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>Journals >Acta Pediátrica de México >Year 2013, Issue 3

Calzada-León R, Ruiz-Reyes ML , Altamirano-Bustamante N, Padrón-Martínez MM
Characteristics of non caloric edulcorants and their use in children
Acta Pediatr Mex 2013; 34 (3)

Language: Español
References: 202
Page: 141-153
PDF: 277.16 Kb.

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This is a descriptive review of the elaboration routes, the physical and chemical characteristics, metabolism and clearance, sweetener level, residual flavor, maximal recommended ingestion, security levels and the assessment of growth and development problems in children (from newborns, including prematures, to the end of puberty), of the main no caloric edulcorants used in Mexico. The no caloric edulcorants included in this review are: aspartame, acesulfame-K, sucralose, sacarin, ciclamates, thaumatin, Dtagatose, estevia and alitame.

Key words: Non caloric edulcorants, aspartame, acesulfame-K, sucralose, sacarin, ciclamates, thaumatin, D-Tagatose, estevia, alitame.


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

  2. Moller SE. Effect of aspartame and protein, administered in phenylalanine-equivalent doses, on plasma neutral amino acids, aspartate, insulin and glucose in man. Pharmacol Toxicol. 1991;68:408-12.

  3. Bradstock MK, Serdula MK, Marks JS, Barnard RJ, Crame NT, Remington PL; Trowbridge FL. Evaluation of reactions to food additives: the aspartame experience. Am J Clin Nutr. 1986;43:464-9.

  4. Magnuson BA, Burdock GA, Doull J, Kroes RM, Marsh GM, Pariza MW, Spencer PS,Waddell WJ, Walker R, Williams GM. Aspartame: a safety evaluation based on current use levels, regulations, and toxicological and epidemiological studies. Crit Rev Toxicol. 2007;37(8):629-727.

  5. Butchko HH, Stargel WW, Comer CP, Mayhew DA, Benninger C, Blackburn GL, de Sonneville LM, Geha RS, Hertelendy Z, Koestner A, Leon AS, Liepa GU, McMartin KE, Mendenhall CL, Munro IC, Novotny EJ, Renwick AG, Schiffman SS, Schomer DL, Shaywitz BA, Spiers PA, Tephly TR, Thomas JA, Trefz FK. Aspartame: review of safety. Regul Toxicol Pharmacol. 2002;35(2 Pt 2):S1-93.

  6. Abdo KM, Camargo CA Jr, Davis D, Egilman D, Epstein SS, Froines J, Hattis D, Hooper K, Huff J, Infante PF, Jacobson MF, Teitelbaum DT, Tickner JA. Letter to U.S. FDA commissioner. Questions about the safety of the artificial sweetener aspartame. Int J Occup Environ Health. 2007;13:449-50.

  7. Butchko HH, Stargel WW. Aspartame: scientific evaluation in the postmarketing period. Regul Toxicol Pharmacol. 2001;34:221-33.

  8. Gurney JG, Pogoda JM, Holly EA, Hecht SS, Preston-Martin S. Aspartame consumption in relation to childhood brain tumor risk: results from a case-control study. J Natl Cancer Inst 1997;89(14):1072-4. Erratum in: J Natl Cancer Inst. 1997;89:1460

  9. Olney JW, Farber NB, Spitznagel E, et al. Increasing brain tumor rates: is there a link to aspartame? J Neuropathol Exp Neurol. 1996;55:1115-23.

  10. Ross JA. Brain tumors and artificial sweeteners? A lesson on not getting soured on epidemiology. Med Pediatr Oncol. 1998;30:7-8.

  11. Gurney JG, Pogoda JM, Holly EA, Hicht SS, Preston-Martin S. Aspartame consumption in relation to childhood brain tumor risk: results from a case-control study. J Natl Cancer Inst. 1997;89:1072-4.

  12. Millichap JG, Yee MM. The diet factor in pediatric and adolescent migraine. Review. Pediatr Neurol. 2003;28:9-15.

  13. Rowan AJ, Shaywitz BA, Tuchman L, French JA, Luciano D, Sullivan CM. Aspartame and seizure susceptibility: results of a clinical study in reportedly sensitive individuals. Epilepsia. 1995;36:270-5.

  14. Shaywitz BA, Anderson GM, Novotny EJ, Ebersole JS, Sullivan CM, Gillespie SM. Aspartame has no effect on seizures or epileptiform discharges in epileptic children. Ann Neurol. 1994;35:98-103.

  15. Saravis S, Schachar R, Zlotkin S, Leiter LA, Anderson GH. Aspartame: effects on learning, behavior, and mood. Pediatrics. 1990;86:75-83.

  16. Krohn JA. Aspartame and attention deficit disorder (ADD). Pediatrics. 1994;94(4 Pt 1):576.

  17. Shaywitz BA, Sullivan CM, Anderson GM, Gilbspie SM, Sullivan B, Shaywitz SE. Aspartame, behavior, and cognitive function in children with attention deficit disorder. Pediatrics. 1994;93:70-5.

  18. Kanarek RB. Does sucrose or aspartame cause hyperactivity in children? Review. Nutr Rev. 1994;52:173-5.

  19. Garriga MM, Berkebile C, Metcalfe DD. A combined singleblind, double-blind, placebo-controlled study to determine the reproducibility of hypersensitivity reactions to aspartame. J Allergy Clin Immunol. 1991.87:821-7.

  20. Rogers PJ, Burley VJ, Alikhanizadeh LA, Blundell JE. Postingestive inhibition of food intake by aspartame: importance of interval between aspartame administration and subsequent eating. Physiol Behav. 1995.57:489-93.

  21. Stregink LD, Lindrgren SD, Brummel MC, Strumbo PJ, Wolraich ML. Erythrocyte L-aspartiol-L-phenylalanine hydroxilase activity and plasma phenilalanine and aspartate concentrations in children consuming diets high in aspartame. Am J Clin Nutr. 1995;62:1206-11.

  22. Schulpis KH, Papassotiriou I, Parthimos T, Tsakiris T, Tsakiris S. The effect of L-cysteine and glutathione on inhibition of Na+, K+-ATPase activity by aspartame metabolites in human erythrocyte membrane. Eur J Clin Nutr. 2006;60:593-7.

  23. Mackey SA, Berlin CM Jr. Effect of dietary aspartame on plasma concentrations of phenylalanine and tyrosine in normal and homozygous phenylketonuric patients. Clin Pediatr (Phila). 1992;31:394-9.

  24. Filer LJ Jr, Stegink LD. Aspartame metabolism in normal adults, phenylketonuric heterozygotes, and diabetic subjects. Diabetes Care. 1989;12:67-74.

  25. Wolf-Novak LC, Stegink LD, Brummel MC, Persson TJ, Filler JrLJ, Bell EF, Ziegler EE, Krause WL. Aspartame ingestion with and without carbohydrate in phenylketonuric and normal subjects: effect on plasma concentrations of amino acids, glucose, and insulin. Metabolism. 1990.39:391-6.

  26. Trefz F, de Sonneville L, Matthis P, Benninger C, Lanz-Engler TB, Bichel H. Neuropsychological and biochemical investigations in heterozygotes for phenylketonuria during ingestion of high dose aspartame (a sweetener containing phenylalanine). Hum Genet. 1994;93:369-74.

  27. Luthra SA, Utz M, Gorman EM, Pikal MJ, Munson EJ, Lubach JW. Carbon-deuterium rotational-echo double-resonance NMR spectroscopy of lyophilized aspartame formulations. J Pharm Sci. 2012;101:283-90.

  28. Tandel KR. Experimental evaluation of antipyretic and analgesic activities of aspartame. Indian J Pharmacol. 2011;43:486-9.

  29. Cheng C, Wu SC. Simultaneous analysis of aspartame and its hydrolysis products of Coca-Cola Zero by on-line postcolumn derivation fluorescence detection and ultraviolet detection coupled two-dimensional high-performance liquid chromatography. J Chromatogr A. 2011;1218:2976-83.

  30. Pradhan S, Shah UH, Mathur A, Sharma S. Experimental evaluation of antipyretic and analgesic activity of aspartame. Indian J Pharmacol. 2011;43:89-90.

  31. Abhilash M, Paul MV, Varghese MV, Nair RH. Effect of longterm intake of aspartame on antioxidant defense status in liver. Food Chem Toxicol. 2011;49:1203-7.

  32. Manion CV, Hochgeschwender U, Edmundson AB, Hugli TE, Gabaglia CR. Dietary aspartyl-phenylalanine-1-methyl ester delays osteoarthritis and prevents associated bone loss in STR/ORT mice. Rheumatology (Oxford). 2011;50(7):1244-9.

  33. Pradhan S, Shah UH, Mathur AG, Sharma S. Aspartame: Sweetener with anti-inflammatory potential? J Pharmacol Pharmacother. 2010;1:113-4.

  34. Polyák E, Gombos K, Hajnal B, Bonyár-Müller K, Szabó S, Gubicskó-Kisbenedek A, Marton K, Ember I. Effects of artificial sweeteners on body weight, food and drink intake. Acta Physiol Hung. 2010;97:401-7.

  35. Alsuhaibani ES. In vivo cytogenetic studies on aspartame. Comp Funct Genomics. 2010. pii: 605921

  36. Magnuson B. Aspartame--facts and fiction. N Z Med J. 2010;123:53-7.

  37. Anton SD, Martin CK, Han H, Coulon S, Cefalu WT, Geiselman P, Williamson DA. Effects of stevia, aspartame, and sucrose on food intake, satiety, and postprandial glucose and insulin levels. Appetite. 2010;55:37-43.

  38. Roberts HJ. Perspective on aspartame-induced pseudotumor cerebri. South Med J. 2009;102:873.

  39. Chuy S, Bell LN. Kinetics of an acid-base catalyzed reaction (aspartame degradation) as affected by polyol-induced changes in buffer pH and pK values. J Food Sci. 2009;74:C56-61.

  40. Rashidian M, Fattahi A. Comparison of thermochemistry of aspartame (artificial sweetener) and glucose. Carbohydr Res. 2009;344:127-33.

  41. Bandyopadhyay A, Ghoshal S, Mukherjee A. Genotoxicity testing of low-calorie sweeteners: aspartame, acesulfame-K, and saccharin. Drug Chem Toxicol. 2008;31:447-57.

  42. National Toxicology Program. NTP report on the toxicology studies of aspartame (CAS No. 22839-47-0) in genetically modified (FVB Tg.AC hemizygous) and B6.129-Cdkn2atm1Rdp (N2) deficient mice and carcinogenicity studies of aspartame in genetically modified [B6.129-Trp53tm1Brd (N5) haploinsufficient] mice (feed studies). Natl Toxicol Program Genet Modif Model Rep. 2005;(1):1-222.

  43. Jankovi SM. Controversies with aspartame. Med Pregl 2003;56(Suppl 1):27-9.

  44. Renwick AG. The metabolism of intense sweeteners. Xenobiotica. 1986;16:1057-71.

  45. Evaluation of certain food additives and contaminants. Twentyseventh Report of the Joint FAO/WHO Expert Committee on Food Additives. World Health Organ Tech Rep Se. 1983;696:1-42.

  46. Food Safety Department, World Health Organization. Food Additives Must Be Used as Sweeteners. Geneva, Switzerland: World Health Organization; 1994. Bulletin 6-10-1994.

  47. Zhang GH, Chen ML, Liu SS, Zhan YH, Quan Y, Qin YM, Deng SP. Effects of mother’s dietary exposure to acesulfame-K in Pregnancy or lactation on the adult offspring’s sweet preference. Chem Senses. 2011;36:763-70.

  48. Lino CM, Costa IM, Pena A, Ferreira R, Cardoso SM. Estimated intake of the sweeteners, acesulfame-K and aspartame, from soft drinks, soft drinks based on mineral waters and nectars for a group of Portuguese teenage students. Food Addit Contam Part A Chem Anal Control Expo Risk Assess. 2008;25:1291-6.

  49. Bandyopadhyay A, Ghoshal S, Mukherjee A. Genotoxicity testing of low-calorie sweeteners: aspartame, acesulfame-K, and saccharin. Drug Chem Toxicol. 2008;31:447-57.

  50. Mukhopadhyay M, Mukherjee A, Chakrabarti J. In vivo cytogenetic studies on blends of aspartame and acesulfame-K. Food Chem Toxicol. 2000;38:75-7.

  51. Mukherjee A, Chakrabarti J. In vivo cytogenetic studies on mice exposed to acesulfame-K--a non-nutritive sweetener. Food Chem Toxicol. 1997;35:1177-9.

  52. Economic Research Service Loss-adjusted annual per capita food supply series, USDA, Food Rev. 2003;25:2-15.

  53. Agriculture Fact Book, 2001-2002. USDA. Chapter 2: Profilling Food Consumption in America. En http//www.usda.gov/ factbook/chapter2.htm

  54. Grotz VL, Henry RR, McGill JB. Lack of effect of sucralose on glucose homeostasis in subjects with type 2 diabetes. J Am Diet Assoc. 2003;103:1607-12.

  55. McNeil Nutritionals. Sucralosa Food Additive Petition (FAP) 7A3987.8-69:2041-20453, presentado el 9 de febrero de 1987.

  56. McNeil Nutritionals. Sucralosa Safety Assessment. Food Chem Toxicol. 2000;38(suppl 2):S1-S129.

  57. Mezitis NH, Maggio CA, Koch P. Glycemic effect of a single high oral dose of the novel sweetener sucralose in patients with diabetes. Diabetes Care. 1996;19:1004-5.

  58. Roberts A, Renwick AG, Sims J, Snodin DJ. Sucralose metabolism and pharmacokinetics in man. Food Chem Toxicol. 2000;38(suppl 2):S31-S41.

  59. Baird IM, Shephard NW, Merritt RJ, Hildick-Smith G. Repeated dose study of sucralose tolerance in human subjects. Food Chem Toxicol. 2000;38(suppl 2):S123-S9.

  60. Grice HC, Goldsmith LA. Sucralose—an overview of the toxicity data. Food Chem Toxicol. 2000;38(suppl 2):S1-S6.

  61. John BA, Wood SG, Hawkins DR. The pharmacokinetics and metabolism of sucralose in the mouse. Food Chem Toxicol. 2000;38(suppl 2):S107-S10.

  62. Sims J, Roberts A, Daniel JW, Ronwick AG. The metabolic fate of sucralose in rats. Food ChemToxicol. 2000;38(suppl 2):S115-S21.

  63. Wood SG, John BA, Hawkins DR. The pharmacokinetics and metabolism of sucralose in the dog. Food Chem Toxicol. 2000;38(suppl 2):S99-S106.

  64. Mann SW, Yuschak MM, Amyes SJ, Aughton P, Finn JP. A combined chronic toxicity/carcinogenicity study of sucralose in Sprague-Dawley rats. Food Chem Toxicol. 2000;38(suppl 2):S71-S89.

  65. Mandel ID, Grotz VL. Dental considerations in sucralose use. J Clin Dent. 2002;13:116-8.

  66. John BA, Wood SG, Hawkins DR. The pharmacokinetics and metabolism of sucralose in the rabbit. Food Chem Toxicol. 2000;38(suppl 2):S111-S3.

  67. John BA, Wood SG, Hawkins DR. The pharmacokinetics and metabolism of sucralose in the mouse. Food Chem Toxicol. 2000;38(suppl 2):S107-S10.

  68. National Institute of Diabetes, Digestive and Kidney Disease (NIH). Synergic effects between sucralose and glucose may trigger the release of GLP-1. Diabetes Care. 2010;32:2184-6.

  69. Ma J, Chang J, Checklin HL, Young RL, Jones KL, Horowitz M, Rayner CK. Effect of the artificial sweetener, sucralose, on small intestinal glucose absorption in healthy human subjects. Am J Physiol Gastrointest Liver Physiol. 2009;296(4):735-9.

  70. Wiklund AK, Breitholtz M, Bengtsson BE, Adolfsson-Erici M. Sucralose - An ecotoxicological challenger? Chemosphere. 2012;86:50-5.

  71. Wu T, Zhao BR, Bound MJ, Checklin HL, Bellon M, Little TJ, Young RL, Jones KL, Horowitz M, Rayner CK. Effects of different sweet preloads on incretin hormone secretion, gastric emptying, and postprandial glycemia in healthy humans. Am J Clin Nutr. 2012;95:78-83.

  72. Huvaere K, Vandevijvere S, Hasni M, Vinkx C, Van Loco J. Dietary intake of artificial sweeteners by the Belgian population. Food Addit Contam Part A Chem Anal Control Expo Risk Assess. 2012;29:54-65.

  73. Brown AW, Bohan Brown MM, Onken KL, Beitz DC. Short-term consumption of sucralose, a nonnutritive sweetener, is similar to water with regard to select markers of hunger signaling and short-term glucose homeostasis in women. Nutr Res. 2011;31:882-8.

  74. Qin X. What made Canada become a country with the highest incidence of inflammatory bowel disease: could sucralose be the culprit? Can J Gastroenterol. 2011;25:511-12.

  75. Mawhinney DB, Young RB, Vanderford BJ, Borch T, Snyder SA. Artificial sweetener sucralose in U.S. drinking water systems. Environ Sci Technol. 2011;45:8716-22.

  76. Viberg H, Fredriksson A. Neonatal exposure to sucralose does not alter biochemical markers of neuronal development or adult behavior. Nutrition. 2011;27:81-5.

  77. Brusick D, Grotz VL, Slesinski R, Kruger CL, Hayes AW. The absence of genotoxicity of sucralose. Food Chem Toxicol. 2010;48:3067-72.

  78. Stroka J, Doncheva I, Spangenberg B. Determination of sucralose in soft drinks by high-performance thin-layer chromatography: interlaboratory study. J AOAC Int. 2009;92:1153-9.

  79. Grotz VL, Munro IC. An overview of the safety of sucralose. Regul Toxicol Pharmacol. 2009;55:1-5.

  80. Grotz VL. Sucralose and migraine. Headache 2008;48:164-5.

  81. Arnold DL, Krewski D, Munro IC. Saccharin: a toxicological and historical perspective. Toxicology. 1983;27:179-256.

  82. Cohen SM. Saccharin: past, present, and future. J Am Diet Assoc. 1986;86:929-31.

  83. Miller SA, Frattali VP. Saccharin. Diabetes Care 1989;12:74-80.

  84. Risch N. Linkage strategies for genetically complex traits. I. Multilocus models. Am J Hum Genet. 1990;46:222-8.

  85. Armstrong B, Lea AJ, Adelstein AM. Cancer mortality and saccharin consumption in diabetics. Br J Prev Soc Med. 1976;30:151-7.

  86. Wynder EL, Goldsmith R. The epidemiology of bladder cancer: a second look. Cancer. 1977;40:1246-68.

  87. Morrison AS, Buring JE. Artificial sweeteners and cancer of the lower urinary tract. N Engl J Med. 1980;302:537-41.

  88. Walker AM, Dreyer NA, Friedlander E, et al. An independent analysis of the National Cancer Institute study on non-nutritive sweeteners and bladder cancer. Am J Public Health. 1982;72:376-81.

  89. Oser BL. Highlights in the history of saccharin toxicology. Food Chem Toxicol. 1985;23:535-42.

  90. Touyz LZ. Saccharin deemed “not hazardous” in United States and abroad. Curr Oncol. 2011;18:213-4.

  91. Chen K, Yan J, Li J, Lv B, Zhao X. c-Fos expression in rat brainstem following intake of sucrose or saccharin. Front Med. 2011;5:294-301.

  92. Yakovenko V, Speidel ER, Chapman CD, Dess NK. Food dependence in rats selectively bred for low versus high saccharin intake. Implications for “food addiction”. Appetite. 2011;57:397-400.

  93. Guillem-Llobat X. The sugar industry, political authorities, and scientific institutions in the regulation of saccharin: Valencia (1888-1939). Ann Sci. 2011;68:401-24.

  94. Bandyopadhyay A, Ghoshal S, Mukherjee A. Genotoxicity testing of low-calorie sweeteners: aspartame, acesulfame-K, and saccharin. Drug Chem Toxicol. 2008;31:447-57.

  95. Whitehouse CR, Boullata J, McCauley LA. The potential toxicity of artificial sweeteners. AAOHN J. 2008;56:251-9.

  96. Chung MS, Suh HJ, Yoo W, Choi SH, Cho YJ, Cho YH, Kim CJ. Daily intake assessment of saccharin, stevioside, D-sorbitol and aspartame from various processed foods in Korea. Food Addit Contam. 2005;22:1087-97.

  97. Parfett CL. Combined effects of tumor promoters and serum on prolifer in mRNA induction: a biomarker sensitive to saccharin, 2,3,7,8-TCDD, and other compounds at minimal concentrations promoting C3H/10T1/2 cell transformation. J Toxicol Environ Health A. 2003;66:1943-66.

  98. Bell W, Clapp R, Davis D, Epstein S, Farber E, Fox DA, Holub B, Jacobson MF, Lijinsky W, Millstone E, Reuber MD, Suzuki D, Temple NJ. Carcinogenicity of saccharin in laboratory animals and humans. Int J Occup Environ Health. 2002;8:387-93.

  99. Renwick AG. A data-derived safety (uncertainty) factor for the intense sweetener, saccharin. Food Addit Contam. 1993;10:337-50.

  100. American Medical Association. Saccharin. Review of safety issues. JAMA. 1985;254(18):2622-4.

  101. American Medical Association. Saccharin. Review of safety issues. Council on Scientific Affairs. JAMA. 1985;254:2622-2624

  102. Oser BL. Highlights in the history of saccharin toxicology. Food Chem Toxicol. 1985;23:535-42.

  103. Arnold DL. Toxicology of saccharin. Fundam Appl Toxicol. 1984;4:674-85.

  104. Arnold DL. Two-generation saccharin bioassays. Environ Health Perspect. 1983;50:27-36.

  105. Coulston F, McChesney E, Benitz KF. Long-term safety evaluation and metabolism of o-benzoic sulfimide (saccharin) in rhesus monkeys. Ecotoxicol Environ Saf. 1978;2:33-48.

  106. Kojima S, Ichibagase H. Studies on synthetic sweetening agents. 8. Cyclohexylamine, a metabolite of sodium cyclamate. Chem Pharm Bull (Tokyo). 1966;14:971-4.

  107. Buss NE, Renwick AG, Donaldson KM, et al. The metabolism of cyclamate to cyclohexylamine and its cardiovascular consequences in human volunteers. Toxicol Appl Pharmacol. 1992;115:199-210.

  108. Scotter MJ, Castle L, Roberts DP, Macarthur R, Brereton PA, Hasnip SK, Katz N. Development and single-laboratory validation of an HPLC method for the determination of cyclamate sweetener in foodstuffs. Food Addit Contam Part A Chem Annual Control Expo Risk Assess. 2009;26:614-22.

  109. Cavicchioli M, Leite CQ, Sato DN, Massabni AC. Synthesis, characterization and antimycobacterial activity of Ag(I)- aspartame, Ag(I)-saccharin and Ag(I)-cyclamate complexes. Arch Pharm (Weinheim). 2007;340:538-42.

  110. Leban I, Rudan-Tasic D, Lah N, Klofutar C. Structures of artificial sweeteners--cyclamic acid and sodium cyclamate with other cyclamates. Acta Crystallogr B. 2007;63(Pt 3):418-25.

  111. Renwick AG, Thompson JP, O’Shaughnessy M, Walter EJ. The metabolism of cyclamate to cyclohexylamine in humans during long-term administration. Toxicol Appl Pharmacol. 2004;196:367-80.

  112. Serra-Majem L, Bassas L, García-Glosas R, Ribas L, Inglés C, Casals I, Saavedra P, Renwick AG. Cyclamate intake and cyclohexylamine excretion are not related to male fertility in humans. Food Addit Contam. 2003;20:1097-104.

  113. Damasceno DC, Goncalves MA, Durante LC, Castro NC, Moura CH, Oliveira CB. Effects of a saccharin and cyclamate mixture on rat embryos. Vet Hum Toxicol. 2003;45:157-9.

  114. Weihrauch MR, Diehl V, Bohlen H. Artificial sweeteners- -are they potentially carcinogenic?]. Med Klin (Munich). 2001;96:670-5.

  115. Hianik T, Rybár P, Svobodová L, Kresák S, Nikolelis DP. Liposome aggregation in presence of the sweeteners cyclamate and saccharine. Pharmazie. 2001;56:633-5.

  116. Higginbotham JD, Snodin DJ, Eaton KK, Daniel JW. Safety evaluation of thaumatin (Talin protein). Food Chem Toxicol. 1983;21:815-23.

  117. Das S, Das AK, Murphy RA, Punwane IC, Nasution MP, Kinghorn AD. Evaluation of the carcinogtenic potential of the intense natural sweateners Stevioside and Rebaudioside A. Caries Res. 1992;26:363-6.

  118. Ohta K, Masuda T, Tani F, Kitabatake N. Introduction of a negative charge at Arg82 in thaumatin abolished responses to human T1R2-T1R3 sweet receptors. Biochem Biophys Res Commun. 2011;413:41-5.

  119. Masuda T, Ohta K, Tani F, Mikami B, Kitabatake N. Crystal structure of the sweet-tasting protein thaumatin II at 1.27Å. Biochem Biophys Res Commun. 2011;410:457-60.

  120. Ohta K, Masuda T, Tani F, Kitabatake N. The cysteine-rich domain of human T1R3 is necessary for the interaction between human T1R2-T1R3 sweet receptors and a sweettasting protein, thaumatin. Biochem Biophys Res Commun. 2011;406:435-8.

  121. Ide N, Sato E, Ohta K, Masuda T, Kitabatake N. Interactions of the sweet-tasting proteins thaumatin and lysozyme with the human sweet-taste receptor. J Agric Food Chem. 2009;57:5884-90.

  122. Ohta K, Masuda T, Ide N, Kitabatake N. Critical molecular regions for elicitation of the sweetness of the sweet-tasting protein, thaumatin I. FEBS J. 2008;275:3644-52.

  123. Johansen HN, Jensen BB. Recovery of energy as SCFA after microbial fermentation of D-tagatose [abstract]. Int J Obes. 1997;21(suppl 2):S50.

  124. Raushel FM, Cleland WW. The substrate and anomeric specificity of fructokinase. J Biol Chem. 1973;248:8174-7.

  125. Normen L, Laerke HN, Jensen BB, Langkilde MD, Andersson H. Small-bowel absorption of D-tagatose and related effects on carbohydrate digestibility: an ileostomy study. Am J Clin Nutr. 2001;73:105-10.

  126. Kruger CL, Whittaker MH, Frankos VH, Schroeder RE. Developmental toxicity study of D-tagatose in rats. Regul Toxicol Pharmacol. 1999;29(2 Pt 2):S29-S35.

  127. Barr RG, Pantel MS, Young SN, Moore GT. The response of crying newborns to sucrose: is it a “sweetness” effect? Physiol Behav. 1999;66:409-17.

  128. Boesch C, Ith M, Jung B, Brueger K, Erban S, Diamantis I, Krois R, Bar A. Effect of oral D-tagatose on liver volume and hepatic glycogen accumulation in healthy male volunteers. Regul Toxicol Pharmacol. 2001;33:257-67.

  129. Bertelsen H, Jensen BB, Buemann B. D-tagatose—a novel low- calorie bulk sweetener with prebiotic properties. World Rev Nutr Diet. 1999;85:98-109.

  130. Buemann B, Toubro S, Raben A, Astrup A. Human tolerance to a single, high dose of D-tagatose. Regul Toxicol Pharmacol. 1999;29:S66-S70

  131. Levin GV. Tagatose, the new GRAS sweetener and health product. J Med Food. 2002;5:23-36.

  132. Livesey G, Brown JC. D-tagatose is a bulk sweetener with zero energy determined in rats. J Nutr. 1996;126:1601-9.

  133. Saunders JP, Donner TW, Sadler JH, Levin GV, Markris NG. Effects of acute and repeated oral doses of D-tagatose on plasma uric acid in normal and diabetic humans. Regul Toxicol Pharmacol. 1999;29:S57-S65.

  134. Donner TW, Magder LS, Zarbalian K. Dietary supplementation with d-tagatose in subjects with type 2 diabetes leads to weight loss and raises high-density lipoprotein cholesterol. Nutr Res. 2010;30:801-6.

  135. Rhimi M, Chouayekh H, Gouillouard I, Maguin E, Bejar S. Production of D-tagatose, a low caloric sweetener during milk fermentation using L-arabinose isomerase. Bioresour Technol. 2011;102:3309-15.

  136. Luecke KJ, Bell LN. Thermal stability of tagatose in solution. J Food Sci. 2010;75:C346-351

  137. Espinosa I, Fogelfeld L. Tagatose: from a sweetener to a new diabetic medication? Expert Opin Investig Drugs. 2010;19:285-94.

  138. Police SB, Harris JC, Lodder RA, Cassis LA. Effect of diets containing sucrose vs. D-tagatose in hypercholesterolemic mice. Obesity (Silver Spring). 2009;17:269-75.

  139. Taylor TP, Fasina O, Bell LN. Physical properties and consumer liking of cookies prepared by replacing sucrose with tagatose. J Food Sci. 2008;73:S145-51.

  140. Lu Y, Levin GV, Donner TW. Tagatose, a new antidiabetic and obesity control drug. Diabetes Obes Metab. 2008;10:109-34.

  141. Oh DK. Tagatose: properties, applications, and biotechnological processes. Appl Microbiol Biotechnol. 2007;76:1-8.

  142. Moore MC. Drug evaluation: tagatose in the treatment of type 2 diabetes and obesity. Curr Opin Investig Drugs. 2006;7:924-935

  143. Koyama E, Kitazawa K, Ohori Y, Izawa O, Katagowa F, Fujino A, Ui M. In vitro metabolism of the glycosidic sweeteners, stevia mixture and, enzymatically modified stevia in human intestinal microflora. Food Chem Toxicol. 2003;41:359-74.

  144. Koyama E, Sakai N, Ohori Y, et al. Absorption and metabolism of glycosidic sweeteners of stevia mixture and their aglycone, steviol, in rats and humans. Food Chem Toxicol. 2003;41:875-83.

  145. Das S, Das AK, Murphy RA. Evaluation of the cariogenic potential of the intense natural sweeteners stevioside and rebaudioside A. Caries Res. 1992;26:363-6.

  146. Cardoso VN, Barbosa MF, Muramoto E, Mesquita CH, Almeida MA. Pharmacokinetic studies of 131I-stevioside and its metabolites. Nucl Med Biol. 1996;23:97-100.

  147. Toskulkao C, Chaturat L, Temcharoen P, Glinsukon T. Acute toxicity of stevioside, a natural sweetener, and its metabolite, steviol, in several animal species. Drug Chem Toxicol. 1997;20:31-44.

  148. Wasuntarawat C, Temcharoen P, Toskulkao C, Munakornkarn P, Suttaji TM, Glinsukonol T. Developmental toxicity of steviol, a metabolite of tevioside, in the hamster. Drug Chem Toxicol. 1998;21:207-22.

  149. Chaturvedula VS, Upreti M, Prakash I. Diterpene glycosides from Stevia rebaudiana. Molecules. 2011;16:3552-62.

  150. Cacciola F, Delmonte P, Jaworska K, Dugo P, Mondello L, Rader JI. Employing ultra high pressure liquid chromatography as the second dimension in a comprehensive two-dimensional system for analysis of Stevia rebaudiana extracts. J Chromatogr A. 2011;1218:2012-8.

  151. Uchiyama H, Tozuka Y, Imono M, Takeuchi H. Transglycosylated stevia and hesperidin as pharmaceutical excipients: dramatic improvement in drug dissolution and bioavailability. Eur J Pharm Biopharm. 2010;76:238-44.

  152. Belscak-Cvitanovi A, Benkovi M, Komes D, Bauman I, Horzi D, Dujmi F, Matijasec M. Physical properties and bioactive constituents of powdered mixtures and drinks prepared with cocoa and various sweeteners. J Agric Food Chem. 2010;58:7187-95.

  153. Sclafani A, Bahrani M, Zukerman S, Ackroff K. Stevia and saccharin preferences in rats and mice. Chem Senses. 2010;35:433-43.

  154. Ulbricht C, Isaac R, Milkin T, Poole EA, Rusie E, Grimes Serrano JM, Weissner W, Windsor RC, Woods J. An evidencebased systematic review of stevia by the Natural Standard Research Collaboration. Cardiovasc Hematol Agents Med Chem. 2010;8:113-27.

  155. Anton SD, Martin CK, Han H, Coulon S, Cefalu WT, Geiselman P, Williamson DA. Effects of stevia, aspartame, and sucrose on food intake, satiety, and postprandial glucose and insulin levels. Appetite. 2010;55:37-43.

  156. Gardana C, Scaglianti M, Simonetti P. Evaluation of steviol and its glycosides in Stevia rebaudiana leaves and commercial sweetener by ultra-high-performance liquid chromatographymass spectrometry. J Chromatogr A. 2010;1217:1463-70.

  157. Goyal SK, Samsher, Goyal RK. Stevia (Stevia rebaudiana) a bio-sweetener: a review. Int J Food Sci Nutr. 2010;61:1-10.

  158. Steinmetz WE, Lin A. NMR studies of the conformation of the natural sweetener rebaudioside A. Carbohydr Res. 2009;344:2533-8.

  159. Roberts A, Munro I. Stevioside and related compounds: therapeutic benefits beyond sweetness. Pharmacol Ther. 2009;122:e1-2.

  160. Atteh JO, Onagbesan OM, Tona K, Decuypere E, Geuns JM, Buyse J. Evaluation of supplementary stevia (Stevia rebaudiana, bertoni) leaves and stevioside in broiler diets: effects on feed intake, nutrient metabolism, blood parameters and growth performance. J Anim Physiol Anim Nutr (Berl). 2008;92:640-9.

  161. Voiland A. Here comes the controversial new sugar substitute stevia. Soon it could sweeten foods from yogurt to diet soda. US News World Rep. 2008;145:90-5.

  162. Sehar I, Kaul A, Bani S, Pal HC, Saxena AK. Immune up regulatory response of a non-caloric natural sweetener, stevioside. Chem Biol Interact. 2008;173:115-21.

  163. Barriocanal LA, Palacios M, Benitez G, Benitez S, Jimenez JT, Jimenez N, Rojas V. Apparent lack of pharmacological effect of steviol glycosides used as sweeteners in humans. A pilot study of repeated exposures in some normotensive and hypotensive individuals and in Type 1 and Type 2 diabetics. Regul Toxicol Pharmacol. 2008;51:37-41.

  164. Ghanta S, Banerjee A, Poddar A, Chattopadhyay S. Oxidative DNA damage preventive activity and antioxidant potential of Stevia rebaudiana (Bertoni) Bertoni, a natural sweetener. J Agric Food Chem. 2007;55(26):10962-7.

  165. Ferreira EB, de Assis Rocha Neves F, da Costa MA, do Prado WA, de Araújo Funari Ferri L, Bazotte RB. Comparative effects of Stevia rebaudiana leaves and stevioside on glycaemia and hepatic gluconeogenesis. Planta Med. 2006;72:691-6.

  166. Chang JC, Wu MC, Liu IM, Cheng JT. Increase of insulin sensitivity by stevioside in fructose-rich chow-fed rats. Horm Metab Res. 2005;37:610-16.

  167. Chen TH, Chen SC, Chan P, Chu YL, Yang HY, Cheng JT. Mechanism of the hypoglycemic effect of stevioside, a glycoside of Stevia rebaudiana. Planta Med. 2005;71:108-13.

  168. Srimaroeng C, Chatsudthipong V, Aslamkhan AG, Pritchard JB. Transport of the natural sweetener stevioside and its aglycone steviol by human organic anion transporter (hOAT1; SLC22A6) and hOAT3 (SLC22A8). J Pharmacol Exp Ther. 2005;313:621-8.

  169. Raskovic A, Gavrilovic M, Jakovljevic V, Sabo J. Glucose concentration in the blood of intact and alloxan-treated mice after pretreatment with commercial preparations of Stevia rebaudiana (Bertoni). Eur J Drug Metab Pharmacokinet. 2004;29:87-90.

  170. Raskovic A, Jakovljevic V, Mikov M, Gavrilovic M. Joint effect of commercial preparations of Stevia rebaudiana Bertoni and sodium monoketocholate on glycemia in mice. Eur J Drug Metab Pharmacokinet. 2004;29:83-6.

  171. Gregersen S, Jeppesen PB, Holst JJ, Hermansen K. Antihyperglycemic effects of stevioside in type 2 diabetic subjects. Metabolism. 2004;53:73-6.

  172. McGarvey BD, Attygalle AB, Starratt AN, Xiang B, Schroeder FC, Brandle JE, Meinwald J. New non-glycosidic diterpenes from the leaves of Stevia rebaudiana. J Nat Prod. 2003;66:1395-8.

  173. Geuns JM. Stevioside. Phytochemistry. 2003;64:913-21.

  174. Sekihashi K, Saitoh H, Sasaki Y. Genotoxicity studies of stevia extract and steviol by the comet assay]. J Toxicol Sci. 2002;27(Suppl 1):1-8.

  175. Bertorelli AM, Czarnowski-Hill JV. Review of present and future use of nonnutritive sweeteners. Diabetes Educ. 1990;16:415-22.

  176. Zygler A, Wasik A, Kot-Wasik A, Namie nik J. Determination of nine high-intensity sweeteners in various foods by highperformance liquid chromatography with mass spectrometric detection. Anal Bioanal Chem. 2011;400:2159-72.

  177. Liu X, Ding L, Liu J, Zhang Y, Huang Z, Wang L, Chen B. Simultaneous determination of six synthetic sweeteners in food by high performance liquid chromatography-tandem mass spectrometry. Se Pu. 2010;28:1020-5.

  178. Zygler A, Wasik A, Namie nik J. Retention behaviour of some high-intensity sweeteners on different SPE sorbents. Talanta. 2010;82:1742-8.

  179. Renwick AG. The intake of intense sweeteners - an update review. Food Addit Contam. 2006;23:327-38.

  180. Glaser D, Tinti JM, Nofre C. Evolution of the sweetness receptor in primates. I. Why does alitame taste sweet in all prosimians and simians, and aspartame only in Old World simians? Chem Senses. 1995;20:573-84.

  181. Schiffman SS, Booth BJ, Carr BT, Losee ML, Sattely-Miller EA, Graham BG. Investigation of synergism in binary mixtures of sweeteners. Brain Res Bull. 1995;38:105-120

  182. Wolraich ML, Lindgren SD, Stumbo PJ, Stegink LD, Appelbaum MI, Kiritsy MC. Effects of diets high in sucrose or aspartame on the behavior and cognitive performance of children. N Engl J Med. 1994;330:301-7.

  183. American Dietetic Association. Position of the American Dietetic Association: use of nutritive and nonnutritive sweeteners. J Am Diet Assoc. 2004;104(2):255-75. Erratum in: J Am Diet Assoc. 2004;104:13.

  184. Husøy T, Mangschou B, Fotland TØ, Kolset SO, Nøtvik Jakobsen H, Tømmerberg I, Bergsten C, Alexander J, Frost Andersen L. Reducing added sugar intake in Norway by replacing sugar sweetened beverages with beverages containing intense sweeteners - a risk benefit assessment. Food Chem Toxicol. 2008;46:3099-105.

  185. Leth T, Jensen U, Fagt S, Andersen R. Estimated intake of intense sweeteners from non-alcoholic beverages in Denmark, 2005. Food Addit Contam Part A Chem Anal Control Expo Risk Assess. 2008;25:662-8.

  186. Renwick AG. The intake of intense sweeteners - an update review. Food Addit Contam. 2006;23:327-338.

  187. “Inactive“ ingredients in pharmaceutical products: update (subject review). American Academy of Pediatrics Committee on Drugs. Pediatrics. 1997;99(2):268-78. Review

  188. Position of the American Dietetic Association: use of nutritive and nonnutritive sweeteners. J Am Diet Assoc. 1993;93:816- 821. Erratum in: J Am Diet Assoc. 1993;93:1104.

  189. Gougeon R, Spindel M, Lee K, Field CJ. Canadian Diabetes Association Nutrition Committee Technical Review: Nonnutritive intense sweeteners in diabetes management. Can J Diab. 2004;28:385-99.

  190. Black RM, Leiter LA, Anderson GH. Consuming aspartame with and without taste: differential effects on appetite and food intake of young adult males. Physiol Behav. 1993;53:459-66.

  191. Holt SH, Sandona N, Brand-Miller JC. The effects of sugarfree vs. sugar-rich beverages on feelings of fullness and subsequent food intake. Int J Food Sci Nutr. 2000;51:59-71.

  192. Rolls BJ, Laster LJ, Summerfelt A. Hunger and food intake following consumption of low-calorie foods. Appetite. 1989;13:115-127

  193. Blackburn GL, Kanders BS, Lavin PT, Keller SD, Whatley J. The effect of aspartame as part of a multidisciplinary weightcontrol program on short- and long-term control of body weight. Am J Clin Nutr. 1997;65:409-18.

  194. Kanders BS, Lavin PT, Kowalchuk MB, et al. An evaluation of the effect of aspartame on weight loss. Appetite. 1988;11(suppl 1):73-84.

  195. Garnier-Sagne I, Leblanc JC,Verger P. Calculation of the intake of three intense sweeteners in young insulin-dependent diabetics. Food Chem Toxicol. 2001;39:745-9.

  196. Toledo MC, Ioshi SH. Potential intake of intense sweeteners in Brazil. Food Addit Contam. 1995;12:799-808.

  197. Mezitis NH, Maggio CA, Koch P, Quddoos A, Allison DB, Pi- Sunyer FX, et al. Glycemic effect of a single high oral dose of the novel sweetener sucralose in patients with diabetes. Diabetes Care. 1996;19:1004-5.

  198. Butchko HH, Stargel WW, Comer CP, Mayhew DA, Benninger C, Blacknurn GL. Aspartame: review of safety. Regul Toxicol Pharmacol. 2002;35:S1-S93.

  199. Shaywitz BA, Anderson GM, Novotny EJ, Ebersola JS, Sullivan CM, Gillespiect SM. Aspartame has no effect on seizures or epileptiform discharges in epileptic children. Ann Neurol. 1994;35:98-103.

  200. Cooper PL, Wahlqvist ML, Simpson RW. Sucrose versus saccharin as an added sweetener in non-insulin-dependent diabetes: short- and medium-term metabolic effects. Diabet Med. 1988;5:676-80.

  201. Chantelau EA, Gosseringer G, Sonnenberg GE, Berger M. Moderate intake of sucrose does not impair metabolic control in pump-treated diabetic out-patients. Diabetologia. 1985;28:204-7.

  202. Saunders JP, Donner TW, Sadler JH, Levin GV, Markris NG. Effects of acute and repeated oral doses of D-tagatose on plasma uric acid in normal and diabetic humans. Regul Toxicol Pharmacol. 1999;29: S57-S65.

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