand mal seizure followed by a profound behavioural change categorised as symptomatic of mania. It was discovered that it was her custom to drink up to a gallon per day of iced tea. In the past she had sweetened the tea with sugar, but during the weeks prior to her seizure she had used aspartame instead. She was taken off all medication and aspartame was eliminated from her diet. Within four days all evidence of manic activity had subsided. She continued to ingest large amounts of iced tea, sweetened with sugar, and experienced no relapse. Walton concludes: This patient's clinical course suggests that high intake of aspartame may have triggered a seizure and subsequent manic episode. In l988 Walton published a further eight cases of seizures linked to aspartame. ASPARTIC ACID (ASPARTATE) As early as l970 Olney presented evidence of aspartate's neurotoxicity; it was on these grounds that he objected to aspartame's approval in l974. Aspartate, like glutamate (MSG), is an amino acid that acts as a neurotransmitter in the brain. it is primarily Olney who is responsible for demonstrating that neurons (brain cells) exposed to excessive amounts of aspartate and glutamate become overstimulated and die. In a series of experiments since the l970s Olney has conclusively demonstrated that glutamate and aspartate administered orally to mice cause cell death in certain areas of the brain. The circumventricular organs, which lack the protection of the blood brain barrier, show the worst evidence of neuronal destruction, even at low doses of glutamate and aspartate. The resulting disruption of the hormone flow meant the infant mice displayed sexual disfunction, obesity and stunted growth. METHANOL Aspartame also contains methanol, which upon ingestion is broken down to formaldehyde and then formic acid. Formaldehyde is a highly toxic known carcinogen that causes retinal damage and acts to alter DNA. NutraSweet and the FDA seek to allay the fears of consumers by arguing that there are other foodstuffs that supply as much or even more methanol, such as citrus fruits and juices. The argument is virtually an insult to the independent scientists and campaigners who are concerned about aspartame. As the FDA and NutraSweet know full well, ripe fruits always contain the natural antidote, ethanol, which protects from methanol poisoning by preventing the conversion to formaldehyde and formate. An important recent study confirms that far from being carried out of the body, the formaldehyde from aspartame accumulates in body tissues. These products were listed as may contain aspartame - check label first. Chewing gums Tea beverages Dry mixes for gelatins, puddings, Refrigerated gelatins beverages and dairy toppings Yogurts Ready to eat cereals Frozen desserts Carbonated soft drinks Biscuit fillings Chewable vitamins Fruit drinks Refrigerated juice based drinks Fruit spreads Frozen novelties Refrigerated puddings Breath mints Hard boiled sweets