8. Phenylalanine The article states: "...the presence of phenylalanine, however, is a potential concern for persons suffering from phenylketornuia (PKU)--a rare genetic disease in which phenylalanine is improperly metabolized. .... But remember that PKU is extremely rare, and that phenylalanine is an important nutrient for the vast majority of people." It is unfortunate that Dr. Leibovitz glosses over such a crucial issue of phenylalanine intake. Everyone in the research community is well-aware of the fact that phenylalanine is an important amino acid and that it is commonly found in many foods. The issue revolves around the intake of a free amino acid that is very quickly absorbed without the presence of other amino acids that commonly make up protein. Never in the history of man has phenylalanine been ingested in free form without the presence of other amino acids on a long-term basis. Protein Digestion & Metabolism ------------------------------ Proteins found in food are made up of building blocks called amino acids. Proteins are in the form of chains of amino acids called "peptides." (Dipeptide = a chain of two amino acids; Tripeptide = a chain of three amino acids; Polypeptide = a chain of four or more amino acids.) Amino acids are rarely found in free form -- i.e., not bound in amino acid chains known as protein molecules. As summarized by Garrison (1990), the digestion of proteins begins when a protein-containing food enters the stomach. Hydrochloric acid, pepsin, and protease enzymes break specific protein links into polypeptides (amino acid chains). When the food reaches the duodenum (part of the small intestine), the enzyme trypsin in the pancreatic juice breaks the polypeptides into dipeptides and tripeptides. As the amino acid chains progress down the small intestine, several enzymes break the amino acid chains into individual amino acids. The amino acids are then absorbed through the intestinal wall and into the bloodstream. The whole process is a long, slow process leading to a gradual absorption of amino acids into the bloodstream. In addition, because proteins from food contains many different amino acids, the ratios between the levels of amino acids in the blood does not change significantly. Phenylalanine Absorption ------------------------ When phenylalanine is taken as part of aspartame, particularly in liquid form, the phenylalanine is absorbed very quickly and can spike the plasma phenylalanine to extremely high levels. The plasma level of the amino acid phenylalanine can rise more than as seven (7) times its average baseline (fasting) value after aspartame ingestion (in liquids such as carbonated beverages) (Stegink 1987a, Matalon 1988). The spike in the plasma phenylalanine level lasts about 2 hours (average). Even lower levels of aspartame cause spikes in the plasma phenylalanine levels (Caballero 1986, Burns 1991). Plasma phenylalanine levels gradually rise after a meal but the levels do not rise nearly as high (Stegink 1987b). Lactating women ingesting fresh aspartame in orange juice were found to have increased phenylalanine levels in their milk (Stegink 1979c). Plasma Phenylalanine/Large Neutral Amino Acids (LNAA) Ratio When a high protein meal is eaten, a number of amino acids gradually enter the bloodstream. Other Large Neutral Amino Acids (LNAAs) in addition to phenylalanine enter the bloodstream after the proteins from the foods are broken down. The other LNAAs are: valine leucine isoleucine tryptophan tyrosine histidine methionine These amino acids tend to be more abundant in foods than phenylalanine. When a protein food is eaten the plasma level of all the LNAAs (including phenylalanine) rises gradually. However, since the other LNAAs are more abundant than phenylalanine, the Phenylalanine/(Other LNAA) ratio goes down (Fernstrom 1979, Maher 1984). In other words the plasma phenylalanine level gradually rises, but to a much less extent than the plasma level of the other LNAAs. Aspartame is the only "food" that contains phenylalanine and no other large neutral amino acids (LNAAs). Therefore, not only can the plasma phenylalanine level spike to high levels after aspartame ingestion, but the plasma phenylalanine/LNAA ratio also increases to very high levels after aspartame ingestion. In other words the phenylalanine level rises, and the other LNAA levels do not rise at all. Several studies have shown that ingestion of aspartame can spike the plasma phenylalanine levels and increase the phenylalanine/LNAA ratio tremendously (Stegink 1987a, Caballero 1986, Stegink 1989, Stegink 1990, Stegink 1979c). Ingestion of an aspartame-containing product along with a glucose or starch-containing product can increase the plasma phenylalanine/LNAA ratio much more than simply ingesting aspartame alone. Martin-Du Pan (1982) showed that doses of glucose as little as 6 grams can cause a drop in plasma LNAA levels by an average of 10%. Twenty-five (25) grams of glucose led to a 30% drop in plasma LNAA levels. Since these reductions in LNAA levels were caused by large decreases in the levels of most large neutral amino acids except phenylalanine which only had a small decrease, the plasma phenylalanine/LNAA ratio will be increased by administration of glucose or starch. Yokogoshi (1984) found this to be the case in studies on rats. Wolf-Novak (1990) confirmed this effect in humans. This large spike in plasma phenylalanine levels and the large increase in the phenylalanine/LNAA ratio after aspartame ingestion is one major difference between protein metabolism and aspartame metabolism. In fact, phenylalanine ingested as part of liquid aspartame-containing products produces a much more severe biochemical change then when phenylalanine is ingested in capsules or slow-dissolving tablets -- much like one would find it in a dietary supplement (Stegink 1987a, Burns 1990). In addition, many free amino acid supplements contain other LNAAs such that the plasma phenylalanine/LNAA ratio would not change significantly. NutraSweet researchers often try to argue that the peak level of the phenylalanine/LNAA ratio is not important, but only the "Area Under the Curve" (AUC) which is a combination of the level and the time the Phenylalanine/LNAA is above the baseline (i.e., fasting) level (Burns 1990). In this way, they try to claim that ingestion of phenylalanine in liquids which tends to spike the phenylalanine quickly and for a short period of time at high levels is the same as taking phenylalanine in capsules which spikes the plasma phenylalanine to a much less extent but for a longer time. One has to leave their brain at the door in order to buy into this argument. First of all, the whole argument falls apart when one realizes that they are using averages of all of the subjects for each time period to calculate the AUCs. Comparing each individual's AUC for liquid aspartame ingestion and capsule aspartame ingestion would show a much larger difference for most people than inappropriately using averages for each time period. Second, even using average measurements for each time period, Stegink (1987a) showed a much greater AUC for liquid aspartame ingestion as opposed to capsule ingestion. Third, capsule ingestion of aspartame, while still different than ingesting a high-protein meal because there are not other LNAAs present, comes closer to what the body is used to as far as the more gradual rise in plasma phenylalanine levels. The human body has never experienced such a sudden and large influx of phenylalanine without other LNAAs present every day for a lifetime. Finally, by using capsules, NutraSweet researchers are testing a different product with a much lower spike on plasma phenylalanine and phenylalanine/LNAA levels. The metabolism is quite different in when ingested in liquid as opposed to capsules. NutraSweet researchers are guessing that this hugh difference doesn't matter. Considering all of the serious health problems being linked to aspartame ingestion, I do not think it is appropriate to base aspartame testing on the wild guesses and wishful thinking of NutraSweet researchers. If they insist upon studying aspartame in capsules, then aspartame should only be sold in freshly prepared capsules. Burns (1991) claims that ingestion of aspartame or sucrose produce similar Phenylalanine/LNAA ratios. First, Burns (1991) inappropriately used the groups' average values for each time period. Second, the phenylalanine levels actually goes down when the sucrose is administered. This is an enormous metabolic difference from the large phenylalanine spikes when aspartame is administered. It is possible that the neutral amino acid transport sites at the blood brain barrier which are normally saturated with phenylalanine and other amino acids become less saturated when sucrose is administered and do not have a similar change in brain chemistry as occurs with aspartame. (See Brain Uptake of Phenylalanine below for details.) Third, the change in the Phenylalanine/LNAA ratio is relatively small when sucrose is given, but extended over a longer period of time than when aspartame is given. Therefore, Burns (1991) had to use the Area Under the Curve (AUC) nonsense to try to prove that the changes are the same with both sucrose and aspartame. Even using this argument, there was a greater increase the phenylalanine/LNAA ratio when aspartame was administered. It is clear that the biochemical changes that occur when sucrose is administered is quite dissimilar to the changes which occurs when aspartame is administered. Finally, it is unclear whether the ingestion of carbohydrates along with aspartame renders the phenylalanine part of aspartame more dangerous. Carbohydrate ingestion lowers the levels of Large Neutral Amino Acids (LNAAs) and therefore the neutral amino acid trasport cites may become unsaturated causing a smaller change in brain chemistry than would otherwise happen with the phenylalanine alone. Removal of Excess Phenylalanine ------------------------------- Excess phenylalanine is converted in the liver to the amino acid tyrosine by the enzyme phenylalanine hydroxylase. Persons who have a genetic defect know as Phenylketonuria (PKU) have little or no phenylalanine hydroxylase activity and can therefore not convert excess phenylalanine in the blood to tyrosine. Excess phenylalanine in the cases of such genetic defects is converted to phenylpyruvic acid and acetyl-phenylalanine and eliminated through the urine (Caballero 1988). However, in cases of PKU, excess phenylalanine can be quite toxic and such persons, who are identified at birth, are told to limit their phenylalanine intake and warned to not ingest aspartame. Persons are considered to be "hyperphenylalaninemic" if they have only 5% to 15% of normal phenylalanine hydroxylase activity (Matalon 1988). PKU and hyperphenylalaninemia are rare conditions that are identified at birth, making up approximately 0.014% of the population (Guttler 1988). Persons who are the carriers of the PKU gene, "PKU heterozygotes," usually have anywhere from 15% to 40% of normal phenylalanine hydroxylase activity (Matalon 1988) and make up approximately 2% of the population (Caballero 1986). PKU heterozygotes are not identified at birth any many people do not know that they are carriers of the PKU gene. Finally, it has been shown that the elderly population tends to have a delayed plasma phenylalanine clearance (Rudman 1991). This would tend to increase their susceptibility to the long-term negative effects of spiking the phenyalalnine/LNAA ratio. Rodent Phenylalanine Metabolism ------------------------------- It is important to understand that rodents metabolize phenylalanine much faster than humans. The conversion of phenylalanine to tyrosine occurs at a rate more than 12 times faster in rats than in humans (Caballero 1988). It takes 60 times the dose of aspartame in rats to produce a similar phenylalanine to tyrosine ratio (and therefore an equivalent change in the phenylalanine/LNAA ratio) as found when humans are given aspartame (Wurtman 1988). Therefore, a dose of aspartame of 1000 mg/kg given to a rat over its lifetime only approximates a dose of 17 mg/kg in humans as far as the phenylalanine part of aspartame is concerned. NutraSweet researchers have tried to claim that it only takes 2 to 6 times the amount of aspartame in mice and rats to cause an equivalent rise in plasma phenylalanine/LNAA ratio as is found in humans (Hjelle 1992). This experiment was conducted by NutraSweet Company and Hazelton Laboratory employees. The phenylalanine measurements in the rats and mice are so different than found by other researchers that they should be discounted. For example, a dose of 200 mg/kg of aspartame given to the rats was found to increase the plasma phenylalanine from 73.6 nmol/ml to 295.0 nmol/ml -- an increase of 4.0 times higher than the base value. The plasma tyrosine levels were found to increase from 91.6 nmol/ml to 212.0 nmol/ml -- a increase of 2.3 times higher than the base value. Wurtman (1983a) found that giving aspartame to rats at 200 mg/kg increased their plasma phenylalanine by only 1.92 times and increase their plasma tyrosine by 2.57 times. This shows that the tyrosine actually increased more than the phenylalanine. This makes sense since the rats convert phenylalanine to tyrosine much quicker than do humans. Yokogoshi (1984) showed similar results to Wurtman (1983a) after giving rats 200 mg/kg of aspartame. The plasma phenylalanine rose to 1.62 times its base value and the plasma tyrosine rose to 2.42 times its base value. Pinto (1988) tested 200 mg/kg of aspartame on mice. After one hour (half of the time alloted by the Wurtman and Yokogoshi experiments listed above), the plasma phenylalanine level was 1.26 times over its base value and the tyrosine was 1.48 times over its base value. The increases were less in this experiment than in Yokogoshi (1984) and Wurtman (1983a) because the measurements occurred at 1 hour, but the ratio of changes in phenylalanine to the changes in tyrosine are similar in all three experiments. For all three studies (Wurtman 1983a, Yokogoshi 1984, Pinto 1988), the plasma tyrosine rose 1.17 to 1.5 times more than the plasma phenylalanine. This is a relatively consistant result. In the NutraSweet-conducted experiment, the plasma phenylalanine rose 1.74 times more than the plasma tyrosine. This result is ridiculous. Even at the 500 mg/kg dosage there results in changes in plasma phenylalanine and tyrosine do not come close to matching any other researchers (Perego 1988, Pinto 1988). The rest of the discussion by Hjelle (1992) simply amounts to twisting of results from previous studies (which is something only someone intimately familiar with the research would be able to discover) and dredging up inaccurate information provided in previous NutraSweet-sponsored "research." The simple fact is that no one but NutraSweet researchers can seem to get rats to spike plasma phenylalanine and phenylalanine/LNAA levels similar to what happens in humans unless they give approximately 60 times the dosage typically tested in humans, i.e., over 1000 mg/kg. If they give less, the rats have increase tyrosine levels more than phenylalanine levels -- something which never occurs in humans with aspartame ingestion. Hjelle (1992) had the nerve to give the appearance that their results were similar to other studies: "The results at 200 mg/kg were similar to those of Yokogoshi (1984). We also obtained results similar to those of Fernstrom et al. (1983) who demonstrated that serum concentrations of PHE [phenylalanine] and tyrosine peaked in rats within 30-60 min. after an oral of 200 mg/kg of aspartame. The Cmaxs, Tmaxs and AUC for PHE and tyrosine at the 200 and 1,000 mg/kg doses of aspartame were generally the same as those calculated from data reported by Romano et al. (1990) who administered bolus doses of 250 and 1,000 mg/kg of aspartame to rats." I guess that since Hjelle (1992) decided to present such ridiculous phenylalanine and tyrosine measurements, it is not surprising that these researchers would go one step further in the insanity and imply that their results are similar to other studies. The plasma phenylalanine and tyrosine changes in Yogokoshi (1984), Fernstrom (1983), and Romano (1990) are enormously different than the changes shown in Hjelle (1992) as anyone who examines these studies can easily see. In fact, Hjelle (1992) goes on to admit at least one major difference: "However, at 1,000 mg/kg, Romano et al. (1990) reported plasma concentrations of PHE that were approximately one half of the current value and AUCs that were not directly proportional to the aspartame dose." Earlier Hjelle (1992) had said his data was "generally the same" as that of Romano (1990). But here he admits that his study had double the phenylalanine levels when 1,000 mg/kg was administered! Such obviously nonsensical results and such a deceptive presentation in this publication of the "research" performed by NutraSweet and Hazelton Laboratory personnel raises a very serious and important question: "If NutraSweet research cannot even honestly and accurately determine plasma phenylalanine and tyrosine levels in rats, how can we believe any study they have performed or will perform on any of their products"? Brain Uptake of Large Neutral Amino Acids (LNAAs) In humans, large neutral amino acids (LNAAs) compete for entry (at the neutral amino acid carrier sites) into the brain across the Blood Brain Barrier (BBB) (Pardridge 1988a). For example, when plasma phenylalanine levels are low, uptake of the LNAA methionine into the brain has been shown to increase. When plasma phenylalanine levels increase, uptake of the LNAA methionine into the brain has been shown to decrease (Comar 1981). Pardridge (1988a) points out that: "In experimental hyperphenylalaninemia, the impairment of brain protein synthesis can be normalized by the coadministration of other large neurtral amino acids that compete with phenylalanine at the neutral amino acid carrier sites within the brain capillary." A rise in the plasma phenylalanine/LNAA ratio leads to an increased uptake of phenylalanine into the brain and a decreased uptake of other LNAAs into the brain (Pardridge 1983). The neutral amino acid carrier sites are normally saturated with neutral amino acids (Pardridge 1986, Smith 1991, Shulkin 1995). Since the affinity for phenylalanine at the neutral amino acid transport sites is high, an increase in the plasma phenylalanine levels without a corresponding increase in the levels of other large neutral amino acids (LNAAs) could saturate the transports sites with phenylalanine and block the availability of other amino acids (Pardrige 1988a). NutraSweet funded a study by Koeppe (1991) where seven subjects received 34 mg/kg of fresh aspartame in a beverage on one day and a placebo drink on another day. Before each ingestion, a positron emission tomography (PET) was performed using [11C]ACHC as a tracer to estimate neutral amino acid transport across the blood brain barrier at different sites. Forty-five (45) minutes after ingestion of the beverage, another PET was performed to determine any changes in transport of neutral amino acids. The authors conclude: "We observed an 11.5% decrease in the amino acid transport rate constant K1 and a smaller decrease in the tissue distribution volume of ACHC (6%). Under conditions of normal dietary use, aspartame is thus unlikely to cause changes in brain amino acid uptake that are measurable by PET." Flaws ----- i. The second PET scan was performed at 45 minutes. This is a major flaw. The researchers based their assumption that plasma phenylalanine levels would peak at 45 minutes on an old study by Stegink (1977) which only showed average values for all subjects at each time period. When individual values are shown such as in Stegink (1987a), one can see the following estimations for peak phenylalanine levels after ingestion: Estimated Time of Peak Subject No. Phenylalanine Level (min.) 1 15 2 15 3 45 4 30 5 30 6 15 7 45 8 30 9 60 10 30 Mean 31.5 As can easily be seen, many of the subjects had plasma phenylalanine peaks at a much earlier time than 45 minutes. One subject had a peak at near 60 minutes. The measured mean peak phenylalanine level from Koeppe 1991 was only 56% of that measured in Stegink (1987a). It is safe to assume that the measured mean peak phenylalanine level from Stegink (1987a) was below the actual mean peak level because measurements occurred only every 15 minutes. It is also a fairly safe assumption that the actual mean peak phenylalanine levels from Stegink (1987a) were approximately twice as high as that measured in this study (Koeppe 1991). Therefore, their average values from the PET scan after aspartame ingestion was closer to measuring amino acid transport after ingestion of 17 mg/kg of aspartame as opposed to 34 mg/kg of aspartame. ii. The researchers based their conclusion on the groups' average change in amino acid transport rate at a particular time. This flaw tends to dismiss the possibility that there can be a differences in phenylalanine transport rates from person to person. One can easily see individual differences in phenyalalnine metabolism by looking at the different levels of peak plasma phenyalalnine from Stegink (1987a). There is probably also differences in the changes in neutral amino acid transport rates from person to person at the same plasma phenylalanine level. iii. The authors tend to dismiss an 11.5% change in the amino acid transport rate constant and a 6% change in the ACHC tissue distribution volume at what really amounts to 17 mg/kg of aspartame. However, one of the major points of concern with ingesting large amounts of free phenylalanine without other LNAAs is that it could cause the brain chemistry to change very slowly, almost imperceptibly over a period of months or years. After a single dose, the researchers found a small, but measurable change. Can these researchers find a change in blockages of arteries after a single dose of a high-fat meal. Or can they find significant changes to lung tissue after smoking a single cigarette? In this case they did find a measurable change after a single dose. Drinking significant amounts of aspartame-containing product regularly may very well cause gradual changes in brain chemistry due to the phenylalanine (not to mention the damage from the other parts of aspartame) over many months or years depending upon a person's susceptibility. The large number of serious neurological adverse reactions reported from medium- and long-term use of aspartame tends to add weight to this argument. iv. These researchers seemed to simply cut-and-paste NutraSweet's nonsensical dosage arguments from other "studies." First of all, they claim that they tested a high dose of aspartame or 34 mg/kg. 34 mg/kg is only two- thirds of the FDA Acceptable Daily Intake. Second, due to errors in timing of the PET scan, they were testing a value closer to 17 mg/kg of aspartame. The researchers further claimed that 34 mg/kg amounts to ~5 liters of diet beverage for a 76.3 kg man. However, they base this figure on 500 mg of aspartame per liter. In reality, there is closer to 600 mg in a liter of aspartame (Tsang 1985). Also, not everyone is a 76.3 kg man. A 50 kg woman would have to drink 2.8 liters of aspartame-containing beverage (or a 2-liter bottle plus a few of aspartame-containing products) to reach 34 mg/kg. The equivalent of a "Super Big Gulp" would nearly reach 17 mg/kg of aspartame (the equivalent amount actually measured in this experiment) for a 50 kg woman. Two cans of diet soda would cause a 25 kg child to reach the 17 mg/kg level. If we discuss diet orange soda, the amounts needed to reach 17 mg/kg are much less. Conclusion ---------- Even if a person ingested less aspartame than was ingested in this experiment, we get back to 1) the fact that there are individual susceptibilities and 2) it is the long-term ingestion that is the major concern as far as the phenylalanine goes, not a single ingestion. General Effects From Changes in Phenylalanine/LNAA Ratio It is nearly impossible to measure the very gradual changes that might occur in brain chemistry after months or years of ingesting phenylalanine from aspartame. We do, however, have some clues from animal studies as well as case histories. Yokogoshi (1984) found that aspartame given to rats significantly affected the brain levels of the amino acids tyrosine, valine, isoleucine, tryptophan, leucine, and phenyalalnine. Administration of aspartame and glucose increased these changes even more. Wurtman (1983a) found that the administration of aspartame plus glucose was shown to block the normal rise in brain 5- hydroxyindole (5-HIAA -- a metabolite of the neurotransmitter serotonin) levels that occur after glucose administration. Who knows what the consequences of regularly blocking a normal change in brain chemistry might be. Coulombe (1986) tested doses of 13, 130, and 650 mg/kg of aspartame on mice. He found significant changes in norephinephrine (NE) in hypothalamus, medulla oblongata, and corpus striatum. He also found changes in dopamine (DA) and various catecholamine metabolistes VMA, HVA, and DOPAC in certain sections of the brain. Finally, no changes in 5-HIAA were found. However, unlike Wurtman (1983a), Coulombe (1986) did not co-administer glucose with aspartame. Coulombe concludes: "Such observed alterations in brain neurotransmitter concentrations may be responsible for the reported clinical and behavioral effects associated with ASM [aspartame] ingestion." During (1988) gave doses of 200, 500, and 1000 mg/kg to rats. When 200 mg/kg was given to rats, there was an increase in basal dopamine (DA) of 59%. This was presumably because at such low doses in rats, the plasma tyrosine levels increase much more than the phenylalanine. At a dose which is more appropriate in mimicing what phenylalanine/tyrosine changes that occur in humans after aspartame administration -- 1000 mg/kg -- dopamine release was reduced by 26%. The authors conclude: "No corresponding changes were observed in the concentrations of DOPAC and HVA with any of the treatments, indicating that changes in brain phenylalanine and tyrosine levels may selectively affect production of the dopamine molecules that are preferentially released into synapses." .... Although the changes in dopamine release (the increase by 59% and the decrease by 26%) were small compared with the changes seen after a drug like amphetamine (2 mg/kg increasing release by 1600%), they may still be sufficient to cause behavioral effects, particularly in animals or humans with impaired nigrostriatal neurons." In addition to the consideration of humans with "impaired nigrostriatal neurons" one must consider the effects of a diminished dopamine release day after day for years. Reilly (1989) claims that aspartame does not alter levels of norephinephrine (NE) , serotonin (5-HT), dopamine (DA) in the rat. She administered 500 mg/kg per day to rats via their drinking water. Flaws ----- i. The changes found in DA by Coulumbe (1986) were to a large extent in areas of the brain not looked at in this experiment. ii. The researchers claim that they were using 10 times the FDA Acceptable Daily Intake (ADI) in this experiment. In reality they gave a total of 500 mg/kg of aspartame to the rats throughout the day. Since it takes 60 times the amount of aspartame to be equivalent to human intake, they were really giving the equivalent of 8.3 mg/kg of aspartame per day. This is less than one-fifth the FDA ADI! iii. The experiment lasted for only 30 days. They gave the equivalent of 8.3 mg/kg to rats for 30 days. This is hardly a good way to measure long-term effect. iv. The brain measurements may not have been at a time when obvious changes would be expected. No details were provided on the timing of the tests. Coulumbe (1986) found changes three hours after a single aspartame dose (650 mg/kg or the equivalent of 11 mg/kg in humans). The brain chemistry may have returned to closer to normal since the animals were not given a significant dose within a few hours of sacrifice. Fernstrom (1983) found that a relatively small dose of aspartame given to rats, 200 mg/kg caused changes in brain levels of phenylalanine and tyrosine. It is not surprising that the brain levels of tyrosine increased more than that of phenylalanine because at a dose of only 200 mg/kg the plasma tyrosine rises more than the plasma phenylalanine in a rat. At this dosage, it was no surprise that after a single administration there was no significant change in brain levels of 5-HT, DA, NE, or various metabolites of these neurotransmitters. Phenylalanine and Psychological/Psychiatry Problems --------------------------------------------------- Medium- to long-term use of real-world aspartame-containing products may precipitate or worsen depression and other psychological conditions. Gradual changes in brain chemistry and function caused by the phenylalanine part of aspartame (and possibly other breakdown products) could easily produce a myriad of problems in susceptible individuals. It is believed by some researchers that excessive spiking of plasma phenylalanine levels can affect the levels of serotonin in the brain and possibly lead to neurological problems such as depression (Pardridge 1986). Since neurological problems including depression seem to be occurring in near epidemic proportions, any change that would further lead to brain chemistry imbalances in the population over a long period of time should be of enormous concern. The U.S. Department of Health and Human Services lists the following figures for persons reporting psychological problems caused by aspartame (DHHS 1993b): Health Problem Count - Change in Mood quality or level 558 - Memory Loss 220 - "Other Neurological" [???] 210 - Sleep Problems 186 One has to bear in mind that it would be extremely difficult for many people to link their psychological problems to aspartame use because 1) aspartame-caused changes in brain chemistry often happeneds very slowly over a very long period of time, and 2) aspartame may not be the only causitive factor involved. In his survey of 551 aspartame reactors, Dr. H.J. Roberts found the following psychological health problems caused by aspartame consumption (Roberts 1988): # of people (%) - Severe depression 139 (25%) - "Extreme irritability" 125 (23%) - "Severe anixiety attacks" 105 (19%) - "Marked personality changes" 88 (16%) - Recent "severe insomnia" 76 (14%) - "Severe aggravation of phobias" 41 (7%) Dr. Leibovitz states: "In that study [Walton (1993)], 13 subjects (8 patients and 5 non-patient volunteers) given 300 mg of aspartame showed increased 'number and severity of symptoms for patients with a history of depression.' The main concern about this study is that 5 (out of 8 patients) were on antidepressants (mainly Prozac) at the same time they were given aspartame." What Dr. Leibovitz did not mention was the following two points: a. The study protocol was written to test 40 subjects for 20 days, but the Institutional Review Board stopped the study due to adverse reactions as described by Dr. Walton: The severity of some of the reactions is noteworthy; three study participants spontaneously reported that they felt they had been "poisoned." One of the three to use this term felt that her symptoms were so severe that she had to discontinue the capsules -- after 3 days of her second week [aspartame]. One patient, a 42-year- old PhD psychologist with a history of recurrent major depression, reported pain in his left eye, followed by retinal detachment requiring emergency surgery. On the day of his surgery (day 4 of his second [placebo] week) he discontinued his capsules and symptoms reporting. Although this event occurred during the placebo week, 6 days after the aspartame had been discontinued, another individual -- one of the three to use the term "poisoned" -- experienced a conjunctival hemorrhage for the first time in her life during the aspartame week. These events led the Chairman of the IRB to halt the project. b. There was a clear statistically significant increase in the overall number of adverse reactions in the depressed group of subjects. Table 1 Placebo Aspartame Headache 63% 88% Nervousness 25% 63% Dizziness 13% 25% Trouble remembering 0% 63% Binge eating 13% 13% Lower back pain 25% 25% Nausea 25% 100% Depression 38% 75% Insomnia 38% 50% Temper 0% 25% More energy 0% 25% Fatigue 0% 25% Malaise 0% 38% Weight loss 13% 0% Pain in eye 13% 0% Negative thoughts 0% 13% Bad taste in mouth 0% 13% Swollen lips 0% 13% Facial numbness 0% 13% Conjunctival hemorrhage 0% 13% Weight gain 0% 13% Irritability 0% 25% Less sleep 0% 0% Diarrhea 0% 0% Nightmares 0% 0% More sleep 0% 0% This experiment conducted by Walton (1993) was intended to test vulnerable patients -- those with mood disorders who may or may not be on antidepressants. Given the enormous number of people in the U.S. with mood disorders and who are on antidepressants, it is very important for thorough independent aspartame research to be conducted on this population. Walton's study showed that the subjects with a history of depression had a clear increase in headaches, nervousness, memory loss, nausea, depression, malaise, and a possible increase in a number of other adverse symtpoms. What would years of aspartame do to such patients? The reason why the non-depressed subjects did not show a statistically significant change in adverse reactions may have been due to the fact that capsules were used and that the study lasted only 20 days -- a short time when compared to a lifetime of use. On the positive side: a. This study lasted 20 days, many times longer than most NutraSweet funded studies. b. It was conducted by a researcher not connected to NutraSweet. In fact, NutraSweet refused to sell Dr. Walton the aspartame because they could not control the outcome of the study. On the negative side: a. Capsules were used to administer the aspartame. Much worse reactions would likely have been encountered had aspartame been ingested in real-world products. b. Only 3/5 of the Acceptable Daily Intake (ADI) was given to the subjects. The absolute minimum that should be tested is the current 50 mg/kg/day ADI. c. The control group should have been similar to the test group in mood disorder and percentage of antidepressents taken. It is difficult to understand how Dr. Leibovitz could minimuze the serious reactions that occurred in the group ingesting aspartame. At the very least, these reactions are a cause for great concern. How anyone could so easily recommend aspartame to the general population after reading this study is beyond me.