Subscribe to RSS
Non-Nutritive Sweeteners in Human Amniotic Fluid and Cord Blood: Evidence of Transplacental Fetal ExposureFunding None.
Objective This study aimed to investigate human fetal exposure to non-nutritive sweeteners (NNS) by analyzing amniotic fluid and umbilical cord blood.
Study Design Concentrations of four NNS (acesulfame-potassium [ace-K], saccharin, steviol glucuronide, and sucralose) were measured in amniotic fluid (n = 13) and cord blood samples (n = 15) using liquid chromatography-mass spectrometry. Amniotic fluid samples were obtained for research purposes at the time of term elective cesarean birth or clinically indicated third trimester amnioreduction at Mercy Hospital for Women (Melbourne, Australia). All except four women were in the fasting state. Cord blood samples were obtained from an independent cohort of newborns whose mothers were enrolled in a separate clinical trial at the National Institutes of Health.
Results Ten of 13 amniotic fluid samples contained at least one NNS (ace-K, saccharin, steviol glucuronide, and/or sucralose). Maximum amniotic fluid NNS concentrations of ace-K, saccharin, steviol glucuronide, and sucralose were 78.9, 55.9, 93.5, and 30.6 ng/mL, respectively. Ace-K and saccharin were present in 100% and 80% of the cord blood samples, with maximal concentrations of 6.5 and 2.7 ng/mL, respectively. Sucralose was not detected and steviol glucuronide was not measurable in any of the cord blood samples.
Conclusion Our results provide evidence of human transplacental transmission of NNS. Based on results predominantly obtained from rodent models, we speculate that NNS exposure may adversely influence the offsprings' metabolic health. Well-designed, prospective clinical trials are necessary to understand the impact of NNS intake during pregnancy on human development and long-term health.
NNS consumption during pregnancy has increased in recent years.
Maternal NNS intake during pregnancy is associated with preterm birth and higher infant weight gain in epidemiologic studies.
In rodents, in utero NNS exposure induces metabolic abnormalities in mothers and their offspring, alters offspring gut microbiota composition, and promotes sweet taste preference in adulthood.
It is presently unknown whether and to what degree maternal NNS ingestion in humans leads to direct in utero exposure.
This study provides the first evidence of in utero NNS exposure in humans and highlights the urgent need to investigate clinical consequences of early life NNS exposure on metabolism, weight, taste preference, and general health.
Keywordsdiet soda - pregnancy - artificial sweetener - sucralose - acesulfame-potassium - saccharin - stevia
Received: 09 December 2020
Accepted: 22 July 2021
09 September 2021 (online)
© 2021. Thieme. All rights reserved.
Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA
- 1 World Health Organization. Sugar intake for adults and children. Accessed 2015 at: https://www.who.int/publications/i/item/97892415490282015
- 2 Dietary Guidelines Advisory Committee. .. Scientific Report of the 2015 Dietary Guidelines Advisory Committee 2015. Accessed February 2015 at: https://health.gov/sites/default/files/2019-09/Scientific-Report-of-the-2015-Dietary-Guidelines-Advisory-Committee.pdf
- 3 Sylvetsky AC, Rother KI. Nonnutritive sweeteners in weight management and chronic disease: a review. Obesity (Silver Spring) 2018; 26 (04) 635-640
- 4 Archibald AJ, Dolinsky VW, Azad MB. Early-life exposure to non-nutritive sweeteners and the developmental origins of childhood obesity: global evidence from human and rodent studies. Nutrients 2018; 10 (02) E194
- 5 Sylvetsky AC, Figueroa J, Rother KI, Goran MI, Welsh JA. Trends in low-calorie sweetener consumption among pregnant women in the United States. Curr Dev Nutr 2019; 3 (04) nzz004
- 6 Halldorsson TI, Strøm M, Petersen SB, Olsen SF. Intake of artificially sweetened soft drinks and risk of preterm delivery: a prospective cohort study in 59,334 Danish pregnant women. Am J Clin Nutr 2010; 92 (03) 626-633
- 7 Azad MB, Sharma AK, de Souza RJ. et al; Canadian Healthy Infant Longitudinal Development Study Investigators. Association between artificially sweetened beverage consumption during pregnancy and infant body mass index. JAMA Pediatr 2016; 170 (07) 662-670
- 8 Plows JF, Morton-Jones J, Bridge-Comer PE. et al. Consumption of the artificial sweetener acesulfame potassium throughout pregnancy induces glucose intolerance and adipose tissue dysfunction in mice. J Nutr 2020; 150 (07) 1773-1781
- 9 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
- 10 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
- 11 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 (09) 763-770
- 12 Sylvetsky AC, Conway EM, Malhotra S, Rother KI. Development of sweet taste perception: implications for artificial sweetener use. Endocr Dev 2017; 32: 87-99
- 13 Sylvetsky AC, Bauman V, Blau JE. et al. Plasma concentrations of sucralose in children and adults. Toxicol Environ Chem 2016; 1-8
- 14 Rother KI, Sylvetsky AC, Walter PJ, Garraffo HM, Fields DA. Pharmacokinetics of sucralose and acesulfame-potassium in breast milk following ingestion of diet soda. J Pediatr Gastroenterol Nutr 2018; 66 (03) 466-470
- 15 Sylvetsky AC, Gardner AL, Bauman V. et al. Nonnutritive sweeteners in breast milk. J Toxicol Environ Health A 2015; 78 (16) 1029-1032
- 16 Sylvetsky AC, Rother KI. Trends in the consumption of low-calorie sweeteners. Physiol Behav 2016; 164 (Pt B): 446-450
- 17 Magnuson BA, Carakostas MC, Moore NH, Poulos SP, Renwick AG. Biological fate of low-calorie sweeteners. Nutr Rev 2016; 74 (11) 670-689
- 18 Schiffman SS, Rother KI. Sucralose, a synthetic organochlorine sweetener: overview of biological issues. J Toxicol Environ Health B Crit Rev 2013; 16 (07) 399-451
- 19 Christ OaR. W. Human experiments with Acetosulfam-14C. Pharmacokinetics after oral administration of 30 mg to three healthy male probands. WHO 1976 Accessed 2021 at: https://pubmed.ncbi.nlm.nih.gov/22577465/
- 20 Colburn WA, Bekersky I, Blumenthal HP. A preliminary report on the pharmacokinetics of saccharin in man: single oral dose administration. J Clin Pharmacol 1981; 21 (04) 147-151
- 21 Roberts A, Renwick AG, Sims J, Snodin DJ. Sucralose metabolism and pharmacokinetics in man. Food Chem Toxicol 2000; 38 (Suppl. 02) S31-S41
- 22 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) 1415-1429
- 23 Bian X, Chi L, Gao B, Tu P, Ru H, Lu K. Gut microbiome response to sucralose and its potential role in inducing liver inflammation in mice. Front Physiol 2017; 8: 487
- 24 Suez J, Korem T, Zeevi D. et al. Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Nature 2014; 514 (7521): 181-186
- 25 Bian X, Tu P, Chi L. et al. Saccharin induced liver inflammation in mice by altering the gut microbiota and its metabolic functions. Food Chem Toxicol. 2017; 107 (Pt B): 530-539
- 26 Bian X, Chi L, Gao B, Tu P, Ru H, Lu K. The artificial sweetener acesulfame potassium affects the gut microbiome and body weight gain in CD-1 mice. PLoS One 2017; 12 (06) e0178426
- 27 Palmnäs MS, Cowan TE, Bomhof MR. et al. Low-dose aspartame consumption differentially affects gut microbiota-host metabolic interactions in the diet-induced obese rat. PLoS One 2014; 9 (10) e109841
- 28 Suez J, Korem T, Zilberman-Schapira G, Segal E, Elinav E. Non-caloric artificial sweeteners and the microbiome: findings and challenges. Gut Microbes 2015; 6 (02) 149-155
- 29 Mennella JA, Jagnow CP, Beauchamp GK. Prenatal and postnatal flavor learning by human infants. Pediatrics 2001; 107 (06) E88
- 30 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 (03) 552-559
- 31 Reid AE, Chauhan BF, Rabbani R. et al. Early exposure to nonnutritive sweeteners and long-term metabolic health: a systematic review. Pediatrics 2016; 137 (03) e20153603
- 32 Rother KI, Sylvetsky AC, Schiffman SS. Non-nutritive sweeteners in breast milk: perspective on potential implications of recent findings. Arch Toxicol 2015; 89 (11) 2169-2171
- 33 Conway EM, Malhotra S, Sylvetsky AC. et al. Maternal and infant exposure to non-nutritive sweeteners: effects on gut and breast milk microbiome. Horm Res Paediatr 2017; 88: 1-628