REVIEW ON: BITTERNESS OF ARTIFICIAL SWEETENERS
Main Article Content
Keywords
Artificial sweeteners, Glucose tolerance, Cancer, Negative effect on Immunity
Abstract
Artificial sweeteners have become ubiquitous in the modern diet, as consumers seek lower-calorie alternatives to sugar-sweetened beverages and foods. This review article delves into the multifaceted aspects of artificial sweeteners, specifically focusing on their bitterness and the potential health implications associated with their consumption. This comprehensive review synthesizes current research findings, offering a holistic understanding of the bitterness and multifaceted health implications of artificial sweeteners. By examining their effects on glucose metabolism, cardiovascular health, toxicity profiles, cancer risks, immune function, and bladder cancer risk, this article aims to inform both the scientific community and the general public about the complex interplay between artificial sweeteners and human health. Ultimately, this knowledge can guide future research, public health policies, and personal dietary choices in an era dominated by these sugar substitutes.
References
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2. Li X et al; Sucralose promotes colitis-associated colorectal cancer risk in a murine model along with changes in microbiota. Frontiers in oncology. 2020 Jun 3; 10: 710.
3. 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 Ph J. 2020 Oct 1; 28(10):1290-300.
4. Kranthi Kumar Poshala, Artificial Sweeteners: A Review, IJESC, Oct 2020, 10(10) , 27416-2742110.
5. Rodriguez-Palacios A et al. The artificial sweetener splenda promotes gut proteobacteria, dysbiosis, and myeloperoxidase reactivity in Crohn’s disease–like ileitis. Inflammatory bowel diseases. 2018 Apr 23; 24(5):1005-20.
6. Christina R. Whitehouse, BSN, RN, Joseph Boul/ata, PharmD, RPh, BCNSp, and Linda A. McCauley, PHD, RN, FAAN, FAAOHN , The Potential Toxicity of Artificial Sweeteners, AAOHN J , Jun2008, 56 (6) , 251-159.
7. Yebra-Biurrun; MC.Artificial sweeteners: A review. Food Additives. 2005 Sep 1; 17(9):733-8.
8. Douglas l. Arnold , Toxicology of Saccharin , Fundamental and applied toxicology, 1984 , 4 , 674-685
9. G. R. Howe , J. D. Burch , A. B. Miller, B. Morrison , P. Gordon, L. Weldon, L. W. Chamber, G. Fodor , G. M. Winsor , Artificial sweeteners and human bladder cancer , The Lencet , 1977 Sep 17 ,578-581.
10. Jotham Suez et al, Artificial sweeteners induce glucose intolerance by altering the gut microbiota, Nature J, 70(1), 1-7
11. Eva S Schernhammer et al; Consumption of artificial sweetener– and sugar-containing soda and risk of lymphoma and leukemia in men and women, Am J Clin Nutr 012;96:1419–28
12. Charlotte Debras et al; Artificial sweeteners and risk of cardiovascular diseases: results from the prospective NutriNet-Santé cohort, The BMJ, 2022;378, 1-12
13. Bishamber D Toora, Seema S, Manju M, Sasmita Mishra; Effect of Artificial Sweeteners on the Blood Glucose Concentration, J O M A, 2018;1(2):81-85.
14. Manfred Kroger, Kathleen Meister, and Ruth Kava; Low-calorie Sweeteners and Other Sugar Substitutes: A Safety Issues, C R I F Sci and F S, 2006, 5, 35-47
15. Pang MD, Goossens GH, Blaak EE. The impact of artificial sweeteners on body weight control and glucose homeostasis. Front Nutr 2021; 7: 598340. doi:10.3389/fnut.2020.598340
16. Feijó FM, Ballard CR, Foletto KC, et al. Saccharin and aspartame, compared with sucrose, induce greater weight gain in adult Wistar rats, at similar total caloric intake levels. Appetite 2013; 60: 203-7. doi:10.1016/j.appet.2012.10.009
17. Kim Y, Je Y. Prospective association of sugar-sweetened and artificially sweetened beverage intake with risk of hypertension. Arch Cardiovasc Dis 2016; 109: 242-53. doi:10.1016/j.acvd.2015.10.005
18. Basson AR, Rodriguez-Palacios A, Cominelli F. Artificial sweeteners: history and new concepts on inflammation. Front Nutr 2021; 8: 746247. doi:10.3389/fnut.2021.746247
19. Risdon S, Meyer G, Marziou A, Riva C, Roustit M, Walther G. Artificial sweeteners impair endothelial vascular reactivity: preliminary results in rodents. Nutr Metab Cardiovasc Dis 2020; 30: 843-6. doi:10.1016/j.numecd.2020.01.014
20. Jang W, Jeoung NH, Cho KH. Modified apolipoprotein (apo) A-I by artificial sweetener causes severe premature cellular senescence and atherosclerosis with impairment of functional and structural properties of apoA-I in lipid-free and lipid-bound state. Mol Cells 2011; 31: 461-70. doi:10.1007/s10059-011-1009-3
21. Suez J, Korem T, Zeevi D, et al. Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Nature 2014; 514: 181-6.doi:10.1038/nature13793
22. Davidson TL, Martin AA, Clark K, Swithers SE. Intake of high-intensity sweeteners alters the ability of sweet taste to signal caloric consequences: implications for the learned control of energy and body weight regulation. Q J Exp Psychol (Hove) 2011; 64: 1430-41.doi:10.1080/17470218.2011.552729
23. Plaza-Diaz J, Pastor-Villaescusa B, Rueda-Robles A, Abadia-Molina F, Ruiz-Ojeda FJ. Plausible biological interactions of low- and noncalorie sweeteners with the intestinal microbiota: an update of recent studies. Nutrients 2020; 12: 1153. doi:10.3390/nu12041153
24. Peters JC, Beck J, Cardel M, et al. The effects of water and nonnutritive sweetened beverages on weight loss and weight maintenance: a randomized clinical trial. Obesity (Silver Spring) 2016; 24:297-304. doi:10.1002/oby.21327
25. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. (2018) 68:394–424. doi: 10.3322/caac.21492
26. Rawla P, Sunkara T, Barsouk A. Epidemiology of colorectal cancer: incidence, mortality, survival, and risk factors. Prz Gastroenterol. (2019) 14:89– 103. doi: 10.5114/pg.2018.81072 Grazioso TP, Brandt M, Djouder N. Diet, microbiota, and colorectal cancer. iScience. (2019) 21:168–87. doi: 10.1016/j.isci.2019.10.011
27. Rapozo DC, Bernardazzi C, de Souza HS. Diet and microbiota in inflammatory bowel disease: the gut in disharmony. World J Gastroenterol. (2017) 23:2124–40. doi: 10.3748/wjg.v23.i12.2124
28. Neuman MG, Nanau RM. Inflammatory bowel disease: role of diet, microbiota, life style. Transl Res. (2012) 160:29– 44. doi: 10.1016/j.trsl.2011.09.001
29. Qin X. Impaired inactivation of digestive proteases by deconjugated bilirubin: the possible mechanism for inflammatory bowel disease. Med Hypotheses. (2002) 59:159–63. doi: 10.1016/S0306-9877(02)00243-8
30. Qin X. Etiology of inflammatory bowel disease: a unified hypothesis. World J Gastroenterol. (2012) 18:1708–22. doi: 10.3748/wjg.v18.i15.1708
31. M. Elcock and R.W. Morgan , Update on artificial sweetners and bladder cancer, regulatory toxicology and pharmacology, 1993, 17 , 35-43.
32. Morgan R.W. and Jain M. G.Bladder cancer Smoking beveagers and artificial sweeteners, Can Med Assn J, 1974, 111(7), 1069-1070
33. Simon D; Yen. S. and Cole P, Coffee drinking and cancer of the lower urinary track, J Nat Cancer Inst, 1975, 54(3), 587-58-91
34. Wynder E. L. and Goldsmith R; The epdermiology of bladder cancer. A second look, Cancer Study Smith, 1977, 40, 1246-1268
35. Tejashree Anil More, Zoya Shaikh and Ahmad Ali; Artificial Sweeteners and their Health Implications: A Review, BIOSCIENCES BIOTECHNOLOGY RESEARCH ASIA, 2021, Vol. 18(2), p. 227-237
36. Tarbell, D.S. and A.T. Tarbell, The Discovery of Saccharin. Journal of Chemical Education, 1978;55(3): 161-2.
37. Bennett, C., et al., Biocatalytic synthesis of disaccharide high intensity sweeterner sucralose via a tetrachlororaffinose intermediate. Biotechnology and Bioengineering, 1992; 39(2): 211-217.
38. Rocha, G., et al., Sucralose sweetener in vivo effects on blood constituents radiolabeling, red blood cell morphology and radiopharmaceutical biodistribution in rats. Applied Radiation and Isotopes, 2011; 69(1):46-51.
39. Goldsmith, L., Acute and subchronic toxicity of sucralose. Food and Chemical Toxicology, 2000;38: 53-69.
40. George, V., et al., Analysis of multiple sweeteners and their degradation products in lassi by HPLC and HPTLC plates. Journal of Food Science and Technology, 2010;47(4):408-413.
41. Mukherjee, A. and J. Chakrabarti, In vivo cytogenetic studies on mice exposed to acesulfame-K—a non-nutritive sweetener. Food and Chemical Toxicology, 1997; 35(12): 1177-1179.
42. Ali, A., et al., Antiglycating potential of acesulfame potassium: an artificial sweetener. Applied Physiology, Nutrition, and Metabolism, 2017;42(10):1054-1063
43. Otabe, A., et al., Advantame–an overview of the toxicity data. Food and Chemical Toxicology, 2011;49:S2-S7.
44. Otabe, A., T. Fujieda, and T. Masuyama, A two-generation reproductive toxicity study of the high-intensity sweetener advantame in CD rats. Food and Chemical Toxicology, 2011;49:S70-S76
45. Nettleton, J. A. et al. Diet soda intake and risk of incident metabolic syndrome and type 2 diabetes in the Multi-Ethnic Study of Atherosclerosis (MESA). Diabetes Care 32, 688–694 (2009).
46. Fitch, C. & Keim, K. S. Position of the Academy of Nutrition and Dietetics: use of nutritive and nonnutritive sweeteners. Journal of the Academy of Nutrition and Dietetics 112, 739–758 (2012).
47. Tordoff, M. G. & Alleva, A. M. Effect of drinking soda sweetened with aspartame or high-fructose corn syrup on food intake and body weight. Am. J. Clin. Nutr. 51, 963–969 (1990).
48. Horwitz, D. L., McLane, M. & Kobe, P. Response to single dose of aspartame or saccharin by NIDDM patients. Diabetes Care 11, 230–234 (1988).
49. Claesson, M. J. et al. Gut microbiota composition correlates with diet and health in the elderly. Nature, 488, 178–184 (2012).
50. Muegge, B. D. et al. Diet drives convergence in gut microbiome functions across mammalian phylogeny and within humans. Science, 332, 970–974 (2011).
51. Turnbaugh, P. J. et al. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature, 444, 1027–1031 (2006).
52. Ley, R. E., Turnbaugh, P. J., Klein, S. & Gordon, J. I. Microbial ecology: human gut microbes associated with obesity. Nature, 444, 1022–1023 (2006).
53. Qin, J. et al. A metagenome-wide association study of gut microbiota in type 2 diabetes. Nature, 490, 55–60 (2012).
54. Henao-Mejia, J. et al. Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity. Nature 482, 179–185 (2012).
2. Li X et al; Sucralose promotes colitis-associated colorectal cancer risk in a murine model along with changes in microbiota. Frontiers in oncology. 2020 Jun 3; 10: 710.
3. 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 Ph J. 2020 Oct 1; 28(10):1290-300.
4. Kranthi Kumar Poshala, Artificial Sweeteners: A Review, IJESC, Oct 2020, 10(10) , 27416-2742110.
5. Rodriguez-Palacios A et al. The artificial sweetener splenda promotes gut proteobacteria, dysbiosis, and myeloperoxidase reactivity in Crohn’s disease–like ileitis. Inflammatory bowel diseases. 2018 Apr 23; 24(5):1005-20.
6. Christina R. Whitehouse, BSN, RN, Joseph Boul/ata, PharmD, RPh, BCNSp, and Linda A. McCauley, PHD, RN, FAAN, FAAOHN , The Potential Toxicity of Artificial Sweeteners, AAOHN J , Jun2008, 56 (6) , 251-159.
7. Yebra-Biurrun; MC.Artificial sweeteners: A review. Food Additives. 2005 Sep 1; 17(9):733-8.
8. Douglas l. Arnold , Toxicology of Saccharin , Fundamental and applied toxicology, 1984 , 4 , 674-685
9. G. R. Howe , J. D. Burch , A. B. Miller, B. Morrison , P. Gordon, L. Weldon, L. W. Chamber, G. Fodor , G. M. Winsor , Artificial sweeteners and human bladder cancer , The Lencet , 1977 Sep 17 ,578-581.
10. Jotham Suez et al, Artificial sweeteners induce glucose intolerance by altering the gut microbiota, Nature J, 70(1), 1-7
11. Eva S Schernhammer et al; Consumption of artificial sweetener– and sugar-containing soda and risk of lymphoma and leukemia in men and women, Am J Clin Nutr 012;96:1419–28
12. Charlotte Debras et al; Artificial sweeteners and risk of cardiovascular diseases: results from the prospective NutriNet-Santé cohort, The BMJ, 2022;378, 1-12
13. Bishamber D Toora, Seema S, Manju M, Sasmita Mishra; Effect of Artificial Sweeteners on the Blood Glucose Concentration, J O M A, 2018;1(2):81-85.
14. Manfred Kroger, Kathleen Meister, and Ruth Kava; Low-calorie Sweeteners and Other Sugar Substitutes: A Safety Issues, C R I F Sci and F S, 2006, 5, 35-47
15. Pang MD, Goossens GH, Blaak EE. The impact of artificial sweeteners on body weight control and glucose homeostasis. Front Nutr 2021; 7: 598340. doi:10.3389/fnut.2020.598340
16. Feijó FM, Ballard CR, Foletto KC, et al. Saccharin and aspartame, compared with sucrose, induce greater weight gain in adult Wistar rats, at similar total caloric intake levels. Appetite 2013; 60: 203-7. doi:10.1016/j.appet.2012.10.009
17. Kim Y, Je Y. Prospective association of sugar-sweetened and artificially sweetened beverage intake with risk of hypertension. Arch Cardiovasc Dis 2016; 109: 242-53. doi:10.1016/j.acvd.2015.10.005
18. Basson AR, Rodriguez-Palacios A, Cominelli F. Artificial sweeteners: history and new concepts on inflammation. Front Nutr 2021; 8: 746247. doi:10.3389/fnut.2021.746247
19. Risdon S, Meyer G, Marziou A, Riva C, Roustit M, Walther G. Artificial sweeteners impair endothelial vascular reactivity: preliminary results in rodents. Nutr Metab Cardiovasc Dis 2020; 30: 843-6. doi:10.1016/j.numecd.2020.01.014
20. Jang W, Jeoung NH, Cho KH. Modified apolipoprotein (apo) A-I by artificial sweetener causes severe premature cellular senescence and atherosclerosis with impairment of functional and structural properties of apoA-I in lipid-free and lipid-bound state. Mol Cells 2011; 31: 461-70. doi:10.1007/s10059-011-1009-3
21. Suez J, Korem T, Zeevi D, et al. Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Nature 2014; 514: 181-6.doi:10.1038/nature13793
22. Davidson TL, Martin AA, Clark K, Swithers SE. Intake of high-intensity sweeteners alters the ability of sweet taste to signal caloric consequences: implications for the learned control of energy and body weight regulation. Q J Exp Psychol (Hove) 2011; 64: 1430-41.doi:10.1080/17470218.2011.552729
23. Plaza-Diaz J, Pastor-Villaescusa B, Rueda-Robles A, Abadia-Molina F, Ruiz-Ojeda FJ. Plausible biological interactions of low- and noncalorie sweeteners with the intestinal microbiota: an update of recent studies. Nutrients 2020; 12: 1153. doi:10.3390/nu12041153
24. Peters JC, Beck J, Cardel M, et al. The effects of water and nonnutritive sweetened beverages on weight loss and weight maintenance: a randomized clinical trial. Obesity (Silver Spring) 2016; 24:297-304. doi:10.1002/oby.21327
25. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. (2018) 68:394–424. doi: 10.3322/caac.21492
26. Rawla P, Sunkara T, Barsouk A. Epidemiology of colorectal cancer: incidence, mortality, survival, and risk factors. Prz Gastroenterol. (2019) 14:89– 103. doi: 10.5114/pg.2018.81072 Grazioso TP, Brandt M, Djouder N. Diet, microbiota, and colorectal cancer. iScience. (2019) 21:168–87. doi: 10.1016/j.isci.2019.10.011
27. Rapozo DC, Bernardazzi C, de Souza HS. Diet and microbiota in inflammatory bowel disease: the gut in disharmony. World J Gastroenterol. (2017) 23:2124–40. doi: 10.3748/wjg.v23.i12.2124
28. Neuman MG, Nanau RM. Inflammatory bowel disease: role of diet, microbiota, life style. Transl Res. (2012) 160:29– 44. doi: 10.1016/j.trsl.2011.09.001
29. Qin X. Impaired inactivation of digestive proteases by deconjugated bilirubin: the possible mechanism for inflammatory bowel disease. Med Hypotheses. (2002) 59:159–63. doi: 10.1016/S0306-9877(02)00243-8
30. Qin X. Etiology of inflammatory bowel disease: a unified hypothesis. World J Gastroenterol. (2012) 18:1708–22. doi: 10.3748/wjg.v18.i15.1708
31. M. Elcock and R.W. Morgan , Update on artificial sweetners and bladder cancer, regulatory toxicology and pharmacology, 1993, 17 , 35-43.
32. Morgan R.W. and Jain M. G.Bladder cancer Smoking beveagers and artificial sweeteners, Can Med Assn J, 1974, 111(7), 1069-1070
33. Simon D; Yen. S. and Cole P, Coffee drinking and cancer of the lower urinary track, J Nat Cancer Inst, 1975, 54(3), 587-58-91
34. Wynder E. L. and Goldsmith R; The epdermiology of bladder cancer. A second look, Cancer Study Smith, 1977, 40, 1246-1268
35. Tejashree Anil More, Zoya Shaikh and Ahmad Ali; Artificial Sweeteners and their Health Implications: A Review, BIOSCIENCES BIOTECHNOLOGY RESEARCH ASIA, 2021, Vol. 18(2), p. 227-237
36. Tarbell, D.S. and A.T. Tarbell, The Discovery of Saccharin. Journal of Chemical Education, 1978;55(3): 161-2.
37. Bennett, C., et al., Biocatalytic synthesis of disaccharide high intensity sweeterner sucralose via a tetrachlororaffinose intermediate. Biotechnology and Bioengineering, 1992; 39(2): 211-217.
38. Rocha, G., et al., Sucralose sweetener in vivo effects on blood constituents radiolabeling, red blood cell morphology and radiopharmaceutical biodistribution in rats. Applied Radiation and Isotopes, 2011; 69(1):46-51.
39. Goldsmith, L., Acute and subchronic toxicity of sucralose. Food and Chemical Toxicology, 2000;38: 53-69.
40. George, V., et al., Analysis of multiple sweeteners and their degradation products in lassi by HPLC and HPTLC plates. Journal of Food Science and Technology, 2010;47(4):408-413.
41. Mukherjee, A. and J. Chakrabarti, In vivo cytogenetic studies on mice exposed to acesulfame-K—a non-nutritive sweetener. Food and Chemical Toxicology, 1997; 35(12): 1177-1179.
42. Ali, A., et al., Antiglycating potential of acesulfame potassium: an artificial sweetener. Applied Physiology, Nutrition, and Metabolism, 2017;42(10):1054-1063
43. Otabe, A., et al., Advantame–an overview of the toxicity data. Food and Chemical Toxicology, 2011;49:S2-S7.
44. Otabe, A., T. Fujieda, and T. Masuyama, A two-generation reproductive toxicity study of the high-intensity sweetener advantame in CD rats. Food and Chemical Toxicology, 2011;49:S70-S76
45. Nettleton, J. A. et al. Diet soda intake and risk of incident metabolic syndrome and type 2 diabetes in the Multi-Ethnic Study of Atherosclerosis (MESA). Diabetes Care 32, 688–694 (2009).
46. Fitch, C. & Keim, K. S. Position of the Academy of Nutrition and Dietetics: use of nutritive and nonnutritive sweeteners. Journal of the Academy of Nutrition and Dietetics 112, 739–758 (2012).
47. Tordoff, M. G. & Alleva, A. M. Effect of drinking soda sweetened with aspartame or high-fructose corn syrup on food intake and body weight. Am. J. Clin. Nutr. 51, 963–969 (1990).
48. Horwitz, D. L., McLane, M. & Kobe, P. Response to single dose of aspartame or saccharin by NIDDM patients. Diabetes Care 11, 230–234 (1988).
49. Claesson, M. J. et al. Gut microbiota composition correlates with diet and health in the elderly. Nature, 488, 178–184 (2012).
50. Muegge, B. D. et al. Diet drives convergence in gut microbiome functions across mammalian phylogeny and within humans. Science, 332, 970–974 (2011).
51. Turnbaugh, P. J. et al. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature, 444, 1027–1031 (2006).
52. Ley, R. E., Turnbaugh, P. J., Klein, S. & Gordon, J. I. Microbial ecology: human gut microbes associated with obesity. Nature, 444, 1022–1023 (2006).
53. Qin, J. et al. A metagenome-wide association study of gut microbiota in type 2 diabetes. Nature, 490, 55–60 (2012).
54. Henao-Mejia, J. et al. Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity. Nature 482, 179–185 (2012).
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Published
Dec 16, 2023
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How to Cite
Aditya Savaliya, Nirav Rathi, & Dr. Pragnesh Patani. (2023). REVIEW ON: BITTERNESS OF ARTIFICIAL SWEETENERS. Journal of Population Therapeutics and Clinical Pharmacology, 30(19), 1976-1984. https://doi.org/10.53555/jptcp.v30i19.4123
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Author Biographies
Aditya Savaliya
Khyati College of Pharmacy, Gujarat Technological University, Ahmedabad, Gujarat, India
Nirav Rathi
Department of Quality Assurance, Khyati College of Pharmacy, Gujarat Technological University, Ahmedabad, Gujarat, India
Dr. Pragnesh Patani
Department of Pharmacology, Khyati College of Pharmacy, Gujarat Technological University, Ahmedabad, Gujarat, India
How to Cite
Aditya Savaliya, Nirav Rathi, & Dr. Pragnesh Patani. (2023). REVIEW ON: BITTERNESS OF ARTIFICIAL SWEETENERS. Journal of Population Therapeutics and Clinical Pharmacology, 30(19), 1976-1984. https://doi.org/10.53555/jptcp.v30i19.4123