NutraSweet
3. Food Additives

Introduction

Most countries with advanced governmental structures regulate foodstuffs that enter the marketplace. In the U.S., several agencies assume responsibility for our health and safety. For example, the Federal Aviation Administration regulates the aviation industry, the Agricultural Department has responsibilities for the quality of meat and other agricultural products that we consume, the Environmental Protection Agency tackles issues of environmental concern, the Occupational Safety and Health Administration oversees workplace health and safety, and the Food and Drug Administration (FDA) approves the drugs, food additives, medical devices, etc., that are presented for use.

When legislation approving the establishment of the FDA was passed in 1906, people were of course eating merrily away! Where to begin regulation was a daunting question. It is evident that many natural foods like corn, carrots, or wheat had been eaten for centuries, so hardly needed to be tested for safety. But as foods became processed prior to purchase at the market, other chemicals were often added to accomplish specific tasks, such as flavor enhancement, improvement of consistency, or preservation. It is these additional compounds that governments want to guarantee as safe. To that end, manufacturers must present data to the FDA that adheres to guidelines established and that ensures that the product is safe if used as intended. Since 1906, several revisions to the food and drug laws have brought us to the review processes and expectations of today. Many food additives had been used for decades prior to FDA’s creation and were believed to be safe based on historical experience. Such additives were/are classified as "generally recognized as safe" (GRAS) and, consequently, have never been thoroughly tested in the special studies designed to do safety analyses.

NutraSweet, however, was discovered after the FDA’s establishment and is classified as a food additive, as are all similar sweeteners. As such, NutraSweet had to clear the rigorous review process required by the FDA before its approval for use in foodstuffs.

The sweetness of NutraSweet was noted in 1965, but it was not until 1981 that the FDA approved its use. Part of that time span was used by the G. D. Searle company to synthesize compounds of similar structure to determine if a closely related material might be a better sweetener, to work on the most cost-efficient and effective manner in which to make the compound, and to protect its property interests through the patent process. But many years were also spent testing the product as required by the FDA. In the almost two decades since first approval, testing continues and the use of NutraSweet remains a rather controversial issue. A trip to the Internet will reveal many anecdotal but scientifically undocumented bulletins regarding health risks associated with the use of NutraSweet.

Saccharin was widely used as a non-nutritive sweetener until being replaced by aspartame, a replacement accelerated by disputed studies suggesting that saccharin might be associated with bladder cancer. One amendment (1958) to the original Food and Drug Act, often called the Delaney Clause or Amendment, sets a zero tolerance for any chemical found to cause cancer in animal testing. Saccharin had been one of those GRAS compounds. When the concerns about saccharin’s safety arose, the FDA removed it from the GRAS list (1977) and was prepared to ban it from use based on the Delaney Clause. However, with no replacement available, and an outcry from those who suggested the risk to people (diabetes patients, people with dental caries, and people who dealt with obesity) from the likely return to natural sugar (fructose and sucrose) far outweighed the risk of cancer, Congress created a special saccharin labeling act that allowed its continued use but required a "may be hazardous to your health" label. Within a few years, however, aspartame, with its rather clean bill of health from testing and its preferred sweetness characteristics, monopolized the market for a non-nutritive sweetener. Saccharin continues to be used today, in a modest manner, with the warning label still required. On your next restaurant visit, check the "Sweet’N Low" label.

Biomedical Considerations

It is likely that the scientists at Searle were excited about the commercial prospects for aspartame when its sweetness was accidentally discovered in 1965 because, though a synthetic material, its two principal components were naturally occurring amino acids found in protein materials and present in foods. Nonetheless, to bring a product to marketplace, the FDA requires several chemical and biochemical assessments of safety.

For example, is a substance acutely toxic? In other words, will it cause an undesirable effect prior to any chemical or metabolic breakdown in the body? Answers to this question are quite easily obtained. More rigorous investigation requires an analysis of the metabolic fate of the product. In the stomach, where gastric juices can act, aspartame is likely to be at least partially if not completely converted to its major component parts, the two natural amino acids – aspartic acid and phenylalanine – and methanol. What is the toxicity of these chemical? Finally, what is the fate of those three chemicals as they pass through the body and undergo their metabolic changes? Again, pronounced effects would be seen immediately, but more subtle effects might not be. Consequently, what does one investigate to assess safety? There are an awful lot of body parts that might be affected, so it is important to establish a protocol for testing, and this is what the FDA has done. Beyond what might be observable in an hour or a day or two is, of course, the concern about effects that might arise from the long-term use of any product. Consequently, studies that project the result of years of use need to be undertaken. Most studies involve test animals, often rodents, whose metabolic processes and tendency towards various maladies (cancer, circulatory problems, etc.) are well studied. It has never been easy, nor without great controversy, to use animal results to predict human effects. Eventually, a human population makes itself available for testing.

As we all know, dosage will have a major effect on results. A glass of water to quench a thirst will be well received; a gallon of water to quench the thirst will likely cause great discomfort. With a product like NutraSweet, an optimal dose is determined by the degree of sweetness desired, but what is the risk if a person drinks one diet soft drink a week versus one a day or one an hour? Also, is there a difference if the person is 60 years old, 16 years old, or 6 years old? Such questions need answers before a product can be marketed. It is not uncommon in testing the safety of a product to overdose the animal subject of the testing. This type of study allows the establishment of a safe dose, especially by exacerbating the development of undesired side effects at high doses. They are much easier to observe. Such tactics can result in considerable controversy, for the argument can be advanced that though a product might cause cancer, say, at a very high concentration, it would never be consumed at that level and that at a lower level the product is acceptably safe. This is, in fact, the controversy that surrounded the saccharin studies that led to the requirement of the health warning. A cancer development occurred with dosages that were beyond a reasonable amount. 

Several pharmacological studies that investigated the effects of aspartame on the endocrine, nervous, gastrointestinal, and reproductive systems have been published. Metabolic studies confirm that aspartame is converted to methanol and the two amino acids in the gastrointestinal tract and does not itself enter the bloodstream unchanged. Both short- and long-term studies show no deleterious effect at a level of minimally 2,000 mg per kg of body weight per day. When the FDA approved the use of aspartame, it cautiously established an acceptable intake of 50 mg/kg/day. If a 12 oz. diet cola contains 180 mg of aspartame, it is easy to calculate how many colas might be consumed, if uncomfortably, by a 150 lb. person adhering to the acceptable intake. Although its safety is backed by considerable scientific support, reports still circulate that aspartame may cause dizziness, headaches, and changes in the brain.

Q. Calculate the number of 12 oz. diet colas that would be consumed by a 150 lb. person to reach the threshold of 50 mg/kg/day.

In addition to those whose body functions would be classified as normal, many people have metabolic dysfunctions or allergies that might limit what nutrients can be tolerated. Since diabetics cannot tolerate glucose, a non-sugar sweetener is a terrific alternative. But can it be tolerated? Thus, it becomes necessary to investigate the tolerance to a substance such as aspartame in people with metabolic defects. This has been done. Some people have an inability to metabolize phenylalanine properly (phenylketonuria, or PKU) and must restrict their diet to exclude foodstuffs that have proteins or amino acids rich in phenylalanine. As a source of phenylalanine, aspartame products require labeling that adequately warns consumers. Check a label. Clinical studies suggest that even people with concerns about phenylalanine content are not likely to consume amounts that pose a health danger, however.

Another concern is the effect that aspartame consumption might have when combined with other foodstuffs. Might there be an unfavorable synergistic effect? Again, various studies suggest that this does not seem to pose problems.

Finally, even though aspartic acid and phenylalanine occur naturally in many sources (as do small quantities of methanol), do they pose an unnecessary threat to health if consumed as aspartame? Methanol is toxic, causing blindness and death if ingested, say, in a quantity akin to the typical consumption of ethanol, grain alcohol, the alcohol of beer and wine. But methanol consumed in the small quantities associated with natural sources, such as fruit, or with aspartame seem quite safe. None of these three components of aspartame bioaccumulate in the body and all are metabolized in a fashion that produces end products harmless to human health in the quantities produced.

Since its commercial introduction in the early 1980s, aspartame has been consumed, sometimes regularly, by millions of people. The testing alluded to in this section occurred not only prior to aspartame’s introduction but also subsequently, and continues today. As mentioned previously, reports of adverse effects still surface. As part of its monitoring process, the FDA has investigated such reports, but no scientific study has ever suggested that aspartame poses any threat to the health of the general population in any specific, identifiable manner. It appears to be a remarkably safe food additive and one that has brought the pleasure of noncaloric sweetness to many a mouthful of food and drink.
Sections in this ChemCase

NutraSweet Concept Map
Biomolecular Concepts
Physical-Chemical Concepts
Food Additives
Chemical Commerce
NutraSweet Case Study Exercise

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© 1999 Kennesaw State University.
Principal Investigator Laurence Peterson; Project Director Matthew Hermes.
Author of this module Sam Stradling.