Consumption of Nonnutritive Sweeteners during Pregnancy
1,3Department of Obstetrics and Gynaecology, SN Medical College, Agra, Uttar Pradesh, India
2Department of Obstetrics and Gynaecology, Rainbow IVF, Agra, Uttar Pradesh, India
4Departmet of Obstetrics and Gynaecology, SUM Hospital, Siksha 'O' Anusandhan (deemed to be University), Bhubaneswar, Odisha, India
Corresponding Author: Ruchika Garg, Department of Obstetrics and Gynaecology, SN Medical College, Agra, Uttar Pradesh, India, Phone: +91 9720004485, e-mail: email@example.com
How to cite this article Garg R, Malhotra J, Kapoor A, et al. Consumption of Nonnutritive Sweeteners during Pregnancy. J South Asian Feder Obst Gynae 2020;12(4):199–202.
Source of support: Nil
Conflict of interest: None
Studies have indicated that practically all pregnant ladies in the world have certain degree of synthetic compounds in their body, for example, phthalates, bisphenol A, flame retardant, tobacco, pesticides, lead, polychlorinated-biphenyl, and mercury.1,2 These synthetic compounds have been related to preterm birth, innate peculiarities, and neuroformative issues. During early fetal advancement, even gentle introduction to such poisonous synthetic concoctions can have enduring negative impacts prompting development of infection from youth to adulthood.1,3
NONNUTRITIVE SWEETENERS AND NONNUTRITIVE SUGARS REGULATION AND LABELING
Nonnutritive sugars (NNS) are zero or low-calorie options in contrast to nutritive sugars. They are generally utilized in nourishments and drinks.6 Right now, there are no rules for NNS utilization in pregnancy, despite collecting proof of unfriendly impacts, after their utilization, in creature models. The American Heart Association suggest restricting included sugar by supplanting it with without sugar choices containing NNS. NNS endorsed for utilization in the United States are Sucralose, Acesulfame-K, Aspartame, Saccharin, and Stevioside.4 Accordingly, NNS use has been accounted for to have expanded from 8.7% to 25.1% in kids and from 26.9% to 41.4% of grown-ups from 1999 to 2000 to 2009 to 2012, with higher utilization in females than males.7 The FDA has approved six NNS and has given ADI (Acceptable Daily Intake) values for each.8
The two difficulties that purchasers are looking after the endorsement by FDA are that initially, NNS amount is not uncovered per serving on huge numbers of the foods and refreshments, and furthermore, NNS is additionally being found in clueless items, for example, ‘no-sugar included’ or ‘decreased sugar’ items, making it hard for buyers to maintain a strategic distance from NNS.
Sugar items with NNS answers to bring down rewards in the sensory system contrasted with sweet nourishments or drinks.9 NNS binds to sweet taste receptors that are found on the tongue as well as in the lungs, digestion tracts, fat tissues, bones, and testicles.10,11
CONSEQUENCES OF NONNUTRITIVE SUGARS CONSUMPTION IN ANIMALS AND HUMANS
Nonnutritive sugars once bound to sweet receptor can trigger insulin increase in people.12–14 It modifies the release of incretin; in this way, when NNS is co-ingested alongside glucose, it builds the measure of glucose retained.15–18 NNS likewise upregulates adipogenesis promoting pathways.19,20 They decline the degree of useful microbes in the body. Saccharin, Aspartame, and Sucralose have bacteriostatic impact on oral microorganisms.21 Saccharin and Acesulfame-K invigorate adipogenesis through AKT (protein kinase B) flagging.19
CONSEQUENCES OF NONNUTRITIVE SUGARS CONSUMPTION IN ANIMALS AND HUMANS
Nonnutritive Sugars Absorption, Distribution, and Excretion during Pregnancy and Lactation
Nonnutritive sugars is adsorbed from the small digestive tract into the circulatory system and is moved to the baby through the placenta and into a newborn child through breastmilk. Some NNS are completely metabolized through others are discharged unmetabolized in the urine, feces, and blood. Sucralose is consumed into the circulatory system and is found in the urine for around 5 days after the day of ingestion. Acesulfame-K is not processed or put away and however discharged out of the system as urine.25 Saccharin is not processed in the system.26 While its greater part is retained, rest of it is disposed of urine, feces, and so forth. Aspartame goes through full assimilation in the GIT giving secondary metabolites, which are invested in the circulatory system.27 Individuals with phenylketonuria, an uncommon inherited disorder, experience issues in utilizing aspartame breakdown item phenylalanine and ought to hence avoid aspartame.28 Steviosides are processed by gut microscopic organisms.29,30
In utero Exposure and Breastmilk
Studies have shown that sucralose can be found in the urine of the newborns proposing in utero transmission through cord blood.31 Acesulfame-K was found in amniotic liquids and urine of fetus in any event when high focuses were found in the placenta proposing NNS filtering.31,32 Saccharin was found in amniotic fluid and fetal bladder just as maternal blood in same amounts.33 Aspartame was not found to go through placenta, since it is completely processed in the GIT.28 Sucralose, Acesulfame-K, and Saccharin can be transferred through breastmilk.34,35 Aspartame is anyway not found in the breastmilk.34
SAFETY OF PERINATAL NONNUTRITIVE SUGARS EXPOSURE
Well-being of NNS utilization during pregnancy and youth has been an issue on which various foundations either have clashing surveys or have not remarked by any means. Notwithstanding, two surveys introducing opposing perspective focuses on the long-term metabolic impacts during gestation and childhood have been found. The main survey from 2016 included examinations from early life exposure however did exclude in utero or breastmilk NNS presentation in light of the fact that no human investigations on this subject were accessible.36 The subsequent study done in 2018 included two investigations of ladies devouring artificially sweetened drinks during pregnancy and lactation, which found that introduction of ASB was related to a higher danger of corpulence in contrast to no ASB exposure.37
Maternal Effects of Nonnutritive Sugars Exposure
There is deficient information on NNS utilization during pregnancy. No examination till date has researched maternal glucose and insulin levels or glucose resilience during pregnancy. A couple of observational investigations in grown-up human populace recommend a relationship between NNS utilization and improvement in metabolic issues;36,38–41 however, no firm end has been drawn with respect to impact of NNS utilization on mother during pregnancy.
OFFSPRING EFFECTS ASSOCIATED WITH IN UTERO NONNUTRITIVE SUGARS EXPOSURE
Birth Weight and Weight Gain
Based on discoveries in rat models, litter size was not influenced in utero in NNS introduction.42 Anyway, constant NNS introduction during lactation period showed a noteworthy decrease in body weight at weaning yet not during childbirth.31,37,42–44 Child’s body weight at adulthood was likewise diminished when exposed to NNS during pregnancy and lactation.37,45–48 A couple of studies uncovered weight gain from birth to adulthood, following in utero NNS exposure.49–53 Prebirth Acesulfame-K introduction have been related to modification of child’s sweet taste47,54 inclination at high fixation yet not at ADI level.46
Liver detoxification was discovered to be less proficient in offspring of women who consumed NNS.
There was a noteworthy increment in firmicutes, a significant gut microbial phylum, and a critical decline in Akkermansia muciniphila in rat offspring(s).31 Increment in Firmicutes has been connected to weight in both mice and human.55 A Muciniphila level is contrarily co-identified with weight gain.56,57
Evidence From Human Studies
Observational studies with respect to NNS introduction are however getting predominant, and information in regard to the equivalent is as yet perplexing and uncommon. The elements that have been featured to demonstrate the abovementioned explanation are many. A portion of the components depend on human cohorts including heterogeneity of tests and tests of self-announced NNS utilization. Studies done on Danish pregnant women watched a little increment in the danger of delivery and asthma in children after utilization of NNS-containing refreshments during pregnancy.58,59 Another research done in Canada uncovered that maternal utilization of ASBs during pregnancy were related to BMI at 1-year-olds.60 Nonetheless, a comparable report held in the United States expressed that there was no noteworthy connection between the prebirth NNS introduction and the BMI of the infant.61
Developing proof from animal studies cautions the utilization of NNS and uncovers certain impacts that weaken digestion in children. Albeit each NNS is extraordinary and can cause distinctive metabolic impacts, and scientists concede to informing the utilization regarding NNS, particularly in individuals with conditions, for example, diabetes mellitus patients, kids, and pregnant ladies. All clinical studies and research that analyze exposure to NNS during pregnancy and its long-term health impacts on mothers and babies are required to inform health associations, dietary rules, and health professionals.
1. Vafeiadi M, Roumeliotaki T, Myridakis A, et al. Association of early life exposure to bisphenol A with obesity and cardiometabolic traits in childhood. Environ Res 2016;146:379–387. DOI: 10.1016/j.envres.2016.01.017.
4. Gardner C, Wylie-Rosett J, Gidding SS, et al. Nonnutritive sweeteners: current use and health perspectives: a scientific statement from the american heart association and the american diabetes association. Diabetes Care 2012;35(8):1798–1808. DOI: 10.2337/dc12-9002.
6. Shearer J, Swithers SE. Artificial sweeteners and metabolic dysregulation: lessons learned from agriculture and the laboratory. Rev Endocr Metab Disord 2016;17(2):179–186. DOI: 10.1007/s11154-016-9372-1.
7. Sylvetsky AC, Jin Y, Clark EJ, et al. Consumption of low-calorie sweeteners among children and adults in the United States. J Acad Nutr Diet 2017;117(3):441–448.e2. DOI: 10.1016/j.jand.2016.11.004.
8. Food and Drug Administration. Additional information about high-intensity sweeteners permitted for use in food in the United States. Available at: http://www.fda.gov/food/food-additives-petitions/additional-information-about-high-intensity-sweeteners-permitted-use-food-united-states .Accessed August 9, 2019.
12. Lertrit A, Srimachai S, Saetung S, et al. Effects of sucralose on insulin and glucagon-like peptide-1 secretion in healthy subjects: a randomized, double-blind, placebo-controlled trial. Nutrition 2018;55-56:125–130. DOI: 10.1016/j.nut.2018.04.001.
13. Romo-Romo A, Aguilar-Salinas CA, Brito-Córdova GX, et al. Sucralose decreases insulin sensitivity in healthy subjects: a randomized controlled trial. Am J Clin Nutr 2018;108(3):485–491. DOI: 10.1093/ajcn/nqy152.
15. Pepino MY. Metabolic effects of non-nutritive sweeteners. Physiol Behav 2015;152:450–455. DOI: 10.1016/j.physbeh.2015.06.024##MargolskeeRF, Dyer J, Kokrashvili Z, et al. T1R3 and gustducin in gut sense sugars to regulate expression of na+-glucose cotransporter 1. Proc Natl Acad Sci USA 2007;104:15075–15080.
16. Jang HJ, Kokrashvili Z, Theodorakis MJ, et al. Gut-expressed gustducin and taste receptors regulate secretion of glucagon-like peptide-1. ProcNatl Acad Sci USA 2007;104(38):15069–15074. DOI: 10.1073/pnas.0706890104.
18. Temizkan S, Deyneli O, Yasar M, 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. Eur J Clin Nutr 2015;69(2):162–166. DOI: 10.1038/ejcn.2014.208.
19. Simon BR, Parlee SD, Learman BS, et al. Artificial sweeteners stimulate adipogenesis and suppress lipolysis independently of sweet taste receptors. J Biol Chem 2013;288(45):32475–32489. DOI: 10.1074/jbc.M113.514034.
21. Prashant GM, Patil RB, Nagaraj T, et al. The antimicrobial activity of the three commercially available intense sweeteners against common periodontal pathogens: an in vitro study. J Contemp Dent Pract 2012;13(6):749–752. DOI: 10.5005/jp-journals-10024-1222.
22. Rodearmel SJ, Wyatt HR, Stroebele N, et al. Small changes in dietary sugar and physical activity as an approach to preventing excessive weight gain: the America on the move family study. Pediatrics 2007;120(4):e869–e879. DOI: 10.1542/peds.2006-2927.
28. Regier DS, Greene, ed. GeneReviews® [Internet]. Seattle, WA: University of Washington; 1993-2020.
29. Koyama E, Kitazawa K, Ohori Y, 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):359–374. DOI: 10.1016/S0278-6915(02)00235-1.
31. Olivier-Van Stichelen S, Rother KI, Hanover JA. Maternal exposure to non-nutritive sweeteners impacts progeny’s metabolism and microbiome. Front Microbiol 2019;10:1360. DOI: 10.3389/fmicb.2019.01360.
32. World Health Organization, Evaluation of certain food additives and contaminants: thirty-seventh report of the Joint FAO/WHO Expert Committee on Food Additives [meeting held in Geneva from 5 to 14 June 1990]. Available at: https://apps.who.int/iris/handle/10665/40288 .Accessed January 6, 2020.
35. Rother KI, Sylvetsky AC, Walter PJ, et al. Pharmacokinetics of sucralose and acesulfame-potassium in breast milk following ingestion of diet soda. J Pediatr Gastroenterol Nutr 2018;66(3):466–470. DOI: 10.1097/MPG.0000000000001817.
36. Gardener H, Rundek T, Markert M, et al. Diet soft drink consumption is associated with an increased risk of vascular events in the northern manhattan study. J Gen Intern Med 2012;27(9):1120–1126. DOI: 10.1007/s11606-011-1968-2.
37. Parlee SD, Simon BR, Scheller EL, et al. Administration of saccharin to neonatal mice influences body composition of adult males and reduces body weight of females. Endocrinology 2014;155(4):1313–1326. DOI: 10.1210/en.2013-1995.
38. 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):754–761. DOI: 10.1161/CIRCULATIONAHA.107.716159.
39. Romo-Romo A, Aguilar-Salinas CA, Brito-Córdova GX, et al. Effects of the non-nutritive sweeteners on glucose metabolism and appetite regulating hormones: systematic review of observational prospective studies and clinical trials. PLoS ONE 2016;11(8):e0161264. DOI: 10.1371/journal.pone.0161264.
40. Dhingra R, Sullivan L, Jacques PF, 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):480–488. DOI: 10.1161/CIRCULATIONAHA.107.689935.
41. de Koning L, Malik VS, Rimm EB, et al. Sugar-sweetened and artificially sweetened beverage consumption and risk of type 2 diabetes in men. Am J Clin Nutr 2011;93(6):1321–1327. DOI: 10.3945/ajcn.110.007922.
42. Morahan HL, Leenaars CHC, Boakes RA, et al. Metabolic and behavioural effects of prenatal exposure to non-nutritive sweeteners: a systematic review and meta-analysis of rodent models. Physiol Behav 2020;213:112696. DOI: 10.1016/j.physbeh.2019.112696.
43. Cohen SM, Cano M, St John MK, et al. Effect of sodium saccharin on the neonatal rat bladder. Scanning Microsc 1995;9:137–147.discussion 148.
45. Garland EM, Shapiro R, Kraft PL, et al. Effects of in utero and postnatal sodium saccharin exposure on the nutritional status of the young rat. II. Dose response and reversibility. Food Chem Toxicol 1991;29(10):669–679. DOI: 10.1016/0278-6915(91)90124-P.
46. Choo E, Dando R. No detriment in taste response or expression in offspring of mice fed representative levels of sucrose or non-caloric sucralose while pregnant. Physiol Behav 2018;184:39–45. DOI: 10.1016/j.physbeh.2017.11.001.
47. Li WL, Chen ML, Liu SS, et al. Sweet preference modified by early experience in mice and the related molecular modulations on the peripheral pathway. J Mol Neurosci 2013;51:225–236.
48. Brunner RL, Vorhees CV, Kinney L, et al. Aspartame: assessment of developmental psychotoxicity of a new artificial sweetener. Neurobehav Toxicol 1979;1:79–86.
50. Taylor JM, Weinberger MA, Friedman L. Chronic toxicity and carcinogenicity to the urinary bladder of sodium saccharin in the in uteroexposed rat. Toxicol Appl Pharmacol 1980;54:57–75.
51. von Poser Toigo E, Huffell AP, Mota CS, et al. Metabolic and feeding behavior alterations provoked by prenatal exposure to aspartame. Appetite 2015;87:168–174.
52. Collison KS, Makhoul NJ, Zaidi MZ, et al. Interactive effects of neonatal exposure to monosodium glutamate and aspartame on glucose homeostasis. Nutr Metab (Lond) 2012;9:58.
53. Collison KS, Makhoul NJ, Zaidi MZ, et al. Gender dimorphism in aspartame-induced impairment of spatial cognition and insulin sensitivity. PLoS ONE 2012;7:e31570.
54. Zhang GH, Chen ML, Liu SS, et al. Effects of mother’s dietary exposure to acesulfame-K in pregnancy or lactation on the adult offspring’s sweet preference. Chem Senses 2011;36:763–770.
55. Ley RE, Bäckhed F, Turnbaugh P, et al. Obesity alters gut microbial ecology. Proc Natl Acad Sci USA 2005;102:11070–11075.
56. Schneeberger M, Everard A, Gómez-Valadés AG, et al. Akkermansia muciniphila inversely correlates with the onset of inflammation, altered adipose tissue metabolism and metabolic disorders during obesity in mice. Sci Rep 2015;5:16643.
57. Everard A, Belzer C, Geurts L, et al. Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity. Proc Natl Acad Sci USA 2013;110:9066–9071.
58. Maslova E, Strøm M, Olsen SF, et al. Consumption of artificially sweetened soft drinks in pregnancy and risk of child asthma and allergic rhinitis. PLoS ONE 2013;8(2):e57261. DOI: 10.1371/journal.pone.0057261.
59. Englund-Ögge L, Brantsæter AL, Haugen M, et al. Association between intake of artificially sweetened and sugar-sweetened beverages and preterm delivery: a large prospective cohort study. Am J Clin Nutr 2012;96(3):552–559. DOI: 10.3945/ajcn.111.031567.
60. Azad MB, Sharma AK, de Souza RJ, et al. Association between artificially sweetened beverage consumption during pregnancy and infant body mass index. JAMA Pediatr 2016;170(7):662–670. DOI: 10.1001/jamapediatrics.2016.0301.
© The Author(s). 2020 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted use, distribution, and non-commercial reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.