The Scotsman reported today on a study in the American Journal of Clinical Nutrition which found that use of high fructose corn syrup coincided with a steep rise in weight problems in the US. Gee... is that surprising? Along with that report is a quick overview of the different man-made sweeteners out there, including aspartame.
The Hindu Business Line reported a couple days ago on a Miami longshoreman, Bartimous Berry (what a name), filing a lawsuit against Coca-Cola C. for selling a different version of Diet Coke at the soda fountains than that used in cans and bottles. The difference? Soda fountain Diet Coke contains a mixture of saccharin and aspartame which Coca-Cola claims is necessary to stabilize fountain syrup before adding carbonated water. The lawsuit alleges that Coca-Cola did so to increase profitability as saccharin is cheaper than aspartame. According to the San Mateo County Times,
Coca-Cola spokesman Dan Schafer said saccharin is used for "product quality reasons" not "money reasons." He said aspartame loses its sweetness faster in a fountain drink than in a canned or bottled soda.Update
I found a brief case study on the approval of aspartame in Enhancing the Regulatory Decision-Making Approval Process for Direct Food Ingredient Technologies: Workshop Summary from the Institute of Medicine . In this account, the approval process is framed with considerably less hype and with very thorough references, e.g., FDA documents.
In 1973, midst the controversies surrounding the use of cyclamate and saccharin, G.D. Searle & Co. submitted a food additive petition for aspartame. This was approved certain "dry" uses, i.e., as a tabletop sweetener and in cold breakfast cereals, powdered beverages, desserts, dessert toppings and chewing gum, but with a caveat. Labels of products containing the sugar substitute were to include the statement "Phenylketonurics: Contains Phenylalanine" as a warning to those with a rare genetic defect preventing the metabolism of phenylalanine, a chemical component of aspartame. Thus, the impression that I and some others may have made that aspartame had been actively rejected by the FDA until Commissioner Hayes is incorrect.
Following the FDA's approval, a number of individuals filed objections and requested a hearing. In conjunction with data discrepancies by a contract laboratory in the toxicological testing of other substances, the agency decided to stay the approval's effective date pending a hearing. Four years later, the FDA convened a three-member Public Board of Inquiry to conduct the hearing. This was quite unusual. Under most circumstances, such a hearing is conducted by an Administrative Law Judge. In this case, the objectors agreed to a modified procedure in which the objectors submitted a list of names from which Board members were then selected.
The Board, while agreeing with the FDA's assessment that aspartame posed no risk to causing brain damage or neuroendocrine function, nevertheless recommended against approval due to unresolved questions regarding brain tumors discovered in rodent studies. This was rejected by the Commissioner who affirmed the original ruling in 1981. It should be mentioned that the case study fails to mention that the Commissioner had been freshly appointed by the Reagan administration. In his decision, the Commissioner commented that "[few] compounds have withstood such detailed testing and close scrutiny". One year later, as a floor amendment to a bill amending the Orphan Drug Act, Searle was granted a patent term extention "to restore some of the time lost during the lengthy delays in securing final FDA approval". This amendment was proposed by Hon. Henry Waxman, who explained it simply as "the Senate amendment extends the patent for a food additive".
In 1982, Searle petioned to have the ruling amended to allow the use of aspartame in carbonated beverages. This was approved the following year. Though several persons filed objections requesting an immediate stay and a public hearing, these were rejected without hearing. In 1985, Community Nutrition Inst., a consumer group, brought a judicial challenge to approval for use in carbonated beverages. The court affirmed the FDA ruling, finding that "the FDA properly denied a hearing after finding that petitioners have raised no material issue regarding the safety of the wet use of aspartame".
Subsequently, the FDA continued to approve additional uses, each time rejecting objections and denying hearing requests, finally approving a petition that aspartame be permitted for use as a general purpose sweetener in 1996.
 Institute of Medicine . Food Forum, Enhancing the regulatory decision-making approval process for direct food ingredient technologies : workshop summary, Washington, D.C.: National Academy Press, 1999.
Several weeks ago, lawsuits were were filed in three separate California courts against twelve companies producing or using aspartame as a sugar substitute in their products. This was reported in the U.N. Observer & International Report which, admittedly, seems rather sketchy. The article was released by the World Natural Health Organization and the National Justice League. While most of the arguments were familiar. this paragraph caught my eye:
Since its discovery in 1965, controversy has raged over the health risks associated with the sugar substitute. From laboratory testing of the chemical on rats, researchers have discovered that the drug induces brain tumors. On Sept 30, l980, the Board of Inquiry of the FDA concurred and denied the petition for approval. In l981, the newly appointed FDA Commissioner, Arthur Hull Hayes, ignored the negative ruling and approved aspartame for dry goods. As recorded in the Congressional Record of 1985, then CEO of Searle Laboratories Donald Rumsfeld said that he would call in his markers to get aspartame approved. Rumsfeld was on President Reagan's transition team and a day after taking office appointed Hayes. No FDA Commissioner in the previous sixteen years had allowed Aspartame on the market.Wait a second, did that just say CEO Donald Rumsfeld, as in Secretary of Defense Donald Rumsfeld. That's scary. Oh man, it is. Wild.
In 1965, while developing an ulcer drug, James M. Schlatter at G.D. Searle accidentally tasted one of his compounds and discovered aspartame. Recalling the event, said Schlatter, "Some of the powder got onto my fingers. When licking my finger to pick up a piece of paper, I noticed a very strong, sweet taste." While this approach of discovery might seem somewhat haphazard, perhaps even dangerous, it was by no means novel. Saccharin, the oldest artificial sweetener, was discovered in 1879 while Ira Remsen and and Constantine Fahlberg were synthesizing coal tar derivatives. Fahlberg discovered the sweetness of one of the compounds at dinner after not thoroughly washing this hands. To uncover which compound, he returned to his lab and sampled bottle after bottle of his chemicals searching for what he had tasted. Thus saccharin was discovered .
 I. Flatow, They all laughed-- : from light bulbs to lasers, the fascinating stories behind the great inventions that have changed our lives, New York: HarperCollins, 1992, pp. 156-160.
In , Hill and Belsito report on the case of a 60-year old Caucasian woman with a 6-month history of eyelid dermatitis. Despite application of a corticosteroid-containing ointment and discontinuation of eyelid cosmetics and nail polishes for 2 months, her rash did not clear. Several years back, in response to a facial dermatitis, she had been patch tested and found to be allergic to formaldehyde, quaternium-15 and fragrances. As expected, her facial dermatitis was resolved by swtiching to formaldehyde-, quaternium-15- and fragrance-free facial and nail cosmetics.
For this current condition, she was again patch tested. Positive reactions occured to formaldehyde (++), quaternium-15 (++), diazolidinyl urea (+), DMDM hydantoin (+) and imidazolidinyl urea (++), with her hair care products and cleansers containing multple sources of these. She was instructed on ways of avoiding such allergens, with particular emphasis on formaldehyde and formaldehyde releasers. Despite doing so for three weeks, her condition improved only slightly. A local pharmacist suggested avoiding aspartame, which she had started using as an artificial sweetner 5 months prior to the onset of her condition (approximately 80 mg per day). Within a week of discontinuing use, her eyelid dermatitis was resolved completely and has yet to recur.
The resolution of the case, of course, naturally suggests that the aspartame was the cause of her eyelid dermatitis. Indeed, following consumption, aspartame is hydrolyzed in the intestine to phenylalanine, aspartic acid, and aspartic acid methyl ester. The methyl ester is converted into methyl alcohol (methanol) and carried by the portal vien to the liver. Here it is oxidized into formaldehyde and then converted into formic acid by alcohol dehydrogenase, aldehyde dehydrogenase and the microsomal oxidase pathway. This process occurs not just in the liver but in other parts of the body containing these enzymes, including the eye.
To be fair, previous studies have shown that does of aspartame beyond 100 mg/kg are required to raise methanol blood levels, hence formaldehyde and formic acid, above contol. This correponds to drinking 35 cans of diet beverage in one sitting for a 70 kg person. Nevertheless, it may well be the case that blood and urine are not the right places to look for formaldehyde.
 A.M. Hill and D.V. Belsito, "Systemic contact dermatitis of the eyelids caused by formaldehyde derived from aspartame?" Contact Dermatitis, vol. 49, pp. 258-259, Nov. 2003.
A scientific-sounding email linking aspartame, a.k.a. Nutrasweet, and multiple sclerosis and systemic lupus was recently circulated to me. While the letter itself has been debunked by the Urban Legends Reference Pages, the prevelance of anti-aspartame sentiment on the web (9/10 of the top 10 hits on Google) suggests there may be something more to this. What's going on?
A search on Pubmed for 'aspartame' yields 754 published scientific papers from 1973 to 2004. A search on Biosis matches 1283 records, though a large number of these have to do with the chemistry of aspartame (and these dealing with important subjects like how to control the release of aspartame from chewing gum).