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Epidemiology and Population Health

Associations of urinary phthalates with body mass index, waist circumference and serum lipids among females: National Health and Nutrition Examination Survey 1999–2004

International Journal of Obesity volume 39, pages 994–1000 (2015)Cite this article

Subjects

Abstract

Background/objectives:

Exposure to environmental chemicals could be one of the contributors to the increasing obesity epidemic. Very little is known about the association of phthalates, ubiquitous chemicals widely used in consumer products, with obesity and lipid metabolism. This study investigated the association of urinary phthalate metabolites and, for the first time, the ratios of the major metabolites of the most common phthalate, di-2-ethylhexyl phthalate, with body mass index (BMI), waist circumference and serum lipid levels in the US female population.

Methods:

This cross-sectional study used the data from the National Health and Nutrition Examination Survey, 1999–2004 and was restricted to women aged ⩾18 years, who were not pregnant and had no history of diabetes. Using multivariate ordered logistic regression, we examined associations of seven urinary phthalate metabolites and their metabolic ratios with the BMI, waist circumferences, total cholesterol, triglycerides and high- and low-density lipoprotein cholesterol.

Results:

BMI was positively associated with monobutyl phthalate (MBP) and mono-2-ethylhexyl phthalate (MEHP) (odds ratio (OR)=1.13; 95% confidence interval (CI), 1.03–1.23 and OR=1.12; 95% CI, 1.03–1.23, respectively). Waist circumference was positively associated with MBP (OR=1.13; 95% CI, 1.03–1.24). A higher ratio of MEHP to mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) was positively associated with both BMI (OR=1.21; 95% CI, 1.09–1.34) and waist circumference (OR=1.20; 95% CI, 1.10–1.31). There were no other significant associations.

Conclusions:

A higher metabolic ratio of MEHP to MEHHP, reflective of slower oxidative conversion of MEHP, is associated with greater BMI and waist circumference.

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References

  1. Diamanti-Kandarakis E, Bourguignon JP, Giudice LC, Hauser R, Prins GS, Soto AM et al. Endocrine-disrupting chemicals: an Endocrine Society Scientific Statement. Endocr Rev 2009; 30: 293–342.

    Article  CAS  Google Scholar 

  2. Center for Disease Control and Prevention (CDC). Fourth National Report on Human Exposure to Environmental Chemicals, CDC: Atlanta, GA, USA, 2009.

  3. Kato K, Silva MJ, Needham LL, Calafat AM . Determination of 16 phthalate metabolites in urine using automated sample preparation and on-line preconcentration/high-performance liquid chromatography/tandem mass spectrometry. Anal Chem 2005; 77: 2985–2991.

    Article  CAS  Google Scholar 

  4. Grün F, Blumberg B . Endocrine disrupters as obesogens. Mol Cell Endocrinol 2009; 304: 19–29.

    Article  Google Scholar 

  5. Holtcamp W . Obesogens: an environmental link to obesity. Environ Health Perspect 2012; 120: a62–a68.

    Article  Google Scholar 

  6. Janesick A, Blumberg B . The role of environmental obesogens in the obesity epidemic. In: Lustig RH (ed). Obesity Before Birth. Endocrine Updates, Vol. 30. Springer: USA, pp 383–399, 2011.

    Chapter  Google Scholar 

  7. Grun F, Blumberg B . Endocrine disrupters as obesogens. Mol Cell Endocrinol 2009; 304: 19–29.

    Article  Google Scholar 

  8. Bell F . Effects of phthalate esters on lipid metabolism in various tissues, cells and organelles in mammals. Environ Health Perspect 1982; 45: 41–50.

    Article  CAS  Google Scholar 

  9. Hurst CH, Waxman DJ . Activation of PPARα and PPARγ by environmental phthalate monoesters. Toxicol Sci 2003; 74: 297–308.

    Article  CAS  Google Scholar 

  10. Grün F, Blumberg B . Perturbed nuclear receptor signaling by environmental obesogens as emerging factors in the obesity crisis. Rev Endocr Metab Disord 2007; 8: 161–171.

    Article  Google Scholar 

  11. Goodman M, Lakind JS, Mattison DR . Do phthalates act as obesogens in humans? A systematic review of the epidemiological literature. Crit Rev Toxicol 2014; 44: 151–175.

    Article  CAS  Google Scholar 

  12. Koch HM, Preuss R, Angerer J . Di(2-ethylhexyl)phthalate (DEHP): human metabolism and internal exposure—an update and latest results. Int J Androl 2006; 29: 155–165; discussion 81–85.

    Article  CAS  Google Scholar 

  13. Silva MJ, Samandar E, Preau Jr JL, Needham LL, Calafat AM . Urinary oxidative metabolites of di(2-ethylhexyl) phthalate in humans. Toxicology 2006; 219: 22–32.

    Article  CAS  Google Scholar 

  14. Frederiksen H, Skakkebaek NE, Andersson A-M . Metabolism of phthalates in humans. Mol Nutr Food Res 2007; 51: 899–911.

    Article  CAS  Google Scholar 

  15. Centers for Disease Control and Prevention (CDC), 2011b. National Health and Nutrition Examination Survey. Available at: http://www.cdc.gov/nchs/nhanes.htm (last accessed 22 May 2014).

  16. NHLBI National Heart, Lung, and Blood Institute and North American Association for the Study of Obesity. Practical Guide on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults, NIH publication No. 00-4084. 2000. National Institutes of Health: Bethesda, MD, USA, 2000.

  17. Misra A, Wasir JS, Vikram NK . Waist circumference criteria for the diagnosis of abdominal obesity are not applicable uniformly to all populations and ethnic groups. Nutrition 2005; 21: 969–976.

    Article  Google Scholar 

  18. Centers for Disease Control and Prevention (CDC) National Center for Health Statistics (NCHS). National Health and Nutrition Examination Survey. Department of Health and Human Services, Centers for Disease Control and Prevention: Hyattsville, MD: USA. Reprint available at: http://www.cdc.gov/nchs/nhanes.htm, (last accessed 30 June 2014).

  19. Centers for Disease Control and Prevention (CDC). National Center for Health Statistics. The National Health and Nutrition Examination Survey: 2003–2004. Laboratory Procedures Manual. Available at: http://www.cdc.gov/nchs/data/nhanes/nhanes_03_04/lab.pdf (last accessed 12 December 2014).

  20. Centers for Disease Control and Prevention (CDC). National Center for Health Statistics. The National Health and Nutrition Examination Survey: 1999–2000. Laboratory Procedures Manual. Available at: http://www.cdc.gov/nchs/data/nhanes/nhanes_03_04/lab.pdf (last accessed 12 December 2014).

  21. Centers for Disease Control and Prevention (CDC). National Center for Health Statistics. The National Health and Nutrition Examination Survey: 2001–2002. Laboratory Procedures Manual. Available at: http://www.cdc.gov/nchs/data/nhanes/nhanes_01_02/specimen_collection_year_3.pdf (last accessed 12 December 2014).

  22. Silva MJ, Malek NA, Hodge CC, Reidy JA, Kato K, Barr DB et al. Improved quantitative detection of 11 urinary phthalate metabolites in humans using liquid chromatography-atmospheric pressure chemical ionization tandem mass spectrometry. J Chromatogr B 2003; 789: 393–404.

    Article  CAS  Google Scholar 

  23. Blount BC, Milgram KE, Silva MJ, Malek NA, Reidy JA, Needham LL et al. Quantitative detection of eight phthalate metabolites in human urine using HPLC-APCI-MS/MS. Anal Chem 2000; 72: 4127–4134.

    Article  CAS  Google Scholar 

  24. Silva MJ, Slakman AR, Reidy JA, Preau Jr JL, Herbert AR, Samandar E et al. Analysis of human urine for fifteen phthalate metabolites using automated solid-phase extraction. J Chromatogr B 2004; 805: 161–167.

    Article  CAS  Google Scholar 

  25. Buckley JP, Palmieri RT, Matuszewski JM, Herring AH, Baird DD, Hartmann KE et al. Consumer product exposures associated with urinary phthalate levels in pregnant women. J Expo Sci Environ Epidemiol 2012; 22: 468–475.

    Article  CAS  Google Scholar 

  26. Hornung RW, Reed LD . Estimation of average concentration in the presence of nondetectable values. Appl Occup Environ Hyg 1990; 5: 46–51.

    Article  CAS  Google Scholar 

  27. Yaghjyan L, Colditz GA, Rosner B, Tamimi RM . Mammographic breast density and subsequent risk of breast cancer in postmenopausal women according to the time since the mammogram. Cancer Epidemiol Biomarkers Prev 2013; 22: 1110–1117.

    Article  Google Scholar 

  28. Barr DB, Silva MJ, Kato K, Reidy JA, Malek NA, Hurtz D et al. Assessing human exposure to phthalates using monoesters and their oxidized metabolites as biomarkers. Environ Health Perspect 2003; 111: 1148–1151.

    Article  Google Scholar 

  29. Koch HM, Rossbach B, Drexler H, Angerer J . Internal exposure of the general population to DEHP and other phthalates—determination of secondary and primary phthalate monoester metabolites in urine. Environ Res 2003; 93: 177–185.

    Article  CAS  Google Scholar 

  30. de Koning L, Merchant AT, Pogue J, Anand SS . Waist circumference and waist-to-hip ratio as predictors of cardiovascular events: meta-regression analysis of prospective studies. Eur Heart J 2007; 28: 850–856.

    Article  Google Scholar 

  31. Choi K, Joo H, Campbell Jr JL, Andersen ME, Clewell Iii HJ . In vitro intestinal and hepatic metabolism of di(2-ethylhexyl) phthalate (DEHP) in human and rat. Toxicol In Vitro 2013; 27: 1451–1457.

    Article  CAS  Google Scholar 

  32. Walker C . Organic Pollutants: An Ecotoxicological Perspective. Taylor & Francis, 2002.

    Google Scholar 

  33. Shaikh MG, Grundy RG, Kirk JM . Reductions in basal metabolic rate and physical activity contribute to hypothalamic obesity. J Clin Endocrinol Metab 2008; 93: 2588–2593.

    Article  CAS  Google Scholar 

  34. Zhang K, Sun M, Werner P, Kovera AJ, Albu J, Pi-Sunyer FX et al. Sleeping metabolic rate in relation to body mass index and body composition. Int J Obes Relat Metab Disord 2002; 26: 376–383.

    Article  CAS  Google Scholar 

  35. Kotlyar M, Carson SW . Effects of obesity on the cytochrome P450 enzyme system. Int J Clin Pharmacol Ther 1999; 37: 8–19.

    CAS  PubMed  Google Scholar 

  36. James-Todd T, Stahlhut R, Meeker JD, Powell SG, Hauser R, Huang T et al. Urinary phthalate metabolite concentrations and diabetes among women in the National Health and Nutrition Examination Survey (NHANES) 2001–2008. Environ Health Perspect 2012; 120: 1307–1313.

    Article  Google Scholar 

  37. Huang P-C, Kuo P-L, Guo Y-L, Liao P-C, Lee C-C . Associations between urinary phthalate monoesters and thyroid hormones in pregnant women. Hum Reprod 2007; 22: 2715–2722.

    Article  CAS  Google Scholar 

  38. Hatch EE, Nelson JW, Qureshi MM, Weinberg J, Moore LL, Singer M et al. Association of urinary phthalate metabolite concentrations with body mass index and waist circumference: a cross-sectional study of NHANES data, 1999–2002. Environ Health 2008; 7: 27.

    Article  Google Scholar 

  39. Duty SM, Ackerman RM, Calafat AM, Hauser R . Personal care product use predicts urinary concentrations of some phthalate monoesters. Environ Health Perspect 2005; 113: 1530–1535.

    Article  CAS  Google Scholar 

  40. Hauser R, Meeker JD, Park S, Silva MJ, Calafat AM . Temporal variability of urinary phthalate metabolite levels in men of reproductive age. Environ Health Perspect 2004; 112: 1734–1740.

    Article  CAS  Google Scholar 

  41. Hoppin JA, Brock JW, Davis BJ, Baird DD . Reproducibility of urinary phthalate metabolites in first morning urine samples. Environ Health Perspect 2002; 110: 515–518.

    Article  CAS  Google Scholar 

  42. Kotlyar M, Carson S . Effects of obesity on the cytochrome P450 enzyme system. Int J Clin Pharmacol Ther 1999; 37: 8–19.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by the National Cancer Institute at the National Institutes of Health (U54 CA 155496), the Agency for Healthcare Research and Quality (K01 HS022330) and Foundation for Barnes-Jewish Hospital.

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Author notes

  1. L Yaghjyan and S-H Chang: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Epidemiology, College of Public Health and Health Professions and College of Medicine, University of Florida, Gainesville, FL, USA

    L Yaghjyan & S Sites

  2. Division of Biostatistics, Washington University in St Louis School of Medicine, St Louis, MO, USA

    Y Ruan

  3. Division of Public Health Sciences, Department of Surgery, Washington University in St Louis School of Medicine, St Louis, MO, USA

    S-H Chang

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  1. L Yaghjyan
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Correspondence to L Yaghjyan.

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Yaghjyan, L., Sites, S., Ruan, Y. et al. Associations of urinary phthalates with body mass index, waist circumference and serum lipids among females: National Health and Nutrition Examination Survey 1999–2004. Int J Obes 39, 994–1000 (2015). https://doi.org/10.1038/ijo.2015.8

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