Aspartame for a CRAN diet?

by Ben Best

In 1987 the Calorie Control Council (Atlanta) reported that approximately 40 million Americans used artificial sweeteners for weight-control. It seems reasonable to ask if a sugar substitute might be of value for reducing calorie consumption.

Some early studies indicated that weight gain among users of artificial sweeteners was actually greater than among non-users [APPETITE 11(supplement):85-91 (1988)]. Claims were made that artificial sweeteners actually stimulates appetite. But a thorough review of the many studies on this question has debunked these claims [PHYSIOLOGY & BEHAVIOR 55:139-143 (1994)]. The fact that people with weight problems show a greater use of artificial sweeteners should not be surprising -- and this fact does not prove that sweeteners produce weight problems or are of no value for restricting calorie intake. What is needed for proof is controlled studies -- and such studies have been done with aspartame.

A review of several studies concluded that -- for both normal & dieting subjects, for both males & females and for both short-term & long-term -- aspartame subsituted for sugar significantly reduced calorie intake by gratifying the desire for sweetness. Dieters using aspartame during the post-dieting period regained half the weight as non-users [WORLD REV NUTR DIET 85:77-87 (1999)].

Aspartame was discovered in 1965 and introduced into the market in 1981. According to the US Department of Agriculture, by 1992 aspartame accounted for 67.4% of artificial sweetening used in the US, saccharin 31.5% and acesulfame-K 1.1%. By weight aspartame is 150-200 times as sweet as sugar.

There are many studies on aspartame that use units of mg/kg, which can be difficult to interpret. For simplicity, I will convert all units into the amount that I, who weigh 52 kilograms, would consume.

Aspartame is the methyl ester of two amino acids: aspartic acid and phenylalanine (the latter is an essential amino acid). Aspartame is rapidly broken-down to amino acids and methanol before absorption into the blood stream. The methanol is metabolized in the liver to formaldehyde and formic acid. Formic acid in methanol poisoning can lead to acidosis and optic nerve damage. Extremely high doses of aspartame (equivalent to 520 mg for me) given to adult male rats resulted in formaldelhyde-adducts to tissue protein, RNA and DNA -- an effect which is prsumably cumulative [LIFE SCIENCES 63(5):337-349 (1998)].

A person of my body weight should begin to exhibit these toxic effects with 50 grams of methanol. This can be contrasted to the 2 mg of methanol that I get with my 30 grams of FIBRE 1. To put things in perspective, the 18 milligrams of aspartame in my FIBRE 1 can be compared to the 131 mg of Aspartame in a 355 ml can of DIET COKE. Soft-drink aspartame releases methanol concentrations comparable to those found in red wine and fruit juices [TOXICOLOGY 50:1-26 (1988)].

An important experiment which looked for possible toxic effects of aspartame is a randomized, double-blind, placebo-controlled study involving over 100 normal human adults [ARCHIVES OF INTERNAL MEDICINE 149:2318-2324 (1989)]. The subjects were given the equivalent (for a 52 kg person) of 4 grams of Aspartame per day for 6 months. There was no statistically significant difference between the blood levels of aspartic acid, phenylalanine, other amino acids, methanol or formic acid between the Aspartame group and controls. Nor was there a statistically significant difference in vital signs or physical complaints -- notably headache, abdominal pain and nausea (commonly reported complaints against Aspartame). Most blood levels of methanol were below the minimum detectable 0.31 mmole/Litre, with the highest individual value in the Aspartame group being 1.0 mmole/Litre and the highest individual value in the control group being 0.84 mmole/Litre. I would have preferred a study that could have detected all levels of methanol.

Another radomized, double-blind study of normal volunteers failed to fiind differences in headache, sedation, reaction-time, cognition or memory between aspartame and non-aspartame subjects, but did find significantly higher plasma phenylalanine accompanied by a small reduction in plasma tryptophan [JOURNAL OF CLINICAL PHARMACOLOGY 30:454-460 (1990)].

Although the above study showed little affect of aspartame on normal adults, abnormal persons may be different. A study of depressed patients likely suffering from monoamine metabolism disturbances showed severe reactions in half the patients on the equivalent of 1.5 grams of aspartame daily -- in contrast to the normal group, which showed no symptoms (there was a placebo group for both depressed patients and controls). [BIOLOGICAL PSYCHIATRY 34:13-17 (1993)]. Subjects with a high vulnerability to migraine headaches showed increased frequency on the equivalent of 1,200 mg per day [HEADACHE 28:10-13 (1988)]. Compared to my 36 mg per day with FIBRE 1, these dosages are very large, but this still stands as evidence that aspartame could cause problems for some people suffering from severe migraines, those with catecholamine-related psychiatric problems, epileptics and (of course) persons with phenyketonuria.

Animal studies have shown that the equivalent of 6.5 grams of aspartame can double the NorEpinephrine concentration in the corpus striatum of the brain of rats. NorEpinephrine and Dopamine in the hypothalamus was increased by two-thirds [TOXICOLOGY AND APPLIED PHARMACOLOGY 83:79-85 (1986)]. The equivalent of about 50 grams per day of aspartame in rats resulted in increased motor activity and learning impairments [see the TOXICOLOGY article cited above]. Note that these dosage levels are VERY high.

As for the use of aspartame to practice CRAN, the ARCHIVES OF INTERNAL MEDICINE article reported no weight change for the aspartame group as compared to the control group. But in that study, aspartame was administered in capsules, so as to be indistinguishable from placebo. Another study noted that the desire for sweetness in most individuals is the highest in the morning. Therefore, the effect of a 500 mg aspartame-sweetened breakfast was contrasted with that of a sucrose-sweetened breakfast. The aspartame group consumed an average of 300 fewer calories per 24-hour period than the control group. [AMERICAN JOURNAL OF CLINICAL NUTRITION 59:338-345 (1994)]

One study gave subjects a large bowl of pudding or jello sweetened with sucrose or aspartame. This was a short-term study using an equal number of male & female between the ages of 18-35 who "were within the normal range of weight for height". The subjects were encouraged to eat as much of the pudding or jello as they wished. Despite the fact that the sucrose added at least an additional 170 calories, there was no difference in the amount of pudding or jello consumed. And there was no statistically significant difference in total calories eaten 2 hours later in a self-selected meal. It didn't even matter much whether subjects were aware or unaware (unblinded or blinded) of whether they were eating sucrose-sweetened or aspartame-sweetened pudding or jello [APPETITE 13:115-127 (1989)]. This would seem to indicate that aspartame can reduce calorie intake on a short-term basis. But what about long-term?

A long-term randomized controlled clinical trial was conducted with 163 obese women who lost an average of 10 kg (22 pounds, 10% of body weight) during a 19-week weight-loss program. The women were randomly divided into aspartame and non-aspartame groups. The women were users or non-users of aspartame both during and after the weight-loss program. Three years after the weight-loss period, the non-aspartame group had gained an average of 9.4 kg (20.7 pounds), whereas the aspartame group had gained an average of 4.6 kg (10.1 pounds). [AMERICAN JOURNAL OF CLINICAL NUTRITION 65:409-418 (1997)]. This result would seem to indicate that aspartame could be of benefit for the practice of CRAN.

Concerns have been raised of an excitotoxic effect from dietary glutamate and aspartate -- particularly in infants and the elderly. Certain regions of the brain, such as the endocrine hypothalamus, lack a blood-brain barrier -- and aspartame has been shown to destroy hypothalamic neurons in infant mice [NEUROTOXICOLOGY 15(3):535-544 (1994)]. However, the primate infant's brain is more well-protected. In fact, human milk has a high content of free amino acids, particulary glutamate & taurine (substantially higher than cow's milk). Glutamate & aspartate (unlike other amino acids) are metabolized in the intestinal epithelium. Glutamate is heavily used as a food additive (as MSG -- MonoSodium Glutamate) with little evidence of neuropathology -- although exacerbation of neurodegenerative disorders is a real possibility [BRAIN RESEARCH REVIEWS 18:293-314 (1993)].

An article in the JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY [55(11):1115-1123 (1996)] raised claims that aspartame causes brain cancer. Circumstantial evidence given referred to a correlation between the introduction of aspartame into the US market and increased brain cancer in the American population. Rat studies reputedly indicated increased brain tumors with aspartame -- and claims were made that nitrosylation of aspartame in the gut results in a potent mutagen.

All of these claims were countered by a study/review in the JOURNAL OF THE NATIONAL CANCER INSTITUTE [89(14):1072-1074 (1997)]. Analysis of cancer patients showed no relationship between aspartame consumption and cancer -- "no suggestion of a dose-response relation based on age at first consumption, number of years of consumption, or frequency of consumption." There had been questions concerning the interpretation of a number of rat experiments, but the FDA finally decided that the evidence did not support an association between aspartame and cancer. Mouse studies had been uniformly negative, and a subsequent rat study also found no association. Analysis of kinetics indicated that nitrosation of aspartame is primarily of the terminal amino group, rather than of the amide (which would be mutagenic). The mutagenic activity of aspartame after nitration was shown to be very weak "at concentrations considerably higher than normal human intake levels".

These results are re-assuring, but for a person who wants/expects to live a very long time, even a very weak mutagenic effect is a matter of concern. Nonetheless, my use of aspartame is limited to Designer Protein and Metamucil. I don't drink coffee or soda pop and the only other "sweets" in my diet are fruits & vegetables.