Exposure to phenols, chlorophenol pesticides, phthalate and PAHs and mortality risk: A prospective study based on 6 rounds of NHANES.

OBJECTIVES: Human exposure to various endocrine disrupting chemicals (EDCs) is widespread and long-lasting. The primary objective of this study was to prospectively evaluate the association of combined exposure of phenols, chlorophenol pesticides, phthalate and polycyclic aromatic hydrocarbons (PAHs) and mortality risk in a representative US population. METHODS: The data on urinary levels of phenols, chlorophenol pesticides, phthalates, and PAH metabolites, were collected from participants aged ≥20 years in six rounds of the National Health and Nutrition Examination Survey (NHANES) (2003-2014). NHANES-linked death records up to December 31, 2015 were used to ascertain mortality status and cause of death. Cox proportional hazards and competing risk models were mainly used for chemical and mortality risk association analysis. The weighted quantile sum (WQS) regression and the least absolute shrinkage and selection operator regression were employed to estimate the association between EDC co-exposure and mortality risk. RESULTS: High levels of mono-n-butyl phthalate, monobenzyl phthalate, and 1-napthol were significantly associated with increased risk of all cause, cardiovascular disease (CVD) and cancer mortality among all participants. WQS index was associated with the risks of all-cause (hazard ratio [HR] = 1.389, 95%CI: 1.155-1.669) and CVD mortality (HR = 1.925, 95%CI: 1.152-3.216). High co-exposure scores were associated with elevated all-cause (HR = 2.842, 95% CI: 1.2.094-3.858), CVD (HR = 1.855, 95% CI: 1.525-2.255), and cancer mortality risks (HR = 2.961, 95% CI: 1.468-5.972). The results of subgroup analysis, competing risk model, and sensitivity analysis were generally consistent with the findings from the main analyses, indicating the robustness of our findings. CONCLUSIONS: This study provided the first epidemiological evidence that co-exposure to EDC at fairly low levels contributed to elevated mortality risk among US adults. The underlying mechanisms for the effects of EDC co-exposure on human health are worthy of future exploration.

Composite dietary antioxidant intake and osteoporosis likelihood in premenopausal and postmenopausal women: a population-based study in the United States.

OBJECTIVE: Osteoporosis is a skeletal disease characterized by low bone mass, reduced bone strength, and increased fracture risk. We aimed to investigate the association between combined dietary antioxidant intake and the likelihood of osteoporosis in premenopausal and postmenopausal women, based on data from the National Health and Nutrition Examination Survey. METHODS: Nutrient intake data were obtained using two 24-hour recalls. Composite dietary antioxidant index (CDAI), which refers to the intake amounts of ß-carotene, vitamin A, vitamin C, vitamin E, selenium, zinc, copper, and iron, was then constructed. Prevalent osteoporosis was defined according to bone mineral density T scores of ≤ -2.5 and self-reports. Multiple logistic and Poisson regression models were used for association analyses. RESULTS: A total of 3,418 participants (1,157 premenopausal and 2,261 postmenopausal women) 40 years or older were included, 776 (22.70%) of whom had prevalent osteoporosis. In terms of individual nutrients, postmenopausal women in the highest CDAI quartiles for dietary ß-carotene, vitamin A, vitamin C, and iron intakes had a low likelihood of osteoporosis. Regarding the CDAI-osteoporosis association, postmenopausal women in the highest quartile were less likely to have osteoporosis (OR Q3 vs Q1 , 0.64; 95% CI, 0.43-0.96; OR Q4 vs Q1 , 0.56; 95% CI, 0.35-0.89; P for trend = 0.013), after controlling for covariates. CONCLUSIONS: CDAI was negatively associated with the likelihood of osteoporosis in postmenopausal women. Our findings suggest that the combined intake of antioxidant nutrients can help reduce the likelihood of osteoporosis in women.

Association Between Water Intake and Mortality Risk-Evidence From a National Prospective Study.

Background: Few studies have explored the association between water intake and mortality risk, and the findings were inconsistent. Objective: This study aimed to explore the water intake-mortality association, utilizing the data from the National Health and Nutrition Examination Survey (NHANES) and the 2015 public-linked mortality files released by the National Center for Health Statistics. Methods: We used the diet- and mortality-linked data of a total of 35,463 adults (17,234 men) aged ≥20 years in the NHANESs 1999-2014 to perform a prospective study. The multivariate-adjusted Cox proportional hazards model was used to explore the associations of the amount of water intake (expressed by total water, plain water, beverage, and food water) and water intake proportion (expressed by the percentage of each kind of water) with mortality risks due to all causes, malignant neoplasms/cancer, and heart disease. The restricted cubic spline plots were adopted to clarify the dose-response relationships among them. Results: With a median of 88 months (interquartile range: 49-136 months) follow-up, a total of 4,915 all-cause deaths occurred, including 1,073 and 861 deaths from malignant neoplasms/cancer and heart disease, respectively. The amount of water intake in either type was negatively associated with all-cause mortality risk. Additionally, the negative linear dose-response relationships of water intake and all-cause mortality risk were found for all types of water except for food water, which followed a non-linear pattern. Similarly, compared to the lowest quartile (beverage water intake: <676 g/day; food water intake: <532 g/day), beverage and food water intakes in the range of 1,033-1,524 and 1,612-3,802 g/day were associated with decreased malignant neoplasms/cancer mortality risk. A U-shaped dose-response relationship was found for beverage water intake and malignant neoplasms/cancer mortality risk and a negative linear dose-response relationship was found for food water intake and malignant neoplasms/cancer mortality risk. Coffee and/or tea consumption was/were negatively associated with mortality risks due to all causes and malignant neoplasms/cancer. No significant associations of water intake proportion and mortality risks were found. Conclusion: Our findings demonstrated that higher water intake is associated with lower mortality risks among the United States population.

Manganese, iron, copper, and selenium co-exposure and osteoporosis risk in Chinese adults.

BACKGROUND & AIMS: Previous experimental studies demonstrated that either deficient or excessive trace elements, such as manganese (Mn), iron (Fe), copper (Cu) and selenium (Se), are detrimental to bone health. Epidemiologic evidence for the effect of the four trace elements on osteoporosis (OP) risk remains inadequate. This cross-sectional study aimed to examine their associations with the OP risk among Chinese adults. METHODS: Concentrations of Mn, Fe, Cu, and Se were measured in plasma using an inductively coupled plasma mass spectrometer among 627 Chinese adults aged ≥ 50 years. Individual effect of the four elements on OP risk was analyzed by logistic regression and Bayesian Kernel Machine Regression (BKMR) models. The latter model was also adopted to examine the exposure-response relationships and joint effects of the four elements on OP risk. RESULTS: The median Mn, Fe, Cu, and Se levels were 4.78, 1026.63, 904.55, and 105.39 µg/L, respectively, in all participants. Inverse associations of Fe and Se levels with OP risk were observed in the logistic regression model. BKMR analysis revealed a U-shape pattern for the Fe-OP association, and a reduced OP risk in response to co-exposure of the four elements above the 50th percentiles but an elevated one in response to that below the 50th percentiles. Sex discrepancy existed in the findings. No interactions were found for the four elements affecting OP risk. CONCLUSIONS: Co-exposure to Mn, Fe, Cu, and Se was associated with improved bone density, where Fe contributed most to the beneficial effect. Further studies are needed to verify these findings and explore the underlying biological mechanism.

Multiple vitamin co-exposure and mortality risk: A prospective study.

BACKGROUND & AIMS: Existing epidemiological studies explored the associations of circulating vitamins and mortality focusing on individual vitamin effects, and controversial findings were obtained. The joint effects of multiple vitamin co-exposure are worth studying. The study aimed to elucidate the associations of circulating vitamins and the joint effects of these vitamins' co-exposure with all-cause and cause-specific mortality risks. METHODS: We prospectively evaluated the associations of the concentrations of six kinds of vitamins (A, D, E, C, B12 and B9) in serum with risks for all-cause and cause-specific mortalities among U.S. adults. Mortality status and cause of death were determined by NHANES-linked public available files dated up to 31 December 2015. An unsupervised K-means clustering method was used to cluster the participants into several vitamin co-exposure patterns. The Cox proportional hazards model was used for statistical analysis. RESULTS: A total of 1404 deaths occurred during a median of 10.9 years follow-up among 8295 participants. In multivariable adjustment, increasing levels of vitamin D were associated with reduced all-cause and cause-specific mortality risks. A J-shaped nonlinear exposure-response relationship was observed between all studied vitamins (except for vitamin D) and all-cause mortality risk. Four co-exposure patterns were generated based on the studied vitamins, as follows: low-level exposure (cluster 1), vitamin A/D exposure (cluster 2), water-soluble vitamin exposure (cluster 3) and high-level exposure (cluster 4). Compared with those in cluster 1, participants in cluster 2 had lower all-cause and cancer mortality risks, with hazard ratios (95% confidence intervals [CIs]) of 0.67 (0.53, 0.85) and 0.45 (0.29, 0.71), respectively. CONCLUSIONS: The findings in this study indicated that high circulating vitamin D levels were associated with reduced mortality risk among U.S. adults. Vitamin co-exposure at moderate levels appropriately contributed to low all-cause and cancer mortality risks. Our findings provided a novel perspective for exploring the joint health effects of multivitamin co-exposure. Future investigations are needed to further unravel the underlying mechanisms of possible vitamin interactions.

Repeated measurements of 21 urinary metabolites of volatile organic compounds and their associations with three selected oxidative stress biomarkers in 0-7-year-old healthy children from south and central China.

Human beings are extensively and concurrently exposed to multiple volatile organic compounds (VOCs, including some Class I human carcinogens), which may induce oxidative stress in human body. Data on urinary metabolites of VOCs (mVOCs) among young children are limited. No studies have examined their inter-day variability of mVOCs and their associations with oxidative stress biomarkers (OSBs) using repeated urine samples from children. In this study, we measured twenty one mVOCs and three OSBs [8-hydroxy-2'-deoxyguanosine (8-OHdG; for DNA), 8-hydroxyguanosine (8-OHG; for RNA], and 4-hydroxy nonenal mercapturic acid (HNEMA; for lipid)] in 390 urine samples of 130 children (three samples on three consecutive days provided by each participant) aged 0-7 years from September 2018 to January 2019 in Shenzhen, south China, and Wuhan, central China. HPMMA (3-hydroxypropyl-1-methyl mercapturic acid/N-Acetyl-S-(3-hydroxypropyl-1-methyl)-l-cysteine), 3HPMA (3-hydroxypropyl mercapturic acid/N-Acetyl-S-(3-hydroxypropyl)-l-cysteine), and ATCA (2-aminothiazoline-4-carboxylic acid) had higher specific gravity-adjusted median concentrations (1 383, 286, and 273 µg/L, respectively) than the others. Intraclass correlation coefficients of mVOCs ranged from 0.29 to 0.71. After false-discovery rate (FDR, defined as FDR q-value < 0.05) adjustment, linear mixed-effects models revealed that 14 mVOCs were positively associated with 8-OHdG (ß range: 0.09-0.37), 11 mVOCs were positively associated with 8-OHG (ß range: 0.08-0.30), and 11 mVOCs were positively associated with HNEMA (ß range: 0.21-0.70) in urine. Considering the weight of the mVOC index accounted for the associations, based on the weighted quantile sum regression model, parent compounds of DHBMA (3,4-dihydroxybutyl mercapturic acid/N-Acetyl-S-(3,4-dihydroxybutyl)-l-cysteine) and t,t-MA (trans,trans-muconic acid) should be listed as priority VOCs for management to mitigate health risks. For the first time, this study characterized the inter-day variability of urinary mVOCs and their associations with selected OSBs (8-OHdG, 8-OHG, and NHEMA) in young, healthy Chinese children.