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Current Diabetes Reviews

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ISSN (Print): 1573-3998
ISSN (Online): 1875-6417

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Review Article

Artificial Sweeteners: Perceptions and Realities

Author(s): Habiba Samreen and Suneela Dhaneshwar*

Volume 19, Issue 7, 2023

Published on: 17 August, 2022

Article ID: e290422204241 Pages: 14

DOI: 10.2174/1573399818666220429083052

Price: $65

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Abstract

Artificial sweeteners (AS) were first introduced as food additives or sugar substitutes more than a century ago with the intention of supplying sweet taste without the high caloric content of sugar. AS are employed in place of sucrose (table sugar) with the view of providing sweetness to foodstuffs and bottled drinks. The end-users, along with producers of canned food and drinks, have long been captivated by the idea of replacing sugar in food items with AS. Foods that use AS in place of sugar have become increasingly common during the past decade. Artificial sugars are normally many folds sweeter than normal sugar possessing low or zero calories, which confers to their public appeal for the management of overweight issues. Due to this, they are, at present, employed by many individuals all over the world, without knowing the potential hazards associated with them. The use of AS in obese, diabetic, and/or heart patients or patients with metabolic syndrome has been approved with caution by The American Heart Association and American Diabetes Association (ADA) as a low-calorie option for normal sugar. Judicious use of sugar substitutes can help in maintaining blood glucose, calories and body weight, thus automatically minimizing the risk factors of diabetes and heart disease. Since the day of their discovery and approval, their safety issue has been quite controversial and debated extensively. The article follows an exhaustive review discussing the history, uses, and chemical features of a wide variety of sweeteners with a focus on their association with diabetes and potential adverse effects on the body.

Keywords: Sugar substitutes, cyclamates, sweetening agents, sweet taste, diabetes mellitus, obesity.

[1]
Walters ED. All about sweeteners. Canada, USA 2009.www.sweetenerbook.com Available from:
[2]
Whitehouse CR, Boullata J, McCauley LA. The potential toxicity of AS. AAOHN J 2008; 56(6): 251-61.
[http://dx.doi.org/10.1177/216507990805600604] [PMID: 18604921]
[3]
Siervo M, Montagnese C, Mathers JC, Soroka KR, Stephan BC, Wells JC. Sugar consumption and global prevalence of obesity and hypertension: An ecological analysis. Public Health Nutr 2014; 17(3): 587-96.
[http://dx.doi.org/10.1017/S1368980013000141] [PMID: 23414749]
[4]
Harvard Health Publishing. AS: Sugar-free, but at what cost? Available from: https://www.health.harvard.edu/blog/artificial-sweeteners-sugar-free-but-at-what-cost-201207165030 (Accessed on Aug 4, 2021).
[5]
Martyn DM, Nugent AP, McNulty BA, et al. Dietary intake of four AS by Irish pre-school children. Food Additives & Contaminants: Part A 2016; 33(4): 592-602.
[PMID: 26939625]
[6]
Fujimaru T, Park JH, Lim J. Sensory characteristics and relative sweetness of tagatose and other sweeteners. J Food Sci 2012; 77(9): S323-8.
[http://dx.doi.org/10.1111/j.1750-3841.2012.02844.x] [PMID: 22908895]
[7]
Chattopadhyay S, Raychaudhuri U, Chakraborty R. Artificial sweeteners - a review. J Food Sci Technol 2014; 51(4): 611-21.
[http://dx.doi.org/10.1007/s13197-011-0571-1] [PMID: 24741154]
[8]
Patil S, Ravi R, Saraswathi G, Prakash M. Development of low calorie snack food based on intense sweeteners. J Food Sci Technol 2014; 51(12): 4096-101.
[http://dx.doi.org/10.1007/s13197-012-0911-9] [PMID: 25477687]
[9]
Findikli Z, Turkoglu S. Determination of the effects of some AS on human peripheral lymphocytes using the comet assay. J Toxicol Environ Health Sci 2014; 6(8): 147-53.
[http://dx.doi.org/10.5897/JTEHS2014.0313]
[10]
Suez J, Korem T, Zeevi D, et al. AS induce glucose intolerance by altering the gut microbiota. Nature 2014; 514(7521): 181-6.
[http://dx.doi.org/10.1038/nature13793] [PMID: 25231862]
[11]
Kauffman GB, Priebe PM. The discovery of saccharin: A centennial retrospect. Ambix 1978; 25(3): 191-207.
[http://dx.doi.org/10.1179/amb.1978.25.3.191] [PMID: 11615708]
[12]
Moskowitz HR. Sweetness and intensity of AS. Percept Psychophys 1970; 8(1): 40-2.
[http://dx.doi.org/10.3758/BF03208930]
[13]
Moskowitz HR. Models of sweetness additivity. J Exp Psychol 1973; 99(1): 88-98.
[http://dx.doi.org/10.1037/h0034733] [PMID: 4714082]
[14]
von Rymon Lipinski GW. Sweeteners. In: Ullmann's Encyclopedia of Industrial Chemistry. Hoboken, New Jersey: Wiley online library, 2000.
[15]
Periyasamy A. Artificial sweeteners. IJRR 2019; 6(1): 120-8.
[16]
Wild S, Roglic G, Green A, Sicree R, King H. Global prevalence of diabetes: Estimates for the year 2000 and projections for 2030. Diabetes Care 2004; 27(5): 1047-53.
[http://dx.doi.org/10.2337/diacare.27.5.1047] [PMID: 15111519]
[17]
Pan XR, Yang WY, Li GW, Liu J. Prevalence of diabetes and its risk factors in China, 1994. Diabetes Care 1997; 20(11): 1664-9.
[http://dx.doi.org/10.2337/diacare.20.11.1664] [PMID: 9353605]
[18]
Shwide-Slavin C, Swift C, Ross T. Nonnutritive sweeteners: Where are we today? Diabetes Spectr 2012; 25(2): 104-10.
[http://dx.doi.org/10.2337/diaspect.25.2.104]
[19]
Imamura F, O’Connor L, Ye Z, et al. Consumption of sugar sweetened beverages, artificially sweetened beverages, and fruit juice and incidence of type 2 diabetes: Systematic review, meta-analysis, and estimation of population attributable fraction. BMJ 2015; 351: h3576.
[http://dx.doi.org/10.1136/bmj.h3576] [PMID: 26199070]
[20]
Tandel KR. Sugar substitutes: Health controversy over perceived benefits. J Pharmacol Pharmacother 2011; 2(4): 236-43.
[http://dx.doi.org/10.4103/0976-500X.85936] [PMID: 22025850]
[21]
Uppal S, Italiya KS, Chitkara D, Mittal A. Nanoparticulate-based drug delivery systems for small molecule anti-diabetic drugs: An emerging paradigm for effective therapy. Acta Biomater 2018; 81: 20-42.
[http://dx.doi.org/10.1016/j.actbio.2018.09.049] [PMID: 30268916]
[22]
Fairchild RM, Daniels CE, Ellis PR. A survey of the use of special food products by diabetics. J Hum Nutr Diet 1990; 3(5): 311-6.
[http://dx.doi.org/10.1111/j.1365-277X.1990.tb00241.x]
[23]
Sylvetsky A, Rother KI, Brown R. Artificial sweetener use among children: Epidemiology, recommendations, metabolic outcomes, and future directions. Pediatr Clin North Am 2011; 58(6): 1467-80.[xi]..
[http://dx.doi.org/10.1016/j.pcl.2011.09.007]] [PMID: 22093863]
[24]
Celaya LS, Kolb E, Kolb N. Solubility of Stevioside and Rebaudioside A in water, ethanol and their binary mixtures. Int J Food Stud 2016; 5(2): 158-66.
[http://dx.doi.org/10.7455/ijfs/5.2.2016.a4]
[25]
Prakash I, Campbell M, San Miguel RI, Chaturvedula VS. Synthesis and sensory evaluation of ent-kaurane diterpene glycosides. Molecules 2012; 17(8): 8908-16.
[http://dx.doi.org/10.3390/molecules17088908] [PMID: 22836210]
[26]
Prakash I, Campbell M, Chaturvedula VS. Catalytic hydrogenation of the sweet principles of Stevia rebaudiana, Rebaudioside B, Rebaudioside C, and Rebaudioside D and sensory evaluation of their reduced derivatives. Int J Mol Sci 2012; 13(11): 15126-36.
[http://dx.doi.org/10.3390/ijms131115126] [PMID: 23203115]
[27]
Hellfritsch C, Brockhoff A, Stähler F, Meyerhof W, Hofmann T. Human psychometric and taste receptor responses to steviol glycosides. J Agric Food Chem 2012; 60(27): 6782-93.
[http://dx.doi.org/10.1021/jf301297n] [PMID: 22616809]
[28]
Brusick DJ. A critical review of the genetic toxicity of steviol and steviol glycosides. Food Chem Toxicol 2008; 46(7): S83-91.
[http://dx.doi.org/10.1016/j.fct.2008.05.002] [PMID: 18556105]
[29]
Wölwer-Rieck U. The leaves of Stevia rebaudiana (Bertoni), their constituents and the analyses thereof: A review. J Agric Food Chem 2012; 60(4): 886-95.
[http://dx.doi.org/10.1021/jf2044907] [PMID: 22250765]
[30]
Lemus-Mondaca R, Vega-Gálvez A, Zura-Bravo L, Ah-Hen K. Stevia rebaudiana Bertoni, source of a high-potency natural sweetener: A comprehensive review on the biochemical, nutritional and functional aspects. Food Chem 2012; 132(3): 1121-32.
[http://dx.doi.org/10.1016/j.foodchem.2011.11.140] [PMID: 29243591]
[31]
Mooradian AD, Smith M, Tokuda M. The role of artificial and natural sweeteners in reducing the consumption of table sugar: A narrative review. Clin Nutr ESPEN 2017; 18: 1-8.
[http://dx.doi.org/10.1016/j.clnesp.2017.01.004] [PMID: 29132732]
[32]
Bamberger M, Landsiedl A. Erythrit in Trentepohlia jolithus. Monatshefte für Chemie und verwandte Teile anderer Wissenschaften 1900; 21(6): 571-3.
[http://dx.doi.org/10.1007/BF01525545]
[33]
Arrigoni E, Brouns F, Amadò R. Human gut microbiota does not ferment erythritol. Br J Nutr 2005; 94(5): 643-6.
[http://dx.doi.org/10.1079/BJN20051546] [PMID: 16277764]
[34]
Goto K, Fukai K, Hikida J, Nanjo F, Hara Y. Isolation and structural analysis of oligosaccharides from yacon (Polymnia sonchifolia). Biosci Biotechnol Biochem 1995; 59(12): 2346-7.
[http://dx.doi.org/10.1271/bbb.59.2346]
[35]
Del Castillo VC, Goldner MC, Armada M. Evaluation of texture profile, color and determination of FOS in yacón products (Smallanthus sonchifolius). Turk J Agric Food Sci Technol 2016; 4(7): 540-4.
[http://dx.doi.org/10.24925/turjaf.v4i7.540-544.694]
[36]
Delzenne NM, Roberfroid MR. Physiological effects of non-digestible oligosaccharides. Lebensm Wiss Technol 1994; 27(1): 1-6.
[http://dx.doi.org/10.1006/fstl.1994.1001]
[37]
Hsiao-Ling Chen RD, Yu-Ho Lu RN, Jiun-Jr Lin MD, Lie-Yon Ko MD. Effects of fructooligosaccharide on bowel function and indicators of nutritional status in constipated elderly men. Nutr Res 2000; 20(12): 1725-33.
[http://dx.doi.org/10.1016/S0271-5317(00)00274-8]
[38]
Yang Y, Tsai CE. Effects of biosynthetic indigestible carbohydrates on digestion and lipid metabolism in rats. Shipin Kexue 1993; 20: 215-8.
[39]
Beylot M. Effects of inulin-type fructans on lipid metabolism in man and in animal models. Br J Nutr 2005; 93(S1) (Suppl. 1): S163-8.
[http://dx.doi.org/10.1079/BJN20041339] [PMID: 15877890]
[40]
Genta S, Cabrera W, Habib N, et al. Yacon syrup: Beneficial effects on obesity and insulin resistance in humans. Clin Nutr 2009; 28(2): 182-7.
[http://dx.doi.org/10.1016/j.clnu.2009.01.013] [PMID: 19254816]
[41]
Alles MJL, Tessaro IC, Noreña CPZ. Concentration and purification of yacon (Smallanthus sonchifolius) root fructooligosaccharides using membrane technology. Food Technol Biotechnol 2015; 53(2): 190-200.
[PMID: 27904348]
[42]
Buerge IJ, Keller M, Buser HR, Müller MD, Poiger T. Saccharin and other AS in soils: Estimated inputs from agriculture and households, degradation, and leaching to groundwater. Environ Sci Technol 2011; 45(2): 615-21.
[http://dx.doi.org/10.1021/es1031272] [PMID: 21142066]
[43]
Miller SA, Frattali VP. Saccharin. Diabetes Care 1989; 12(1): 74-80.
[http://dx.doi.org/10.2337/diacare.12.1.74] [PMID: 2653753]
[44]
Arnold DL. Toxicology of saccharin. Fundam Appl Toxicol 1984; 4(5): 674-85.
[http://dx.doi.org/10.1016/0272-0590(84)90088-5] [PMID: 6391996]
[45]
International Sweeteners Association. Saccharin fact sheet Available from: www.sweeteners.org/pdf/fsSaccharin_English.pdf (Accessed April 23, 2008).
[46]
Bobde J. Artificial Sweetners. J Clin Diabetol 2016; 3(1)
[47]
Weihrauch MR, Diehl V. Artificial sweeteners-do they bear a carcinogenic risk? Ann Oncol 2004; 15(10): 1460-5.
[http://dx.doi.org/10.1093/annonc/mdh256] [PMID: 15367404]
[48]
Fukushima S, Arai M, Nakanowatari J, Hibino T, Okuda M, Ito N. Differences in susceptibility to sodium saccharin among various strains of rats and other animal species. Gann 1983; 74(1): 8-20.
[PMID: 6840440]
[49]
Negro F, Mondardini A, Palmas F. Hepatotoxicity of saccharin. N Engl J Med 1994; 331(2): 134-5.
[http://dx.doi.org/10.1056/NEJM199407143310220] [PMID: 8208266]
[50]
Oser BL. Highlights in the history of saccharin toxicology. Food Chem Toxicol 1985; 23(4-5): 535-42.
[http://dx.doi.org/10.1016/0278-6915(85)90148-6] [PMID: 3839202]
[51]
Nill AG. The history of aspartame Available from: https://dash.harvard.edu/handle/1/8846759
[52]
Aspartame. Recent Study on Aspartame and Cancer Critically Flawed. Available from: https://aspartame.org/recent-study-aspartame-cancer-critically-flawed/ (Accessed on March 21, 2021).
[53]
Palese M, Tephly TR. Metabolism of formate in the rat. J Toxicol Environ Health 1975; 1(1): 13-24.
[http://dx.doi.org/10.1080/15287397509529305] [PMID: 1185816]
[54]
Soffritti M, Belpoggi F, Tibaldi E, Esposti DD, Lauriola M. Life-span exposure to low doses of aspartame beginning during prenatal life increases cancer effects in rats. Environ Health Perspect 2007; 115(9): 1293-7.
[http://dx.doi.org/10.1289/ehp.10271] [PMID: 17805418]
[55]
Blumenthal HJ, Vance DA. Chewing gum headaches. Headache 1997; 37(10): 665-6.
[http://dx.doi.org/10.1046/j.1526-4610.1997.3710665.x] [PMID: 9439090]
[56]
Roberts HJ. Aspartame-induced thrombocytopenia. South Med J 2007; 100(5): 543-4.
[http://dx.doi.org/10.1097/SMJ.0b013e31802fa4d7] [PMID: 17534100]
[57]
Butchko HH, Stargel WW. Aspartame: Scientific evaluation in the postmarketing period. Regul Toxicol Pharmacol 2001; 34(3): 221-33.
[http://dx.doi.org/10.1006/rtph.2001.1500] [PMID: 11754527]
[58]
Klug C, von Rymon Lipinski GW, Acesulfame K. Sweeteners and sugar alternatives in food technology 1988.
[59]
Mukherjee A, Chakrabarti J. In vivo cytogenetic studies on mice exposed to acesulfame-K-a non-nutritive sweetener. Food Chem Toxicol 1997; 35(12): 1177-9.
[http://dx.doi.org/10.1016/S0278-6915(97)85469-5] [PMID: 9449223]
[60]
Additional Information about High-Intensity Sweeteners Permitted for Use in Food in the United States. Available from: https://www.fda.gov/food/food-additives-petitions/additional-information-about-high-intensity-sweeteners-permitted-use-food-united-states (Accessed on July 13, 2021).
[61]
Roberts A, Renwick AG, Sims J, Snodin DJ. Sucralose metabolism and pharmacokinetics in man. Food Chem Toxicol 2000; 38 (Suppl. 2): S31-41.
[http://dx.doi.org/10.1016/S0278-6915(00)00026-0] [PMID: 10882816]
[62]
Grice HC, Goldsmith LA. Sucralose-an overview of the toxicity data. Food Chem Toxicol 2000; 38: 1-6.
[http://dx.doi.org/10.1016/S0278-6915(00)00023-5]
[63]
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): S123-9.
[http://dx.doi.org/10.1016/S0278-6915(00)00035-1] [PMID: 10882825]
[64]
Witt J. Discovery and development of neotame. World Rev Nutr Diet 1999; 85: 52-7.
[http://dx.doi.org/10.1159/000059702] [PMID: 10647335]
[65]
Nofre C, Tinti JM. Neotame: Discovery, properties, utility. Food Chem 2000; 69(3): 245-57.
[http://dx.doi.org/10.1016/S0308-8146(99)00254-X]
[66]
Neotame as a sweetener and flavour enhancer‐Scientific opinion of the panel on food additives, flavourings, processing aids and materials in contact with food. EFSA J 2007; 5(11): 581.
[http://dx.doi.org/10.2903/j.efsa.2007.581]
[67]
Mayhew DA, Comer CP, Stargel WW. Food consumption and body weight changes with neotame, a new sweetener with intense taste: Differentiating effects of palatability from toxicity in dietary safety studies. Regul Toxicol Pharmacol 2003; 38(2): 124-43.
[http://dx.doi.org/10.1016/S0273-2300(03)00074-6] [PMID: 14550755]
[68]
Brown RJ, de Banate MA, Rother KIAS. Artificial sweeteners: A systematic review of metabolic effects in youth. Int J Pediatr Obes 2010; 5(4): 305-12.
[http://dx.doi.org/10.3109/17477160903497027] [PMID: 20078374]
[69]
Pearlman M, Obert J, Casey L. The association between AS and obesity. Curr Gastroenterol Rep 2017; 19(12): 64.
[http://dx.doi.org/10.1007/s11894-017-0602-9] [PMID: 29159583]
[70]
Bokulich NA, Blaser MJ. A bitter aftertaste: Unintended effects of AS on the gut microbiome. Cell Metab 2014; 20(5): 701-3.
[http://dx.doi.org/10.1016/j.cmet.2014.10.012] [PMID: 25440050]
[71]
Riera CE, Vogel H, Simon SA, Coutre JL. AS and salts producing a metallic taste sensation activate TRPV1 receptors. Am J Physiol Regul Integr Comp Physiol 2007; 293(2): R626-34.
[http://dx.doi.org/10.1152/ajpregu.00286.2007] [PMID: 17567713]
[72]
Sharecare. What are common brand names of AS? Available from: https://www.sharecare.com/health/artificial-sweeteners/what-common-brand-artificial-sweeteners (Accessed on March 28, 2021).
[73]
World Health Organization. Inter-Organization Programme for the Sound Management of Chemicals. IPCS risk assessment terminology. 2004.
[74]
Bellisle F, Drewnowski A. Intense sweeteners, energy intake and the control of body weight. Eur J Clin Nutr 2007; 61(6): 691-700.
[http://dx.doi.org/10.1038/sj.ejcn.1602649] [PMID: 17299484]
[75]
Schernhammer ES, Bertrand KA, Birmann BM, Sampson L, Willett WC, Feskanich D. Consumption of artificial sweetener- and sugar-containing soda and risk of lymphoma and leukemia in men and women. Am J Clin Nutr 2012; 96(6): 1419-28.
[http://dx.doi.org/10.3945/ajcn.111.030833] [PMID: 23097267]
[76]
Bosetti C, Gallus S, Talamini R, et al. Artificial sweeteners and the risk of gastric, pancreatic, and endometrial cancers in Italy. Cancer Epidemiol Biomarkers Prev 2009; 18(8): 2235-8.
[http://dx.doi.org/10.1158/1055-9965.EPI-09-0365] [PMID: 19661082]
[77]
Lim U, Subar AF, Mouw T, et al. Consumption of aspartame-containing beverages and incidence of hematopoietic and brain malignancies. Cancer Epidemiol Biomarkers Prev 2006; 15(9): 1654-9.
[http://dx.doi.org/10.1158/1055-9965.EPI-06-0203] [PMID: 16985027]
[78]
McCullough ML, Teras LR, Shah R, Diver WR, Gaudet MM, Gapstur SM. Artificially and sugar-sweetened carbonated beverage consumption is not associated with risk of lymphoid neoplasms in older men and women. J Nutr 2014; 144(12): 2041-9.
[http://dx.doi.org/10.3945/jn.114.197475] [PMID: 25342696]
[79]
Mishra A, Ahmed K, Froghi S, Dasgupta P. Systematic review of the relationship between artificial sweetener consumption and cancer in humans: Analysis of 599,741 participants. Int J Clin Pract 2015; 69(12): 1418-26.
[http://dx.doi.org/10.1111/ijcp.12703] [PMID: 26202345]
[80]
Toews I, Lohner S, de Gaudry DK, Sommer H, Meerpohl JJ. Association between intake of non-sugar sweeteners and health outcomes: Systematic review and meta-analyses of randomised and non-randomised controlled trials and observational studies. BMJ 2019; 364.
[81]
Qurrat-ul-Ain, Khan SA. Artificial sweeteners: Safe or unsafe? J Pak Med Assoc 2015; 65(2): 225-7.
[PMID: 25842566]
[82]
Fagherazzi G, Vilier A, Saes Sartorelli D, Lajous M, Balkau B, Clavel-Chapelon F. Consumption of artificially and sugar-sweetened beverages and incident type 2 diabetes in the Etude Epidemiologique aupres des femmes de la Mutuelle Generale de l’Education Nationale-European Prospective Investigation into Cancer and Nutrition cohort. Am J Clin Nutr 2013; 97(3): 517-23.
[http://dx.doi.org/10.3945/ajcn.112.050997] [PMID: 23364017]
[83]
Daher MI, Matta JM, Nour AM. Non-nutritive sweeteners and type 2 diabetes: Should we ring the bell? Diabetes Res Clin Pract 2019; 155: 107786.
[84]
Pang MD, Goossens GH, Blaak EE. The impact of artificial sweeteners on body weight control and glucose homeostasis. Front Nutr 2021; 7: 598340.
[http://dx.doi.org/10.3389/fnut.2020.598340] [PMID: 33490098]
[85]
Halldorsson TI, Strøm M, Petersen SB, Olsen SF. Intake of artificially sweetened soft drinks and risk of preterm delivery: A prospective cohort study in 59,334 Danish pregnant women. Am J Clin Nutr 2010; 92(3): 626-33.
[http://dx.doi.org/10.3945/ajcn.2009.28968] [PMID: 20592133]
[86]
Garland EM, Shapiro R, Wehner JM, et al. Effects of dietary iron and folate supplementation on the physiological changes produced in weanling rats by sodium saccharin exposure. Food Chem Toxicol 1993; 31(10): 689-99.
[http://dx.doi.org/10.1016/0278-6915(93)90139-P] [PMID: 8225126]
[87]
Azad MB, Abou-Setta AM, Chauhan BF, et al. Nonnutritive sweeteners and cardiometabolic health: A systematic review and meta-analysis of randomized controlled trials and prospective cohort studies. CMAJ 2017; 189(28): E929-39.
[http://dx.doi.org/10.1503/cmaj.161390] [PMID: 28716847]
[88]
Rogers PJ, Hogenkamp PS, de Graaf C, et al. Does low-energy sweetener consumption affect energy intake and body weight? A systematic review, including meta-analyses, of the evidence from human and animal studies. Int J Obes 2016; 40(3): 381-94.
[http://dx.doi.org/10.1038/ijo.2015.177] [PMID: 26365102]
[89]
Uebanso T, Ohnishi A, Kitayama R, et al. Effects of low-dose non-caloric sweetener consumption on gut microbiota in mice. Nutrients 2017; 9(6): 560.
[http://dx.doi.org/10.3390/nu9060560] [PMID: 28587159]
[90]
Bian X, Chi L, Gao B, Tu P, Ru H, Lu K. The artificial sweetener acesulfame potassium affects the gut microbiome and body weight gain in CD-1 mice. PLoS One 2017; 12(6): e0178426.
[http://dx.doi.org/10.1371/journal.pone.0178426] [PMID: 28594855]
[91]
Alkafafy M-S, Ibrahim ZS, Ahmed MM, El-Shazly SA. Impact of aspartame and saccharin on the rat liver: Biochemical, molecular, and histological approach. Int J Immunopathol Pharmacol 2015; 28(2): 247-55.
[http://dx.doi.org/10.1177/0394632015586134] [PMID: 26015492]
[92]
Glendinning JI, Hart S, Lee H, et al. Low-calorie sweeteners cause only limited metabolic effects in mice. Am J Physiol Regul Integr Comp Physiol 2020; 318(1): R70-80.
[http://dx.doi.org/10.1152/ajpregu.00245.2019] [PMID: 31693385]
[93]
Suez J, Korem T, Zeevi D, et al. Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Nature 2014; 514(7521): 181-6.
[http://dx.doi.org/10.1038/nature13793] [PMID: 25231862]
[94]
Zhao X, Yan J, Chen K, Song L, Sun B, Wei X. Effects of saccharin supplementation on body weight, sweet receptor mRNA expression and appetite signals regulation in post-weanling rats. Peptides 2018; 107: 32-8.
[http://dx.doi.org/10.1016/j.peptides.2018.07.006] [PMID: 30055207]
[95]
Esquinas-Requena JL, Lozoya-Moreno S, García-Nogueras I, Atienzar-Núñez P, Sánchez-Jurado PM, Abizanda P. Anemia increases mortality risk associated with frailty or disability in older adults. The FRADEA Study. Aten Primaria 2020; 52(7): 452-61.
[http://dx.doi.org/10.1016/j.aprim.2019.07.001] [PMID: 31506204]
[96]
Azeez OH, Alkass SY, Persike DS. Long-term saccharin consumption and increased risk of obesity, diabetes, hepatic dysfunction, and renal impairment in rats. Medicina (Kaunas) 2019; 55(10): 681.
[http://dx.doi.org/10.3390/medicina55100681] [PMID: 31601053]
[97]
Swithers SE, Davidson TL. A role for sweet taste: Calorie predictive relations in energy regulation by rats. Behav Neurosci 2008; 122(1): 161-73.
[http://dx.doi.org/10.1037/0735-7044.122.1.161] [PMID: 18298259]
[98]
Foletto KC, Melo Batista BA, Neves AM, et al. Sweet taste of saccharin induces weight gain without increasing caloric intake, not related to insulin-resistance in Wistar rats. Appetite 2016; 96: 604-10.
[http://dx.doi.org/10.1016/j.appet.2015.11.003] [PMID: 26555482]
[99]
Frank GK, Oberndorfer TA, Simmons AN, et al. Sucrose activates human taste pathways differently from artificial sweetener. Neuroimage 2008; 39(4): 1559-69.
[http://dx.doi.org/10.1016/j.neuroimage.2007.10.061] [PMID: 18096409]
[100]
Van Opstal AM, Hafkemeijer A, van den Berg-Huysmans AA, et al. Brain activity and connectivity changes in response to nutritive natural sugars, non-nutritive natural sugar replacements and artificial sweeteners. Nutr Neurosci 2021; 24(5): 395-405.
[http://dx.doi.org/10.1080/1028415X.2019.1639306] [PMID: 31288630]
[101]
Shil A, Chichger H. Artificial sweeteners negatively regulate pathogenic characteristics of two model gut bacteria, E. coli and E. faecalis. Int J Mol Sci 2021; 22(10): 5228.
[http://dx.doi.org/10.3390/ijms22105228] [PMID: 34063332]
[102]
Abou-Donia MB, El-Masry EM, Abdel-Rahman AA, McLendon RE, Schiffman SS. Splenda alters gut microflora and increases intestinal p-glycoprotein and cytochrome p-450 in male rats. J Toxicol Environ Health A 2008; 71(21): 1415-29.
[http://dx.doi.org/10.1080/15287390802328630] [PMID: 18800291]
[103]
Boonkaewwan C, Toskulkao C, Vongsakul M. Anti-inflammatory and immunomodulatory activities of stevioside and its metabolite steviol on THP-1 cells. J Agric Food Chem 2006; 54(3): 785-9.
[http://dx.doi.org/10.1021/jf0523465] [PMID: 16448183]
[104]
Alavala S, Sangaraju R, Nalban N, et al. Stevioside, a diterpenoid glycoside, shows anti-inflammatory property against Dextran Sulphate Sodium-induced ulcerative colitis in mice. Eur J Pharmacol 2019; 855: 192-201.
[http://dx.doi.org/10.1016/j.ejphar.2019.05.015] [PMID: 31075241]
[105]
Farid A, Hesham M, El-Dewak M, Amin A. The hidden hazardous effects of stevia and sucralose consumption in male and female albino mice in comparison to sucrose. Saudi Pharm J 2020; 28(10): 1290-300.
[http://dx.doi.org/10.1016/j.jsps.2020.08.019] [PMID: 33132722]
[106]
Bian X, Tu P, Chi L, Gao B, Ru H, Lu K. Saccharin induced liver inflammation in mice by altering the gut microbiota and its metabolic functions. Food Chem Toxicol 2017; 107(Pt B): 530-9.
[http://dx.doi.org/10.1016/j.fct.2017.04.045]] [PMID: 28472674]
[107]
Andrejić BM, Mijatović VM, Samojlik IN, Horvat OJ, Ćalasan JD, Đolai MA. The influence of chronic intake of saccharin on rat hepatic and pancreatic function and morphology: Gender differences. Bosn J Basic Med Sci 2013; 13(2): 94-9.
[http://dx.doi.org/10.17305/bjbms.2013.2372] [PMID: 23725505]
[108]
Amin KA, AlMuzafar HM. Alterations in lipid profile, oxidative stress and hepatic function in rat fed with saccharin and methyl-salicylates. Int J Clin Exp Med 2015; 8(4): 6133-44.
[PMID: 26131217]
[109]
Golonka R, Yeoh BS, Vijay-Kumar M. Dietary additives and supplements revisited: The fewer, the safer for gut and liver health. Curr Pharmacol Rep 2019; 5(4): 303-16.
[http://dx.doi.org/10.1007/s40495-019-00187-4] [PMID: 32864300]
[110]
Maruo T, Sakamoto M, Ito C, Toda T, Benno Y. Adlercreutzia equolifaciens gen. nov., sp. nov., an equol-producing bacterium isolated from human faeces, and emended description of the genus Eggerthella. Int J Syst Evol Microbiol 2008; 58(Pt 5): 1221-7.
[http://dx.doi.org/10.1099/ijs.0.65404-0] [PMID: 18450717]
[111]
Bajaj JS, Hylemon PB, Ridlon JM, et al. Colonic mucosal microbiome differs from stool microbiome in cirrhosis and hepatic encephalopathy and is linked to cognition and inflammation. Am J Physiol Gastrointest Liver Physiol 2012; 303(6): G675-85.
[http://dx.doi.org/10.1152/ajpgi.00152.2012] [PMID: 22821944]
[112]
Chamulitrat W, Jordan SJ, Mason RP, et al. Targets of nitric oxide in a mouse model of liver inflammation by Corynebacterium parvum. Arch Biochem Biophys 1995; 316(1): 30-7.
[http://dx.doi.org/10.1006/abbi.1995.1006] [PMID: 7840629]
[113]
Collins JW, Chervaux C, Raymond B, et al. Fermented dairy products modulate Citrobacter rodentium-induced colonic hyperplasia. J Infect Dis 2014; 210(7): 1029-41.
[http://dx.doi.org/10.1093/infdis/jiu205] [PMID: 24706936]
[114]
Ng SC, Lam EF, Lam TT, et al. Effect of probiotic bacteria on the intestinal microbiota in irritable bowel syndrome. J Gastroenterol Hepatol 2013; 28(10): 1624-31.
[http://dx.doi.org/10.1111/jgh.12306] [PMID: 23800182]
[115]
Guo Y, Zhu SL, Wu YK, He Z, Chen YQ. Omega-3 free fatty acids attenuate insulin-promoted breast cancer cell proliferation. Nutr Res 2017; 42: 43-50.
[http://dx.doi.org/10.1016/j.nutres.2017.04.008] [PMID: 28633870]
[116]
Mata-Pérez C, Sánchez-Calvo B, Padilla MN, et al. Nitro-fatty acids in plant signaling: New key mediators of nitric oxide metabolism. Redox Biol 2017; 11: 554-61.
[http://dx.doi.org/10.1016/j.redox.2017.01.002] [PMID: 28104576]
[117]
Adaramoye OA, Akanni OO. Effects of long-term administration of aspartame on biochemical indices, lipid profile and redox status of cellular system of male rats. J Basic Clin Physiol Pharmacol 2016; 27(1): 29-37.
[http://dx.doi.org/10.1515/jbcpp-2014-0130] [PMID: 26247507]
[118]
Ashok I, Sheeladevi R. Oxidant stress evoked damage in rat hepatocyte leading to triggered nitric oxide synthase (NOS) levels on long term consumption of aspartame. J Food Drug Anal 2015; 23(4): 679-91.

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