Effect of Chronic Commercial Sweeteners Consumption in Lymphocytes of Peyer’s Patches

Main Article Content

Julio Andrés Guzmán-Cruz
Beatríz Elina Martínez-Carrillo
Arturo G. Rillo
José Arturo Castillo-Cardiel
Flor de María Cruz-Estrada

Abstract

Aims: To know the effect of chronic commercial sweeteners consumption in lymphocytes of Peyer’s patches.

Study Design: A prospective, longitudinal, comparative and experimental study.

Place and Duration of Study: The study was conducted in the Nutrition Research Laboratory of the Faculty of Medicine of Universidad Autónoma del Estado de México (UAEMéx) between August 2018 and May 2019 and was approved by the Bioethics Committee.

Materials and Methods: Two groups of male mice of different strains were used: 1) Balb/c and 2) CD1, both at 8 weeks-old age. The groups were divided into 4 subgroups: 1) Control (without sweetener), 2) Sucrose (table sugar, 41.66 mg/mL), and two groups of commercial sweeteners 3) Splenda® (sucralose 1.2%, with a concentration of 4.16 mg/mL), and 4) Svetia® (Steviol glycoside 0.025 g with a concentration of 4.16 mg/mL). The mice consumed the supplementation for 6 weeks. Also, were quantified plasma glucose, percentage of lymphocytes from Peyer’s patches, water and food consumption weekly.

Results: Mice increased their body weight after 6 weeks of treatment. The animals of Control and Sucrose subgroups showed a significant body weight gain of 5 g compared with the Splenda® and Svetia® subgroups, which increased only 4 g. In the subgroup treated with Splenda®, the blood glucose was reduced significantly. Svetia® and Control groups consumed more water without sweetener. The differences in food consumption were between the subgroups, not between the strains. By the end, the percentage of lymphocytes from Peyer´s patches increased in the Sucrose subgroup but decreased significantly in other subgroups.

Conclusion: The consumption of sweeteners may modify the lymphocyte population of Peyer's patches in the small intestine and this variation depends on the frequency of consumption the strain of the rodents and the type of sweetener.

Keywords:
Sweeteners, Peyer´s patches, lymphocytes, body weight, blood glucose, water consumption

Article Details

How to Cite
Guzmán-Cruz, J. A., Martínez-Carrillo, B., Rillo, A., Castillo-Cardiel, J., & Cruz-Estrada, F. de. (2019). Effect of Chronic Commercial Sweeteners Consumption in Lymphocytes of Peyer’s Patches. European Journal of Nutrition & Food Safety, 9(4), 354-364. https://doi.org/10.9734/ejnfs/2019/v9i430082
Section
Original Research Article

References

Fernstrom JD, Navia JL. Workshop summary. The Journal of Nutrition. 2012; 142(6):1170S–2S.
DOI: 10.3945/jn.111.149823

Ifland JR, Preuss HG, Marcus MT, Rourke KM, Taylor WC, Burau K, et al. Refined food addiction: A classic substance use disorder. Med Hypotheses. 2009;72(5): 518–26.
DOI: 10.1016 /j.mehy.2008.11.035

Jones JM, Elam K. Sugars and health: is there an issue? J Am Diet Assoc. 2003;103(8):1058-60.
DOI: 10.1053/JADA.2003.50563

Tran C, Tappy L. Sucrose, glucose, fructose consumption: What are the impacts on metabolic health? Rev Med Suisse. 2012;8(331)513, 515-8.

Cardello HM, Da Silva MA, Damasio MH. Measurement of the relative sweetness of stevia extract, aspartame and cyclamate/ saccharin blend as compared to sucrose at different concentrations. Plant Foods Hum Nutr. 1999;54(2):119-30.

Food and Drug Administration agency. No Calories Sweet. FDA. 2011;1.
(Accessed 20 May 2019)
Available:http://www.fda.gov/fdac/features/2006/406_sweeteners.html

Tandel KR. Sugar substitutes: Health controversy over perceived benefits. J Pharmacol Pharmacother. 2011;2(4):236-43.
DOI: 10.4103 / 0976-500X.85936

Mennella JA, Pepino MY, Reed DR. Genetic and environmental determinants of bitter perception and sweet preferences. Paediatrics. 2005;115(2):e216-22.
DOI: 10.1542 / peds.2004-1582

Margolskee RF. Molecular mechanisms of bitter and sweet taste transduction. J Biol Chem. 2002;277(1):1-4.
DOI: 10.1074 / jbc.R100054200

Bellisle F, Drewnowski A. Intense sweeteners, energy intake and the control of body weight. Eur J Clin Nutr. 2007; 61(6):691-700.
DOI: 10.1038 / sj.ejcn.1602649

Garcia-Almeida JM, Casado Fdez GM, Garcia Aleman J. A current and global review of sweeteners. Regulatory aspects. Nutr Hosp. 2013;28(Suppl 4):17–31.
DOI: 10.3305 / nh.2013.28.sup4.6793

Schiffman SS, Rother KI. Sucralose, a synthetic organochlorine sweetener: Overview of biological issues. J Toxicol Environ Health Part B. 2013;16(7):399–451.
DOI: 10.1080 / 10937404.2013.842523

Renwick AG. The intake of intense sweeteners - an update review. Food Addit Contam. 2006;23(4):327-38.
DOI: 10.1080 / 02652030500442532

Duffy, Valerie B, Sigman-Grant, Madeleine, et al. Position of the American Dietetic Association: Use of nutritive and nonnutritive sweeteners. J Am Diet Assoc. 2004;104(2):255-75.
DOI: 10.1016 / j.jada.2003.12.001

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 subjetcts. Eur J Clin Nutr. 2011; 65(4):508-13.
DOI: 10.1038/ejcn.2010.291

Baird IM, Shepard NW, Merritt RJ, Hildick-Smith G. Repeated dose study of sucralose tolerance in human subjects. Food Chem Toxicol. 2000;38(Suppl 2): S123-9.

Davis EA. Functionality of sugars: physicochemical interactions in foods. Am J Clin Nutr. 1995;62(Suppl 1):170S-7S. DOI: 10.1093 / ajcn / 62.1.170S

Chan P, Xu DY, Liu JC, Chen YJ, Tomlinson B, Huang WP, et al. The effect of stevioside on blood pressure and plasma catecholamines in spontaneously hypertensive rats. Life Sci. 1998;63(19): 1679-84.

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. Regul Toxicol Pharmacol. 2008;51(1):37-41.
DOI: 10.1016 / j.yrtph.2008.02.006

Chatsudthipong V, Muanprasat C. Stevioside and related compounds: Therapeutic benefits beyond sweetness. Pharmacol Ther. 2009;121(1):41-54.
DOI: 10.1016 / j.pharmthera.2008.09.007

Koyama E, Kitazawa K, Ohori Y, Izawa O, Kakegawa K, Fujino A, et al. In vitro metabolism of the glycosidic sweeteners, stevia mixture and enzymatically modified stevia in human intestinal microflora. Food Chem Toxicol. 2003;41(3):359-74.

Geuns JM. Stevioside. Phytochemistry. 2003;64(5):913-21.

Popkin BM, Nielsen SJ. The sweetening of the world's diet. Obes Res. 2003;11(11): 1325-32.
DOI: 10.1038 / oby.2003.179

Mehnert H. Sugar substitutes in the diabetic diet. Int Z Vitam Ernahrungsforsch Beih. 1976;15:295-324.

Ikeda T. Sugar substitutes: Reasons and indications for their use. Int Dent J. 1982;32(1):33-43.

Arnold DL. Two-generation saccharin bioassays. Environ Health Perspect. 1983;50:27-36.
DOI: 10.1289 / ehp.835027

Murphy KT, Walport M. Inmunobiología de Janeway. 7th Ed: McGRAW-HILL: Interamericana Editores; 2009.

Mackie RI, Sghir A, Gaskins HR. Developmental microbial ecology of the neonatal gastrointestinal tract. Am J Clin Nutr. 1999;69(5):1035S-45S.
DOI: 10.1093 / ajcn / 69.5.1035s

David A. Hughes LGD, Adrianne Bendich. Diet and Human Immune Function. 1st Ed: Humana Press; 2004.

Aguilera Montilla N, Pérez Blas M, López Santalla M, Martín Villa JM. Mucosal immune system: A brief review. Immunol. 2004;23:207-16.
DOI: 10.1371 / journal.pbio.1001397

Brandtzaeg P, Kiyono H, Pabst R, Russell MW. Terminology: Nomenclature of mucosa-associated lymphoid tissue. Mucosal Immunol. 2008;1(1):31-7.
DOI: 10.1038 / mi.2007.9

Forchielli ML, Walker WA. The role of gut-associated lymphoid tissues and mucosal defence. Br J Nutr. 2005;93(Suppl 1): S41-8.

Farstad IN, Halstensen TS, Lien B, Kilshaw PJ, Lazarovits AI, Brandtzaeg P. Distribution of beta 7 integrins in human intestinal mucosa and organized gut-associated lymphoid tissue. Immunology. 1996;89(2):227-37.
DOI: 10.1046/j.1365-2567.1996.d01-727.x

Lefrancois L. Development, trafficking, and function of memory T-cell subsets. Immunol Rev. 2006;211:93-103.
DOI: 10.1111 / j.0105-2896.2006.00393.x

Neutra MR, Pringault E, Kraehenbuhl JP. Antigen sampling across epithelial barriers and induction of mucosal immune responses. Annu Rev Immunol. 1996;14: 275-300.
DOI: 10.1146/annurev.immunol.14.1.275

Sanchez A, Reeser JL, Lau HS, Yahiku PY, Willard RE, McMillan PJ, et al. Role of sugars in human neutrophilic phagocytosis. Am J Clin Nutr. 1973;26(11): 1180-4.
DOI: 10.1093 / ajcn / 26.11.1180

Goldsmith LA. Acute and subchronic toxicity of sucralose. Food Chem Toxicol. 2000;38 (Suppl 2):S53-69.

Berry C, Brusick D, Cohen SM, Hardisty JF, Grotz VL, Williams GM. Sucralose non-carcinogenicity: A review of the scientific and regulatory rationale. Nutr Cancer. 2016;68(8):1247–1261.
DOI: 10.1080/01635581.2016.1224366

Mortensen A. Sweeteners permitted in the European Union: Safety aspects Scandinavian Journal of food & Nutrition. 2006;50(30):104-116.
DOI: 10.1080/17482970600982719

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(2):115-21.
DOI: 10.1016 / j.cbi.2008.01.008

Chaiwat Boonkaewwan CT, Molvibha Vongsakul. Anti-inflammatory and immunomodulatory activities of stevioside and its metabolite steviol on THP-1 cells. J Agric Food Chem. 2006;54:785-9.
DOI: 10.1021/jf0523465

Boonkaewwan C, Ao M, Toskulkao C, Rao MC. Specific immunomodulatory and secretory activities of stevioside and steviol in intestinal cells. J Agric Food Chem. 2008;56(10):3777-84.
DOI: 10.1021 / jf072681o

Rosales-Gómez CA, Martínez-Carrillo BE, Reséndiz-Albor AA, Ramírez-Durán N, Valdés-Ramos R, Mondragón-Velásquez T, et al. Chronic consumption of sweeteners and its effect on glycaemia, cytokines, hormones and lymphocytes of GALT in CD1 mice. Biomed Res Int. 2018:1345282.
DOI: 10.1155/2018/1345282.
eCollection 2018.

Stern D, Piernas C, Barquera S, Rivera JA, Popkin BM, Caloric beverages were major sources of energy among children and adults in Mexico, 1999-2012. J Nutr. 2014; 144(6):949-56.
DOI: 10.3945/jn.114.190652

Martinez-Carrillo BE, Jarillo-Luna RA, Rivera-Aguilar V, Campos-Rodríguez R, The effect of a high fat or high carbohydrate diet on the immune system of young Balb/c mice. Proc Nutr Soc, 2010;69(OCE3):E305.
DOI: doi.org/10.1017/S0029665110000947

Martínez-Carrillo BE, Jarillo-Luna RA, Campos-Rodríguez R, Valdés-Ramos R, Rivera-Aguilar V. Effect of diet and exercise on the peripheral immune system in young Balb/c mice. Biomed Res Int. 2015;458470.
DOI: 10.1155/2015/458470
Epub 2015 Nov 8.

García-Iniesta L, Martínez-Carrillo BE, Valdés-Ramos R, Jarillo-Luna RA, Escoto-Herrera JA, Reséndiz-Albor A. Relationship between prolonged sweetener consumption and chronic stress in the production of carbonylated proteins in blood lymphocytes. European Journal of Nutrition & Food Safety. 2017;7(4):220-232.
Available:https://doi.org/10.9734/EJNFS/2017/36313

Escoto-Herrera JA, Martínez-Carrillo BE, Ramírez-Durán N, Ramírez-Saad H, Valdés-Ramos R. Chronic consumption of sweeteners increases carbonylated protein production in lymphocytes from mouse lymphoid organs. European Journal of Nutrition & Food Safety. 2017;7(4):209-219.
DOI: doi.org/10.9734/EJNFS/2017/36772

Norma Oficial Mexicana. Especificaciones Técnicas para la producción, cuidado y uso de los animales de laboratorio. NOM-062-ZOO-1999, 1999. Spanish.

Nettleton JA, Lutsey PL, Wang Y, Lima JA, Michos ED, Jacobs DR. Diet soda intake and risk of incident metabolic syndrome and type 2 diabetes in the Multi-Ethnic Study of Atherosclerosis (MESA). Diabetes Care. 2009;32:688-694.

Dalle-Donne I, Aldini G, Carini M, Colombo R, Rossi R, Milzani A. Protein carbonylation, cellular dysfunction, and disease progression. J Cell Mol Med. 2006;10(2):389–406.

Thomas JEG, Michael J. Stevia: It's not just about calories. Open Obesity Journal. 2010;2:101-9.

Moreno-Martínez MGR, Sánchez-González DJ. Efecto de los edulcorantes no nutritivos (aspartame y sucralosa) en el peso de las ratas. Estudio prospectivo, controlado, aleatorizado, doble ciego. Revista de Sanidad Militar. 2011;65(4): 168-75. Spanish.

Drewnowski A, Bellisle F. Liquid calories, sugar, and body weight. Am J Clin Nutr. 2007;85(3):651-61.
DOI: 10.1093 / ajcn / 85.3.651

Dragsted LO, Daneshvar B, Vogel U, Autrup HN, Wallin H, Risom L, et al. A sucrose-rich diet induces mutations in the rat colon. Cancer Res. 2002;62(15): 4339-45.

Feinle C, O'Donovan D, Horowitz M. Carbohydrate and satiety. Nutrition Reviews. 2002;60(6):155-69.
DOI: 10.1093 / ajcn / 61.4.960S

Constantino CF, Salas G, G Tovar C, Duran-de-Bazua C, Gracia I, Macias L, et. al. Effects on body mass of laboratory rats after ingestion of drinking water with sucrose, fructose, aspartame, and sucralose additives. The Open Obesity Journal. 2010;2:116-24.
DOI: 10.2174 / 1876823701002010116

Martínez A, Madrid JA, López-Espinoza A, Vivanco P. Consumo de soluciones endulzadas en octodones (Octodón-degú). Acta Comportamentalia. 2009;17:141-53. Spanish.
Available:http://www.revistas.unam.mx/index.php/acom/article/view/18145

Margolskee RF, Dyer J, Kokrashvili Z, Salmon KS, Ilegems E, Daly K, et al. T1R3 and gustducin in gut sense sugars to regulate expression of Na+-glucose cotransporter 1. Proc Natl Acad Sci USA. 2007;104(38):15075-80.
DOI: 10.1073 / pnas.0706678104

Bello NT, Hajnal A. Male rats show an indifference-avoidance response for increasing concentrations of the artificial sweetener sucralose. Nutrition Research. 2005;25:693-9.
DOI: 10.1016/j.nutres.2005.07.003

Sclafani A, Bahrani M, Zukerman S, Ackroff K. Stevia and saccharin preferences in rats and mice. Chem Senses. 2010;35(5):433-43.
DOI: 10.1093 / chemse / bjq033

Valenstein Valenstein ES. Selection of nutritive and nonnutritive solutions under different conditions of need. J Comp Physiol Psychol. 1967;63:429–433.

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. Br J Nutr. 2010;104(6): 803-6.
DOI: 10.1017 / S0007114510001327

Ferland A, Brassard P, Poirier P. Is aspartame really safer in reducing the risk of hypoglycemia during exercise in patients with type 2 diabetes? Diabetes Care. 2007;30(7):e59.
DOI: 10.2337 / dc06-1888

Wang Z, Xue L, Guo C, Han B, Pan C, Zhao S, et al. Stevioside ameliorates high-fat diet-induced insulin resistance and adipose tissue inflammation by downregulating the NF-kappaB pathway. Biochem Biophys Res Commun. 2012; 417(4):1280-5.
DOI: 10.1016 / j.bbrc.2011.12.130

Koyama E, Sakai N, Ohori Y, Kitazawa K, Izawa O, Kakegawa K, et al. Absorption and metabolism of glycosidic sweeteners of stevia mixsture and their aglycone, stevion, in rats and humans. Food Chem Toxicol. 2003;41(6):875-83.

Garcia D, Ramos AJ, Sanchis V, Marin S. Effect of Equisetum arvense and Stevia rebaudiana extracts on growth and mycotoxin production by Aspergillus flavus and Fusarium verticillioides in maize seeds as affected by water activity. Int J Food Microbiol. 2012;153(1-2):21-7.
DOI: 10.1016 / j.ijfoodmicro.2011.10.010

Kau AL, Ahern PP, Griffin NW, Goodman AL, Gordon JI. Human nutrition, the gut microbiome and the immune system. Nature. 2011;474(7351):327-36.
DOI: 10.1038 / nature10213

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(9):511.

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. DOI: 10.1080 / 15287390802328630

Podolsky DK. The current future understanding of inflammatory bowel disease. Best Pract Res Clin Gastroenterol. 2002;16(6):933-43.

Cabarrocas J, Savidge TC, Liblau RS. Role of enteric glial cells in inflammatory bowel disease. Glia. 2003;41(1):81-93. DOI: 10.1002 / glia.10169

Qin X. Etiology of inflammatory bowel disease: A unified hypothesis. World J Gastroenterol. 2012;18(15):1708-22.
DOI: 10.3748 / wjg.v18.i15.1708