aspartame is safe at normal intake dosages
Health Effects of the Artificial Sweetener Aspartame
Jeanne Wahlen
Aspartame, currently used as a replacement for natural sweeteners, is a popular sweetener because it is approximately 180 to 200 times sweeter than sugar, does not contain significant calories, and does not promote tooth decay. More than half the population of the United States uses aspartame. With this popularity have come health concerns pertaining to the consumption of aspartame. This article considers the physical characteristics, chemistry, and metabolism of aspartame and finds that, for all but a very small percentage of the population, such concerns are unwarranted.
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Introduction
Americans are known for having a sweet tooth. Over the years, artificial sweeteners have been introduced to curb the effects of consuming too much natural sweetener, such as sugar (sucrose). Artificial sweeteners provide sweetness to foods and beverages, and, unlike natural sugars, do not contain many calories and do not promote tooth decay. However, anecdotal evidence has suggested that aspartame causes other health problems, including headaches, gas, confusion, and brain tumors [Roberts, 1990; Olney and others, 1996]. Consequently, in spite of being one of the most thoroughly tested food additives [O'Brien and Gelardi, 1991], controversy continues to surround the use of aspartame in foods and beverages.
To clarify what aspartame is and what happens when it is ingested, the first part of this paper describes the physical characteristics and chemistry of aspartame. Also discussed are results from various experiments performed on the stability of aspartame in dry and aqueous conditions. The second part of the paper examines the nutritional value and metabolism of aspartame in the human body and the results from the most pertinent experiments conducted on aspartame's three metabolites. These chemical and biological descriptions reveal that aspartame is safe for human consumption in all but a very small percentage of the population.
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Physical Characteristics and Chemistry
Aspartame is a white, odorless, crystalline powder with a sweet taste that closely resembles that of sucrose. As seen in Figure 1, aspartame is a dipeptide composed of two amino acids : L-phenylalanine as the methyl ester (Phe) and L-aspartic acid (Asp). The stability of aspartame is important because it is used in many foods and beverages. The quality and taste of products containing aspartame depend on its stability. For that reason, manufacturers of foods and beverages need to know the shelf life of the items in order to sell their products.
Figure 1. L-aspartyl-L-phenylalanine methyl ester [O'Brien Nabors and Gerlardi, 1991].
The breakdown of aspartame can follow two pathways and depends on pH, temperature, and moisture conditions. One pathway involves the breakdown of the ester bond in methanol. The ester bond is hydrolyzed, and the dipeptide aspartylphenylalanine and methanol are produced. The other pathway involves the cyclization of aspartame into diketopiperazine (DKP). In turn, DKP can be hydrolyzed into aspartylphenylalanine. It is interesting to note that both of the pathways produce the same end component (aspartylphenylalanine), but the second pathway eliminates the production of methanol. Ultimately, aspartylphenylalanine is hydrolyzed into phenylalanine and aspartic acid [O'Brien Nabors and Gelardi, 1991]. Figure 2 shows the products from the two pathways upon which aspartame breaks down. The next two subsections of this article present a discussion of the breakdown aspartame in foods and beverages.
Figure 2. Typical chemical reactions by which aspartame breaks down [Filer Jr. and Stegink, 1984].
Dry Stability. When aspartame is used in dry applications the stability is quite good [O'Brien Nabors and Gelardi, 1991]. However, the stability is affected under high temperatures. Figure 3 shows the rates of aspartame decomposition to form DKP at different temperatures. Notice that more than 80 percent of the aspartame decomposes after 4 hours at a temperature of 150°C (about 300°F). Under normal storage conditions of 25°C, dry aspartame will not decompose.
Figure 3. Rates of aspartame decomposition to form DKP at 105°C, 120°C and 150°C [O'Brien and Gelardi, 1991].
Solution Stability. In aqueous solution, aspartame primarily decomposes into DKP, and the rate of decomposition in solution is highly affected by temperature and pH [Hough and others, 1979]. Beverage items are stored under many different conditions. More important, not all beverage items are pH neutral (pH=7), like water. Thus, the stability of aspartame in aqueous systems is an important area of study. At 25 °C, aspartame is most stable with a pH between 3 and 5 [Filer Jr. and Stegink, 1984].
Figure 4 shows the levels of aspartame versus time for solutions of various pH values at 80°C. The more horizontal the line is, the more stable aspartame is at that pH value. Aspartame is often used in products where the stability conditions are not ideal. For example, aspartame is used as a sweetener in hot beverages, such as coffee, tea, and hot cocoa. However, higher temperature beverages are consumed within a reasonably short period of time, minimizing the decomposition of aspartame. Another example is the use of aspartame in the production of ice cream, which can have a pH ranging from 6.5 to 7.0. The use of aspartame here is acceptable because the ice cream is at a low temperature.
Figure 4. Stability of aspartame in different pH solutions at 80°C [Filer Jr. and Stegink, 1984].
Because soft drinks are mostly acidic and stored at low temperature, aspartame is appropriate for the use in them. However, humans can be exposed to considerable DKP through consumption of soft drinks that have been exposed to high temperatures or stored for a long period of time (about 260 days). Individuals who consume aspartame are likely to consume DKP at some time or another. However, studies done with humans and animals show that DKP is poorly absorbed. Approximately 96 percent of ingested DKP is rapidly eliminated in the urine. Thus, the low levels of DKP resulting from consuming decomposed aspartame are not harmful to the human body [Tschanz and others, 1996]. Most consumers will not notice products containing decomposed aspartame because the by-products do not produce a bad taste [Filer Jr. and Stegink, 1984].
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Metabolism
Aspartame is composed of methanol and two naturally occurring amino acids: aspartic acid and phenylalanine. Because aspartame breaks down into these amino acids in the body, it behaves like a protein, providing an energy value of 4 kcal/g. This energy value is the same as sugar, but since aspartame is used in only very small quantities, food and beverage manufacturers can advertise their products as "calorie-free." The amounts of aspartame in some common products are shown in Table 1.
Table 1. Levels of aspartame in common consumer items [Kretchmer, 1991].
Product Category Serving Size Aspartame Content
(mg)
Dry sweetener 1 packet 35
Diet soft drink 12 oz 180
Hot chocolate 6 oz 50
Gelatin dessert 4 oz 95
Instant pudding 4 oz 25
Breakfast cereal 1 cup 55
Yogurt 8 oz 124
Aspartame began appearing in foods and beverages after 1976, when the United States Food and Drug Administration (FDA) approved aspartame for table use and as an ingredient in some dry foods [O'Brien and Gelardi, 1991]. Along with this acceptance, the FDA set an acceptable daily intake (ADI) level in order to help prevent people from consuming too much of the sweetener. The level that the FDA set is 50 mg-aspartame/kg body weight, which is an extremely large amount for humans to consume. For example, a 150-pound person must consume 97 packets of dry sweetener, or 19 cans of diet soft drink, in one day to reach this level, while a 200-pound person must consume 130 packets, or 25 cans. It is almost impossible for a person to consume this much aspartame, even if he or she consumes several different products. A 150-pound person would need to drink a 12-pack of diet soft drink and eat 5 gelatin desserts, 6 bowls of cereal, and 4 servings of yogurt in one day to reach the ADI level.
No matter how much aspartame a person consumes, after it is eaten, aspartame absorbs into the body, where it breaks down into methanol, aspartic acid, and phenylalanine. Although all three of these metabolites naturally occur in the body, each can cause harm when consumed separately in high doses [Kretchmer and Hollenbeck, 1991]. Because it is these metabolites that can be harmful and not aspartame itself, studies into the safety of aspartame examine how consuming the sweetener affects the levels of methanol, aspartic acid, and phenylalanine in the body.
Effects of Methanol. About 10 percent by weight of aspartame is released as methanol. In the body, methanol converts into formaldehyde and formate. Because formate can cause blindness and metabolic acidosis [Tephly and McMartin, 1984], methanol is toxic when humans consume it in large quantities. In order for the body to accumulate a significant amount of formate, a human must consume 200 to 500 mg of methanol per kg of body weight [Food and Drug Administration, 1984], an amount that corresponds to drinking 600 to 1700 cans of diet soft drink at once.
Researchers have studied whether methanol levels in the blood rise significantly when humans consume aspartame. In one study, subjects were given 34 mg-aspartame/kg body weight. Blood levels did not rise detectably [Filer Jr. and Stegink, 1989]. Another experiment showed that blood methanol levels did not rise even when subjects consumed 200 mg-aspartame/kg body weight [Stegink and Filer Jr., 1984]. In long term studies, researchers found that when humans consume aspartame, the resulting formate production is balanced by excretion, so that blood levels of formate do not change [Leon and others, 1989].
Another indication that humans can safely consume products sweetened with aspartame is that these products contain less methanol than some natural food substances. For example, fruit juices contain an average of 140 mg-methanol/L, but an aspartame-sweetened diet soft drink contains only 56 mg-methanol/L [Kretchmer and Hollenbeck, 1991]. According to this data, the methanol in aspartame poses no risk to humans.
Effects of Aspartic Acid. Aspartame is approximately 40 percent by weight aspartic acid [Stegink and Filer Jr., 1984]. Aspartic acid acts as an excitatory neurotransmitter in the central nervous system. Consequently, large doses of it can cause brain damage [Kretchmer and Hollenbeck, 1991]. Under normal conditions, aspartic acid does not harm humans because it is excluded from the brain by the blood-brain barrier, but at high doses it can cross the barrier and cause damage.
These characteristics are exhibited not only by aspartic acid, but also by another amino acid, glutamate. Glutamate is found in monosodium glutamate (MSG), which is a common food additive. Because humans who consume aspartic acid in aspartame are also likely to consume glutamate in MSG, researchers have studied both the dosage levels of aspartic acid and the synergistic effects with MSG.
In one study on aspartic acid and glutamate, humans were given approximately 200 mg-aspartame/kg body weight. The combined plasma levels of aspartic acid and glutamate peaked at about 7 mM/100 mL [Stegink and others, 1980]. This level is only one-twentieth of that necessary to cause brain damage in infant mice [Kretchmer and Hollenbeck, 1991]. According to this data, humans who consume aspartame do not have to worry about being harmed by combined levels of aspartic acid and glutamate.
Effects of Phenylalanine. The last 50 percent by weight of aspartame is composed of the amino acid phenylalanine. This chemical causes brain damage and dysfunction in humans who have the genetic disease phenylketonuria (PKU). In order to have PKU, a human must be homozygous for the defective gene; that is, he or she must have inherited the PKU gene from both parents. A person who has PKU cannot metabolize phenylalanine, a defect that allows the amino acid to build up to harmful levels in the blood. Most people with PKU are diagnosed at birth, and immediately are put on diets that restrict foods containing phenylalanine, including aspartame. However, if PKU goes undetected and the diet is not altered, the person will acquire extreme, irreversible mental retardation within the first few months of his or her life.
Individuals who are homozygous for the PKU gene are not the only people concerned about the effects of consuming phenylalanine through aspartame. It is also possible for humans to be heterozygous for PKU, or to have inherited one gene that is normal and one that contains PKU. These individuals show no signs of the PKU disease, but they metabolize phenylalanine 50 percent more slowly than normal humans [Kretchmer and Hollenbeck, 1991]. This slow breakdown could allow more phenylalanine to accumulate within the blood of PKU-heterozygous individuals than the blood of normal people; consequently, researchers have studied whether people who are heterozygous for PKU could be harmed if they consume aspartame.
A series of studies looked into this possibility. In one experiment, twelve normal individuals (six men, six women) and eight women heterozygous for PKU were given 34 mg-aspartame/kg body weight in one serving after a period of fasting. The levels of phenylalanine in the blood were only 5 microM/100 mL higher for the PKU-heterozygous subjects. According to this research, this small increase in phenylalanine concentration does not pose a risk to PKU-heterozygous individuals [Kretchmer and Hollenbeck, 1991].
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Conclusion
This article has investigated the health effects of consuming aspartame and has found that, in general, aspartame is safe for human use. A study of the physical characteristics of aspartame showed that dry aspartame is quite stable in ambient temperatures, but decomposes into DKP at higher temperatures. The stability of aspartame in solution depends on temperature and pH. Low temperatures and acidic conditions promote the greatest stability. However, even though most beverages are acidic and are stored at low temperatures, aspartame eventually decomposes. Individuals are likely to consume DKP, but research shows that the body almost flushes itself of this decomposition product.
A review of aspartame's metabolism showed that the human body breaks down aspartame into three compounds: methanol, aspartic acid, and phenylalanine. Although methanol is toxic to the human body, research has established that the consumption of products containing aspartame will not lead to toxic levels of methanol. The same conclusion applies to aspartic acid. However, only a small amount of phenylalanine can cause severe brain damage in individuals with the genetic disease phenylketonuria. These individuals must avoid products with aspartame. To date, no substantial evidence indicates that aspartame harms the rest of the population.
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Glossary
Acidosis:an abnormal increase in the acidity of the body's fluids, caused either by accumulation of acids or by depletion of bicarbonates. (Back)
Amino Acids: the building blocks of all proteins, which contain an amino group (-NH2) attached to one of the carbon atoms. (Back)
Ester Bond: bond in an organic compound produced by the reaction between a carboxylic acid and an alcohol (-C -O-C- ). (Back)
Excitatory Neurotransmitter: a chemical substance released in the brain that produces toxic effects on neurons in the brain by causing a lethal overstimulation of the receptors that will control other cells (for instance, a muscle cell). (Back)
Homozygous: The condition in which a pair of genes occupying the same locus on a pair of chromosomes are identical to one another. (Back)
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References
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Author's Note: Jeanne Wahlen has graduated with a bachelor of science in chemical engineering. She studied technical communication under Professor Gisela Kutzbach. (Back to Beginning)