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Is NutraSweet® Safe?
by Scott Toste, Pharm.D., R.Ph.
Copyright © 1996-2002




Introduction
Aspartame, the artificial sweetener commercially marketed as NutraSweet® and Equal®, is found in numerous food products.  Since its approval by the FDA in July of 1981, there have been numerous reports of adverse effects and even a few deaths associated with its use.  The FDA monitors these reports through its Adverse Reaction Monitoring System, a passive surveillance program.  In most cases, information obtained from the complainants' medical records as well as data on consumption patterns, temporal relationships, and challenge tests did not support the claim that the occurrence of the vast majority of adverse effects was linked to the consumption of aspartame.(1)  The Centers for Disease Control (CDC) has also reviewed numerous complaints and concluded that some individuals may exhibit vague, but not dangerous, symptoms due to an unusual sensitivity to aspartame, but that the product is generally safe.(2)  The Council on Scientific Affairs of the American Medical Association has also concluded that aspartame is safe to use in normal people and does not cause any serious adverse health effects.(3)   According to these sources only people with phenylketonuria (PKU) need to take special precautions when using aspartame because of the build up of the degradation product, phenylalanine.

Despite the reassurance of government and scientific agencies, many people are uneasy about using aspartame.  The media occasionally spotlights the product, presenting information from scientific and pseudoscientific sources on the dangers of aspartame.   Some people have become scared of the product and this distrust is compounded by an association with another artificial sweetener, saccharin, which has produced cancer in rats at high doses.  An organization exists called the Aspartame Consumer Safety Network (ACSN, PO Box 780634, Dallas, TX  75378), founded in 1987 and claiming to “serve as a support group and clearinghouse for vital information.”  When searching the Internet, entire Web sites can be found that are vigorously dedicated to the collection and dissemination of information on the adverse effects produced by consuming aspartame and possible conspiracies by manufactures to cover up this information.(4)   People use the Internet to share anecdotal information about the negative health effects that they suspect the sweetener has produced in them.  This information is organized and long lists of adverse reactions have been generated such as:  headaches, nausea, vertigo, hearing loss, tinnitus, insomnia, numbness of extremities, blurred vision, blindness/eye problems, memory loss, slurred speech, mild to suicidal depression, personality changes, mood changes, anxiety attacks, hyperactivity (child or adult), gastrointestinal disorders, seizures, skin lesions, muscle cramps, joint pain, fatigue, premenstrual syndrome, menstrual irregularities, chest pain, arrhythmias, and edema.  Aspartame is also claimed to trigger or mimic the following illnesses:  chronic fatigue syndrome, Epstein-Barr, post-polio syndrome, Lyme disease, Meniere's disease, Alzheimer's disease, ALS, epilepsy, multiple sclerosis, hypothyroidism, mercury sensitivity from amalgam dental fillings, fibromyalgia, Graves disease, lupus, non-Hodgkins lymphoma, attention deficit and hyperactivity disorder.

It appears that in one way or another, aspartame has been blamed for just about any ill that a person can experience.  In the medical community this type of blanket approach produces skepticism and an attitude that trivializes any actual adverse effect that can be produced by aspartame.  The rest of this article will be devoted to a review of the current scientific literature that explores actual adverse effects of aspartame consumption.

Discussion
First, what is aspartame?  It is an artificial sweetener used in many foods as an alternative to sugar.  It has some caloric value, but since it is 180 times sweeter than sugar, it is not used in amounts large enough to account for many calories.  Aspartame is completely hydrolyzed in the intestine to methanol and two amino acids, aspartic acid and phenylalanine.  The methanol is further metabolized to formaldehyde and eventually CO2.  Formaldehyde is a toxic substance but it is interesting to note that one 4 oz. banana produces 6 times the amount of methanol that one 36 mg packet of aspartame produces (see table below for comparison with other foods).  The amount of methanol produced from an average person’s consumption of aspartame is easily handled by the body(3).  The two amino acids are absorbed by the body and enter the normal metabolic pathways just as if they had come from a natural protein source.(2,3)

Phenylketonurics must limit the amount of phenylalanine in their diet.  Individuals with PKU lack an enzyme used to metabolize phenylalanine, one of the amino acid break down products of aspartame.  Excessive amounts of phenylalanine in the body can lead to brain damage, especially in infants.  For this reason, the FDA requires a warning on foods containing aspartame, notifying phenylketonurics of the phenylalanine content.  Although people with PKU should always monitor the amount of phenylalanine they ingest, research has found that the average consumption of aspartame does not significantly raise plasma levels of the amino acid beyond the normal range in heterozygous phenylketonurics.  Homozygous phenylketonurics, however, should avoid aspartame if possible. (5,6,7)

There has been some concern that aspartame may produce too high of aspartic acid levels in the body.  Glutamate, another amino acid similar to aspartic acid, has demonstrated some neurotoxicity leading to questions about aspartic acid’s safety.  No evidence of aspartic acid neurotoxicity has been found, however.  It is unlikely that toxic amounts of the substance could be ingest from aspartame (see table below).(3) Diketopiperazine (DKP), a metabolite of aspartic acid has been found to be nontoxic in animal studies(8).

The FDA has established an Acceptable Daily Intake (ADI) for artificial food sweetners.  The ADI for aspartame is 50 mg / kg of body weight / day.  This is equivalent to about 17 twelve-ounce cans of 100% aspartame sweetened soft drink consumed daily by a 70 kg person (or 97 packets of Equal®).  The ADI represents a level of consumption that, if maintained daily for the rest of the persons life, would be deemed safe by a wide margin.(2,3)

There have been reports of aspartame causing seizures.  The FDA and the CDC have investigated these claims and were unable to find convincing evidence of a cause-effect relationship (1,3).  Two recent studies have found no correlation between high levels of aspartame ingestion and increased seizure activity (9,10).  Another study has reported a change in the EEG patterns of children with epilepsy when given aspartame, however this finding did not correlate with actual seizure activity and only one dimension of the measured EEG was significantly different from the control (11).  Based upon the evidence available, aspartame does not seem to lower seizure threshold significantly.

Aspartame has also been implicated in many behavioral changes in children.  Several studies have investigated any possible effect on hyperactivity, cognition and other behavioral problems.  None of the studies found any significant effect of aspartame on behavioral or cognitive functioning of children.(3,12,13)

There is mixed evidence that aspartame can produce or exacerbate headaches.  Most studies find that it is no more likely than placebo to cause headaches in the general population (3).  Some studies, however, find that a small group of people are sensitive to aspartame and ingestion may produce headaches especially if they have a history of migraine headaches (3,14).

Concern has also developed over the ability of commercial pilots to safely fly airplanes after the ingestion of aspartame.  Studies conducted on this topic have found no detriment in a pilots performance, but have been criticized because they are based on a single, large dose of aspartame.  One study conducted using chronic ingestion of aspartame established better evidence that it produces no change in pilots cognitive performance. (15)

Aspartame is hydrolyzed to phenylalanine, a large neutral amino acid, which could potentially compete with levodopa for uptake into the brain of Parkinson’s patients receiving the drug.  It has been found, however, that aspartame consumption in amounts well in excess of what would be consumed by heavy users of aspartame-sweetened products has no adverse effect on Parkinson’s Disease patients.(16)

Dermatological reactions have also been associated with aspartame.  Such reactions are very rare and the supporting evidence is sketchy.  A clinical trial found aspartame no more likely than placebo to cause urticaria and/or angioedema reactions in subjects with a history of hypersensitivity to aspartame.  On the other hand, there are case reports of hypersensitive individuals who developed urticaria after double-blinded rechallenge with aspartame.  There have also been two cases of aspartame causing granulomatous panniculitis (an inflammatory reaction of subcutaneous fat).(3)

Aspartame has failed to show any carcinogenic effect in experimental animal studies.  It also does not appear to have any teratogenic effect during pregnancy.(3)

There is currently no research exploring the effects of aspartame on multiple sclerosis, Alzheimer’s Disease or amyotrophic lateral sclerosis (ALS).

Conclusion
Overall, there is a substantial amount of evidence supporting the safety of aspartame in the general public.  Since the components that it is broken down to (methanol, aspartic acid and phenylalanine) are found in greater quantities in common everyday foods, it is unlikely that a person will become toxic or experience adverse effects from aspartame.  There is also little chance that the dangerous, even life threatening, effects that some people attribute to aspartame are indeed true.  It is possible, however, that a very small subset of our population is sensitive to the artificial sweetener and may exhibit benign symptoms such as a headache, nausea, and dermatological reactions.



 Comparison of Amino Acid and Methanol Content of Various Foods
Typical Dietary Serving
Aspartic Acid (mg)
Phenylalanine (mg)
Methanol (mg)
Aspartame
(36 mg/packet)
14.5
18
3.49
Hamburger (4 oz)
1800
880
--
Chicken (4 oz)
2080
910
--
Lima Beans (4 oz)
1750
1350
trace
Tomato Juice (8 oz)
290
45
47
Banana (4 oz)
135
50
21
Cherries (4 oz)
95
15
20



References

1.    Tollefson L, Barnard RJ. An analysis of FDA passive surveillance reports of seizures associated with consumption of aspartame. Journal of the American Dietetic Assoc 1992 May;92(5):598-601.

2.    Whitney, Cataldo, Rolfes. Understanding Normal and Clinical Nutrition. Minneapolis: West Publishing Company 1994:128.

3.    Aspartame monograph. Micromedex 1996.

4.    http://www.tiac.net/users/mgold/aspartame/aspartame.html

5.    Trefz F, de Sonneville L, Matthis P, Benninger C, Lanz-Englert B, Bickel H.  Neuropsychological and biochemical investigations in heterozygotes  for phenylketonuria during ingestion of high dose aspartame (a sweetener containing phenylalanine). Human Genetics 1994 Apr;93(4):369-74.

6.    Curtius HC, Endres W,  Blau N. Effect of high-protein meal plus aspartame ingestion on plasma phenylalanine concentrations in obligate heterozygotes for phenylketonuria. Metabolism: Clinical & Experimental 1994 Apr;43(4):413-6.

7.    Mackey SA, Berlin CM.  Effect of dietary aspartame on plasma concentrations of phenylalanine and tyrosine in normal and homozygous phenylketonuric patients. Clinical Pediatrics 1992 Jul;31(7):394-9.

8.    Garriga MM, Metcalfe DD. Aspartame intolerance. Annals of Allergy 1988 Dec;61(6 Pt 2):63-9.

9.    Rowan AJ, Shaywitz BA, Tuchman L, French JA, Luciano D, Sullivan CM. Aspartame and seizure susceptibility: results of a clinical study in reportedly sensitive individuals. Epilepsia 1995 Mar;36(3):270-5.

10.    Shaywitz BA,  Anderson GM, Novotny EJ, Ebersole JS, Sullivan CM, Gillespie SM. Aspartame has no effect on seizures or epileptiform discharges in epileptic children.. Annals of Neurology 1994 Jan;35(1):98-103.

11.    Camfield PR, Camfield CS, Dooley JM, Gordon K, Jollymore S, Weaver DF. Aspartame exacerbates EEG spike-wave discharge in children with generalized absence epilepsy: a double-blind controlled study. Neurology 1992 May;42(5):1000-3.

12.    Stegink LD, Lindgren SD, Brummel MC, Stumbo PJ, Wolraich ML. Erythrocyte L-aspartyl-L-phenylalanine hydrolase activity and plasma phenylalanine and aspartate concentrations in children consuming diets high in aspartame. American Journal of Clinical Nutrition 1995 Dec;62(6):1206-11.

13.    Shaywitz BA, Sullivan CM, Anderson GM, Gillespie SM, Sullivan B, Shaywitz SE. Aspartame, behavior, and cognitive function in children with attention deficit disorder. Pediatrics 1994 Jan;93(1):70-5.

14.    Van den Eeden SK, Koepsell TD, Longstreth WT Jr, van Belle G, Daling JR, McKnight B. Aspartame ingestion and headaches: a randomized crossover trial. Neurology 1994 Oct;44(10):1787-93.

15.    Stokes AF, Belger A, Banich MT, Bernadine E. Effects of alcohol and chronic aspartame ingestion upon performance in aviation relevant cognitive tasks. Aviation Space & Environmental Medicine 1994 Jan;65(1):7-15.

16.    Karstaedt PJ, Pincus JH. Aspartame use in Parkinson's disease. Neurology 1993 Mar;43(3 Pt 1):611-3.



Courtesy of Pharmacy & Health Information at www.TostePharmD.net/pharm
Copyright © 1996-2002, Scott Toste, Pharm.D. R.Ph.