NONNUTRITIVE SWEETENERS

II. NONNUTRITIVE SWEETENERS

A. Saccharin

1. History Saccharin was first synthesized in the United States in 1879 by two chemists (Remsen

and Fahlberg, 1879). Essentially the same production method is still used by many manu- facturers. Initially saccharin was used as an antiseptic and a preservative, but its potential as a food sweetening agent was soon established. Saccharin was first introduced as a food additive in the United States in 1900, and immediately concern over its safety arose. In Europe the use of saccharin increased during the two world wars due to the lack of sugar. Since World War II the consumption of saccharin has steadily increased due to the wide- spread acceptance of special dietary and dietetic foods even though its safety has repeat- edly been questioned (National Research Council/National Academy of Sciences, 1978). Only recently, since the introduction of aspartame, has a small decline in the increase in saccharin consumption taken place.

2. Chemistry Saccharin is a general name used for saccharin, sodium saccharin, and calcium saccharin.

The molecular formula of saccharin is C 7 H 5 NO 3 S, and the structural formula is presented in Fig. 1 . Chemically saccharin is 1,2-benzisothiazol-3(2H)-one-1,1-dioxide and its so-

Figure 1 The chemical structures of the most important nonnutritive sweeteners.

Saccharin can be produced by two methods, either from toluene and chlorosulfonic acid (Remsen and Fahlberg, 1879) or from methyl anthranilate (National Research Council/National Academy of Sciences, 1978). Saccharin and sodium saccharin do not occur in nature. Manufactured saccharin and sodium saccharin are white crystalline pow- ders that are stable at both high temperatures (up to 300 °C) and low temperatures. [This stability has been questioned by Kroyer and Washu¨ttl (1982).] Both compounds are soluble in water and ethanol. In dilute aqueous solutions they are about 300 times sweeter than

a solution containing an equal concentration by weight of sucrose.

3. Technological Properties Saccharin and its calcium and sodium salts are very stable under almost all food processing

conditions, and they also have a long shelf life ( Table 2 ). It remains to be further studied whether the reactions of saccharin and many food components are as significant as indi- cated by Kroyer and Washu¨ttl (1982). Saccharin is at present the only noncaloric sweetener that appears to be stable during cooking and baking of food products and can be utilized in most drugs, special dietary products, and cosmetics. However, saccharin tends to have

a slight to moderate metallic or bitter aftertaste. This aftertaste can be masked by the use of lactose or by combining saccharin with aspartame or other sweeteners. When combined with other sweeteners, saccharin usually has a synergistic effect on the sweetness and thereby the total amount of noncaloric sweeteners can be reduced (Hyvo¨nen, 1980).

4. Intake In the United States the major uses of saccharin include soft drinks, tabletop sweeteners,

and dietetic foods. Similar usage patterns are also found in most European countries. Saccharin and sodium saccharin have other uses in cosmetics and pharmaceuticals. It is estimated that, despite all the adverse publicity about its potential hazards to health, some

Table 2 Some Properties of Nonnutritive Sweeteners Sweetness in

Stability

relation to ADI a Sweetener

(mg/kg body weight) Acesulfame K

sucrose

Aftertaste

In solution

During heating

0–9 Aspartame

Very slight, bitter

Stable

Stable

Unstable, sweetness may disappear 40 Cyclamate

Prolonged sweetness

Not stable in acid conditions

0–7 Saccharin

Chemical flavor

Relatively stable

Relatively stable

2.5 Stevioside

Bitter metallic

Stable in pH ⬍ 2.0

Relatively stable

Not acceptable Talin

Bitter

Relatively stable

Relatively stable

Not specified Sucralose

Licorice-like

Relatively stable

Stable at neutral to low pH

0–15 a WHO and European Union Scientific Committee on Food.

Stable

Stable Stable

5. Toxicology of Saccharin

a. Metabolism and Short-Term Toxicity. Saccharin itself is absorbed slowly but almost completely from the gut after oral administration, and it is rapidly excreted in the urine as unchanged saccharin. The remaining saccharin is excreted unchanged in feces (Renwick, 1983,1985). Therefore, metabolites are not likely to cause toxic effects. Saccharin does not increase the urinary excretion of dietary oxalate in mice, and therefore oxalate crystals are not likely to be involved with saccharin toxicity or bladder effects (Salminen and Salminen, 1986a). Although most mutagenicity studies are negative, saccharin has been indicated to pose mutagenic properties at least in the host-mediated assay. This test proved that highly purified saccharin itself was not mutagenic, but the urine of mice treated with saccharin exhibited mutagenic activity in Salmonella typhimurium TA 100 strain (Bat- zinger et al., 1977). However, most studies on mutagenicity have indicated that sodium saccharin is nonreactive to DNA and inactive as a gene mutagen in vitro (Ashby, 1985).

b. Long-Term Toxicity. Saccharin has been the subject of a very large number of long- term toxicity tests. In some long-term rat studies an induction of a higher incidence of bladder cancer was found among rats consuming saccharin. This incidence has been ob- served in several long-term rat studies conducted by the U.S. Food and Drug Administra- tion, the Wisconsin Alumni Research Foundation (Tisdel et al., 1974), and the Interna- tional Research and Development Corporation (1983). All these studies indicated that high dietary levels (5–7.5%) increase the incidence of urinary bladder tumors in rats. In the latest studies the effect was clearest, and even a dose-response relation was observed (Carlborg, 1985). However, a possibility of a threshold dose level for the bladder effects has recently been suggested (Carlborg, 1985). Numerous additional studies have been conducted on the bladder carcinogenicity and cocarcinogenicity of saccharin. The results appear to support weak carcinogenicity and possible cocarcinogenicity or promotion effect of saccharin. A review of some of these studies has been completed by Cranmer (1980) and more recently by Cohen (1985).

c. Epidemiological Studies on Saccharin. The safety of saccharin has been assessed in many epidemiological studies involving both normal subjects and diabetics (Hoover and Strasser, 1980; Morrison and Buring, 1980; Wynder and Stellman, 1980). Most studies in many population groups including diabetics have failed to demonstrate any statistical evidence of an association between human bladder cancer and saccharin consumption (Morgan and Wong, 1985). However, most studies are inadequate in many ways and cannot determine exact saccharin consumption figures. On the other hand, diabetics, who are significant users of saccharin and other nonnutritive sweeteners, form a special group with different dietary habits than the general population. Therefore, results from epidemio- c. Epidemiological Studies on Saccharin. The safety of saccharin has been assessed in many epidemiological studies involving both normal subjects and diabetics (Hoover and Strasser, 1980; Morrison and Buring, 1980; Wynder and Stellman, 1980). Most studies in many population groups including diabetics have failed to demonstrate any statistical evidence of an association between human bladder cancer and saccharin consumption (Morgan and Wong, 1985). However, most studies are inadequate in many ways and cannot determine exact saccharin consumption figures. On the other hand, diabetics, who are significant users of saccharin and other nonnutritive sweeteners, form a special group with different dietary habits than the general population. Therefore, results from epidemio-

The idea that saccharin may be a weak carcinogen in the rat appears to be evident on the basis of numerous animal studies. At present, the linkage between animal studies and human studies is difficult for risk evaluation purposes, but it appears that saccharin is unlikely to present a cancer risk at present average exposure rates. However, since alternative nonnutritive sweeteners are currently available it is easy to utilize these when- ever technological and consumer preference aspects require saccharin substitution with other sweeteners.

6. Regulatory Status The Joint FAO/WHO Expert Committee on Food Additives (JECFA) has established an

acceptable daily intake (ADI) of 2.5 mg/kg body weight. Saccharin is currently being used almost worldwide. However, restrictions of use to only a limited number of products apply in most countries. In 1977, the U.S. Food and Drug Administration proposed a ban on saccharin in the United States. The proposal resulted in a congressional moratorium on the saccharin ban pending further toxicity studies. This moratorium has been extended several times to allow more studies to be completed. Studies have thus accumulated and as new sweeteners have become available the use of saccharin has decreased.

B. Cyclamates

1. History Sodium cyclamate was synthesized in 1937, but it was first produced commercially in the

United States in 1950. Now cyclamates are produced in many countries including Japan, Germany, Spain, Taiwan, and Brazil (IARC, 1980). Due to regulatory decisions the use of cyclamates decreased in the 1960s. Recently, after the allocation of a new acceptable daily intake value by JECFA, the use has started to increase again.

2. Chemistry Cyclamates is a group name used for the following compounds: cyclamic acid, sodium

cyclamate, and calcium cyclamate. The molecular formula for calcium cyclamate is

C 12 H 24 CaN 2 O 6 S 2 ⋅ 2H 2 O; and the structural formula is presented in Fig. 1 . Cyclamates are chemically synthesized products that are not found in nature. They are synthesized from cyclohexylamine by sulfonation of various chemicals (chlorosulfonic acid, sulfamic acid) followed by neutralization with hydroxides (IARC, 1980).

Cyclamates are stable at both high and low temperatures. They provide a sweet taste that is 30 times sweeter than sugar ( Table 2 ). Cyclamates are easily soluble in water and can be used as noncaloric sweeteners in most foods, including soft drinks, confections, desserts, and processed fruits and vegetables. Cyclamates have a synergistic sweetening effect when combined with saccharin. Sodium and calcium cyclamates have been used mainly in the form of the 10:1 cyclamate/saccharin mixture.

3. Toxicology

a. Metabolism of Cyclamate. Cyclamate is absorbed partially from the intestine, and

a variable amount is converted to cyclohexylamine by microorganisms in the large bowel. In humans the conversion of cyclamate is thought to be limited but may vary mark- a variable amount is converted to cyclohexylamine by microorganisms in the large bowel. In humans the conversion of cyclamate is thought to be limited but may vary mark-

After cyclamate administration in some nonhuman mammals, N-hydroxycyclo- hexylamine has been found in urine. Cyclohexanol and cyclohexane have also been re- ported as trace metabolites of cyclamate in rats, rabbits, guinea pigs, monkeys, and hu- mans, probably arising from metabolism of cyclohexylamine (Renwick and Williams, 1972).

b. Short-Term Toxicity. Although many short-term tests have been conducted, there have been no assays for mammalian cell DNA damage and gene mutation for cyclamate and no DNA damage test for cyclohexylamine.

Tests for gene mutations in bacteria have been negative for cyclamate and cyclohex- ylamine. Positive tests include some short-term tests like mammalian cytogenetic tests. In vitro studies have shown tumor-promoting properties for cyclamate (IARC, 1980; FDA, 1985; National Research Council, 1985).

c. Carcinogenicity and Epidemiological Studies. In two carcinogenicity studies, cocar- cinogenic and tumor-promoting activities for cyclamate were observed. In one study cycla- mate was incorporated into the bladders of mice, and in the other cyclamate was fed to rats after N-methyl-N-nitrosourea had been instilled into the bladder. However, these studies were of problematic design, and the results have been questioned (DeSesso, 1987).

In one bioassay, rats dosed with a 10 : 1 cyclamate/saccharin mixture were reported to develop urinary bladder cancer. Two later attempts to duplicate the results of the initial study failed to show carcinogenicity. Numerous other studies demonstrate that even after ingestion of high doses of cyclamate throughout the lifetime of laboratory animals, cycla- mate does not cause cancer.

Epidemiological studies in humans indicate that there is suggestive evidence that the use of cyclamate/saccharin mixtures may be associated with a small increase in the risk of bladder cancer. In addition to carcinogenicity data there are some adverse effects observed in laboratory animals such as testicular atrophy in animals exposed to cyclohexy- lamine. The clarification of these adverse effects as well as sone other questions give rise to the need for further studies. Epidemiological monitoring should be continued, compar- ing heavy and long-term users. The promoter or cocarcinogenic role of cyclamate should also be elucidated (National Research Council, 1985).

Cyclamates themselves appear not to be carcinogenic, and epidemiological studies support this conclusion (IARC, 1980; FDA, 1985; National Research Council, 1985).

4. Use and Intake There is little information about the use of cyclamates in different countries. Therefore

it is not known whether the proposed acceptable daily intake is exceeded by some con- sumer groups. However, data from the United States before the ban of cyclamate in 1977 are available and indicate that the greatest intake is from beverages and sugar substitutes. According to this information it has been calculated that a person who is a 90th percentile consumer of cyclamate in all products would have a daily consumption of cyclamate of

5. Regulatory Status of Cyclamates The Joint FAO/WHO Expert Committee on Food Additives established in 1967 a tempo-

rary acceptable daily intake of 50 mg/kg body weight for total cyclamates. This was withdrawn in 1970, and a temporary ADI of 4 mg/kg body weight expressed as cyclamic acid was recommended in 1977 (WHO, 1978). The most recent European assessment raises the ADI to 9 mg/kg body weight.

In the United States cyclamate was approved for use as a nonnutritive sweetening agent in 1950. In 1969, the FDA banned the use of cyclamate in food because its safety was questioned. The data on carcinogenicity were reexamined in 1976 by a National Can- cer Institute Committee, in 1984 by the FDA Cancer Assessment Committee, and in 1985 by the National Research Council Committee. All the committees have concluded that experimental and epidemiological evidence does not indicate that cyclamate is carcino- genic. However, cyclamates were not approved for food use in the United States.

In 1984 the Commission of the European Communities issued a report on sweeteners and established an ADI value for cyclamate ( Table 2 ). More than 40 countries in Europe, Asia, North and South America, and Africa have approved cyclamate as nonnutritive sweetening agent.

C. Aspartame

1. History Aspartame was discovered accidentially in the G. D. Searle laboratories by J. M. Schlatter

in the early 1960s. Since the discovery safety studies on aspartame have been carefully conducted by Searle laboratories and by many other independent research laboratories. In the early 1980s aspartame was approved in many countries as an alternative sweetener to saccharin and cyclamate.

2. Chemistry Chemically, aspartame is the methyl ester of L-aspartyl-L-phenylalanine. Aspartame is

produced from the amino acids phenylalanine and aspartic acid. Preliminary amino acids can be produced by fermentation.

Aspartame is an odorless white crystalline powder and has a clean sweet taste. It is slightly soluble in water and sparingly soluble in alcohol. The sweetening potency of aspartame is 150–200 times that of sucrose (Table 2). Aspartame provides 4 kcal/g. Under certain moisture, temperature, and pH conditions, the O-methyl ester bond is hydrolyzed, forming the dipeptide aspartylphenylalanine and methanol. Alternatively, methanol may

be eliminated by the cyclization of aspartame to form its diketopiperazine (DKP), which in turn can be hydrolyzed to aspartylphenylalanine and then ultimately to aspartate and phenylalanine ( Fig. 2 ). When these compounds are formed in food products, a loss of sweetness is perceived (Stegink and Filer, 1984; Homler, 1984). However, the stability of aspartame in dry products is good. In addition to sweetening, aspartame also enhances some food flavors (Homler, 1984).

3. Technological Properties Aspartame provides sugarlike sweetness both in foods and as a tabletop sweetener, but

Figure 2 Typical chemical reactions by which aspartame is converted to nonsweet compounds. [According to Homler (1984).]

Stegink and Filer (1984). Aspartame is an excellent sweetener for dry products like pow- dered drinks or tabletop sweeteners. At high temperature or low pH, aspartame is gradually hydrolyzed and aspartylphenylalanine and methanol are produced. Since these compounds are not sweet, a loss of sweetness is observed in foods that have an extremely low pH or in foods heated for long periods. Aspartame can be easily used in chewing gum, instant coffee, and tea. Aspartame is also suitable for the sweetening of most soft drinks, dairy products such as yogurts and ice cream, and dessert mixes (Homler, 1984). Soft drink manufacturers often increase the stability of aspartame by raising the product pH slightly and controlling the inventory. Soft drinks are usually sweetened with a saccharin/aspar- tame mixture that further increases the stability. Notable sweetness differences are ob- served only after an excessive storage time and a 40% loss in aspartame concentration (Anonymous, 1986).

In most cases sugar cannot simply be replaced by aspartame due to the functional differences between the two. Therefore, a complete reformulation of the product is often needed. Aspartame provides a clear sugarlike sweetness, but the physical and functional properties have to be supplied by suitable bulking agents and carbohydrates. For instance, polydextrose can be utilized as a bulking agent in many aspartame-sweetened foods. In some applications such as powdered beverage mixes, bulk reduction can be beneficial, reducing the packaging and shipping costs (Homler, 1984).

4. Intake The metabolism of aspartame yields, on a weight per weight basis, is approximately 50%

phenylalanine, 40% aspartic acid, and 10% methanol. It has been calculated that daily replacement of all sweeteners with aspartame (using a sweetener ratio of 180 : 1) would increase the phenylalanine intake by 12% and aspartic acid intake by 5%. It is clear that aspartame is not likely to alter daily phenylalanine and aspartic acid intake (3.6 and 6.8

g, respectively) appreciably. The potential extreme intakes of aspartame have been calcu- lated and estimated using various methods. The highest daily intakes have been estimated for young children (10 mg/kg body weight) and diabetics (8 mg/kg body weight), while g, respectively) appreciably. The potential extreme intakes of aspartame have been calcu- lated and estimated using various methods. The highest daily intakes have been estimated for young children (10 mg/kg body weight) and diabetics (8 mg/kg body weight), while

5. Toxicology

a. Metabolism. Aspartame can be absorbed and metabolized in two major ways. In both cases large doses of aspartame release aspartate, phenylalanine, and methanol to the portal blood, and these compounds are metabolized and/or excreted.

Phenylalanine makes up over half of the aspartame molecule and is an essential component of body proteins that cannot be synthesized by mammals. The metabolism and nutritional roles of phenylalanine and tyrosine are linked (Stegink and Filer, 1984). Some ingested aspartame is transaminated to glutamate. There are different interactions between glutamate and aspartate metabolism.

b. Long-Term and Carcinogenicity Studies. Some food sweetened with aspartame might contain the diketopiperazine derivative (DKP) at levels up to 5% of the amount of aspartame added. Therefore DKP has also been subjected to intensive toxicological testing (WHO, 1980).

Extensive data have been reported to support the safety of aspartame. Mutagenicity and reproduction studies do not indicate any adverse effects. Mouse data obtained from chronic feeding studies were negative. The results of one long-term rat study with aspar- tame were consistent with an increased incidence of intracranial neoplasms in the treated animals. However, the increase was not dose or sex related, and the overall incidence was within that previously observed in untreated animals of the same strain. Furthermore, no such increase was seen in two subsequent long-term studies with aspartame. The DKP study results were negative (WHO, 1980).

c. Other Safety Issues Related to Aspartame. Regarding the aspartic acid moiety of aspartame, there was concern that aspartame, either alone or in combination with gluta- mate, may cause focal brain lesions and endocrine disorders. Both glutamate, which is widespread in the food supply, and aspartame in high concentrations have shown neuro- toxic effects on rodents. Although the metabolism of aspartame in humans is similar to that of phenylalanine and aspartic acid, clinical studies involving both adults and children have indicated no untoward effects at levels higher than can be expected for the sweetener in a normal diet.

Phenylketonuria (PKU) is a human genetic disorder of phenylalanine metabolism. In PKU phenylalanine is metabolized poorly and accumulates in blood and tissues. Grossly elevated plasma phenylalanine levels are associated with harmful health effects.

Aspartame in combination with dietary carbohydrates might alter brain neurotrans- mitter activity. In rats the administration of glucose and aspartame (200 mg/kg) by gavage increased brain levels of tyrosine and phenylalanine and decreased brain serotonin concen- tration. Plasma phenylalanine concentrations were also increased in fasted humans, who received large doses of aspartame and confections containing sucrose. However, a nine- month study on infant monkeys showed neither abnormalities nor physical or behavioral impairment when they were removed from high aspartame/phenylalanine diets (Council of Scientific Affairs, 1985).

Plasma phenylalanine concentration normally ranges from 6 to 12 µ mol/dL. The toxic threshold for plasma phenylalanine is 100 µ mol/dL for normal persons including Plasma phenylalanine concentration normally ranges from 6 to 12 µ mol/dL. The toxic threshold for plasma phenylalanine is 100 µ mol/dL for normal persons including

Approximately 10% by weight of aspartame is converted to methanol. Therefore the potential toxicity of markedly elevated blood methanol concentration must also be reconsidered. Ingestion of large doses of the substance by special population groups that may have increased sensitivity (due to infancy, pregnancy, lactation, heterozygosity for PKU) has been specially observed in toxicology studies.

The FDA has reported that in clinical studies, measurable blood levels of methanol have not been detected until loading doses of aspartame exceeded the projected 99th per- centile exposure level of 34 mg/kg (Council on Scientific Affairs, 1985).

Available evidence suggests that normal consumption of aspartame is safe because consumption of aspartame from foods is far below any suspected toxic levels. These data do not provide evidence for serious adverse health effects, although certain individuals might have an unusual sensitivity to the product.

6. Regulatory Status The FAO/WHO Joint Expert Committee on Food Additives has recommended an accept-

able daily intake of 40 mg/kg body weight for humans for aspartame. Simultaneously an ADI value of 7.5 mg/kg body weight was given for diketopiperazine.

In 1981 aspartame was approved in the United States for use in tabletop sweeteners and dry beverage mixes. Further testing of the safety of aspartame was recommended. Later in 1983 aspartame was approved for use in beverages and many other foods (Federal Register , 1981; Stegink and Filer, 1984).

Aspartame has been approved for use in most European countries, in the United States, and in Canada.

D. Acesulfame K

1. History Acesulfame K is one of the most recently introduced nonnutritive sweeteners. It was devel-

oped by Hoechst Company in West Germany in 1967 and has only recently been recom- mended for use in foods in several countries.

2. Chemistry Acesulfame K is a name utilized for the potassium salt of 6-methyl-1,2,3-oxathiazine-

4(3)-one-2,2-dioxide. The composition of acesulfame K is C 4 H 4 NO 4 KS. The compound is freely soluble in water and forms a neutral solution. Acesulfame K is not hygroscopic, and it decomposes during heating at temperatures over 235 °C ( Table 2 ). The molecular weight of the compound is 201.2. At room temperature acesulfame K is an intensely sweet (150–200 times sweeter than sucrose), white, odorless, crystalline powder.

3. Food Technological Uses Major uses will probably include soft drinks, tabletop sweeteners, and chewing gum. In

pharmaceutical areas, mouthwashes and toothpastes may be included (Higginbotham,

4. Toxicology Acesulfame K was first evaluated by JECFA in 1981, but some shortcomings were found

in long-term carcinogenicity studies and therefore no acceptable daily intake value was allocated (WHO, 1981). Also, mouse carcinogenicity studies were found not to meet the requirements of the expert group, although the study was carried out according to good laboratory practice at the time of completion. Additional studies showed that acesulfame K is not mutagenic and not carcinogenic in the rat. The present toxicological information appears to be complete and the safety of acesulfame K established.

5. Regulatory Status An acceptable daily intake of 0–9 mg/kg body weight has been allocated for acesulfame

K (WHO, 1983). In Britain the Food Additives and Contaminants Committee (1982) rec- ommended the use of acesulfame K in various foods; and Switzerland, Germany, Ireland, Denmark, and Sweden have approved some food uses. In some countries it has been accepted for toothpastes and mouthwashes.

E. Thaumatin

1. Chemistry Thaumatin (Thalin) is a macromolecular protein sweetener with a molecular weight of

around 22,000. The major protein constituents of the sweetener consist of the normal amino acids except for histidine, which is absent. The extensive disulfide cross-linking confers thermal stability and resistance to denaturation. The tertiary structure of the poly- peptide chain gives thaumatin its sweet character. Cleavage of just one disulfide bridge results in a loss of sweet taste (Iyengar, 1979).

Thaumatin is purified from the fruit of the West African perennial plant Thaumato- coccus danielli . A small amount of organic nonprotein impurity remains in the commercial products. This consists principally of the arabinogalactan and arabinoglucuronoxylan poly- saccharides, both of which are normal constituents of plant gums.

Thaumatin is 2000–3000 times sweeter than sucrose. It is stable in freeze-dried form. Degradation is unlikely to occur in acidic materials. The protein structure is unstable when baked or broiled ( Table 2 ).

2. Use and Intake Although the primary organoleptic property of thaumatin is sweetness, its main use is as

a flavor enhancer (Higginbotham, 1983). It acts synergistically with saccharin, acesulfame K, and stevioside. The major applications include chewing gum, savory flavor, dairy prod- ucts, animal feeds, and pet foods.

Potential daily intake estimates based on American food consumption figures indi- cate that the maximum daily intake would be less than 2 mg per capita (about 0.03 mg/ kg/day).

3. Toxicology

a. Metabolism. Thaumatin is completely metabolized to its constituent amino acids before absorption. The measured digestibility of thaumatin has been at least as great as a. Metabolism. Thaumatin is completely metabolized to its constituent amino acids before absorption. The measured digestibility of thaumatin has been at least as great as

It has been demonstrated that thaumatin is not allergenic, mutagenic, or teratogenic. Both short-term tests and clinical human exposure studies, some at exaggerated levels, showed no adverse effects. However, long-term studies have not been conducted. It has been questioned whether sufficient data exist for the safety assessment of thaumatin. In any case thaumatin has a long history as a sweetening agent in West Africa and has been used for many years in Japan without any reported reactions.

4. Regulatory Status In 1983 thaumatin was evaluated by JECFA (WHO, 1983). Specifications were prepared,

but an ADI could not be established without data from long-term studies and adequate studies in humans. In 1985 an ADI of ‘‘not specified’’ was allocated for thaumatin, indicat- ing that it does not represent any hazard to health.

The Commission of the European Communities has accepted thaumatin for use as

a sweetener in foods. Thaumatin was first permitted in Japan in 1979 as a natural food. In the United States and Switzerland it is permitted in chewing gum as a flavor enhancer. In the United Kingdom the use of thaumatin in food is not restricted, and in Australia it is permitted as a flavor enhancer.

F. Sucralose

Sucralose is the generic name of a relatively new intense sweetener made from ordinary sugar. Sucralose was first discovered in 1976, and it is a unique sweetener as it is made from ordinary sugar. It is a thrichloro derivative of the C-4 epimer galactosucrose which is not broken down during its passage through the gastrointestinal tract and thus does not provide calories. Sucralose tastes like sugar, but it is about 600 times sweeter. However, the taste profile is similar to sucrose and it can be used for almost all applications where sucrose is used. The sweetness does not react with food components or other ingredients and sucralose has good water solubility. Sucralose has excellent product stability even under high temperatures and it can be used in a broad range of food products.

1. Safety

A large number of studies have proven that sucralose is safe for human consumption. Sucralose does not break down in the gastrointestinal tract or accumulate in fatty tissues (McLean et al., 2000). Sucralose is also noncariogenic. It is currently evaluated by several regulatory bodies and it has received approval in Canada, Australia, and Russia. The ADI for sucralose has been set at a level of 15 mg/kg/day.

G. Other Nonnutritive Sweeteners

In addition to the traditional and extensively studied nonnutritive sweeteners, a growing number of new compounds have been suggested as sugar substitutes. Some of these are In addition to the traditional and extensively studied nonnutritive sweeteners, a growing number of new compounds have been suggested as sugar substitutes. Some of these are

Glycyrrhizin is a terpene glycoside extracted from licorice root. It consists of the salts of glycyrrhizic acid and is reported to be 50–180 times sweeter than sucrose. How- ever, the sweetness is perceived slowly, and it it followed by licorice aftertaste. Glycyrr- hizin is mainly used in Japan for soy products to control saltiness (Crossby and Wingard, 1979; Anonymous, 1986). In the United States glycyrrhizin is used as a flavoring agent.

Neosugar is a fructo-oligosaccharide produced enzymatically from sucrose. It has 40–60% of the sweetness of sucrose and is claimed not to be extensively metabolized in the gastrointestinal tract (Anonymous, 1986). Neosugar represents a new model of devel- oping oligosaccharides that are not metabolized in the body. Some oligosaccharides may

be metabolized by specific types of intestinal bacteria to produce desirable metabolites and to promote desired types of intestinal bacteria. However, more research is needed to prove the safety and usefulness of these compounds (Anonymous, 1985).

Phyllodulcin is 200–300 times sweeter than sucrose. It is a 3,4-dihydroxy-isocoum- arin compound with a licoricelike flavor (Crossby, 1976). Miraculin is a glycoprotein derived from the African plant Richardella dulcifica. Miraculin is actually not a sweetener but a taste-modifying glycoprotein. In sour or tart foods miraculin exhibits a sweet taste that may last for several hours (Janelm et al., 1985).

A recent development in the plant extract field is hernandulcin, which is a sweet plant extract from the Mexican herb Lippia dulcis. Hernandulcin has a sweetness of 1000 times that of sucrose (Compadre et al., 1985).

Dulcin is a synthetic sweetener that is chemically p-phenetolcarbamide. It has been reported to cause cancer in laboratory animals and is therefore not accepted for food use in most countries (WHO, 1968).

Stevioside is a widely used high-intensity sweetener in Japan, where the fact that it is a plant extract allows it to be included in the class of natural food additives. Stevioside can be extracted from the leaves of Stevia rebaudiana, which is cultivated in Japan, Korea, and some South American countries. The sweetness of stevioside varies according to the plant source and the food in which it is used. Relative sweetness values varying between 100 and 300 have been quoted in the literature ( Table 2 ).

Stevioside is used in Japan in soft drinks, candy, and chewing gum. It has also been used in many sugar-free or diebetic foods either alone or in combination with other nonnutritive sweeteners. However, little information exists about the toxicological proper- ties of stevioside, and therefore it has not been approved for food use in most European or North American countries. The Joint FAO/WHO Expert Committee of Food Additives has not evaluated stevioside, but the European Commission considered stevioside unac- ceptable for food additive use (Commission of the European Communities, 1984).

Most nonnutritive sweeteners described here are either not generally accepted or are approved for food use in only a few countries. Japan is often an exception and allows the use of natural compounds in foods. In Europe and the United States these compounds have only a very limited use at present.