Biology 202
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Can We Tell if Aspartame is Safe?

Laura Chivers

Aspartame, or Nutrasweet as many know it, is found in numerous food substances that millions of Americans consume every day. Sodas, vitamins, cookies, gum and much more contains this man-made sweetener discovered by accident in 1965 (1). Approved for use in dry goods by the FDA in 1981 and for carbonated beverages in 1983 (2), most consumers presume that aspartame is a safe, calorie-free alternative to sugar. However, a quick web search using the word "aspartame" in the key field will bring up a myriad of websites that proclaim the dangers of aspartame. These websites seemed to be rather hysterical to me, but as a recently diagnosed hypoglycemic who has been eating an increased amount of this substance lately, I was concerned by these sites. Many other sites, (often from reputable organizations like the Diabetes Society and the Multiple Sclerosis foundation (3)) attest to the safety and benefits of aspartame. Therefore, I set out to discover why some people think aspartame might be so harmful and to conclude what evidence would need to be found in order to support their idea and conclude that aspartame is unsafe.

First, the undeniable facts. Aspartame is made of three chemicals: aspartic acid (40%), phenylalanine (50%), and methanol (10%). Phenylalanine and aspartic acid are both amino acids, while methanol (methyl alcohol) is a known toxin. Aspartame is hydrolyzed in the intestinal tract into these three elements. Methanol can also become "free methanol" before it enters the body if it is heated to a temperature above 86 degrees Fahrenheit.

The reason some feel that aspartame might not be safe is because it breaks down into these three elements, which may say are toxic to the body and brain. To see why, let us examine them individually and see what each amy do to the body and brain.

Methanol is used in making aspartame as a "glue" to bind the phenylalanine and the aspartic acid together. In the small intestine, the methanol is released from the compound when the enzyme chymotrypsin encounters the methyl group of the aspartame (1). The enzyme alcohol dehydrogenase metabolizes the methanol and produces formaldehyde (a deadly neurotoxin), which is then converted into formic acid (4). Within cells, formaldehyde and its breakdown products damage cellular proteins (including microtubules and proteins) (5), impair DNA function (increasing the likeliness of oncogene activation (cancer) and birth defects) (5), and cause retinal damage (1), among other things. Formic acid causes acidosis or the overall increase in acid in the body and inhibits metabolism (1). The effects of methanol and its products seem to be cumulative, since methanol is excreted slowly (4). The recommended limit of the toxin methanol is 7.8mg/day; the skeptic sites suggest that a one liter diet soda contains approximately 56 mg (1), suggesting that the neurotoxin is having it's effect on the cells (including the neurons) of many aspartame users.

Phenylalanine is an amino acid that is converted to tyrosine (the amino acid precursor to dopamine and norepinephrine) by an enzyme, phenylalanine hydroxilase. Patients suffering from the genetic disorder phenylketonurea are missing this enzyme and accumulate high levels of phenylalanine in their brains, which leads to brain damage. However many of the websites claimed that ingesting large amounts of aspartame causes the blood levels of phenylalanine to increase dramatically as the aspartame is broken into phenylalanine and aspartate in the small intestine. Unlike PKU fetuses and children, normal children have the enzyme to convert phenylalanine (for more info on PKU see (A) ). However, with such high levels they may not be able to convert it all, and it could build up and cause symptoms similar to those in PKU children (esp. brain damage). This 2-5 fold increase in blood concentration reported by Elsas (6) could be much more magnified in fetuses because of the concentrative effects of the placenta and could also have an effect on the rapidly growing brains of children (6). These changes in blood level concentration are associated with the slowing of electroencephalograms and prolongation of cognitive function tests in human (6), suggesting that the elevated levels of phenylalanine are causing brain function to slow somehow. High phenylalanine levels also cause serotonin levels to drop, which leads to emotional disorders such as depression.

Although I did not find a reason for why the phenylalanine would do this, I am curious to know if it is because so much phenylalanine is trying to cross the blood-brain barrier that other precursors to neurotransmitters have trouble gaining access to the brain. If the amino acid precursors required to create neurotransmitters were low in the brain, the production of neurotransmitters would be low as well. Neurons would not have much (or possibly even enough) neurotransmitter to pass their message on to the next neuron. Replenishing of the neurotransmitter in the neuron that fired would take longer, so the neuron could not send another signal as fast. This would seem to slow the brain's activity. This build-up could be fatal when there is so much blockage that crucial messages necessary for life are unable to be sent because not enough neurotransmitter exists. This also seems consistent with the lowered serotonin levels, since the phenylalanine would also hinder the access of the precursor to serotonin from entering the brain, keeping it from being synthesized. However, this is just a thought. However, if it is true that aspartame creates these high phenylalanine levels which build up and cause problems, then aspartame users would be at high risk for brain activity slowing, brain damage, and even death.

The final ingredient in aspartame is aspartate, or aspartic acid. Also an amino acid, it is one of several amino acids that some claim to be "excitotoxins" (2) . According to the theory, these excitotoxins become excitatory neurotransmitters in the nervous system. The excitotoxin aspartate is converted in the liver to glutamate, the universal excitatory neurotransmitter in the brain (7) . In normal cases, a small amount of glutamate is released and the cell fires. If the neurotransmitter increases beyond an optimal level, the cell begins to fire abnormally. At even higher concentrations, the cell undergoes excitotoxicity, or a delayed cell death in which it fires to death(7). This occurs because the excitatory neurotransmitter attaches to a specialized family of receptors, which open the calcium channels on the neuron's cell membrane and allow calcium ions to flow in (7) . This causes a cascade of events that result in free radical generation that damage cell membranes and DNA (for an explanation of free radicals, see (B) ), and lipid peroxidation, which destroys the cell and intracellular membranes and kills the neuron (7). Thus increased consumption of aspartate could create problems for anyone, it should be especially dangerous for anyone suffering from diseases that are related to problems with DNA damage or lipid peroxidation, as aspartate would tend to exacerbate the problem(7).

After having read all the proposed problems of the ingredients in aspartame, it is easy to wonder why it is still on the market at all, let alone a part of so many products with only a warning that it contains phenylalanine. But, as mentioned earlier, many sites attest to the safety of the product, say that all three substances are found naturally in foods we eat and even suggest that the web authors on the skeptics pages don't have a full understanding of the psychopharmacology of the substances (3).

Proponents of the safety of aspartame suggest that glutamate occurs naturally in the brain, so it is not important if aspartate is converted into glutamate, which then goes into the brain (1) . Methanol is found in many foods such as fruits and alcoholic beverages, often in much higher concentrations . (3) And phenylalanine is in much higher concentration in an egg, a glass of milk or a hamburger (8) . Since they are in our foods and in our bodies already, they are safe to eat. They have also shown that even with excessive use of aspartame, aspartic acid levels do not build up in the blood (9) . With normal use of aspartame, methanol levels did not rise in children or adults(3) . Furthermore, though methanol blood levels rose in people using large amounts of aspartame (14,000mg/day), levels of formic acid, which is responsible for the blindness and acidosis resulting from methanol poisoning, did not rise (3) .

Since these things seem to confirm the safety of aspartame as a food additive, what would we need to see to "prove" that aspartame is in fact dangerous? Regarding aspartate, one would have to show that aspartame increased levels of aspartate in the body, which in turn led to a significant increase in glutamate above the small quantity naturally present in the nervous system. One would need to show also that the increased glutamate was present in the parts of the brain where the specialized receptors are. One would then need to show that the glutamate acted on these receptors and caused abnormal firing leading to toxicity, free radical release, and lipid peroxidation.

In the case of methanol, people have argued that it is unimportant that methanol is found in other foods because usually it is present in compound with ethanol (1) . Ethanol competes for the same enzyme and is thus a sort of "antidote" for methanol poisoning. In aspartame, methanol is not present with ethanol, and thus may be processed more quickly and be more potent. Although this is true and would support the findings that methanol levels increase with excess use, no conclusive evidence has been found to show that an increase in methanol levels increases the levels of formic acid (3) . Therefore, in order to conclude that methanol makes aspartame unsafe, one would need to show that formic acid levels are increased in some way.

Finally, phenylalanine is in fact in smaller quantity in one can of soda than in other foods. For instance, one can of diet soda contains 100mg phenylalanine, an egg has 300mg, and a hamburger has 900mg (8) . For a normal person who has the enzyme to convert phenylalanine to tyrosine, this amount does not sound dangerous. However when used excessively, an elevated blood level of phenylalanine would be a first step to showing that it may not be safe. The finding that elevated blood levels lead to elevated brain levels of phenylalanine would be the next step. Following that, seeing a prolonged increase in phenylalanine in the brain over time would suggest that perhaps the brain was receiving more phenylalanine than it could process. Then one would need to show that the above average level of phenylalanine was causing problems in the brain (possibly related to letting in precursors to neurotransmitters). If, consistent with the findings of serotonin, one found that other neurotransmitters were low as well when phenylalanine levels were high, one could make a strong argument that the phenylalanine was blocking other amino acids from being able to be synthesized into neurotransmitters. This would suggest that phenylalanine was causing large problems in brain communication and would not be safe.

Although I was scared when I first came upon these websites, I could find little suggesting that any of the evidence for the danger of aspartame has been found in a research setting. I have noticed that most of the cases where the evidence shows a change may have been due to aspartame (such as elevated blood levels) seem to occur only when large quantities of aspartame were ingested. Therefore, my personal choice will be to continue to use aspartame, but only in small quantities. However, I hope that the FDA and other institutions and researchers will continue to study aspartame, because although the evidence has not yet been found, it is possible that aspartame does in fact cause harm. Because of this, caution and moderation seem like the smart way to enjoy aspartame safely.

WWW Sources

1) AspartameˇThe Bad News! , a hysterics page, but with some references

2) Aspartame The Bitter Truth , another hysterics page w/references

3) Aspartame: No Danger , from the Multiple Sclerosis Foundation

4) Methanol , from the Emergency Medicine and Primary Homecare page

5) Neurotoxic Interaction of MSG, Aspartame, and other Toxins , text from Dr. Markle, as self-appointed expert on aspartame

6) Statement for the US Senate , Dr. Elsas's testamony at a Senate hearing

7) Electrotoxins, Neurodegeneration and Neurodevelopment , explanation of neurotoxins by Dr. Blaylock

8) Aspartame and the Internet , Nutrasweet in Europe site

9) A Dozen Straight Answers about Aspartame Safety , The Nutrasweet Company site

Supplemental WWW Sources

A) What is PKU?, , from PKU website

B) A Word About Free Radicals ,from the MetaMetrix Nutrition Resource

C) Fantastic ExposŽ , click on link for Real Audio of Fox % News in Washington DC's exposŽ on aspartame

D)Sugar Substitutes ,Sugar Substitutes, great recap of substitutes and the FDA's position on them

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