A cluster-randomized crossover trial of organic diet impact on biomarkers of exposure to pesticides and biomarkers of oxidative stress/inflammation in primary school children

Despite suggestive observational epidemiology and laboratory studies, there is limited experimental evidence regarding the effect of organic diet on human health. A cluster-randomized 40-day-organic (vs. 40-day-conventional) crossover trial was conducted among children (11–12 years old) from six schools in Cyprus. One restaurant provided all organic meals, and adherence to the organic diet intervention was measured by parent-provided diet questionnaire/diary data. Biomarkers of pyrethroid and neonicotinoid pesticide exposures were measured using tandem mass spectrometry, and oxidative stress/inflammation (OSI) biomarkers using immunoassays or spectrophotometry. Associations were assessed using mixed-effect regression models including interactions of treatment with time. Seventy-two percent of neonicotinoid biomarkers were non-detectable and modeled as binary (whether detectable). In post-hoc analysis, we considered the outcome of age-and-sex-standardized BMI. Multiple comparisons were handled using Benjamini-Hochberg correction for 58 regression parameters. Outcome data were available for 149 children. Children had lower pesticide exposures during the organic period (pyrethroid geometric mean ratio, GMR = 0.297; [95% confidence interval (95% CI): 0.237, 0.373], Q-value < 0.05); odds for detection of neonicotinoids (OR = 0.651; [95% CI: 0.463, 0.917), Q-value < 0.05); and decreased OSI biomarker 8-OHdG (GMR = 0.888; [95% CI: 0.808, 0.976], Q-value < 0.05). An initial increase was followed by a countervailing decrease over time in the organic period for OSI biomarkers 8-iso-PGF2a and MDA. BMI z-scores were lower at the end of the organic period (β = -0.131; [95% CI: 0.179, -0.920], Q-value < 0.05). Energy intake during the conventional period was reported to be higher than the recommended reference levels. The organic diet intervention reduced children’s exposure to pyrethroid and neonicotinoid pesticides and, over time lowered biomarkers of oxidative stress/inflammation (8-iso-PGF2a, 8-OHdG and MDA). The several-week organic diet intervention also reduced children’s age- and-sex-standardized BMI z-scores, but causal inferences regarding organic diet’s physiological benefits are limited by the confounding of the organic diet intervention with caloric intake reduction and possible lifestyle changes during the trial

Association of Cardiometabolic Genes with Arsenic Metabolism Biomarkers in American Indian Communities: The Strong Heart Family Study (SHFS)

Background: Metabolism of inorganic arsenic (iAs) is subject to inter-individual variability, which is explained partly by genetic determinants. Objectives: We investigated the association of genetic variants with arsenic species and principal components of arsenic species in the Strong Heart Family Study (SHFS). Methods: We examined variants previously associated with cardiometabolic traits (~ 200,000 from Illumina Cardio MetaboChip) or arsenic metabolism and toxicity (670) among 2,428 American Indian participants in the SHFS. Urine arsenic species were measured by high performance liquid chromatography–inductively coupled plasma mass spectrometry (HPLC-ICP-MS), and percent arsenic species [iAs, monomethylarsonate (MMA), and dimethylarsinate (DMA), divided by their sum × 100] were logit transformed. We created two orthogonal principal components that summarized iAs, MMA, and DMA and were also phenotypes for genetic analyses. Linear regression was performed for each phenotype, dependent on allele dosage of the variant. Models accounted for familial relatedness and were adjusted for age, sex, total arsenic levels, and population stratification. Single nucleotide polymorphism (SNP) associations were stratified by study site and were meta-analyzed. Bonferroni correction was used to account for multiple testing. Results: Variants at 10q24 were statistically significant for all percent arsenic species and principal components of arsenic species. The index SNP for iAs%, MMA%, and DMA% (rs12768205) and for the principal components (rs3740394, rs3740393) were located near AS3MT, whose gene product catalyzes methylation of iAs to MMA and DMA. Among the candidate arsenic variant associations, functional SNPs in AS3MT and 10q24 were most significant (p \u3c 9.33 × 10–5). Conclusions: This hypothesis-driven association study supports the role of common variants in arsenic metabolism, particularly AS3MT and 10q24

The Southeast Alaska Tribal Ocean Research (SEATOR) Partnership: Addressing Data Gaps in Harmful Algal Bloom Monitoring and Shellfish Safety in Southeast Alaska

Many communities in Southeast Alaska harvest shellfish such as mussels and clams as an important part of a subsistence or traditional diet. Harmful algal blooms (HABs) of phytoplankton such as Alexandrium spp. produce toxins that can accumulate in shellfish tissues to concentrations that can pose a hazard for human health. Since 2013, several tribal governments and communities have pooled resources to form the Southeast Alaska Tribal Ocean Research (SEATOR) network, with the goal of minimizing risks to seafood harvest and enhancing food security. SEATOR monitors toxin concentrations in shellfish and collects and consolidates data on environmental variables that may be important predictors of toxin levels such as sea surface temperature and salinity. Data from SEATOR are publicly available and are encouraged to be used for the development and testing of predictive algorithms that could improve seafood risk assessment in Southeast Alaska. To date, more than 1700 shellfish samples have been analyzed for paralytic shellfish toxins (PSTs) in more than 20 locations, with potentially lethal concentrations observed in blue mussels (Mytilus trossulus) and butter clams (Saxidomus gigantea). Concentrations of PSTs exhibit seasonality in some species, and observations of Alexandrium are correlated to sea surface temperature and salinity; however, concentrations above the threshold of concern have been found in all months, and substantial variation in concentrations of PSTs remain unexplained.Funding: The views expressed in this paper are those of the authors and do not reflect the views of the National Oceanic and Atmospheric Administration. Funding for this work was provided by the Saltonstall-Kennedy Grant Program (Award NA17NMF4270238). Gribble’s e ort was supported by grants from the National Institute of Environmental Health Sciences (R01ES029165 and P30ES019776).Ye

Potentially Heterogeneous Cross-Sectional Associations of Seafood Consumption with Diabetes and Glycemia in Urban South Asia.

Aims: In this study, we aimed to estimate cross-sectional associations of fish or shellfish consumption with diabetes and glycemia in three South Asian mega-cities. Methods: We analyzed baseline data from 2010-2011 of a cohort (n = 16,287) representing the population ≥20 years old that was neither pregnant nor on bedrest from Karachi (unweighted n = 4017), Delhi (unweighted n = 5364), and Chennai (unweighted n = 6906). Diabetes was defined as self-reported physician-diagnosed diabetes, fasting plasma glucose ≥126 mg/dL (7.0 mmol/L), or glycated hemoglobin A1c (HbA1c) ≥6.5% (48 mmol/mol). We estimated adjusted and unadjusted odds ratios for diabetes using survey estimation logistic regression for each city, and differences in glucose and HbA1c using survey estimation linear regression for each city. Adjusted models controlled for age, gender, body mass index, waist-height ratio, sedentary lifestyle, educational attainment, tobacco use, an unhealthy diet index score, income, self-reported physician diagnosis of high blood pressure, and self-reported physician diagnosis of high cholesterol. Results: The prevalence of diabetes was 26.7% (95% confidence interval: 24.8, 28.6) in Chennai, 36.7% (32.9, 40.5) in Delhi, and 24.3% (22.0, 26.6) in Karachi. Fish and shellfish were consumed more frequently in Chennai than in the other two cities. In Chennai, the adjusted odds ratio for diabetes, comparing more than weekly vs. less than weekly fish consumption, was 0.81 (0.61, 1.08); in Delhi, it was 1.18 (0.87, 1.58), and, in Karachi, it was 1.30 (0.94, 1.80). In Chennai, the adjusted odds ratio of prevalent diabetes among persons consuming shellfish more than weekly versus less than weekly was 1.08 (95% CI: 0.90, 1.30); in Delhi, it was 1.35 (0.90, 2.01), and, in Karachi, it was 1.68 (0.98, 2.86). Conclusions: Both the direction and the magnitude of association between seafood consumption and glycemia may vary by city. Further investigation into specific locally consumed seafoods and their prospective associations with incident diabetes and related pathophysiology are warranted

Association of Cardiometabolic Genes with Arsenic Metabolism Biomarkers in American Indian Communities: The Strong Heart Family Study (SHFS)

BACKGROUND: Metabolism of inorganic arsenic (iAs) is subject to inter-individual variability, which is explained partly by genetic determinants. OBJECTIVES: We investigated the association of genetic variants with arsenic species and principal components of arsenic species in the Strong Heart Family Study (SHFS). METHODS: We examined variants previously associated with cardiometabolic traits (~ 200,000 from Illumina Cardio MetaboChip) or arsenic metabolism and toxicity (670) among 2,428 American Indian participants in the SHFS. Urine arsenic species were measured by high performance liquid chromatography-inductively coupled plasma mass spectrometry (HPLC-ICP-MS), and percent arsenic species [iAs, monomethylarsonate (MMA), and dimethylarsinate (DMA), divided by their sum × 100] were logit transformed. We created two orthogonal principal components that summarized iAs, MMA, and DMA and were also phenotypes for genetic analyses. Linear regression was performed for each phenotype, dependent on allele dosage of the variant. Models accounted for familial relatedness and were adjusted for age, sex, total arsenic levels, and population stratification. Single nucleotide polymorphism (SNP) associations were stratified by study site and were meta-analyzed. Bonferroni correction was used to account for multiple testing. RESULTS: Variants at 10q24 were statistically significant for all percent arsenic species and principal components of arsenic species. The index SNP for iAs%, MMA%, and DMA% (rs12768205) and for the principal components (rs3740394, rs3740393) were located near AS3MT, whose gene product catalyzes methylation of iAs to MMA and DMA. Among the candidate arsenic variant associations, functional SNPs in AS3MT and 10q24 were most significant (p < 9.33 × 10-5). CONCLUSIONS: This hypothesis-driven association study supports the role of common variants in arsenic metabolism, particularly AS3MT and 10q24. Citation: Balakrishnan P, Vaidya D, Franceschini N, Voruganti VS, Gribble MO, Haack K, Laston S, Umans JG, Francesconi KA, Goessler W, North KE, Lee E, Yracheta J, Best LG, MacCluer JW, Kent J Jr., Cole SA, Navas-Acien A. 2017. Association of cardiometabolic genes with arsenic metabolism biomarkers in American Indian communities: the Strong Heart Family Study (SHFS). Environ Health Perspect 125:15-22; http://dx.doi.org/10.1289/EHP251

Stepped-wedge cluster-randomised controlled trial to assess the cardiovascular health effects of a managed aquifer recharge initiative to reduce drinking water salinity in southwest coastal Bangladesh: study design and rationale.

INTRODUCTION: Saltwater intrusion and salinisation have contributed to drinking water scarcity in many coastal regions globally, leading to dependence on alternative sources for water supply. In southwest coastal Bangladesh, communities have few options but to drink brackish groundwater which has been associated with high blood pressure among the adult population, and pre-eclampsia and gestational hypertension among pregnant women. Managed aquifer recharge (MAR), the purposeful recharge of surface water or rainwater to aquifers to bring hydrological equilibrium, is a potential solution for salinity problem in southwest coastal Bangladesh by creating a freshwater lens within the brackish aquifer. Our study aims to evaluate whether consumption of MAR water improves human health, particularly by reducing blood pressure among communities in coastal Bangladesh. METHODS AND ANALYSIS: The study employs a stepped-wedge cluster-randomised controlled community trial design in 16 communities over five monthly visits. During each visit, we will collect data on participants' source of drinking and cooking water and measure the salinity level and electrical conductivity of household stored water. At each visit, we will also measure the blood pressure of participants ≥20 years of age and pregnant women and collect urine samples for urinary sodium and protein measurements. We will use generalised linear mixed models to determine the association of access to MAR water on blood pressure of the participants. ETHICS AND DISSEMINATION: The study protocol has been reviewed and approved by the Institutional Review Boards of the International Centre for Diarrheal Disease Research, Bangladesh (icddr,b). Informed written consent will be taken from all the participants. This study is funded by Wellcome Trust, UK. The study findings will be disseminated to the government partners, at research conferences and in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT02746003; Pre-results

Heritability and Preliminary Genome-Wide Linkage Analysis of Arsenic Metabolites in Urine

Background: Arsenic (III) methyltransferase (AS3MT) has been related to urine arsenic metabolites in association studies. Other genes might also play roles in arsenic metabolism and excretion

Groundwater Chemistry and Blood Pressure: A Cross-Sectional Study in Bangladesh.

Background: We assessed the association of groundwater chemicals with systolic blood pressure (SBP) and diastolic blood pressure (DBP). Methods: Blood pressure data for ≥35-year-olds were from the Bangladesh Demographic and Health Survey in 2011. Groundwater chemicals in 3534 well water samples from Bangladesh were measured by the British Geological Survey (BGS) in 1998-1999. Participants who reported groundwater as their primary source of drinking water were assigned chemical measures from the nearest BGS well. Survey-adjusted linear regression methods were used to assess the association of each groundwater chemical with the log-transformed blood pressure of the participants. Models were adjusted for age, sex, body mass index, smoking status, geographical region, household wealth, rural or urban residence, and educational attainment, and further adjusted for all other groundwater chemicals. Results: One standard deviation (SD) increase in groundwater magnesium was associated with a 0.992 (95% confidence interval (CI): 0.986, 0.998) geometric mean ratio (GMR) of SBP and a 0.991 (95% CI: 0.985, 0.996) GMR of DBP when adjusted for covariates except groundwater chemicals. When additionally adjusted for groundwater chemicals, one SD increase in groundwater magnesium was associated with a 0.984 (95% CI: 0.972, 0.997) GMR of SBP and a 0.990 (95% CI: 0.979, 1.000) GMR of DBP. However, associations were attenuated following Bonferroni-correction for multiple chemical comparisons in the full-adjusted model. Groundwater concentrations of calcium, potassium, silicon, sulfate, barium, zinc, manganese, and iron were not associated with SBP or DBP in the full-adjusted models. Conclusions: Groundwater magnesium had a weak association with lower SBP and DBP of the participants

Linkage Analysis of Urine Arsenic Species Patterns in the Strong Heart Family Study

Arsenic toxicokinetics are important for disease risks in exposed populations, but genetic determinants are not fully understood. We examined urine arsenic species patterns measured by HPLC-ICPMS among 2189 Strong Heart Study participants 18 years of age and older with data on ∼400 genome-wide microsatellite markers spaced ∼10 cM and arsenic speciation (683 participants from Arizona, 684 from Oklahoma, and 822 from North and South Dakota). We logit-transformed % arsenic species (% inorganic arsenic, %MMA, and %DMA) and also conducted principal component analyses of the logit % arsenic species. We used inverse-normalized residuals from multivariable-adjusted polygenic heritability analysis for multipoint variance components linkage analysis. We also examined the contribution of polymorphisms in the arsenic metabolism gene AS3MT via conditional linkage analysis. We localized a quantitative trait locus (QTL) on chromosome 10 (LOD 4.12 for %MMA, 4.65 for %DMA, and 4.84 for the first principal component of logit % arsenic species). This peak was partially but not fully explained by measured AS3MT variants. We also localized a QTL for the second principal component of logit % arsenic species on chromosome 5 (LOD 4.21) that was not evident from considering % arsenic species individually. Some other loci were suggestive or significant for 1 geographical area but not overall across all areas, indicating possible locus heterogeneity. This genome-wide linkage scan suggests genetic determinants of arsenic toxicokinetics to be identified by future fine-mapping, and illustrates the utility of principal component analysis as a novel approach that considers % arsenic species jointly

Drinking Water Salinity, Urinary Macro-Mineral Excretions, and Blood Pressure in the Southwest Coastal Population of Bangladesh.

Background Sodium (Na+) in saline water may increase blood pressure ( BP ), but potassium (K+), calcium (Ca2+), and magnesium (Mg2+) may lower BP . We assessed the association between drinking water salinity and population BP . Methods and Results We pooled 6487 BP measurements from 2 cohorts in coastal Bangladesh. We used multilevel linear models to estimate BP differences across water salinity categories: fresh water (electrical conductivity, <0.7 mS/cm), mild salinity (electrical conductivity ≥0.7 and <2 mS/cm), and moderate salinity (electrical conductivity ≥2 and <10 mS/cm). We assessed whether salinity categories were associated with hypertension using multilevel multinomial logistic models. Models included participant-, household-, and community-level random intercepts. Models were adjusted for age, sex, body mass index ( BMI ), physical activity, smoking, household wealth, alcohol consumption, sleep hours, religion, and salt consumption. We evaluated the 24-hour urinary minerals across salinity categories, and the associations between urinary minerals and BP using multilevel linear models. Compared with fresh water drinkers, mild-salinity water drinkers had lower mean systolic BP (-1.55 [95% CI : -3.22-0.12] mm Hg) and lower mean diastolic BP (-1.26 [95% CI : -2.21--0.32] mm Hg) adjusted models. The adjusted odds ratio among mild-salinity water drinkers for stage 1 hypertension was 0.60 (95% CI : 0.43-0.84) and for stage 2 hypertension was 0.56 (95% CI : 0.46-0.89). Mild-salinity water drinkers had high urinary Ca2+, and Mg2+, and both urinary Ca2+ and Mg2+ were associated with lower BP. Conclusions Drinking mild-salinity water was associated with lower BP , which can be explained by higher intake of Ca2+ and Mg2+ through saline water