Aspartame CYCLAMATES Three similar compounds, namely sodium cyclamate, calcium cyclamate and cyclamic acid are collectively referred to as the "cyclamates." They are about thirty times sweeter than sugar and are chemically more stable than saccharin or aspartame. Some of a cyclamate dose is excreted by the body unchanged, but some is converted to a cyclohexylamine, a compound whose safety has been questioned. Like saccharin, cyclamates were granted 'Generally Recognized as Safe" Status in the U.S. in 1958 based on years of apparent problem free use. This status was rescinded in 1969 when bladder tumors were discovered in rats which had been fed a cyclamate-saccharin (10:1) mixture. Since saccharin was a minor component of this mixture, cyclamates were implicated in the tumor formation. The 1969 study by the independent Food and Drug Research Laboratories was widely criticized, and never reproduced with a statistically significant number of animals. In fact, more recent studies on rats, mice, dogs, hamsters and monkeys, using both cyclamates and their breakdown product, cyclohexylarnine, have shown no effect on cancer rates. Indeed, unlike saccharin, the question of whether cyclamates are carcinogenic or co-carcinogenic at all, has not been adequately answered. Neither has the allegation that cyclamates are mutagenic, that is, capable of producing genetic damage which can be inherited, been substantiated. ASPARTAME The only reproducible effect of cyclamates has been testicular atrophy in rats when fed large doses. This problem, which has not been seen in humans, is caused by the metabolic product cyclohexylamine. Taking into account the maximum dose at which no such effect is observed in rats, and building in a hundred fold safety factor, it is possible to arrive at an "Accepted Daily Intake" of cyclamate which represents an insignificant risk. Accordingly, the Health Protection Branch in Canada allows cyclamate as a tabletop sweetener. The U.S. ban on cyclamates is still in effect, but may be rescinded in light of the fact that the Food and Drug Administration has reviewed the large number of studies submitted to it in the 1980s and has concluded that neither cyclamates nor cyclohexylamine are carcinogens. Aspartame cannot be considered a 'non-caloric" sweetener since it is broken down in the digestive tract into its components which are absorbed and metabolized. These components, aspartic acid, phenylalanine and methanol account for the 4 calories per gram energy rating of aspartame. However, since the substance is about 180 times sweeter than sugar, very little needs to be used in foods and beverages to achieve a satisfactory degree of sweetness. Diet drinks normally contain about 60 milligrams per 100 milliliters, which translates to roughly 200 milligrams per serving. Industry figures show that 99% of aspartame users consume less than 34 mg per kg of body weight per day. For a seventy kg person this means less than 2.38 grams. The average consumption is about 500 milligrams per day. Aspartame cannot be used in cooked or baked foods since it breaks down into its components and loses its sweetening power. Aspartame is the most widely researched food additive to have ever come on the market. As with any other newly introduced substance, reports of adverse reactions were expected since no amount of testing can preclude idiosyncratic reactions in a small minority of the population. In reality, the number of such reports has been unusually small. Over 70 million people in North America use aspartame on a regular basis, yet the number of reported complaints average only around three hundred per year. The majority of complaints (67%) refer to headaches, dizziness, visual difficulties and mood alterations. Gastrointestinal problems (24%) and allergic symptoms such as hives, rashes and swelling of tissues (15%) have also been reported. On occasion seizures have been linked with aspartame exposure. In most instances these difficulties were noted only with amounts of aspartame exceeding normal use. Double blind challenges have been carried out with aspartame. At Duke University, in one of the best designed such studies, the effects of a single large dose of aspartame in people who had claimed to be sensitive to the substance was investigated. The results showed no difference in headache frequency, blood pressure, or blood histamine concentrations (a measure of allergenic potential) between the experimental and control groups. In another study at the University of Illinois involving diabetics, subjects in the placebo group actually had more reactions than those in the aspartame group. On the other hand, surveys by physicians in headache clinics reveal that aspartame precipitates headaches about 8% of the time. This kind of conflicting data is characteristic of the research on the possible side effects of aspartame. Reported anecdotal experiences are not confirmed by carefully controlled scientific studies. This of course does not mean that the problems are not real, but does imply that in many cases the symptoms may not be caused by aspartame. People get headaches, upset stomachs, aches and pains of all kinds on a regular basis for no easily determined reason. If they recall having consumed aspartame when one of these ailments strikes, the sweetener may be judged to be guilty by association. This is even more likely if people are familiar with some of the adverse publicity that aspartame has received. At least one study has, however, confirmed allergic symptoms such as hives and swelling in sensitive individuals. It is unclear how the allergy comes about, since none of the components of aspartame are believed to be capable of producing allergic reactions. It has been suggested that diketopiperazine, a compound which forms when aspartame decomposes may be responsible. A number of theoretical possibilities have been advanced to account for aspartame associated problems. The three breakdown products of aspartame are all toxic in high doses. Phenylalanine is an essential amino acid which must be included in the diet for normal growth and maintenance, but sustained high blood levels can lead to brain damage. This is of major concern to the one out of roughly twenty thousand children who are born with an inherited condition called phenylketonurea or PKU. These children cannot metabolize phenylalanine, which then builds up to dangerous levels in their brains. The condition therefore necessitates a severe curtailment of phenylalanine intake at least for the first six years of life. This means that aspartame, due to its phenylalanine content, is not suitable for PKU sufferers and consequently requires a warning to that effect on products in which it is an ingredient. In the general population, phenylalanine levels in the blood after aspartame ingestion are in the same range as after eating any protein containing food. Even at abusive amounts, equivalent to a child swallowing 100 sweetener tablets, levels do not rise above those which are considered to be safe in children afflicted with PKU. Dr. Richard Wurtman, a noted MIT researcher, has suggested that some of the untoward effects of aspartame may be caused by a sudden increase in brain phenylalanine levels, especially when the sweetener is consumed along with foods high in carbohydrates. Carbohydrates trigger insulin release into the bloodstream, which in turn makes it easier for phenylalanine to be absorbed by the brain. According to Wurtman, such a sudden increase in brain phenylalanine levels can cause depression, sleep problems, headaches and even seizures. These ideas have not been confirmed in human studies, and Wurtrnan, who uses aspartame moderately himself, feels the problem is only significant when consumption of aspartame is unnecessarily high. The effects of aspartic acid, another aspartame breakdown product, have also been rigorously examined. Administration of extremely large amounts to non human primates produced no damage even though blood levels were greatly elevated. In humans, even high doses are quickly eliminated. Most significantly, aspartic acid levels in the blood are not increased after eating aspartame containing foods or when drinking sweetened beverages even at the rate of three drinks in four hours. Source: Fenster, A.E., Harpp, J.A., and Schwarcz. The World of Chemistry Part I, 1994 (p. 90-92).