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Artificial sweeteners

Definition

Artificial sweeteners, which are also called sugar substitutes, alternative sweeteners, or non-sugar sweeteners, are substances used to replace sugar in foods and beverages. They can be divided into two large groups: nutritive sweeteners, which add some energy value (calories) to food; and nonnutritive sweeteners, which are also called high-intensity sweeteners because they are used in very small quantities as well as adding no energy value to food. Nutritive sweeteners include the natural sugars—sucrose (table sugar; a compound of glucose and fructose), fructose (found in fruit as well as table sugar), and galactose (milk sugar)—as well as the polyols, which are a group of carbohydrate compounds that are not sugars but provide about half the calories of the natural sugars. The polyols are sometimes called sugar replacers,

Artificial sweeteners

SweetenerTimes sweeter than sugarCaloriesBrand name(s)
aspartame2004 kcal/gNutrasweet and Equal
saccharin200–7000Sweet’N Low, Twin,and Necta Sweet
acesulfame-K (potassium)2000Sunett and Sweet One
neotame7,000–13,0000Neotame
sucralose6000Splenda

SOURCE: Food and Drug Administration, U.S. Department of Health and Human Services.

(Illustration by GGS Information Services/Thomson Gale.)

sugar-free sweeteners, sugar alcohols, or novel sugars. Polyols occur naturally in plants but can also be produced commercially. They include such compounds as sorbitol, mannitol, xylitol, and hydrogenated starch hydrolysates.

Nonnutritive sweeteners are synthetic compounds that range between 160 and 13,000 times as sweet as sucrose, which is the standard for the measurement of sweetness. There are five nonnutritive sweeteners approved by the Food and Drug Administration (FDA) for use in the United States as of 2007. They are saccharin, aspartame, acesulfame potassium (or acesulfame-K), sucralose, and neotame. There are other nonnutritive sweeteners that have been approved for use elsewhere in the world by the Scientific Committee on Food (SCF) of the European Commission, the Joint Expert Committee of Food Additions (JECFA) of the United Nations Food and Agricultural Organization, and the World Health Organization (WHO) but have not been approved by the FDA. These substances are alitame, cyclamate, neohesperidine dihydrochalcone, stevia, and thaumatin. All of these will be described in further detail below.

The FDA uses two categories to classify both nutritive and nonnutritive sweeteners for regulatory purposes. Some are classified as food additives, which is a term that was introduced by the Federal Food, Drug, and Cosmetic (FD&C) Act of 1938. This legislation was passed by Congress in response to a mass poisoning tragedy that took the lives of over a hundred people in 1937. A company in Tennessee that manufactured an antibacterial drug known as sulfanilamide, which had been used safely in powdered or pill form to treat childhood infections, dissolved the sulfanilamide in diethylene glycol—related to the active ingredient in automobile antifreeze—in order to market it as a liquid medicine. Diethylene glycol is highly

KEY TERMS

Acceptable daily intake level (ADI)—The level of a substance that a person can consume every day over a lifetime without risk. The ADIs for artificial sweeteners are very conservative measurements.

Carcinogen—A substance or other agent that causes cancer. Some artificial sweeteners have been banned in the United States on the grounds that they may be carcinogens.

Food additive—Defined by the Federal Food, Drug, and Cosmetic Act (FD&C) of 1938 as “any substance, the intended use of which results directly or indirectly, in its becoming a component or otherwise affecting the characteristics of food.”

Excipient—An inert substance, such as certain gums or starches, used to make drugs easier to take by allowing them to be formulated into tablets or liquids. Some artificial sweeteners are used as excipients.

Fructose—A simple sugar that occurs naturally in sucrose and fruit. It can be added in combination with sucrose in the form of high-fructose corn syrup (HFCS) to sweeten foods because it is sweeter than sucrose. Large amounts of fructose can cause diarrhea in infants and young children.

Generally recognized as safe (GRAS)—A phrase used bythefederal governmentto refer to exceptions to the FD&C Act of 1938 as modified by the Food Additives Amendment of 1958. Sweeteners that have a scientific consensus on their safety, based on either their use prior to 1958 or to well-known scientific information, may be given GRAS status.

Gulf war syndrome (GWS)—A disorder characterized by a wide range of symptoms, including skin rashes, migraine headaches, chronic fatigue, arthritis, and muscle cramps, possibly related to military service in the Persian Gulf war of 1991. GWS was briefly attributed to the troops’ high consumption of beverages containing aspartame, but this explanation has been discredited.

High-intensity sweetener—Another term for nonnutritive sweetener, used because these substances add sweetness to food with very little volume.

Nonnutritive sweetener—Any sweetener that offers little or no energy value when added to food.

Nutritive sweetener—Any sweetener that adds some energy value to food.

Phenylketonuria (PKU)—A rare inherited metabolic disorder resulting in accumulation of phenylalanine, an amino acid, in the body. It can lead to mental retardation and seizures. People with PKU should not use products containing the artificial sweetener aspartame because it is broken down into phenylalanine (and other products) during digestion.

Sucrose—The natural sweetener commonly used as table sugar; sucrose is a compound of two simple sugars, glucose and fructose. It is used as the standard for measuring the sweetening power of high-intensity artificial sweeteners.

toxic to human beings and household pets, causing painful death from kidney failure. In 1937 there was no requirement for medications to be tested for toxicity before being placed on the market. The FD&C Act of 1938 thus included a legal definition of a food additive “any substance, the intended use of which results directly or indirectly, in its becoming a component or otherwise affecting the characteristics of food”

The FDA asks the following questions in evaluating a proposed new sweetener as a food additive:

  • How is the sweetener made?
  • What are its properties when it is added to foods or beverages?
  • How much of the sweetener will be digested or otherwise absorbed by the body?
  • Are certain groups of people likely to be more susceptible than others to the additive?
  • Does the sweetener have any known toxic effects, including hereditary disorders or cancer?

Other sweeteners are classified as generally regarded as safe or GRAS, and are not defined for legal purposes as food additives. The GRAS category was created in 1958 when the FD&C Act was modified by the passage of the Food Additives Amendment. A sweetener, whether nutritive or nonnutritive, can be given GRAS status on the basis of “experience based on common use in food” or a scientific consensus represented by published studies. Sorbitol and a few other polyols have GRAS status along with the natural sugars. Most artificial sweeteners, however, are considered food additives by the FDA.

Purpose

Artificial sweeteners are used in food products for several reasons: to lower the calorie content of soda pop and other sweet treats as part of weight reduction and weight maintenance diets; to assist patients with diabetes in controlling blood sugar levels more effectively; and to lower the risk of tooth decay. They are also added as excipients (inert substances used to make drugs easier to take in tablet or liquid form) to some prescription medications to disguise unpleasant tastes because they do not react with the active drug ingredients as natural sugars sometimes do. Sorbitol and mannitol are commonly added to toothpaste, mouthwash, breath mints, cough drops, cough syrups, sugarless gum, over-the-counter liquid antacids, and similar personal oral care products to add bulk to the product’s texture as well as minimize the risk of tooth decay.

In addition to adding a sweet flavor, artificial sweeteners are also used in the manufacture of baked goods, beverages, syrups, and other food products to improve texture, add bulk, retard spoilage, or as part of a fermentation process. The polyols in particular are used to retard spoilage because they do not support the growth of mold or bacteria to the same extent as natural sugars.

Nutritive sweeteners

  • Natural sugars. Natural sugars, which are also called primary sweeteners, include sucrose, a compound of glucose and fructose commonly used in crystalline form as table sugar; and fructose, which is a simple sugar found in sucrose and fruit, and is added to foods and beverages in combination with sucrose as high-fructose corn syrup or HFCS. These sweeteners provide about 4 calories per gram. Fructose is sweeter than sucrose; thus smaller amounts of it can be used to sweeten foods and drinks, which allows for some reduction in calories.
  • Polyols. Polyols provide between 1.6 calories per gram (mannitol) and 3 calories per gram (hydrogenated starch hydrolysates). They are absorbed very slowly and incompletely during digestion, which is why they can be beneficial to patients with diabetes who want to avoid sudden or sharp increases in blood sugar levels.

Nonnutritive sweeteners approved by the FDA

There are five nonnutritive sweeteners approved by the FDA for use in the United States as of 2007:

  • Acesulfame potassium (acesulfame-K). Acesulfame potassium is a high-intensity nonnutritive sweetener that is about 200 times sweeter than sucrose; 95% of it is excreted from the body unchanged. It was discovered by a German company, Hoechst AG, in 1967. It was first approved by the FDA for use in nonalcoholic beverages in 1998 and for general use in 2003. In addition to its usefulness in reducing the calorie content of foods, in diabetic diets, and in not promoting tooth decay, acesulfame potassium remains stable at the high temperatures used for cooking and baking, has a long shelf life, does not leave any bitter aftertaste, and combines well with other sweeteners. It is sold under the brand names ACK, Sunett, Sweet & Safe, and Sweet One.
  • Aspartame. Aspartame, which is also about 200 times sweeter than sugar, was discovered in 1965 by a researcher at Searle Laboratories working on antiulcer medications. It is unusual among nonnutritive sweeteners in that it is completely broken down during digestion into its basic components—the amino acids aspartic acid and phenylalanine plus a small amount of methanol. Aspartame was approved by the FDA for tabletop use in 1981 and for use in carbonated beverages in 1983. As of the early 2000s, the United States uses 75% of the aspartame produced in the world, 70% of this amount consumed in diet beverages. Aspartame is the nonnutritive sweetener that has received the greatest amount of negative attention in the mass media because of a rumor that it caused Gulf War syndrome (GWS) in veterans of the Persian Gulf conflict of 1991, and because of a study done in Europe in 2005 that linked aspartame to two types of cancer (leukemia and lymphomas) in female laboratory rats. In response to the 2005 European study, the National Cancer Institute (NCI) conducted a study of half a million people in the United States in 2006 and found no connection between cancer rates and aspartame consumption. The details of this study can be found in a fact sheet available on the NCI website. Another study conducted by the National Toxicology Program (NTP) of the National Institute of Environmental Health Sciences (NIEHS) of aspartame as a possible carcinogen found no evidence that the sweetener causes cancer in humans. Aspartame is sold under the brand names NutraSweet, Equal, and Sugar Twin (blue box).
  • Saccharin. Saccharin is the oldest nonnutritive sweetener, having been discovered in 1879 by a chemist working at Johns Hopkins University. It is about 200 to 700 times as sweet as sugar. It was used extensively during World Wars I and II, when sugar was rationed in the United States as well as in Europe. It is still the least expensive high-intensity sweetener used around the world—about 65 million pounds per year in the late 1990s. Saccharin passes through the body essentially unchanged. It was so widely used in the United States that it was considered a GRAS substance when the Food Additives Amendment was passed in 1958, but it lost that status when studies performed on laboratory rats in the 1970s indicated that it might cause bladder cancer. At that point Congress mandated that all foods containing saccharin must carry a warning label that they might be hazardous to health. Later studies indicated that the bladder tumors in rats are caused by a mechanism that does not operate in humans, and that there is no evidence that saccharin is unsafe for humans. In 2000 the NTP took saccharin off its list of carcinogens and the saccharin-warning label was removed from food. Details of the controversy over saccharin and cancer can be found on the NCI website. Saccharin is presently sold under the trade names of Sweet ’N Low, Sweet Twin, and Necta Sweet.
  • Sucralose. Sucralose is unusual in that it is the only nonnutritive sweetener made from sugar, but it is about 600 times as sweet as table sugar. Sucralose is manufactured from sugar by substituting three chlorine atoms for three hydroxyl groups in the sugar molecule. Only about 11 % of sucralose is absorbed during digestion; the remainder is excreted unchanged. The FDA approved sucralose in 1998 as a tabletop sweetener and in 1999 as a general-purpose sweetener. The acceptable daily intake (ADI) for sucralose is 5 mg per kilogram of body weight per day. Like acesulfame potassium, sucralose is highly heat-stable and works well in foods that must be baked or cooked. Sucralose is sold under the trade name Splenda for table use.

Nonnutritive sweeteners not approvedfor use in the United States

  • Alitame. Alitame is a compound of aspartic acid, D-alanine, and an amide; it is 2000 times sweeter than sugar. In 1986 it was reviewed by the FDA, which found the application to be deficient. As of 2007, alitame is approved for use only in Australia, New Zealand, Mexico, Colombia, and China.
  • Cyclamate. Cyclamate, which is about 30 times sweeter than sugar, was used as a nonnutritive sweetener in the United States until 1969, when it was shown to cause cancer in laboratory rats when combined with saccharin. Although cyclamate by itself was found by the National Academy of Sciences not to be a carcinogen in 1985 and is approved for use in over 50 countries, it has not been reinstated by the FDA for use in the United States as of 2007.
  • Neohesperidine dihydrochalcone. Neohesperidine dihydrochalcone is a compound that is about 1500 times sweeter than sugar and adds a slight licorice flavor to foods and beverages. The FDA considers neohesperidone GRAS as a flavoring but not as a sweetener.
  • Stevia. Stevia is a sweetener derived from a shrub native to South America. The FDA has not received sufficient scientific evidence to indicate that stevia is safe for use as a food additive.
  • Thaumatin. Thaumatin is an intensely sweet mixture of proteins that also acts as a flavor enhancer. The FDA has given thaumatin GRAS status as a flavor adjunct but has not approved it as a sweetener as of 2007.

Precautions

Artificial sweeteners are generally regarded as safe when used appropriately. The official position of the American Dietetic Association is that nutritive and nonnutritive sweeteners are safe as long as one’s diet follows the current federation recommendations for nutrition.

Some specific artificial sweeteners must be used cautiously by certain groups of people:

  • Polyols: Some polyols—most commonly mannitol and sorbitol—have a laxative effect in some people if they are consumed in large amounts (more than 50 g/day of sorbitol or 20 g/day of mannitol). Persons with diabetes may wish to limit their consumption of products containing polyols or increase their use gradually until they see how their bodies react to these sweeteners.
  • Aspartame: Because aspartame is broken down in the body to the amino acid phenylalanine, foods or beverages containing aspartame should not be used by persons with phenylketonuria (PKU), a rare inherited disease that causes phenylalanine to accumulate in the body. The FDA requires all products containing aspartame sold in the United States to be labeled with the following warning: “Phenylketonurics: Contains Phenylalanine.” Although the breakdown products of neotame also include phenylalanine, the amount is so small that it does not affect people with PKU.

Interactions

There are no known interactions with prescription drugs caused by the use of nutritive or nonnutritive sweeteners. As was noted above, some nonnutritive sweeteners are considered useful excipients for medications precisely because they are chemically inert.

Parental concerns

There have been concerns expressed about the use of artificial sweeteners by children because children consume more sweeteners, both nutritive and nonnutritive, per pound of body weight on a daily basis than adults. The use of fruit juice and other sweet beverages by children has greatly increased since the 1980s; however, studies indicate that even children who drink large amounts of diet soda and other beverages usually remain well below the ADI levels for aspartame and other nonnutritive sweeteners. The chief risk to children’s digestive health is fructose, which is found in such popular children’s drinks as apple juice. Fructose is incompletely digested by children below the age of 18 months and may cause diarrhea in older children. Children diagnosed with nonspecific diarrhea maybenefit from being given smaller amounts of fruit juice to drink.

During the early 1990s, some researchers identified a possible connection between high levels of aspartame consumption and attention-deficit hyperactivity disorder (ADHD) in children. Two studies published in 1994 in Pediatrics and the New England Journal of Medicine respectively, however, found no connection between aspartame and ADHD, even when the children were given 10 times the normal daily amount of aspartame. Aspartame and other nonnutritive sweeteners, however, may have an additive effect on nerve cell development when they are combined with food colorings. This possibility was suggested by a 2006 study of laboratory mice in the United Kingdom, but the implications for humans are far from clear.

High intake of sweeteners added to food is of greatest concern during adolescence. As people age, they generally lower their intake of calories from added sugars. Fewer than 10% of adults over age 50 derive more than 25% of their daily calories from sugars, which is the maximal intake value established by the IOM. Nearly a third of adolescent females exceed this level, however, with almost a third of the extra sugar intake coming from carbonated beverages sweetened with high-fructose corn syrup. Although the rise in obesity in children and adolescents is a complex problem that cannot be attributed to a single factor, preliminary studies suggest that nonnutritive sweeteners may be useful in reducing adolescents’ consumption of drinks sweetened with HFCS.

BOOKS

Nabors, Lyn O’Brien, ed. Alternative Sweeteners, 3rd ed. New York: M. Dekker, 2001.

PERIODICALS

“Artificial Sweeteners: No Calories ... Sweet!” FDA Consumer 40 (July-August 2006). Available online at http://www.fda.gov/fdac/features/2006/406_sweeteners.html (accessed March 22, 2007).

Henkel, John. “Sugar Substitutes: Americans Opt for Sweetness and Lite.” FDA Consumer, February 2006. Available online at http://www.cfsan.fda.gov/—dms/fdsugar.html (accessed March 22, 2007).

Lau, K., W. G. McLean, D. P. Williams, and C. V. Howard. “Synergistic Interactions between Commonly Used Food Additives in a Developmental Neurotoxicity Test.” Toxicological Sciences 90 (March 2006): 178–187.

Shaywitz, B. A., C. M. Sullivan, G. M. Anderson, et al. “Aspartame, Behavior, and Cognitive Function in Children with Attention Deficit Disorder. Pediatrics 93 (January 1994): 70–75.

Wax, Paul M. “Elixirs, Diluents, and the Passage of the 1938 Federal Food, Drug, and Cosmetic Act.” Annals of Internal Medicine 122 (March 15, 1995): 456–461. Available online at http://www.annals.org/cgi/content/full/122/6/456 (accessed March 23, 2007).

Wolraich, M. L., S. D. Lindgren, P. J. Stumbo, et al. “Effects of Diets High in Sucrose or Aspartame on the Behavior and Cognitive Performance of Children.” New England Journal of Medicine 330 (February 3, 1994): 301–307.

OTHER

American Dietetic Association (ADA). Position Statement on the Use of Nutritive and Nonnutritive Sweeteners Available online at http://www.eatright.org/cps/rde/xchg/ada/hs.xsl/home_3794_ENU_HTML.htm. This position paper was adopted by the ADA’s House of Delegates on October 18,1992; reaffirmed on September 6, 1996; and reaffirmed again on June 22, 2000. It will remain in effect until December 31, 2009.

National Cancer Institute (NCI) Fact Sheet. Artificial Sweeteners and Cancer: Questions and Answers Bethesda, MD: NCI, 2006. Available online at http://www.cancer.gov/cancertopics/factsheet/Risk/artificial-sweeteners.

National Cancer Institute (NCI) Fact Sheet. Aspartame and Cancer: Questions and Answers Bethesda, MD: NCI, 2006. Available online at http://www.cancer.gov/cancertopics/factsheet/AspartameQandA.

Office of Food Additive Safety. Guidance for Industry: Frequently Asked Questions about GRAS College Park, MD: Office of Food Additive Safety, 2004. Available online at http://www.cfsan.fda.gov/-dms/grasguid.html.

ORGANIZATIONS

American Dietetic Association (ADA). 120 South Riverside Plaza, Suite 2000, Chicago, IL 60606-6995. Telephone: (800): 877-1600. Website: http://www.eatright.org.

Dietitians of Canada/Les die´te´tistes du Canada (DC). 480 University Avenue, Suite 604, Toronto, Ontario, Canada M5G 1V2. Telephone: (416) 596-0857. Website: http://www.dietitians.ca.

Institute of Medicine (IOM). 500 Fifth Street NW, Washington, DC 20001. Telephone: (202) 334-2352. Website: http://www.iom.edu.

National Cancer Institute (NCI). NCI Public Inquiries Office, 6116 Executive Boulevard, Room 3036A, Bethesda, MD 20892-8322. Telephone: (800) 4-CANCER. Website: http://www.cancer.gov/.

National Toxicology Program (NTP). Report on Carcinogens. P.O. Box 12233, MD EC-14, Research Triangle Park, NC 27709. Telephone: (919) 541-4096. Website: http://ntp.niehs.nih.gov/ntpweb/index.cfm?objectid=7182FF48-BDB7-CEBA-F8980E5DD01A1E2D.

Office of Food Additive Safety, HFS-200, Center for Food Safety and Applied Nutrition, Food and Drug Administration, 5100 Paint Branch Parkway, College Park, MD 20740. Telephone: (301) 436-1200. Website: http://www.cfsan.fda.gov/list.html.

U. S. Food and Drug Administration (FDA). 5600 Fishers Lane, Rockville, MD 20857-0001. Telephone: (888) INFO-FDA. Website: http://www.fda.gov/default.htm.

Rebecca J. Frey, Ph.D.


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