Faculty Bibliography

Some medical practices have been ingrained in custom for decades, long after "proof" that they were effective was established. It is necessary to periodically reevaluate these practices, as newer theories and research may challenge the evidence upon which they were based. An example is the decades' old practice of recommending a 4-mg (4,000-µg) supplement of folic acid to women who are at risk for recurrent neural tube defect (NTD) during pregnancy. This recommendation was based on findings from a randomized clinical trial in 1991. Since then, multiple studies have confirmed the utility of 400-800 µg of folic acid in lowering both primary and recurrent risks of NTDs, but no studies have established any further reduction in risk with doses over 1 mg. Current understanding of folic acid metabolism during pregnancy suggests that at higher doses, above ∼1 mg, there is not increased absorption. Recent evidence suggests that 4 mg folic acid supplementation may not be any more effective than lower doses for the prevention of recurrent NTDs. Thus, we recommend that it is time for clinicians to reexamine their reliance on this outdated recommendation and consider using current recommendations of 400-800 µg per day for all patients in conjunction with assessment of maternal folate status.

PURPOSE OF REVIEW/OBJECTIVE:Non-alcoholic fatty liver disease (NAFLD) is the most prominent chronic liver disease in Western countries, affecting approximately 25% of the population worldwide. Sex-specific differences in the development of NAFLD are apparent. While obesity and insulin resistance are major contributors to the increasing prevalence of NAFLD, a growing body of literature suggests that exposure to persistent endocrine-disrupting chemicals (pEDCs) may also play a role. This review summarizes recent (2011 and later) scientific literature investigating exposures to pEDCs, specifically persistent organic pollutants (POPs), and NAFLD, with a focus on sex-specific associations. RECENT FINDINGS/RESULTS:The overwhelming majority of studies were conducted in single-sex animal models and provide biological evidence that exposures to 2,3,7,8-tetrachlorodibenzo-p-dioxin polychlorinated biphenyls, and other POPs or POP mixtures are negatively associated with liver health. There were four cross-sectional epidemiological studies in humans that reported associations for several POPs, including polychlorinated biphenyls and perfluorinated chemicals, with elevated liver enzymes. Only one of these studies, using a sample of gastric bypass surgery patients, examined sex-specific associations of POPs and liver enzymes, finding adverse associations among women only. The noticeable lack of studies investigating how differences (i.e., biochemical, physiological, and behavioral) between men and women may influence associations of pEDCs and NAFLD represents a large research gap in environmental health. Sexual dimorphism in metabolic processes throughout the body, including the liver, is established but often overlooked in the designs and analyses of studies. Other factors identified in this review that may also act to modulate associations of environmental chemicals and NAFLD are reproductive status and dietary nutrient intakes, which also remain understudied in the literature. Despite knowledge of sexual dimorphism in the actions of pEDCs, as well as in metabolic processes related to NAFLD development, few experimental or epidemiological studies have investigated sex-dependent associations. Future studies, especially those in humans, should be designed to address this research need. Consideration of other factors, such as reproductive status, dietary intakes, and mixtures of chemicals with varying endocrine-disrupting capabilities, should be explored.

Phenolic compounds represent a class of environmental chemicals with potential endocrine disrupting capabilities. We investigated longitudinal associations of childhood exposures to phenols, from both man-made and natural sources, and subsequent measures of adiposity among girls enrolled in The Breast Cancer and Environment Research Program, 2004-2007. Baseline (ages 6-8 years) urinary concentrations were obtained for creatinine and phenol metabolites: enterolactone, genistein, daidzein, benzophenone-3, bisphenol A, sum of parabens (methyl, ethyl, and propyl parabens), 2,5-dichlorophenol, and triclosan. Body mass index, waist circumference, and percent body fat were measured at annual or semi-annual exams through 2015 (n = 1,017). Linear mixed effects regression estimated how baseline concentrations of phenols (tertile groups) related to changes in girls' adiposity measurements from ages 7 through 15 years. Enterolactone was inversely associated with body mass index, waist circumference, and percent body fat, while 2,5-dichlorophenol was positively associated with these measurements. A non-monotonic association was observed for triclosan and girls' adiposity; however, it was due to effect modification by baseline overweight status. Triclosan was positively associated with adiposity only among overweight girls. These results suggest that exposure to specific phenols during childhood may influence adiposity through adolescence.

BACKGROUND: Phthalates are environmental chemicals that may play a role in the development of obesity. Few studies have investigated longitudinal associations between postnatal phthalate exposures and subsequent anthropometric measurements in children. METHODS: We collected data as part of The Breast Cancer and Environment Research Program at three US sites. A total of 1,239 girls, aged 6-8 years, were enrolled in 2004-2007. We categorized baseline phthalate exposures, assessed from creatinine-corrected urinary concentrations of low-molecular weight phthalate metabolites, as low, <78; medium, 78 to <194; and high, >/=194 mug/g creatinine and of high-molecular weight phthalates as low, <111; medium, 111-278; and high, >/=278 mug/g creatinine. Anthropometric measurements were collected through 2012 (n = 1,017). Linear mixed effects regression estimated how baseline low and high-molecular weight phthalate concentrations related to changes in girls' body mass index (BMI), height, and waist circumference at ages 7-13 years. RESULTS: Low-molecular weight phthalates were positively associated with gains in BMI and waist circumference. Predicted differences in BMI and waist circumference between girls with high versus low concentrations of low-molecular weight phthalates increased from 0.56 (95% confidence interval [CI]: -0.02, 1.1) to 1.2 kg/m (95% CI: 0.28, 2.1) and from 1.5 (95% CI: -0.38, 3.3) to 3.9 cm (95% CI: 1.3, 6.5), respectively. High-molecular weight phthalates were negatively associated with height but only among girls who were normal weight at baseline (BMI