Effects of the Non-Nutritive Sweeteners on Glucose Metabolism and Appetite Regulating Hormones: Systematic Review of Observational Prospective Studies and Clinical Trials

Alonso Romo-Romo, Carlos A Aguilar-Salinas, Griselda X Brito-Córdova, Rita A Gómez Díaz, David Vilchis Valentín, Paloma Almeda-Valdes, Alonso Romo-Romo, Carlos A Aguilar-Salinas, Griselda X Brito-Córdova, Rita A Gómez Díaz, David Vilchis Valentín, Paloma Almeda-Valdes

Abstract

Background: The effects of non-nutritive sweeteners (NNS) on glucose metabolism and appetite regulating hormones are not clear. There is an ongoing debate concerning NNS use and deleterious changes in metabolism.

Objectives: The aim of this review is to analyze the scientific available evidence regarding the effects of NNS on glucose metabolism and appetite regulating hormones.

Data sources and study eligibility criteria: We identified human observational studies evaluating the relation between NNS consumption and obesity, diabetes, and metabolic syndrome, in addition to clinical trials evaluating the effects of NNS in glucose metabolism and appetite regulating hormones.

Results: Fourteen observational studies evaluating the association between NNS consumption and the development of metabolic diseases and twenty-eight clinical trials studying the effects of NNS on metabolism were included. Finally, two meta-analyses evaluating the association between the consumption of NNS-containing beverages and the development of type 2 diabetes were identified.

Conclusions: Some observational studies suggest an association between NNS consumption and development of metabolic diseases; however, adiposity is a confounder frequently found in observational studies. The effects of the NNS on glucose metabolism are not clear. The results of the identified clinical trials are contradictory and are not comparable because of the major existing differences between them. Studies evaluating specific NNS, with an adequate sample size, including a homogeneous study group, identifying significant comorbidities, with an appropriate control group, with an appropriate exposure time, and considering adjustment for confounder variables such as adiposity are needed.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1. Flow diagram of the systematic…
Fig 1. Flow diagram of the systematic search.

References

    1. Barquera S, Hernandez-Barrera L, Tolentino ML, Espinosa J, Ng SW, Rivera JA, et al. Energy intake from beverages is increasing among Mexican adolescents and adults. The Journal of nutrition. 2008;138(12):2454–61. 10.3945/jn.108.092163 .
    1. Shankar P, Ahuja S, Sriram K. Non-nutritive sweeteners: review and update. Nutrition. 2013;29(11–12):1293–9. 10.1016/j.nut.2013.03.024 .
    1. Food U.S. and Drug Administration. Additional Information about High-Intensity Sweeteners Permitted for use in Food in the United States 2015 [updated 05/25/2015; cited 2016 02/01/2016]. Available: .
    1. European Food Safety Authority [Internet]. Sweetners [cited 2016 Feb 01]. Available: .
    1. Pepino MY. Metabolic effects of non-nutritive sweeteners. Physiology & behavior. 2015;152(Pt B):450–5. 10.1016/j.physbeh.2015.06.024
    1. Qurrat ul A, Khan SA. Artificial sweeteners: safe or unsafe? JPMA The Journal of the Pakistan Medical Association. 2015;65(2):225–7. .
    1. Bhupathiraju SN, Pan A, Malik VS, Manson JE, Willett WC, van Dam RM, et al. Caffeinated and caffeine-free beverages and risk of type 2 diabetes. The American journal of clinical nutrition. 2013;97(1):155–66. 10.3945/ajcn.112.048603
    1. Schulze MB, Manson JE, Ludwig DS, Colditz GA, Stampfer MJ, Willett WC, et al. Sugar-sweetened beverages, weight gain, and incidence of type 2 diabetes in young and middle-aged women. Jama. 2004;292(8):927–34. 10.1001/jama.292.8.927 .
    1. de Koning L, Malik VS, Rimm EB, Willett WC, Hu FB. Sugar-sweetened and artificially sweetened beverage consumption and risk of type 2 diabetes in men. The American journal of clinical nutrition. 2011;93(6):1321–7. 10.3945/ajcn.110.007922
    1. InterAct C, Romaguera D, Norat T, Wark PA, Vergnaud AC, Schulze MB, et al. Consumption of sweet beverages and type 2 diabetes incidence in European adults: results from EPIC-InterAct. Diabetologia. 2013;56(7):1520–30. 10.1007/s00125-013-2899-8 .
    1. Dhingra R, Sullivan L, Jacques PF, Wang TJ, Fox CS, Meigs JB, et al. Soft drink consumption and risk of developing cardiometabolic risk factors and the metabolic syndrome in middle-aged adults in the community. Circulation. 2007;116(5):480–8. 10.1161/CIRCULATIONAHA.107.689935 .
    1. Lutsey PL, Steffen LM, Stevens J. Dietary intake and the development of the metabolic syndrome: the Atherosclerosis Risk in Communities study. Circulation. 2008;117(6):754–61. 10.1161/CIRCULATIONAHA.107.716159 .
    1. Fowler SP, Williams K, Resendez RG, Hunt KJ, Hazuda HP, Stern MP. Fueling the obesity epidemic? Artificially sweetened beverage use and long-term weight gain. Obesity. 2008;16(8):1894–900. 10.1038/oby.2008.284 .
    1. Palmer JR, Boggs DA, Krishnan S, Hu FB, Singer M, Rosenberg L. Sugar-sweetened beverages and incidence of type 2 diabetes mellitus in African American women. Archives of internal medicine. 2008;168(14):1487–92. 10.1001/archinte.168.14.1487
    1. Nettleton JA, Lutsey PL, Wang Y, Lima JA, Michos ED, Jacobs DR Jr. Diet soda intake and risk of incident metabolic syndrome and type 2 diabetes in the Multi-Ethnic Study of Atherosclerosis (MESA). Diabetes care. 2009;32(4):688–94. 10.2337/dc08-1799
    1. Duffey KJ, Steffen LM, Van Horn L, Jacobs DR Jr., Popkin BM. Dietary patterns matter: diet beverages and cardiometabolic risks in the longitudinal Coronary Artery Risk Development in Young Adults (CARDIA) Study. The American journal of clinical nutrition. 2012;95(4):909–15. 10.3945/ajcn.111.026682
    1. 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. The American journal of clinical nutrition. 2013;97(3):517–23. 10.3945/ajcn.112.050997 .
    1. Sakurai M, Nakamura K, Miura K, Takamura T, Yoshita K, Nagasawa SY, et al. Sugar-sweetened beverage and diet soda consumption and the 7-year risk for type 2 diabetes mellitus in middle-aged Japanese men. European journal of nutrition. 2014;53(4):1137–8. 10.1007/s00394-014-0681-4 .
    1. O'Connor L, Imamura F, Lentjes MA, Khaw KT, Wareham NJ, Forouhi NG. Prospective associations and population impact of sweet beverage intake and type 2 diabetes, and effects of substitutions with alternative beverages. Diabetologia. 2015;58(7):1474–83. 10.1007/s00125-015-3572-1
    1. Pepino MY, Tiemann CD, Patterson BW, Wice BM, Klein S. Sucralose affects glycemic and hormonal responses to an oral glucose load. Diabetes care. 2013;36(9):2530–5. 10.2337/dc12-2221
    1. Suez J, Korem T, Zeevi D, Zilberman-Schapira G, Thaiss CA, Maza O, et al. Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Nature. 2014;514(7521):181–6. 10.1038/nature13793 .
    1. Hall WL, Millward DJ, Rogers PJ, Morgan LM. Physiological mechanisms mediating aspartame-induced satiety. Physiology & behavior. 2003;78(4–5):557–62. .
    1. 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. Nutrition research. 2011;31(12):882–8. 10.1016/j.nutres.2011.10.004 .
    1. Temizkan S, Deyneli O, Yasar M, Arpa M, Gunes M, Yazici D, et al. Sucralose enhances GLP-1 release and lowers blood glucose in the presence of carbohydrate in healthy subjects but not in patients with type 2 diabetes. European journal of clinical nutrition. 2015;69(2):162–6. 10.1038/ejcn.2014.208 .
    1. Nehrling JK, Kobe P, McLane MP, Olson RE, Kamath S, Horwitz DL. Aspartame use by persons with diabetes. Diabetes care. 1985;8(5):415–7. .
    1. Okuno G, Kawakami F, Tako H, Kashihara T, Shibamoto S, Yamazaki T, et al. Glucose tolerance, blood lipid, insulin and glucagon concentration after single or continuous administration of aspartame in diabetics. Diabetes research and clinical practice. 1986;2(1):23–7. .
    1. Horwitz DL, McLane M, Kobe P. Response to single dose of aspartame or saccharin by NIDDM patients. Diabetes care. 1988;11(3):230–4. .
    1. Cooper PL, Wahlqvist ML, Simpson RW. Sucrose versus saccharin as an added sweetener in non-insulin-dependent diabetes: short- and medium-term metabolic effects. Diabetic medicine: a journal of the British Diabetic Association. 1988;5(7):676–80. .
    1. Colagiuri S, Miller JJ, Edwards RA. Metabolic effects of adding sucrose and aspartame to the diet of subjects with noninsulin-dependent diabetes mellitus. The American journal of clinical nutrition. 1989;50(3):474–8. .
    1. Rodin J. Comparative effects of fructose, aspartame, glucose, and water preloads on calorie and macronutrient intake. The American journal of clinical nutrition. 1990;51(3):428–35. .
    1. Härtel B G H. Schneider B. Bier A.. The influence of sweetener solutions on the secretion of insulin and blood glucose level. Ernährungsunschau. 1993;40(4):152–5.
    1. Mezitis NH, Maggio CA, Koch P, Quddoos A, Allison DB, Pi-Sunyer FX. Glycemic effect of a single high oral dose of the novel sweetener sucralose in patients with diabetes. Diabetes care. 1996;19(9):1004–5. .
    1. Melanson KJ, Westerterp-Plantenga MS, Campfield LA, Saris WH. Blood glucose and meal patterns in time-blinded males, after aspartame, carbohydrate, and fat consumption, in relation to sweetness perception. The British journal of nutrition. 1999;82(6):437–46. .
    1. Grotz VL, Henry RR, McGill JB, Prince MJ, Shamoon H, Trout JR, et al. Lack of effect of sucralose on glucose homeostasis in subjects with type 2 diabetes. Journal of the American Dietetic Association. 2003;103(12):1607–12. 10.1016/j.jada.2003.09.021 .
    1. Gregersen S, Jeppesen PB, Holst JJ, Hermansen K. Antihyperglycemic effects of stevioside in type 2 diabetic subjects. Metabolism: clinical and experimental. 2004;53(1):73–6. .
    1. Barriocanal LA, Palacios M, Benitez G, Benitez S, Jimenez JT, Jimenez N, et al. 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. Regulatory toxicology and pharmacology: RTP. 2008;51(1):37–41. 10.1016/j.yrtph.2008.02.006 .
    1. Maki KC, Curry LL, Reeves MS, Toth PD, McKenney JM, Farmer MV, et al. Chronic consumption of rebaudioside A, a steviol glycoside, in men and women with type 2 diabetes mellitus. Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association. 2008;46 Suppl 7:S47–53. 10.1016/j.fct.2008.05.007 .
    1. Ma J, Bellon M, Wishart JM, Young R, Blackshaw LA, Jones KL, et al. Effect of the artificial sweetener, sucralose, on gastric emptying and incretin hormone release in healthy subjects. American journal of physiology Gastrointestinal and liver physiology. 2009;296(4):G735–9. 10.1152/ajpgi.90708.2008
    1. Anton SD, Martin CK, Han H, Coulon S, Cefalu WT, Geiselman P, et al. Effects of stevia, aspartame, and sucrose on food intake, satiety, and postprandial glucose and insulin levels. Appetite. 2010;55(1):37–43. 10.1016/j.appet.2010.03.009
    1. Ma J, Chang J, Checklin HL, Young RL, Jones KL, Horowitz M, et al. Effect of the artificial sweetener, sucralose, on small intestinal glucose absorption in healthy human subjects. The British journal of nutrition. 2010;104(6):803–6. 10.1017/S0007114510001327 .
    1. Ford HE, Peters V, Martin NM, Sleeth ML, Ghatei MA, Frost GS, et al. Effects of oral ingestion of sucralose on gut hormone response and appetite in healthy normal-weight subjects. European journal of clinical nutrition. 2011;65(4):508–13. 10.1038/ejcn.2010.291 .
    1. Steinert RE, Frey F, Topfer A, Drewe J, Beglinger C. Effects of carbohydrate sugars and artificial sweeteners on appetite and the secretion of gastrointestinal satiety peptides. The British journal of nutrition. 2011;105(9):1320–8. 10.1017/S000711451000512X .
    1. Maersk M, Belza A, Holst JJ, Fenger-Gron M, Pedersen SB, Astrup A, et al. Satiety scores and satiety hormone response after sucrose-sweetened soft drink compared with isocaloric semi-skimmed milk and with non-caloric soft drink: a controlled trial. European journal of clinical nutrition. 2012;66(4):523–9. 10.1038/ejcn.2011.223 .
    1. Wu T, Zhao BR, Bound MJ, Checklin HL, Bellon M, Little TJ, et al. Effects of different sweet preloads on incretin hormone secretion, gastric emptying, and postprandial glycemia in healthy humans. The American journal of clinical nutrition. 2012;95(1):78–83. 10.3945/ajcn.111.021543 .
    1. Brown RJ, Walter M, Rother KI. Effects of diet soda on gut hormones in youths with diabetes. Diabetes care. 2012;35(5):959–64. 10.2337/dc11-2424
    1. Olalde-Mendoza L, Moreno-Gonzalez YE. [Modification of fasting blood glucose in adults with diabetes mellitus type 2 after regular soda and diet soda intake in the State of Queretaro, Mexico]. Archivos latinoamericanos de nutricion. 2013;63(2):142–7. .
    1. Bryant CE, Wasse LK, Astbury N, Nandra G, McLaughlin JT. Non-nutritive sweeteners: no class effect on the glycaemic or appetite responses to ingested glucose. European journal of clinical nutrition. 2014;68(5):629–31. 10.1038/ejcn.2014.19
    1. Greenwood DC, Threapleton DE, Evans CE, Cleghorn CL, Nykjaer C, Woodhead C, et al. Association between sugar-sweetened and artificially sweetened soft drinks and type 2 diabetes: systematic review and dose-response meta-analysis of prospective studies. The British journal of nutrition. 2014;112(5):725–34. 10.1017/S0007114514001329 .
    1. Imamura F, O'Connor L, Ye Z, Mursu J, Hayashino Y, Bhupathiraju SN, 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 10.1136/bmj.h3576

Source: PubMed

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