PEDIATRIC DENTiSTRY/Copyright ©1984 byThe American Academy of Pediatric Dentistry

Volume 6 Number 3

Aspartame m a review

William F. Waggoner, DDS, MS

AbstractAspartame (APM), a newly available synthetic

sweetener approximately 180-200 times sweeter thansucrose, was approved for marketing by the FDA in 1981following several years of scientific review. It is availablein the United States for use as a sweetener in breakfastcereals, powdered beverages, gelatins, puddings, fillings,whipped toppings, chewing gum, soft drinks and as atable-top sweetener. Research to date has shown noharmful effects of APM consumption on the generalpopulation when consumed in amounts as much as two tothree times the maximum expected daily ingestion levels.Aspartame is not indicated for use by individuals whohave phenylketonuria. Dental research on APM has beenlimited thus far and its effect on dental health is yet to beestablished.

Aspartame (APM), a synthetic sweetener for food

and beverages, was given final approval for market-ing by the Food and Drug Administration (FDA) 1981. A dipeptide based on two naturally occurringamino acids, aspartame is digested like a protein bythe body and is 180-200 times as sweet as sucrose.The objectives of this paper are to review aspartame’sapproval by the FDA, to examine the dental researchon aspartame, and to discuss the impact of this newsweetener on the dental health of the pediatric pop-ulation.

BackgroundAspartame was discovered accidentally in the late

1960s as a dipeptide having a pronounced sweet taste.1

It is a synthetic combination of two amino acids, as-partic acid and phenylalanine. It is classified as a low-calorie, synthetic sweetener containing four kcal/gm.Because of its intense sweetness, only small amountsare required for sweetening. The amount of APM re-quired to produce the sweetness equivalent to oneteaspoon of sucrose produces only .1 kcal, comparedto 16 kcal in one teaspoon of sugar. APM is marketedin the United States by G.D. Searle and Company

under the names NutraSweet~ and Equal®. Equal,the powder, table-top form of APM, contains less than1 gm of carbohydrate and provides 4 kcal per packet.According to reports from the manufacturer’s tastetests, APM tastes more like sucrose than other sugarsubstitutes, and lacks the bitter after-taste of sac-charin.

Aspartame may be used as a sugar replacement ina number of products such as breakfast cereals, top-ping mixes, frostings, confections, chewing gum, drymix beverages, and yogurt. It also can be used inacidic foods such as fruit juices, soft drinks, and as atable-top sweetener (Figure 1). However, its uses arelimited because APM becomes unstable at high tem-peratures and in alkaline environments. It cannot beused for baking or frying because it breaks down toform a substance known as diketopiperazine, whichreduces sweetness.2 APM-sweetened soft drinks havebeen available in Canada for the past two years buthave not been available in the United States untilrecently. The delay was due primarily because ofquestions about APM’s stability. When stored at lessthan ideal conditions, APM slowly loses sweetnessin an acid solution, to the point where 50% of theinitial sweetener has dissipated after six months.However, over the first 100 days this is a barely dis-cernable difference in taste. As most soft drinks areconsumed within 100 days of manufacture, the po-tential loss of sweetness is minimized3s and this isno longer considered a deterent to placing the APM-sweetened beverages on the market. Also, by com-bining APM with the more stable sweetener, sac-charin, the loss of sweetness due to APM’s instabilityis minimized further.

The functional and property differences of APM donot make it suitable as a blanket substitute for sugar.However, it may be used in a variety of ways. APMcan: (1) sweeten foods; (2) enhance flavors [particu-larly fruit flavors]; (3) reduce calories; (4) reduce ume and weight of presweetened products; (5) super-

PEDIATRIC DENTISTRY: September 1984/Vol. 6 No. 3 153

300-400

D

Figure 1. More than 80 aspartame-sweetened products areavailable. These include soft drinks, dry beverage mixes,breakfast cereals, flavored gelatin and pudding mixes,whipped toppings, chewing gums, and a table-top sweet-ener.

sweeten products by adding concentrated sweetnessas a small fraction of the total weight; (6) reduce vis-cosity, stickiness, or other properties associated withsugar; and (7) reduce sucrose consumption when in-dicated.5

Figure 2 illustrates the relative sweetness of APMand several other sweetening agents in comparisonto sucrose. APM, saccharin, and cyclamates are in-tensely sweeter than sucrose.

Aspartame's PDA ApprovalApproval of APM marketing to the public was a

lengthy process involving several reviews before finalapproval. Beginning in 1973, four years followingAPM's discovery, Searle petitioned the PDA for ap-proval to market APM as a sweetening agent in cer-tain foods.

In July, 1974, the PDA granted approval for APM'suse as petitioned, with three conditions regarding fi-nal product labeling. First, the label of any food con-taining APM was required to bear the followingstatement: "PHENYLKETONURICS: CONTAINS PHENYL-ALANINE." This was required to alert persons whomust restrict their phenylalanine intake carefully (adiscussion of the condition follows in a later section).The second condition was that when APM was to beused as a table-top sweetener, its label was requiredto bear instructions indicating that APM not be usedin cooking or baking. The third condition stated thatAPM-containing foods which were being marketedfor special dietary uses were required to be labeledin compliance with the PDA's special dietary foodsregulation.6

Subsequent to approval, two parties formally ob-jected to the approval on safety grounds, primarily

1OU

D

D

nAspartame Sacchanr

SWEETENING AGENTS

Figure 2. Relative sweetness of several sweeteners in com-parison to sucrose.

the use of APM by children, asserting that the prod-uct might cause brain damage resulting in mental re-tardation, endocrine dysfunction, or both. Furtherhearings on APM's safety were ordered by the PDAand Searle agreed to delay the marketing of APMtemporarily, pending resolution of the safety ques-tions.

In December, 1975, the PDA ordered an immediatestay of APM's approval because the original safetystudies conducted by Searle were brought into ques-tion. The original data from these studies was auditedand reviewed by an independent third party, Uni-versities Associated for Research and Education inPathology (UAREP). In 1978, the UAREP report tothe PDA concluded the Searle studies were valid.

Following this, a Board of Inquiry was appointedin 1979. The Board was composed of three scientists,agreed upon by Searle, the PDA, and the parties for-mally protesting APM's approval. The Board wascharged with the responsibility to help resolve thefollowing three issues and make appropriate recom-mendations to the commissioner of the PDA.

Issue 1: Whether the ingestion of APM, either aloneor with glutamate, posed a risk of contrib-uting to mental retardation, brain damage,or undesirable effects on neuroendocrineregulatory systems

Issue 2: Whether the ingestion of APM may inducebrain neoplasms in rats

Issue 3: Based on findings of the above two issues,(a) should APM be allowed for use in foods?(b) if APM is allowed for use in foods, whatlabeling statements should be required?7

Upon review, the Board found that evidence didnot indicate that APM would pose an increased riskto mental retardation. However, they did not rule outthe possibility that APM might induce brain tumorsin rats. For this reason, in October, 1980, the Board

154 ASPARTAME—A REVIEW: Waggoner

recommended that APM not be approved for use infoods, pending further study.

In July, 1981, the commissioner of the FDA, ArthurHayes, Jr., disagreed with the Board’s concerns aboutbrain tumors in rats and concluded that the availabledata established with reasonable certainty that APMdid not cause brain tumors in laboratory rats. There-fore, he granted final approval to Searle to manufac-ture and market APM for use in foods. The conditionsof labeling were the same as those required whenAPM was given its initial approval. 8 Following thecommissioner’s approval, two of the three membersof the Board of Inquiry were convinced by the com-missioner’s rebuttal to their findings and approvedrelease of the sweetener to the marketplace.9 In a sep-arate decision in July, 1983, approval was given formarketing APM in soft drinks in the United States.l°

Saftey IssuesIn light of the lengthy APM approval process, it is

important to examine the issues of safety which wereposed and which delayed its approval for a numberof years. The main issues all have been stated pre-viously, but they deserve further attention.

PKUThe risk associated with APM ingestion to the pop-

ulation of individuals who suffer from phenylketon-uria (PKU) is well recognized1~ and undisputed. PKUis a genetic disorder that prevents phenylalanine me-tabolism and may lead to a progressive mental retar-dation if intake is not limited strictly. Individuals withPKU are almost always diagnosed shortly after birthand, when placed on restricted phenylalanine diets,do not develop brain damage. Because phenylalanineis one of the products of the hydrolysis of APM inthe gut, 12 it should not be included in these individ-uals’ diets, and hence, the FDA’s labeling require-ment for all foods containing APM.

Concerns have been raised regarding the safety ofAPM ingestion by individuals that are heterozygousfor PKU, that is, an unaffected carrier of the PKUgene, and also for the fetus with undiagnosed PKU.However, these concerns appear to be unfounded.Two studies 13,14 involving PKU heterozygotes dem-onstrated no harmful effects to these individuals. Thesweetener, when given in large doses, was well tol-erated and showed no untoward medical or biochem-ical changes. In one of the studies, 14 patients whoingested 100 mg/kg daily (a very large dose) dem-onstrated plasma levels of phenylalanine which in-creased, but did not reach toxic levels.

Maternal HyperphenylalanemiaThere is evidence that harm may be done to the

fetus of a woman with hyperphenylalanemia, which

is a condition whereby a person’s plasma phenylal-anine levels are higher than normal, but lower thana person with PKU. The danger of a woman’s de-veloping hyperphenylalaninemia through ingestionof APM is highly improbable. According to FDA cal-culations, a 60 kg adult would need to consume 600APM tablets or 24 liters of APM-sweetened beveragein a single sitting to reach the toxic threshold for fetalharm.8 There are, however, several thousand womenwho reach childbearing age each year whose naturalblood levels of phenylalanine fluctuate wildly, and inwhom a smaller dose of APM could endanger thefetus. It is felt that these women are more vulnerableto the effects of phenylalanine that exists naturally inmilk and meats and other high protein foods than toAPM. Since it is impossible to keep the women fromconsuming these foods, it makes little sense to keepAPM off the market for this reason.

Focal Brain Lesions/Neuroendocrine ChangesA second toxicity issue raised was whether the con-

sumption of APM, either alone or with glutamate (i.e.,as monosodium glutamate) poses a risk to humansof causing focal brain lesions and associated neu-roendocrine changes which have been demonstratedin animals. Toxicity in this issue is related to concen-trations of another metabolite of APM, aspartic acid.

Work by Olney and Ho18 demonstrated damage tothe hypothalamus when large doses of glutamate andaspartate were given to laboratory animals. The af-fected areas of the hypothalamus also are involvedin endocrine control via the pituitary. Significantly,it is believed that the lesions could be produced by asingle surge of glutamate and aspartate above sometoxic threshold. These lesions have been demon-strated in neonatal mice administered high dosagesof glutamate/aspartic acid by gavage,ls,~9 but have notbeen found in primates.19 The Board of Inquiry con-cluded that the amount of APM that would need tobe ingested in a human diet in a single sitting toproduce the lesions seen in rodents would be pro-hibitively high. The Board also concluded that therewas not sufficient evidence that aspartic acid poten-tiated the effect of plasma glutamate to a significantdegree.

MethanolIn addition to metabolites phenylalanine and as-

partic acid, methanol also is formed by the degra-dation of APM. Few data on methanol toxicity areavailable. Toxicity from methanol appears to resultfrom its metabolism to formaldehyde, which then ismetabolized rapidly to formic acid, leading to the ac-cumulation of formates. However, no formate is de-tected in the blood or urine after APM ingestion atlevels as high as 200 mg/kg.2°

PEDIATRIC DENTISTRY: September 1984/Vol. 6 No. 3 155

Brain TumorsThe other major issue of concern was that APM

may induce brain tumors in rats. The Bureau of Foodsrequires all food additives be assessed for carcino-genic potential in two rodent species, usually themouse and the rat. Negative findings in both speciesis required for approval. Searle submitted the re-quired studies and. all parties agreed the mouse datato be negative; however, the data from three rat stud-ies came under question. In one study the controlgroup of rats had a higher incidence of tumors thanthe group exposed to APM, though not statisticallysignificant. This result the Board termed bizarre andin its view justified dismissal of the study results.Searle, the FDA’s Bureau of Foods, and ultimatelythe commissioner viewed the findings as a statisticalanomaly and held the study to be valid.

Upon issuing his final approval, the commissionerstated that "few compounds have withstood such de-tailed testing and repeated, close scrutiny, and theprocess through which aspartame has gone shouldprovide the public with additional confidence con-cerning its safety.’’8

It is noteworthy that APM ingestion has shown nountoward effects when consumed by healthy chil-dren and adolescents,15 by noninsulin-dependent di-abetics, 16 and by young adults during weightreduction.17

Dental Research Involving AspartameThe effects of APM on dental caries has been ex-

amined in only a limited manner to date. Most of theavailable data are based on in vitro experiments andhave yielded conflicting results. Consequently, littleis known about the effects of APM on dental health.

Breakdown of APM begins in the oral cavity assalivary enzymes begin to hydrolize it as protein. 21 Incontrast to the metabolites of sucrose (glucose, fruc-tose, and lactic acid), the metabolites of APM, (as-partic acid and phenylalanine) would not appear tocontribute significantly to the decay process as cari-ogenic factors. Hence, one would expect the cari-ogenic potential of APM to be very low and thus apotentially strong preventive dentistry advancementwhen used as a sucrose replacement. Caustion mustbe expressed, however, before becoming overly ex-cited about the prospects. It is unlikely that APM everwill replace sucrose completely because of APM’sinstability at high heat and over long periods of time.APM also lacks the bulk of sucrose which is desirablein some products. With this realization, most of thestudies which have been completed have examinedthe effects of APM when present in addition to glu-cose or sucrose.

Linke and Chang22 studied the effects of APM anda number of other su.crose substitutes on growth pat-

terns and acid production of a glucose-grown mutansstrain in vitro. They found that although APM alonecould not sustain growth of the strains, when it waspresent in solution with glucose, it had little effect onthe growth of S. mutans. Additionally, APM had noeffect on the acid production of S. mutans during glu-cose fermentation. Somewhat different findings havebeen reported by others combining APM and su-crose.

Olson23,24 examined the effects of APM when pres-ent in sucrose solution on adherent plaque formationof S. mutans in vitro. His findings, in part, were inagreement with Linke and Chang22 in that he foundno effect by APM on acid production and also thatAPM alone formed no adherent plaque. However, hefound that APM combined with sucrose yielded asignificant decrease in adherent plaque. It was feltthat the decrease could be a result of one or morefactors, including effects on the extracellular en-zymes, on the ability of the bacteria to adhere, or onthe ability of glucan to adhere.

Mishiro and Kaneko25 also examined the acid pro-duction of plaque in glucose and APM mixtures. Incontrast to the previously mentioned studies, theyexamined the response of plaque in human wholesaliva. Their results were also in contrast to the oth-ers. Tlqey reported an increase in acid production ofthe mixture of APM and glucose, but, unexpectedly,an inhibited fall of pH of the plaque in the APM/glucose mixture. In other words, APM in combina-tion with glucose seemed to be enhancing the lacticacid production of the plaque, yet inhibiting a fall inpH equal to the fall seen with glucose alone. Theseeffects of APM could not be substituted by the con-stitutive amino acids, L-aspartic acid and L-phenyl-alanine, nor was there a difference in buffer capacitybetween APM and an amino acid solution.

Still other changes in pH have been reported withAPM. Soparkar et al. 26 carried out an in vivo studyexamining the effects of different chewing gums onplaque pH. Utilizing a Kleinberg-type antimony elec-trode to measure plaque pH, they found that twocommercially available sugarless gums, and a gumcontaining sorbitol, mannitol, and APM produced anincrease in plaque pH, differing markedly from thedepression of plaque pH produced by a chewing gumcontaining sucrose. In addition, when the APM gumwas chewed for a 5-minute period 20 minutes follow-ing a sucrose rinse, the depressed pH rose rapidlyabove the initial level and then recovered to the initiallevel, while a sugar gum caused a relatively smallerrise and then a quick return to lower levels. APMalone as a sweetening agent was not evaluated so itis difficult to extrapolate any effects for which theAPM may have been directly responsible. The au-thors do not offer explanations for the observed

156 ASPARTAME--A REVIEW: Waggoner

changes in pH levels.Only limited study has been reported thus far ex-

amining the effect of APM on dental caries. Reussnerand Galimidi27 carried out an investigation on labo-ratory rats inoculated with S. mutans and maintainedon a modified basal cariogenic diet with either APMor saccharin added. APM demonstrated an insignif-icant dose-related decrease in buccal caries and insig-nificant decreases in occlusal dentinal caries. Saccharinshowed a dose-related, significant decrease in occlu-sal dentinal caries. Similar findings have been re-ported by Tanzer and Slee.28 In a later study, Reussneret al. 29 reported that APM reduced acid-induced en-amel demineralization in laboratory rats. A saccharinsolution of equivalent sweetness showed no such re-duction.

Table I summarizes the dental research involvingAPM which, as stated previously, is limited to dateand has given inconsistent findings. Both depressionand elevation of plaque pH have been attributed toAPM. When present in combination with glucose orsucrose APM has been shown to have no effect onacid production, but other investigations have shownit to produce increases in acid production. Clearly,further studies are indicated to examine more closelythe effect of APM on the dental disease process.

Aspartame and the Pediatric Population

The impact of the sweetener APM on the popula-tion and specifically the dental health of the pediatricpopulation is yet to be observed. It would seem thatthere could be some observable changes. A reductionof ingested sucrose is one such favorable response.The APM-sweetened products which are availablecurrently and those proposed -- such as breakfastcereals, dry mix beverages and soft drinks -- areproducts which are consumed heavily in the pediatricage group. (A complete list of products currentlymarketed containing APM is available from the man-ufacturer, a) Substitution of the APM-sweetenedproducts should decrease sucrose ingestion and po-tentially improve dental health. This, however, is yetto be shown, and any possible contributions to im-proved dental health would be merely speculative atthis time. Certainly research in this area would bevaluable.

Questions might be raised concerning the amountsof APM ingested by children, especially children withpoorly supervised dietary habits who. consume manysoft drinks and other sweets daily. This was consid-ered by the FDA before issuing final approval in 1981and again with the approval of APM’s use in softdrinks in 1983.l° Estimated consumption levels were

Searle Food Resources, Inc.; Subsidiary of G.D. Searle and Co.Box 1111, Skokie, IL 60077.

Table 1. Relative Sweetness of Sweetening Agents Com-pared to Sucrose

SUMMARY OF FINDINGS OF DENTAL RESEARCH INVOLVINGASPARTAME

Effect on Growth of S. MutansAPM alone does not sustain S. mutans growthAPM with glucose yields normal S. mutans growthAPM alone forms no adherent plaqueAPM with sucrose yields a decrease in adherent plaque

Effect on Acid Production and Plaque pHAPM with glucose shows acid production equal to glu-cose aloneAPM with glucose shows an increase in acid productionbut an inhibited fall in pHAPM with sucrose shows acid production equal to su-crose aloneAPM with sorbitol and mannitol produces and maintainsan increase in plaque pH which has been depressed witha sucrose rinse

Effect on Enamel Demineralization and CariesAPM reduces the amount of acid-induced enamel de-mineralization compared to a sucrose controlAPM added to the diet of laboratory rats fed a basal car-iogenic diet produces no significant changes in caries

computed in several ways. Included were calcula-tions based on: (1) substitution of APM for all sucrosein the diet and (2) substitution of APM for all dietarycarbohydrate, both yielding levels obviously muchhigher than would ever be expected due to the factthat APM never will replace sucrose totally. Based onthese calcuations, the intake value of 34 mg/kg/daywas used in the assessment of possible toxicologicalrisks. This figure represents the highest value ob-tained from any of the estimates of potential con-sumption. Levels two or four times the amount ofthis high estimate were used in investigations withhuman subjects with no ill effects observed.15,16 Evenhigher dosages have been used in animal studies.1°

Based on projected maximum APM consumption lev-els, the commissioner of the FDA concluded that allavailable evidence established that these were "far,far below any level ever suspected of being toxic.’’~

With the final approval in 1981, Searle agreed to mon-itor actual APM use levels to ensure that actual useremained well below suspected toxic levels. Thismonitoring is ongoing.

Summary

Research at this time indicates that APM ingestedwithin the suggested guidelines is safe for humanconsumption with no known harmful effects. The onlyexceptions are individuals with phenylketonuria whoare advised against its ingestion.

No long-term human consumption studies areavailable at this time. Dental research on APM has

PEDIATRIC DENTISTRY: September 1984/Vol. 6 No. 3 157

been slight and with mixed conclusions as to APM’seffect on the dental disease process. Aspartame’s im-pact on general dietary habits, reduction of sucroseintake, and dental health are yet to be documented.

Dr. Waggoner is an assistant professor, Department of Pedodon-tics, University of Oklahoma College of Dentistry, 1001 Stanton L.Young Blvd., Oklahoma City, OK 73190. Reprint requests shouldbe sent to him.

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5. Bost RG, Ripper A: Aspartame: a commercially feasible as-partic acid-based sweetener, in Sweetners and Dental Caries,Shaw JH, Rousos GG, eds. Sp Suppl Feeding, Weight andObesity Abstracts, 1978 pp 269-81.

6. US Department of Health, Education and Welfare. Food andDrug Administration. Aspartame. Federal Register 39:27317-20, 1974.

7. US Department of Health, Education and Welfare. Food andDrug Administration. Aspartame. Ruling on Objections Fed-eral Register. 31716-18, 1979.

8. US Department of Health, Education and Welfare. Food andDrug Administration. Aspartame, Commissioner’s final de-cision. Federal Register 46:38285-308, 1981.

9. Smith RJ: Aspartalne approved despite risks. Science 213:986-87, 1981.

10. US Department of Health, Education and Welfare. Food andDrug Administration. Aspartame: Final rule. Federal Register3137(~82, 1983.

11. Koch R, Schaeffler G, Shaw KN: Results of loading doses ofaspartame by two phenylketonuric children compared withtwo normal children. J Toxicol Environ Health 2:459-69, 1976.

12. Ranney RE, Oppermann JA, Muldoon E, McMahon FG:Comparative metabolism of aspartame in experimental ani-mals and humans. J Toxicol Environ Health 2:441-51, 1976.

13. Koch R, Shaw KN, Williamson M, Haber M: Use of aspartamein phenylketonuric heterozygous adults. J Toxicol Environ

Health 2:453-57, 1976.14. Stegink LD, Filer LJ, Baker GL, McDonnell JE: Effect of an

abuse dose of aspartame upon plasma and erythrocyte levelsof amino acids in phenylketonuric heterozygous and normaladults. J Nutr 1110:2216-24, 1980.

15. Frey GH: Use of aspartame by apparently healthy childrenand adolescents. J Toxicol Environ Health 2:401-15, 1976.

16. Stern SB, Bleicher SJ, Flores A, Gombos G, Recitas D, Shu J:Administration of aspartame in noninsulin-dependent dia-betics. J Toxicol Environ Health 2:429-39, 1976.

17. Knoop RH, Brandt K, Arky A: Effects of aspartame in youngpersons during weight reduction. J Toxicol Environ Health2:417-28, 1976.

18. Olney J, Ho OL: Brain damage in infant mice following oralintake of glutamate, aspartate, or cysteine. Nature 227:609-10, 1970.

19. Reynolds WA, Butler V, Lemkey-Johnston N: Hypothalamicmorphology following ingestion of aspartame or MSG in theneonatal rodent and primate: a preliminary report. J ToxicolEnviron Health 2:471-80, 1976.

20. Stegink LD, Filer LJ, Baker GL, Brummel MC, Tephly TR:Aspartame metabolism in human subjects, in Health and SugarSubstitutes (proceedings of ERGOB Conference, Geneva, 1978).Basel, Switzerland; S Karger, 1978 pp 160-65.

21. Longton RW, Cole JS: Oral and alimentary canal response toaspartame, an artificial sweetener. J Dent Res 55:B240, 1976.

22. Linke HA, Chang CA: Physiological effects of sucrose sub-stitutes and artificial sweeteners on growth pattern and acidproduction of glucose-grown S mutans strain in vitro. Z Na-turforch 31:245-51, 1976.

23. Olson B: Adherent plaque formation studies on the sweeteneraspartarne. J Dent Res 54:102, 1975.

24. Olson B: An in vitro study of the effects of artificial sweet-eners on adherent plaque formation. J Dent Res 56:1426, 1977.

25. Mishiro Y, Kaneko H: Effect of a dipeptide, aspartame, onlactic acid production in human whole saliva. J Dent Res56:1427, 1977.

26. Soparkar PM, Newman MB, Hein JW: Comparable effects ofsaccharin- and aspartame-sweetened sugarless gums on plaquepH. J Dent Res 57:196, 1978.

27. Reussner G, Galimidi A: Effects of aspartame and saccharinon dental caries in rats. J Dent Res 60:315, 1981.

28. Tanzer JM, Slee AM: Saccharin inhibits tooth decay in labo-ratory models. JADA 106:331-33, 1983.

29. Reussner G, Galimidi A, Coccodrilli G: Effects of aspartameand saccharin on tooth enamel demineralization. J Dent Res61:182, 1982.

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dersigned author transfers all copyright ownership of the manuscript entitled (name of the article) to the AmericanAcademy of Pediatric Dentistry should the work be published. The undersigned author warrants that the article

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158 ASPARTAME--A REVIEW: Waggoner