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Reviews in Endocrine and Metabolic Disorders
Published in: Reviews in Endocrine and Metabolic Disorders 2/2016

01-06-2016

Artificial sweeteners and metabolic dysregulation: Lessons learned from agriculture and the laboratory

Authors: Jane Shearer, Susan E. Swithers

Published in: Reviews in Endocrine and Metabolic Disorders | Issue 2/2016

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Abstract

Escalating rates of obesity and public health messages to reduce excessive sugar intake have fuelled the consumption of artificial sweeteners in a wide range of products from breakfast cereals to snack foods and beverages. Artificial sweeteners impart a sweet taste without the associated energy and have been widely recommended by medical professionals since they are considered safe. However, associations observed in long-term prospective studies raise the concern that regular consumption of artificial sweeteners might actually contribute to development of metabolic derangements that lead to obesity, type 2 diabetes and cardiovascular disease. Obtaining mechanistic data on artificial sweetener use in humans in relation to metabolic dysfunction is difficult due to the long time frames over which dietary factors might exert their effects on health and the large number of confounding variables that need to be considered. Thus, mechanistic data from animal models can be highly useful because they permit greater experimental control. Results from animal studies in both the agricultural sector and the laboratory indicate that artificial sweeteners may not only promote food intake and weight gain but can also induce metabolic alterations in a wide range of animal species. As a result, simple substitution of artificial sweeteners for sugars in humans may not produce the intended consequences. Instead consumption of artificial sweeteners might contribute to increases in risks for obesity or its attendant negative health outcomes. As a result, it is critical that the impacts of artificial sweeteners on health and disease continue to be more thoroughly evaluated in humans.
Literature
1.
2.
Ng M, Fleming T, Robinson M, Thomson B, Graetz N, Margono C, et al. Global, regional, and national prevalence of overweight and obesity in children and adults during 1980–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet (London). 2014;384:766–81.CrossRef
3.
Harnack L, Stang J, Story M. Soft drink consumption among US children and adolescents: nutritional consequences. J Am Diet Assoc. 1999;99:436–41.CrossRefPubMed
4.
Tremblay MS, Willms JD. Is the Canadian childhood obesity epidemic related to physical inactivity? Int J Obes Relat Metab Disord. 2003;27:1100–5.CrossRefPubMed
5.
Martinez Steele E, Baraldi LG, da Costa Louzada ML, Moubarac J-C, Mozaffarian D, Monteiro CA. Ultra-processed foods and added sugars in the US diet: evidence from a nationally representative cross-sectional study. BMJ Open. 2016;6:e009892.CrossRefPubMedPubMedCentral
6.
Moubarac J-C, Martins APB, Claro RM, Levy RB, Cannon G, Monteiro CA. Consumption of ultra-processed foods and likely impact on human health. Evidence from Canada. Public Health Nutr. 2013;16:2240–8.CrossRefPubMed
7.
Poti JM, Mendez MA, Ng SW, Popkin BM. Is the degree of food processing and convenience linked with the nutritional quality of foods purchased by US households? Am J Clin Nutr US. 2015;101:1251–62.CrossRef
8.
Singh GM, Micha R, Khatibzadeh S, Lim S, Ezzati M, Mozaffarian D. Estimated global, regional, and national disease burdens related to sugar-sweetened beverage consumption in 2010. Circulation. 2015;132:639–66. 2015/07/01 ed.CrossRefPubMedPubMedCentral
9.
United States Department of Agriculture. Dietary Guidelines for Americans, 2015–2020. 8Th Ed. 2015.
10.
International survey shows most consumers worry about extra sugar. NewHope360.com [Internet]. 2015 Apr 10.
11.
Sylvetsky AC, Welsh JA, Brown RJ, Vos MB. Low-calorie sweetener consumption is increasing in the United States. Am J Clin Nutr. 2012;96:640–6. 2012/08/03 ed.CrossRefPubMedPubMedCentral
12.
13.
Butchko HH, Stargel WW, Comer CP, Mayhew DA, Benninger C, Blackburn GL, et al. Aspartame: review of safety. Regul Toxicol Pharmacol. 2002;35:S1–93. 2002/08/16 ed.CrossRefPubMed
14.
Magnuson BA, Burdock GA, Doull J, Kroes RM, Marsh GM, Pariza MW, et al. Aspartame: a safety evaluation based on current use levels, regulations, and toxicological and epidemiological studies. Crit Rev Toxicol. 2007;37:629–727. 2007/09/11 ed.CrossRefPubMed
15.
Swithers SE. Not-so-healthy sugar substitutes? Curr. Opin. Behav. Sci. 2016;106–10.
16.
Nowlis GH, Kessen W. Human newborns differentiate differing concentrations of sucrose and glucose. Science. 1976;191:865–6.CrossRefPubMed
17.
Ganchrow JR, Steiner JE, Canetto S. Behavioral displays to gustatory stimuli in newborn rat pups. Dev Psychobiol. 1986;19:163–74.CrossRefPubMed
18.
Nelson LF, Hazel LN, Moore AA, Maddock HM, Ashton GC, Culbertson CC, et al. Baby pigs have a sweet tooth. Iowa Farm Sci. 1953;17:3–6.
19.
Hanson LE, Rutledge EA, JMR and EFF. Dry rations for pigs weaned at 3 weeks. Minn Agr Exp Sta Mimeo Minn Agr Exp Sta Mimeo. 1954;H-124.
20.
Lewis CJ, Catron DV, Combs GE, Ashton GC, Culbertson CC. Sugar in pig starters. J Anim Sci. 1955;14:1103–15.CrossRef
21.
Sterk A, Schlegel P, Mul AJ, Ubbink-Blanksma M, Bruininx EM. Effects of sweeteners on individual feed intake characteristics and performance in group-housed weanling pigs. J Anim Sci. 2008;86:2990–7.CrossRefPubMed
22.
Ponce CH, Brown MS, Silva JS, Schlegel P, Rounds W, Hallford DM. Effects of a dietary sweetener on growth performance and health of stressed beef calves and on diet digestibility and plasma and urinary metabolite concentrations of healthy calves. J Anim Sci US. 2014;92:1630–8.CrossRef
23.
Siurana A, Wall EH, Rodriguez M, Castillejos L, Ferret A, Calsamiglia S. The effect of dietary supplementation of artificial sweetener on performance of milk-fed calves. In: Shanks RD, editor. J. Anim. Sci. Vol. 92, E-Supplement 2Journal Dairy Sci. Vol. 97, E-Supplement 1. Kansas City, MO; 2014. p. 816.
24.
Soulet C. SUCRAM®, the white-gold taste enhancer from PANCOSMA. Engromix Website. 2015.
25.
Bigos A, Palkowska E, Rosolowska-Huszca D. Effect of artificial and natural sweeteners on glucose and insulin in plasma of rats. J Pre-Clin Clin Res. 2012;6:93–7.
26.
Mitsutomi K, Masaki T, Shimasaki T, Gotoh K, Chiba S, Kakuma T, et al. Effects of a nonnutritive sweetener on body adiposity and energy metabolism in mice with diet-induced obesity. Metabolism US. 2014;63:69–78.CrossRef
27.
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;71:1415–29. 2008/09/19 ed.CrossRefPubMed
28.
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;514:181–6. 2014/09/19 ed.PubMed
29.
Foletto KC, Melo Batista BA, Neves AM, de Matos Feijo F, Ballard CR, Marques Ribeiro MF, et al. Sweet taste of saccharin induces weight gain without increasing caloric intake, not related to insulin-resistance in Wistar rats. Appetite. 2015/11/12 ed. 2015.
30.
Feijo Fde M, Ballard CR, Foletto KC, Batista BA, Neves AM, Ribeiro MF, 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. 2012/10/24 ed.CrossRefPubMed
31.
Swithers SE, Davidson TL. A role for sweet taste: calorie predictive relations in energy regulation by rats. Behav Neurosci. 2008;122:161–73. 2008/02/27 ed.CrossRefPubMed
32.
Swithers SE, Sample CH, Davidson TL. Adverse effects of high-intensity sweeteners on energy intake and weight control in male and obesity-prone female rats. Behav Neurosci. 2013;127:262–74. 2013/02/13 ed.CrossRefPubMedPubMedCentral
33.
Martinez C, Gonzalez E, Garcia RS, Salas G, Constantino-Casas F, Macias L, et al. Effects on body mass of laboratory rats after ingestion of drinking water with sucrose, fructose, aspartame, and sucralose additives ~ !2009-03-31 ~ !2010-11-25 ~ !2010-08-26 ~ !. Open Obes J. [Hilversum] :; 2010. p. 116–24.
34.
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. Obes (Silver Spring). 2008;16:1894–900. 2008/06/07 ed.CrossRef
35.
Bleich SN, Wolfson JA, Vine S, Wang YC. Diet-beverage consumption and caloric intake among US adults, overall and by body weight. Am J Public Health. 2014;104:e72–8. 2014/01/18 ed.CrossRefPubMedPubMedCentral
36.
Fowler SP, Williams K, Hazuda HP. Diet soda intake is associated with long-term increases in waist circumference in a biethnic cohort of older adults: the San Antonio Longitudinal Study of Aging. J Am Geriatr Soc. 2015;63:708–15. 2015/03/18 ed.CrossRefPubMedPubMedCentral
37.
Swithers SE. Artificial sweeteners produce the counterintuitive effect of inducing metabolic derangements. Trends Endocrinol Metab. 2013;24:431–41. 2013/07/16 ed.CrossRefPubMedPubMedCentral
38.
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;58:1474–83. 2015/05/07 ed.CrossRefPubMedPubMedCentral
39.
40.
Mueller NT, Jacobs DRJ, MacLehose RF, Demerath EW, Kelly SP, Dreyfus JG, et al. Consumption of caffeinated and artificially sweetened soft drinks is associated with risk of early menarche. Am J Clin Nutr US. 2015;102:648–54.CrossRef
41.
Carwile JL, Willett WC, Spiegelman D, Hertzmark E, Rich-Edwards J, Frazier AL, et al. Sugar-sweetened beverage consumption and age at menarche in a prospective study of US girls. Hum Reprod. 2015;30:675–83.CrossRefPubMedPubMedCentral
42.
Charalampopoulos D, McLoughlin A, Elks CE, Ong KK. Age at menarche and risks of all-cause and cardiovascular death: a systematic review and meta-analysis. Am J Epidemiol US. 2014;180:29–40.CrossRef
43.
44.
Provencher V, Polivy J, Herman CP. Perceived healthiness of food. If it’s healthy, you can eat more! Appetite. England. 2009;52:340–4.
45.
Forwood SE, Ahern A, Hollands GJ, Fletcher PC, Marteau TM. Underestimating calorie content when healthy foods are present: an averaging effect or a reference-dependent anchoring effect? PLoS One US. 2013;8:e71475.CrossRef
46.
Carels RA, Harper J, Konrad K. Qualitative perceptions and caloric estimations of healthy and unhealthy foods by behavioral weight loss participants. Appetite. 2006;46:199–206.CrossRefPubMed
47.
Chernev A. The dieter’s paradox. J Consum Psychol Elsevier. 2011;21:178–83.CrossRef
48.
Macdiarmid J, Blundell J. Assessing dietary intake: who, what and why of under-reporting. Nutr Res Rev. 1998;11:231–53.CrossRefPubMed
49.
Duca FA, Bauer PV, Hamr SC, Lam TK. Glucoregulatory relevance of small intestinal nutrient sensing in physiology, bariatric surgery, and pharmacology. Cell Metab. 2015;22:367–80.CrossRefPubMed
50.
Nelson G, Hoon MA, Chandrashekar J, Zhang Y, Ryba NJ, Zuker CS. Mammalian sweet taste receptors. Cell. 2001;106:381–90.CrossRefPubMed
51.
Tellez LA, Han W, Zhang X, Ferreira TL, Perez IO, Shammah-Lagnado SJ, et al. Separate circuitries encode the hedonic and nutritional values of sugar. Nat Neurosci US. 2016;19:465–70.CrossRef
52.
Swithers SE, Laboy AF, Clark K, Cooper S, Davidson TL. Experience with the high-intensity sweetener saccharin impairs glucose homeostasis and GLP-1 release in rats. Behav Brain Res. 2012;233:1–14. 2012/05/09 ed.CrossRefPubMedPubMedCentral
53.
54.
Sato S, Hokari R, Kurihara C, Sato H, Narimatsu K, Hozumi H, et al. Dietary lipids and sweeteners regulate glucagon-like peptide-2 secretion. Am J Physiol Gastrointest Liver Physiol. 2013;304:G708–14.CrossRefPubMed
55.
Moran AW, Al-Rammahi M, Zhang C, Bravo D, Calsamiglia S, Shirazi-Beechey SP. Sweet taste receptor expression in ruminant intestine and its activation by artificial sweeteners to regulate glucose absorption. J Dairy Sci. 2014;97:4955–72.CrossRefPubMed
56.
Jang HJ, Kokrashvili Z, Theodorakis MJ, Carlson OD, Kim BJ, Zhou J, et al. Gut-expressed gustducin and taste receptors regulate secretion of glucagon-like peptide-1. Proc Natl Acad Sci U S A. 2007;104:15069–74. 2007/08/29 ed.CrossRefPubMedPubMedCentral
57.
58.
Gorboulev V, Schurmann A, Vallon V, Kipp H, Jaschke A, Klessen D, et al. Na(+)-D-glucose cotransporter SGLT1 is pivotal for intestinal glucose absorption and glucose-dependent incretin secretion. Diabetes. 2012;61:187–96.
59.
Palmnas MS, Cowan TE, Bomhof MR, Su J, Reimer RA, Vogel HJ, et al. Low-dose aspartame consumption differentially affects gut microbiota-host metabolic interactions in the diet-induced obese rat. PLoS One. 2014;9:e109841. 2014/10/15 ed.CrossRefPubMedPubMedCentral
60.
Wisen O, Johansson C. Gastrointestinal function in obesity: motility, secretion, and absorption following a liquid test meal. Metabolism. 1992;41:390–5.CrossRefPubMed
61.
Nguyen NQ, Debreceni TL, Bambrick JE, Chia B, Wishart J, Deane AM, et al. Accelerated intestinal glucose absorption in morbidly obese humans: relationship to glucose transporters, incretin hormones, and glycemia. J Clin Endocrinol Metab. 2015;100:968–76.CrossRefPubMed
62.
Pepino MY, Tiemann CD, Patterson BW, Wice BM. S. K. Sucralose affects glycemic and hormonal responses to an oral glucose load. Diabetes Care. 2013;36:2530–5.CrossRefPubMedPubMedCentral
63.
Ley RE, Backhed F, Turnbaugh P, Lozupone CA, Knight RD, Gordon JI, et al. Obesity alters gut microbial ecology. Proc Natl Acad Sci U S A. 2005;102:11070–5.CrossRefPubMedPubMedCentral
64.
Backhed F, Ding H, Wang T, Hooper LV, Koh GY, Nagy A, et al. The gut microbiota as an environmental factor that regulates fat storage. Proc Natl Acad Sci U S A. 2004;101:15718–23. 2004/10/27 ed.CrossRefPubMedPubMedCentral
65.
66.
Karlsson FH, Fak F, Nookaew I, Tremaroli V, Fagerberg B, Petranovic D, et al. Symptomatic atherosclerosis is associated with an altered gut metagenome. Nat Commun. 2012;3:1245. 2012/12/06 ed.CrossRefPubMedPubMedCentral
67.
Tremaroli V, Backhed F. Functional interactions between the gut microbiota and host metabolism. Nature. 2012;489:242–9. 2012/09/14 ed.CrossRefPubMed
68.
Daly K, Darby AC, Hall N, Nau A, Bravo D, Shirazi-Beechey SP. Dietary supplementation with lactose or artificial sweetener enhances swine gut Lactobacillus population abundance. Br J Nutr. 2014;111 Suppl:S30–5.
69.
Daly K, Darby AC, Hall N, Wilkinson MC, Pongchaikul P, Bravo D, et al. Bacterial sensing underlies artificial sweetener-induced growth of gut Lactobacillus. Env Microbiol 2015.
70.
Rettig S, Tenewitz J, Ahearn G, Coughlin C. Sucralose causes a concentration dependent metabolic inhibition of the gut flora Bacteroides, B. fragilis and B. uniformis not observed in the Firmicutes, E. faecalis and C. sordellii (1118.1). FASEB J. 2014;28:1118.1.
71.
Anderson RL, Kirkland JJ. The effect of sodium saccharin in the diet on caecal microflora. Food Cosmet Toxicol. 1980;18:353–5.CrossRefPubMed
72.
Frankenfeld CL, Sikaroodi M, Lamb E, Shoemaker S, Gillevet PM. High-intensity sweetener consumption and gut microbiome content and predicted gene function in a cross-sectional study of adults in the United States. Ann Epidemiol. 2015.
73.
Konstantinov SR, Favier CF, Zhu WY, Williams BA, Klus J, Souffrant W-B, et al. Microbial diversity studies of the porcine gastrointestinal ecosystem during weaning transition. Anim Res. 2004;53:317–24.CrossRef
74.
75.
Frankenfeld CL, Sikaroodi M, Lamb E, Shoemaker S, Gillevet PM. High-intensity sweetener consumption and gut microbiome content and predicted gene function in a cross-sectional study of adults in the United States. Ann Epidemiol. 2015;25:736–42. e4.CrossRefPubMed
76.
Lozupone CA, Stombaugh JI, Gordon JI, Jansson JK, Knight R. Diversity, stability and resilience of the human gut microbiota. Nature. 2012;489:220–30. 2012/09/14 ed.CrossRefPubMedPubMedCentral
77.
Martínez I, Stegen JC, Maldonado-Gómez MX, Eren AM, Siba PM, Greenhill AR, et al. The gut microbiota of rural papua new guineans: composition, diversity patterns, and ecological processes. Cell Rep. 2015;11:527–38.CrossRefPubMed
Metadata
Title
Artificial sweeteners and metabolic dysregulation: Lessons learned from agriculture and the laboratory
Authors
Jane Shearer
Susan E. Swithers
Publication date
01-06-2016
Publisher
Springer US
Published in
Reviews in Endocrine and Metabolic Disorders / Issue 2/2016
Print ISSN: 1389-9155
Electronic ISSN: 1573-2606
DOI
https://doi.org/10.1007/s11154-016-9372-1

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