Major Gaps in Understanding Dietary Supplement Use in Health and Disease.

Precise dietary assessment is critical for accurate exposure classification in nutritional research, typically aimed at understanding how diet relates to health. Dietary supplement (DS) use is widespread and represents a considerable source of nutrients. However, few studies have compared the best methods to measure DSs. Our literature review on the relative validity and reproducibility of DS instruments in the United States [e.g., product inventories, questionnaires, and 24-h dietary recalls (24HR)] identified five studies that examined validity (n = 5) and/or reproducibility (n = 4). No gold standard reference method exists for validating DS use; thus, each study's investigators chose the reference instrument used to measure validity. Self-administered questionnaires agreed well with 24HR and inventory methods when comparing the prevalence of commonly used DSs. The inventory method captured nutrient amounts more accurately than the other methods. Reproducibility (over 3 months to 2.4 years) of prevalence of use estimates on the questionnaires was acceptable for common DSs. Given the limited body of research on measurement error in DS assessment, only tentative conclusions on these DS instruments can be drawn at present. Further research is critical to advancing knowledge in DS assessment for research and monitoring purposes.

Self-Reported Dietary Supplement Use Is Reproducible and Relatively Valid in the Cancer Prevention Study-3 Diet Assessment Substudy.

BACKGROUND: Dietary supplement use is common, particularly among cancer survivors and those at increased risk for cancer. OBJECTIVE: The objectives of this study were to assess 1-year test-retest reproducibility of dietary supplement use reported via food frequency questionnaire (FFQ-1 vs FFQ-2) and relative validity in comparison to repeated 24-hour dietary recalls (FFQ-2 vs DRs). DESIGN: This ancillary study was conducted within a large prospective cohort, the American Cancer Society's Cancer Prevention Study-3. PARTICIPANTS/SETTING: Between 2015 and 2016, 684 participants in the United States (64% women; 62% non-Hispanic White, 23% non-Hispanic Black, and 15% Hispanic) completed two FFQs and up to six unannounced telephone interviewer-administered DRs over 1 year as part of the Cancer Prevention Study-3 Diet Assessment Substudy. PRIMARY OUTCOME MEASURES: FFQs queried current multivitamin-mineral supplement (≥10 components) use, frequency and dose (range) for seven supplements taken individually or as part of a complex (individual/complex) including calcium, vitamins D, C, and E, folic acid, fish oil, and glucosamine. DRs allowed exact reporting of supplement frequency and dose. STATISTICAL ANALYSES: Weighted κ statistics were used to evaluate reproducibility between FFQ-1 and FFQ-2 and Spearman correlation coefficients assessed agreement between supplemental nutrient amounts assessed by FFQ-2 and the average of DRs. RESULTS: Just more than half of the participants reported taking multivitamin-mineral supplements on the baseline FFQ. Kappa statistics for the comparison of categorical responses between FFQ-1 and FFQ-2 were 0.67 for multivitamin-mineral supplements. Kappas for individual/complex supplements ranged from 0.47 for folic acid to 0.74 for vitamin D, with a mean of 0.64. Results were similar between men and women. Spearman correlation coefficients comparing FFQ-2 with the average of DRs (validity) for nutrient intakes from all sources ranged from 0.65 (fish oil for women) to 0.77 (vitamin D for men and calcium for women); results were similar among men and women. CONCLUSIONS: These findings suggest the FFQ used in Cancer Prevention Study-3 has good reproducibility over 1 year and yields estimates comparable to a more detailed assessment for commonly consumed dietary supplements.

Coffee Consumption and Invasive Breast Cancer Incidence among Postmenopausal Women in the Cancer Prevention Study-II Nutrition Cohort.

BACKGROUND: There is limited evidence of a potential inverse association between coffee, particularly caffeinated coffee, consumption and postmenopausal breast cancer risk, and few studies have examined this association by tumor hormone receptor status. To provide further evidence, we examined total, caffeinated, and decaffeinated coffee consumption in relation to postmenopausal invasive breast cancer incidence overall, and by tumor estrogen receptor (ER) and/or progesterone receptor (PR) subtype. METHODS: Among 57,075 postmenopausal women in the Cancer Prevention Study-II Nutrition Cohort who were cancer free and reported coffee intake in 1999, we identified 2,980 women diagnosed with invasive breast cancer during follow-up through June 2015. Multivariable-adjusted Cox proportional hazards regression was used to compute hazard ratios (HR) and 95% confidence intervals (CI). RESULTS: Neither total, caffeinated, nor decaffeinated coffee consumption was associated with invasive breast cancer risk; HRs (95% CIs) comparing consumption of ≥2 cups per day with <1 cup per month were 0.99 (0.89-1.11), 0.96 (0.87-1.06), and 1.06 (0.95-1.19), respectively. Similarly, coffee consumption was not associated with risk of hormone receptor-positive (ER+ or PR+) or hormone receptor-negative (ER- and PR-) breast tumors. CONCLUSIONS: These findings do not support an association between coffee consumption and invasive breast cancer risk among postmenopausal women. IMPACT: This large prospective study contributes to the limited evidence on coffee consumption and breast cancer risk, finding no association overall or by tumor receptor subtype.

Prenatal Omega-3 and Omega-6 Polyunsaturated Fatty Acids and Childhood Atopic Dermatitis.

BACKGROUND: Atopic dermatitis is a common childhood disease, potentially influenced by prenatal nutritional exposures such as polyunsaturated fatty acids (PUFAs). OBJECTIVE: In a racially diverse cohort, we hypothesized that childhood atopic dermatitis would be associated with higher prenatal omega-6 (n-6) and lower omega-3 (n-3) PUFAs. METHODS: We included mother-child dyads, births 2006 to 2011, enrolled in the University of Tennessee Health Sciences Center Conditions Affecting Neurocognitive Development in Early Childhood cohort. Primary exposures included second trimester plasma n-3 and n-6 PUFA status and the ratio of the two (n-6:n-3). We assessed child current atopic dermatitis symptoms in the previous 12 months at age approximately 4 to 6 years. We investigated the association between PUFA exposures and atopic dermatitis using multivariable logistic regression, adjusting for potential confounders. We assessed for effect modification by maternal prenatal smoking, atopic disease history, and child sex. RESULTS: Among 1131 women, 67% were African American and 42% had an atopic disease history; 17% of children had atopic dermatitis. Higher prenatal n-6 PUFAs were associated with increased relative odds of child atopic dermatitis (adjusted odds ratio: 1.25; confidence interval: 1.01-1.54 per interquartile range difference), and interaction models demonstrated that this association was seen in dyads in which the women had a history of atopic disease. Neither prenatal n-3 PUFAs nor n-6:n-3 were associated with child atopic dermatitis. CONCLUSION: In this racially diverse cohort, higher second trimester n-6 PUFAs were associated with atopic dermatitis in children of women with atopy. PUFAs may represent a modifiable risk factor for atopic dermatitis, particularly in individuals with a familial predisposition.

Prenatal polyunsaturated fatty acids and child asthma: Effect modification by maternal asthma and child sex.

BACKGROUND: Findings on prenatal polyunsaturated fatty acid (PUFA) intake and child wheeze and asthma have been inconsistent. OBJECTIVE: We sought to examine associations between prenatal PUFA status and child wheeze/asthma and modifying effects of maternal asthma/atopy, child sex, and maternal race. METHODS: Analyses included 1019 mother-child dyads with omega-3 (n-3) and omega-3 (n-6) PUFAs measured in second-trimester plasma; n-6/n-3 ratios were calculated. Child wheeze/asthma outcomes ascertained at age 4 to 6 years included ever physician-diagnosed asthma, current wheeze (symptoms past 12 months), current asthma (diagnosis and medication and/or symptoms past 12 months), and current diagnosed asthma. Each PUFA indicator and outcome was analyzed in separate models using modified Poisson regression with interaction terms. RESULTS: In quartile (Q) analyses, higher n-6 PUFAs were associated with increased risk of ever (risk ratio [RR] high vs low [RR Q4 vs Q1], 1.70; 95% CI, 1.07-2.71) and current (RR Q4 vs Q1, 1.70; 95% CI, 1.07-2.71) diagnosed asthma, whereas n-3 PUFAs were associated with lower risk (RR Q4 vs Q1, 0.59; 95% CI, 0.33-1.03) of current diagnosed asthma (Ptrend < .05 for all). Higher n-6 PUFAs were associated with a higher risk of all respiratory outcomes among children born to women with asthma (Pinteraction < .05 for all outcomes). A significant 3-way interaction between child sex, maternal asthma, and n-6/n-3 PUFA indicated that male children born to women with asthma and a higher ratio had the highest risk across wheeze/asthma outcomes (Pinteraction < .05). CONCLUSIONS: Associations between prenatal PUFA status and childhood wheeze/asthma were modified by maternal history of asthma and child sex.

Dietary quality, as measured by the Alternative Healthy Eating Index for Pregnancy (AHEI-P), in couples planning their first pregnancy.

OBJECTIVE: Dietary quality (DQ), as assessed by the Alternative Healthy Eating Index for Pregnancy (AHEI-P), and conception and pregnancy outcomes were evaluated. DESIGN: In this prospective cohort study on couples planning their first pregnancy. Cox proportional hazards regression assessed the relationship between AHEI-P score and clinical pregnancy, live birth and pregnancy loss. SETTING: Participants were recruited from the Northeast region of the USA.Participants: Healthy, nulliparous couples (females, n 132; males, n 131; one male did not enrol). RESULTS: There were eighty clinical pregnancies, of which sixty-nine resulted in live births and eleven were pregnancy losses. Mean (sd) female AHEI-P was 71·0 (13·7). Of those who achieved pregnancy, those in the highest tertile of AHEI-P had the greatest proportion of clinical pregnancies; however, this association was not statistically significant (P = 0·41). When the time it took to conceive was considered, females with the highest AHEI-P scores were 20 % and 14 % more likely to achieve clinical pregnancy (model 1: hazard ratio (HR) = 1·20; 95 % CI 0·66, 2·17) and live birth (model 1: HR = 1·14; 95 % CI 0·59, 2·20), respectively. Likelihood of achieving clinical pregnancy and live birth increased when the fully adjusted model, including male AHEI-P score, was examined (clinical pregnancy model 4: HR = 1·55; 95 % CI 0·71, 3·39; live birth model 4: HR = 1·36; 95 % CI 0·59, 3·13). CONCLUSIONS: The present study is the first to examine AHEI-P score and achievement of clinical pregnancy. DQ was not significantly related to pregnancy outcomes, even after adjustments for covariates.

Diet Quality of Pregnant American Indian Women in the Northern Plains.

INTRODUCTION: We examined diet quality and intake of pregnancy-specific micronutrients among pregnant American Indian women in the Northern Plains. METHODS: We conducted an analysis of nutrition data from the Prenatal Alcohol and SIDS and Stillbirth (PASS) Network Safe Passage Study and the PASS Diet Screener study (N = 170). Diet intake, including dietary supplementation, was assessed by using three 24-hour recalls conducted on randomly selected, nonconsecutive days. Diet intake data were averaged across the participant's recalls and scored for 2 dietary indices: the Healthy Eating Index 2010 (HEI-2010) and the Alternate Healthy Eating Index for Pregnancy (AHEI-P). We also assessed nutrient adequacy with Dietary Reference Intakes for pregnancy. RESULTS: On average, participants were aged 26.9 (standard deviation [SD], 5.5) years with a pre-pregnancy body mass index of 29.8 (SD, 7.5) kg/m2. Mean AHEI-P and HEI-2010 scores (52.0 [SD, 9.0] and 49.2 [SD, 11.1], respectively) indicated inadequate adherence to dietary recommendations. Micronutrient intake for vitamins D and K, choline, calcium, and potassium were lower than recommended, and sodium intake was higher than recommended. CONCLUSION: Our findings that pregnant American Indian women are not adhering to dietary recommendations is consistent with studies in other US populations. Identifying opportunities to partner with American Indian communities is necessary to ensure effective and sustainable interventions to promote access to and consumption of foods and beverages that support the adherence to recommended dietary guidelines during pregnancy.

Association Between Maternal 2nd Trimester Plasma Folate Levels and Infant Bronchiolitis.

Objectives Viral bronchiolitis is the most common cause of infant hospitalization. Folic acid supplementation is important during the periconceptional period to prevent neural tube defects. An area of investigation is whether higher prenatal folate is a risk factor for childhood respiratory illnesses. We investigated the association between maternal 2nd trimester plasma folate levels and infant bronchiolitis. Methods We conducted a retrospective cohort analysis in a subset of mother-infant dyads (n = 676) enrolled in the Conditions Affecting Neurocognitive Development and Learning in Early Childhood study and Tennessee Medicaid. Maternal folate status was determined using 2nd trimester (16-28 weeks) plasma samples. Bronchiolitis diagnosis in the first year of life was ascertained using International Classification of Diagnosis-9 codes from Medicaid administrative data. We used multivariable logistic regression to assess the adjusted association of prenatal folate levels and infant bronchiolitis outcome. Results Half of the women in this lower-income and predominately African-American (84%) study population had high levels of folate (median 2nd trimester level 19.2 ng/mL) and 21% of infants had at least one bronchiolitis healthcare visit. A relationship initially positive then reversing between maternal plasma folate and infant bronchiolitis was observed that did not reach statistical significance (poverall = .112, pnonlinear effect = .088). Additional adjustment for dietary methyl donor intake did not significantly alter the association. Conclusions for Practice Results did not confirm a statistically significant association between maternal 2nd trimester plasma folate levels and infant bronchiolitis. Further work is needed to investigate the role of folate, particularly higher levels, in association with early childhood respiratory illnesses.

Associations of dietary fat with risk of early neoplasia in the proximal colon in a population-based case-control study.

PURPOSE: Excess dietary fat consumption is strongly associated with the risk of colorectal cancer, but less is known about its role in the earliest stages of carcinogenesis, particularly within the proximal colon. In the following case-control study, we evaluated the relationship between the intake of dietary fats and the frequency of early proximal neoplasia [aberrant crypt foci (ACF) or polyps], detectable by high-definition colonoscopy with contrast dye-spray. METHODS: Average-risk screening individuals underwent a high-definition colonoscopy procedure as part of larger ongoing clinical study of precancerous lesions in the proximal colon. Dietary fat intake was assessed using the Block Brief Food Frequency Questionnaire, which estimates average dietary intake based on 70 food items. The diets of individuals with no endoscopically identifiable lesions (n = 36) were compared to those with either ACF or polyps detected in the proximal colon. RESULTS: In multivariate analysis, high dietary intake of total polyunsaturated fatty acids (PUFAs) and intake of omega-6 and omega-3 fatty acids were positively associated with neoplastic lesions in the proximal colon. When comparing ACF and polyp groups separately, a positive association was observed for both proximal polyps (OR 2.28; CI 1.16-7.09) and ACF (OR 2.86; CI 1.16-7.09) for total PUFA intake. Furthermore, the prevalence of proximal ACF was increased with higher intake of omega-6 (OR 3.54; CI 1.32-9.47) and omega-3 fatty acids (OR 2.29; CI 1.02-5.13), although there was no discernible difference in the omega-6/omega-3 ratio. CONCLUSIONS: These results suggest that dietary PUFAs may be positively associated with risk of early neoplasia in the proximal colon. This study provides further evidence that dietary PUFA composition may play an important role in altering the microenvironment within the human colon.

Associations of Coffee Drinking and Cancer Mortality in the Cancer Prevention Study-II.

Background: Associations of coffee consumption with cancer mortality are inconsistent for many types of cancer, and confounding by smoking is an important concern.Methods: Cox proportional hazards regression was used to estimate multivariable-adjusted HRs for coffee consumption associated with death from all cancers combined and from specific cancer types among 922,896 Cancer Prevention Study-II participants ages 28-94 years who completed a four-page questionnaire and were cancer free at baseline in 1982.Results: During follow-up through 2012, there were 118,738 cancer-related deaths. There was a nonlinear association between coffee consumption and all-cancer death among current smokers and former smokers and no association among never smokers. Among nonsmokers, a 2 cup/day increase in coffee consumption was inversely associated with death from colorectal [HR = 0.97; 95% confidence interval (CI) 0.95-0.99], liver [HR = 0.92; 95% CI, 0.88-0.96], and female breast (HR = 0.97; 95% CI, 0.94-0.99) cancers, and positively associated with esophageal cancer-related death (HR = 1.07; 95% CI, 1.02-1.12). For head and neck cancer, a nonlinear inverse association was observed starting at 2-3 cups per day (HR = 0.72; 95% CI, 0.55-0.95), with similar associations observed at higher levels of consumption.Conclusions: These findings are consistent with many other studies that suggest coffee drinking is associated with a lower risk of colorectal, liver, female breast, and head and neck cancer. The association of coffee consumption with higher risk of esophageal cancer among nonsmokers in our study should be confirmed.Impact: These results underscore the importance of assessing associations between coffee consumption and cancer mortality by smoking status. Cancer Epidemiol Biomarkers Prev; 26(10); 1477-86. ©2017 AACR.

Association of vitamin D intake and serum levels with fertility: results from the Lifestyle and Fertility Study.

OBJECTIVE: To evaluate the role of vitamin D intake and serum levels on conception of clinical pregnancy and live birth. DESIGN: Prospective cohort study. SETTING: Academic medical centers. PATIENT(S): Healthy, nulliparous women, age 18-39 years, and their male partners. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Clinical pregnancy and live birth were compared between those who did or did not meet the vitamin D estimated average requirement (EAR) intake (10 µg/d) and with serum 25-hydroxyvitamin D (25(OH)D) considered at risk for inadequacy or deficiency (<50 nmol/L) or sufficient (≥50 nmol/L). RESULT(S): Among 132 women, 37.1% did not meet the vitamin D EAR and 13.9% had serum levels at risk for inadequacy or deficiency. Clinical pregnancies were significantly higher among women who met the vitamin D EAR (67.5% vs. 49.0%) and with sufficient serum 25(OH)D (64.3% vs. 38.9%) compared with those who did not. Live births were higher among those who met the vitamin D EAR (59.0% vs. 40.0%). The adjusted odds ratio (AOR) of conceiving a clinical pregnancy was significantly higher among those who met the EAR (AOR = 2.26; 95% confidence interval [CI], 1.05-4.86) and had sufficient serum 25(OH)D (AOR = 3.37; 95% CI, 1.06-10.70). The associations were not significant after controlling for selected nutrients and dietary quality. CONCLUSION(S): Women with vitamin D intake below EAR and serum 25(OH)D levels at risk for inadequacy or deficiency may be less likely to conceive and might benefit from increased vitamin D intake to achieve adequacy. CLINICAL TRIAL REGISTRATION NUMBER: NCT00642590.

Exposure to phytoestrogens in utero and age at menarche in a contemporary British cohort.

Phytoestrogens are estrogenic compounds that occur naturally in plants. Phytoestrogens can cross the placenta, and animal studies have found associations between in utero exposure to phytoestrogens and markers of early puberty. We investigated the association between in utero exposure to phytoestrogens and early menarche (defined as <11.5 years of age at onset) using data from a nested case-control study within the Avon Longitudinal Study of Parents and Children, a longitudinal study involving families living in the South West of England. Concentrations of six phytoestrogens were measured in maternal urine samples collected during pregnancy. Logistic regression was used to explore associations between tertiles of phytoestrogen concentrations and menarche status, with adjustment for maternal age at menarche, maternal education, pre-pregnancy body mass index (BMI), child birth order, duration of breastfeeding, and gestational age at sample collection. Among 367 mother-daughter dyads, maternal median (interquartile range) creatinine-corrected concentrations (in µg/g creatinine) were: genistein 62.1 (27.1-160.9), daidzein 184.8 (88.8-383.7), equol 4.3 (2.8-9.0), O-desmethylangolensin (O-DMA) 13.0 (4.4-34.5), enterodiol 76.1 (39.1-135.8), and enterolactone 911.7 (448.1-1558.0). In analyses comparing those in the highest tertile relative to those in the lowest tertile of in utero phytoestrogen exposure, higher enterodiol levels were inversely associated with early menarche (odds ratio (OR)=0.47; 95% confidence interval (CI): 0.26-0.83), while higher O-DMA levels were associated with early menarche (OR=1.89; 95% CI: 1.04-3.42). These findings suggest that in utero exposure to phytoestrogens may be associated with earlier age at menarche, though the direction of association differs across phytoestrogens.

Interaction of vitamin E isoforms on asthma and allergic airway disease.

Prospective epidemiological studies, observational cross-sectional studies and some randomised prevention trials have demonstrated inconsistent findings of the impact of vitamin E on asthma risk. The goals of this study were to explore whether this differing association of vitamin E on asthma risk is due to an interaction of vitamin E isoforms. To address this question, in a population-based asthma incidence study we assessed the interaction between the plasma concentrations of vitamin E isoforms α-tocopherol and γ-tocopherol on asthma risk. Second, to understand the mechanisms of any interaction of these isoforms, we conducted experimental supplementation of α-tocopherol and γ-tocopherol isoforms in mice on the outcome of allergic airway inflammation. We found that in the highest γ-tocopherol tertile, low levels of α-tocopherol were associated with increased asthma risk, while highest tertile α-tocopherol levels trended to be protective. Similarly, in a mouse model of asthma, diet supplementation with α-tocopherol decreased lung inflammation in response to house dust mite (HDM) challenge. In contrast, diet supplementation with γ-tocopherol increased lung inflammation in response to HDM. These human and animal studies provide evidence for the competing effects of the vitamin E isoforms, in physiological concentrations, on asthma and allergic airway disease.

Influence of Obesity on Breast Density Reduction by Omega-3 Fatty Acids: Evidence from a Randomized Clinical Trial.

Preclinical data indicate that omega-3 fatty acids (n-3FA) potentiate the chemopreventive effect of the antiestrogen (AE) tamoxifen against mammary carcinogenesis. The role of n-3FA in breast cancer prevention in humans is controversial. Preclinical and epidemiologic data suggest that n-3FA may be preferentially protective in obese subjects. To directly test the protective effect of n-3FA against breast cancer, we conducted a 2-year, open-label randomized clinical trial in 266 healthy postmenopausal women (50% normal weight, 30% overweight, 20% obese) with high breast density (BD; ≥25%) detected on their routine screening mammograms. Eligible women were randomized to one of the following five groups (i) no treatment, control; (ii) raloxifene 60 mg; (iii) raloxifene 30 mg; (iv) n-3FA lovaza 4 g; and (v) lovaza 4 g plus raloxifene 30 mg. The 2-year change in BD, a validated biomarker of breast cancer risk, was the primary endpoint of the study. In subset analysis, we tested the prespecified hypothesis that body mass index (BMI) influences the relationship between plasma n-3FA on BD. While none of the interventions affected BD in the intention-to-treat analysis, increase in plasma DHA was associated with a decrease in absolute breast density but only in participants with BMI >29. Our results suggest that obese women may preferentially experience breast cancer risk reduction from n-3FA administration.

Dietary Iron and Colorectal Cancer Risk: A Review of Human Population Studies.

Iron is an essential micronutrient that is involved in many redox processes and serves as an integral component in various physiological functions. However, excess iron can cause tissue damage through its pro-oxidative effects, potentiating the development of many diseases such as cancer through the generation of reactive oxidative species. The two major forms of iron in the diet are heme and nonheme iron, both of which are found in several different foods. In addition to natural food sources, intake of nonheme iron may also come from fortified foods or in supplement form. This review summarizes the results of human population studies that have examined the role of dietary iron (heme and nonheme), heme iron alone, and iron from supplements in colorectal carcinogenesis.

Maternal Folic Acid Supplementation During Pregnancy and Early Childhood Asthma.

BACKGROUND: Asthma is one of the most common chronic childhood diseases. While folic acid supplementation around conception helps prevent neural tube defects, an animal model suggests that it may be a risk factor for respiratory diseases, although epidemiologic studies have had conflicting results. We investigated the timing of folic acid-containing prescription filling during pregnancy and child asthma. METHODS: In a retrospective cohort study of 104,428 children, born 1996-2005, and their mothers enrolled in Tennessee Medicaid, we investigated the association of filling folic acid-containing prescriptions during pregnancy and childhood asthma at ages 4.5-6 years. We categorized women into exposure groups based on prescription filling centered around the first trimester: no folic acid prescription exposure, exposure in first trimester only, exposure after first trimester, and exposure in first trimester and beyond. We defined asthma using asthma-specific healthcare visits and medication fills. Using logistic regression models, we investigated the relationship adjusting for potential confounders. RESULTS: Overall 15% of children had asthma. Compared with children born to women with no folic acid prescription exposure, children born to women with exposures in the first trimester only or first trimester and later had increased relative odds of asthma (adjusted odds ratios = 1.2, 95% confidence interval = 1.1, 1.3, and 1.2, 95% confidence interval = 1.2, 1.3); no association was seen in children born to women exposed after the first trimester. CONCLUSION: Timing of folic acid-containing prescription filling during pregnancy was associated with childhood asthma. Our findings contribute to understanding of the role of prenatal nutritional supplements on child respiratory health.

Identification and monitoring of metabolite markers of dry bean consumption in parallel human and mouse studies.

SCOPE: Aim of the study was to identify and monitor metabolite markers of dry bean consumption in parallel human and mouse studies that each had shown chemopreventive effects of dry bean consumption on colorectal neoplasia risk. METHODS AND RESULTS: Using LC/mass spectroscopy ± ESI and GC/mass spectroscopy, serum metabolites of dry beans were measured in 46 men before and after a 4-week dry bean enriched diet (250 g/day) and 12 mice that received a standardized diet containing either 0 or 10% navy bean ethanol extract for 6 weeks; we also investigated fecal metabolites in the mice. The serum metabolites identified in these controlled feeding studies were then investigated in 212 polyp-free participants from the Polyp Prevention Trial who self-reported either increased (≥+31 g/day from baseline), high dry bean intake of ≥42 g/day in year 3 or low, unchanged dry bean consumption of <8 g/day; serum was analyzed from baseline and year 3. Serum pipecolic acid and S-methyl cysteine were elevated after dry bean consumption in human and mouse studies and reflected dry bean consumption in the Polyp Prevention Trial. CONCLUSION: Serum levels of pipecolic acid and S-methyl cysteine are useful biomarkers of dry bean consumption.

Comparative effects of two different forms of selenium on oxidative stress biomarkers in healthy men: a randomized clinical trial.

Epidemiologic and laboratory studies indicate that dietary selenium protects against prostate cancer. Results from clinical trials suggest that selenium-enriched yeast (SY) but not selenomethionine (SeMet) may be effective at reducing prostate cancer risk. Our objectives were to directly compare for the first time the effects of SeMet and SY on prostate cancer relevant biomarkers in men. We performed a randomized double blind, placebo-controlled trial of SY (200 or 285 µg/day) and SeMet (200 µg/day) administered for 9 months in 69 healthy men. Primary endpoints included blood levels of selenium-containing compounds and oxidative stress biomarkers [urine 8-hydroxy-2'-deoxyguanosine (8-OHdG) and 8-iso-prostaglandin-F2α (8-iso-PGF2α) and blood glutathione (GSH)]. Secondary endpoints included plasma glucose and PSA levels. Compliance was high in all groups (>95%). Plasma selenium levels were increased 93%, 54%, and 86% after 9 months in SeMet and low- and high-dose SY groups, respectively, and returned to baseline levels after a 3-month washout (P < 0.05). Levels of 8-OHdG and 8-iso-PGF2α were decreased 34% and 28%, respectively, after 9 months in the high-dose SY group (P < 0.05). These decreases were greatest in individuals with low baseline plasma levels of selenium (<127 ng/mL). No changes in serum PSA or blood glucose and GSH were observed. Overall, we showed for the first time, reductions in biomarkers of oxidative stress following supplementation with SY but not SeMet in healthy men. These findings suggest that selenium-containing compounds other than SeMet may account for the decrease in oxidative stress.

Association of folic acid supplementation during pregnancy and infant bronchiolitis.

Viral bronchiolitis affects 20%-30% of infants; because there is no known effective treatment, it is important to identify risk factors that contribute to its pathogenesis. Although adequate folate intake during the periconceptional period prevents neural tube defects, animal data suggest that higher supplementation may be a risk factor for child respiratory diseases. Using a population-based retrospective cohort of 167,333 women and infants, born in 1995-2007 and enrolled in the Tennessee Medicaid program, we investigated the association between the filling of folic acid-containing prescriptions and infant bronchiolitis. We categorized women into the following 4 groups in relation to the first trimester: "none" (no prescription filled), "first trimester only," "after first trimester," and "both" (prescriptions filled both during and after the first trimester). Overall, 21% of infants had a bronchiolitis diagnosis, and 5% were hospitalized. Most women filled their first prescriptions after the fifth to sixth weeks of pregnancy, and most prescriptions contained 1,000 µg of folic acid. Compared with infants born to women in the "none" group, infants born to women in the "first trimester only" group had higher relative odds of bronchiolitis diagnosis (adjusted odds ratio = 1.17, 95% confidence interval: 1.11, 1.22) and greater severity (adjusted odds ratio = 1.16, 95% confidence interval: 1.11, 1.22). This study's findings contribute to an understanding of the implications of prenatal nutritional supplement recommendations for infant bronchiolitis.

Female dietary antioxidant intake and time to pregnancy among couples treated for unexplained infertility.

OBJECTIVE: To determine whether increased antioxidant intake in women is associated with shorter time to pregnancy (TTP) among a cohort of couples being treated for unexplained infertility. DESIGN: Secondary data analysis of a randomized controlled trial. SETTING: Academic medical center associated with a private infertility center. PATIENTS: Females with unexplained infertility. INTERVENTIONS: None. MAIN OUTCOME MEASURE(S): The time it took to establish a pregnancy that led to a live birth. RESULT(S): Mean nutrient intake exceeded the estimated average requirement (EAR) for vitamins C and E. No differences in mean intake of any of the antioxidants were noted between women who delivered a live-born infant during the study period vs. those who did not. In multivariable models, intake of ß-carotene from dietary supplements was associated with shorter TTP among women with body mass index (BMI) ≥25 kg/m(2) (hazard ratio [HR] 1.29, 95% confidence interval [CI] 1.09-1.53) and women <35 y (HR 1.19, 95% CI 1.01-1.41). Intake of vitamin C from dietary supplements was associated with shorter TTP among women with BMI <25 kg/m(2) (HR 1.09, 95% CI 1.03-1.15) and women <35 y (HR 1.10, 95% CI 1.02-1.18). Intake of vitamin E from dietary supplements among women ≥35 y also was associated with shorter TTP (HR 1.07, 95% CI 1.01-1.13). CONCLUSION(S): Shorter TTP was observed among women with BMI <25 kg/m(2) with increasing vitamin C, women with BMI ≥25 kg/m(2) with increasing ß-carotene, women <35 y with increasing ß-carotene and vitamin C, and women ≥35 y with increasing vitamin E. CLINICAL TRIAL REGISTRATION NUMBER: NCT00260091.