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Background: Although adolescent diet has been proposed to contribute to prostate cancer (PCa) development, no studies have investigated the relation between adolescent dietary patterns and PCa risk or mortality., Methods: Using data from 164,079 men in the NIH-AARP Diet and Health Study, we performed factor analysis to identify dietary patterns at ages 12-13 years and then used Cox proportional hazards regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of total (n = 17,861), non-advanced (n = 15,499), advanced (n = 2362), and fatal PCa (n = 832)., Results: Although not entirely consistent across analyses, a higher adolescent plant-based pattern (characterised by vegetables, fruits, and dark bread) score was associated with slightly reduced risks of total (fully adjusted HR Q5vs.Q1  = 0.93, 95% CI: 0.89-0.98, p trend=0.003) and non-advanced PCa (HR = 0.91, 95% CI: 0.87-0.96, p trend<0.001), whereas no associations were observed for advanced or fatal PCa, or for Western modern (characterised by sweets, processed meat, beef, cheese, and pizza) or Western traditional (characterised gravy, eggs, potatoes and white bread) patterns., Conclusion: We found evidence to support a modest, protective role for a plant-based dietary pattern during adolescence on PCa risk. If confirmed in future studies, our findings may help to inform the development of new, primary prevention strategies for PCa., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Although fruit and vegetable intake during adolescence, a potentially sensitive time period for prostate cancer (PCa) development, has been proposed to protect against PCa risk, few studies have investigated the role of adolescent plant product intake in PCa development., Methods: Intake of various vegetables, fruit, and grains by males at ages 12-13 y was examined in relation to later PCa risk and mortality in the NIH-AARP Diet and Health Study. Cox proportional hazards regression was used to calculate HRs and 95% CIs of nonadvanced (n = 14,238) and advanced (n = 2,170) PCa incidence and PCa mortality (n = 760) during 1,729,896 person-years of follow-up., Results: None of the plant products examined were associated consistently with all PCa outcomes. However, greater adolescent intakes of tomatoes (P-trend = 0.004) and nonstarch vegetables (P-trend = 0.025) were associated with reduced risk of nonadvanced PCa, and greater intakes of broccoli (P-trend = 0.050) and fruit juice (P-trend = 0.019-0.025) were associated with reduced risk of advanced PCa and/or PCa mortality. Positive trends were also observed for greater intakes of fruit juice (P-trend = 0.002), total fruit (P-trend = 0.014), and dark bread (P-trend = 0.035) with nonadvanced PCa risk and for greater intakes of legumes (P-trend < 0.001), fiber (P-trend = 0.001), and vegetable protein (P-trend = 0.013-0.040) with advanced PCa risk or PCa mortality., Conclusions: Our findings do not provide strong evidence to suggest that adolescent plant product intake is associated with reduced PCa risk., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Background: Adolescent intake of animal products has been proposed to contribute to prostate cancer (PCa) development because of its potentially carcinogenic constituents and influence on hormone levels during adolescence., Methods: We used data from 159,482 participants in the NIH-AARP Diet and Health Study to investigate associations for recalled adolescent intake of red meat (unprocessed beef and processed red meat), poultry, egg, canned tuna, animal fat and animal protein at ages 12-13 years with subsequent PCa risk and mortality over 14 years of follow-up. Cox proportional hazard regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) of total (n = 17,349), advanced (n = 2,297) and fatal (n = 804) PCa., Results: Suggestive inverse trends were observed for adolescent unprocessed beef intake with risks of total, advanced and fatal PCa (multivariable-adjusted P-trends = 0.01, 0.02 and 0.04, respectively). No consistent patterns of association were observed for other animal products by PCa outcome., Conclusion: We found evidence to suggest that adolescent unprocessed beef intake, or possibly a correlate of beef intake, such as early-life socioeconomic status, may be associated with reduced risk and mortality from PCa. Additional studies with further early-life exposure information are warranted to better understand this association., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Evidence regarding lignan consumption in relation to coronary heart disease (CHD) risk remains limited and mixed., Objectives: The aim of this study was to prospectively examine associations between lignan intake and CHD risk in U.S. men and women., Methods: We prospectively followed 214,108 men and women in 3 cohorts who did not have cardiovascular disease or cancer at baseline. Diet was repeatedly assessed using a validated food frequency questionnaire every 2-4 years since baseline., Results: During 5,517,225 person-years of follow-up, we documented 10,244 CHD cases, including 6,283 nonfatal myocardial infarction and 3,961 fatal CHD cases. In multivariable-adjusted analyses, comparing extreme quintiles, the pooled hazard ratios of CHD were 0.85 (95% CI: 0.79-0.92) for total lignans, 0.76 (95% CI: 0.71-0.82) for matairesinol, 0.87 (95% CI: 0.81-0.93) for secoisolariciresinol, 0.89 (95% CI: 0.83-0.95) for pinoresinol, and 0.89 (95% CI: 0.83-0.95) for lariciresinol (all P values for trend ≤0.003). Nonlinear relationships were found for total lignan, matairesinol, and secoisolariciresinol: the risk reduction plateaued at intakes above approximately 300 μg/d, 10 μg/d, and 100 μg/d, respectively (P < 0.01 for all nonlinearity). The inverse associations for total lignan intake appeared to be more apparent among participants with higher total fiber intake (P = 0.04 for interaction). In addition, lignan intake was more strongly associated with plasma concentrations of enterolactone when fiber intake was higher., Conclusions: Increased long-term intake of lignans was associated with a significantly lower risk of total CHD in both men and women. Possible synergistic effects may exist between lignan and fiber intake in relation to CHD risk reduction, possibly through enhancing the production of enterolignans., Competing Interests: Funding Support and Author Disclosures The NHS, NHSII, and HPFS studies and the current analysis are supported by National Institutes of Health grants UM1 CA186107, P01 CA87969, R01 CA49449, R01 HL034594, R01 HL088521, U01 CA176726, R01 CA67262, U01 CA167552, R01 HL035464, R01 HL060712, and R01 DK120870. The funding sources did not participate in the design or conduct of the study; collection, management, analysis or interpretation of the data; or preparation, review, or approval of the manuscript. The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Trimethylamine-N-oxide (TMAO) is a compound that is present in seafood and produced through human gut microbial metabolism of its precursors. Previous studies have suggested that elevated TMAO concentrations are associated with an increased risk of cardiovascular events. However, the association between diet and TMAO concentrations in free-living adult populations has not been adequately described., Objectives: The objective of this study was to identify dietary predictors of plasma TMAO concentrations., Methods: TMAO concentrations were assessed in 2 fasting plasma samples collected 6 mo apart among 620 healthy men. Short-term and long-term dietary intakes were assessed during the same time-frame of blood collections via repeated 7-d dietary records (7DDRs) and a semiquantitative food-frequency questionnaire (SFFQ), respectively. We grouped individual food items into 21 groups and regressed against averaged TMAO concentrations. We also assessed the association between dietary scores and TMAO concentrations., Results: In models adjusted for demographic characteristics and mutually adjusted for food groups, SFFQ-assessments of fish and egg intakes were significantly associated with increased TMAO concentration (β = 0.082; 95% CI: 0.021, 0.14; P = 0.009 for fish; β = 0.065; 95% CI: 0.004, 0.13; P = 0.039 for egg). The positive association between fish consumption and TMAO concentration was replicated in the 7DDR-assessments (β = 0.12; 95% CI: 0.060, 0.18; P < 0.001). There was no association between red meat intake and TMAO concentrations. The unhealthful plant-based diet index (uPDI) was inversely associated (β = -0.013; 95% CI: -0.021, -0.005; P = 0.001) and healthy dietary scores were positively correlated with TMAO concentration., Conclusions: TMAO concentration was significantly associated with fish intake, but not with red meat consumption. uPDI, an unhealthy dietary pattern, was inversely related to TMAO concentration. As such, this study suggests that in free-living populations, higher circulating concentrations of TMAO cannot simply be interpreted as a marker of unhealthy food intake or an unhealthy dietary pattern., (Copyright © The Author(s) on behalf of the American Society for Nutrition 2020.)

Background: Preterm birth (PTB), small for gestational age (SGA), and low birth weight (LBW) are risk factors for morbidity and mortality among infants. High-quality maternal diets during pregnancy may protect against these adverse birth outcomes., Objectives: The aim of this study was to prospectively examine the association of maternal dietary diversity and quality during pregnancy with birth outcomes among women in Dar es Salaam, Tanzania., Methods: We analyzed data from 7553 HIV-negative pregnant women enrolled in a multivitamin trial at 12-27 weeks of gestation. Dietary intake was assessed using 24-h dietary recalls. Dietary diversity scores (DDS; range: 0-10) were computed as the number of food groups consumed by women, using FAO's Minimum Dietary Diversity for Women index. The Prime Diet Quality Score (PDQS; range: 0-42) assessed maternal diet quality based on consumption of 21 healthy and unhealthy food groups. Log binomial regression methods were used to assess associations of DDS and PDQS with PTB, SGA, LBW, and fetal loss., Results: In the previous 24 h, 99.9% of all women had consumed cereal and staples, 57.9% meats, 4.7% eggs, and 0.5% nuts and seeds. Median DDS was 3.0 (IQR: 2.5-3.5). For the PDQS, all women consumed ≥4 servings/wk of green leafy vegetables and refined grains. Higher DDS was associated with lower risk of SGA (RR highest compared with lowest quintile: 0.74; 95% CI: 0.62, 0.89). Higher PDQS was associated with lower risk of PTB (RR highest compared with lowest quintile: 0.55; 95% CI: 0.46, 0.66), LBW (RR: 0.53; 95% CI: 0.40, 0.70), and fetal loss (RR: 0.53; 95% CI, 0.34, 0.82)., Conclusions: PDQS was inversely associated with PTB, LBW, and fetal loss, and DDS was inversely associated with SGA. These findings suggest that in addition to dietary diversity, diet quality should be considered as important in understanding dietary risk factors for poor birth outcomes.This trial was registered at clinicaltrials.gov as NCT00197548., (Copyright © The Author(s) on behalf of the American Society for Nutrition 2020.)

Background & Aims: Specific nutritional components are likely to induce intestinal inflammation, which is characterized by increased levels of interleukin 6 (IL6), C-reactive protein (CRP), and tumor necrosis factor-receptor superfamily member 1B (TNFRSF1B) in the circulation and promotes colorectal carcinogenesis. The inflammatory effects of a diet can be estimated based on an empiric dietary inflammatory pattern (EDIP) score, calculated based on intake of 18 foods associated with plasma levels of IL6, CRP, and TNFRSF1B. An inflammatory environment in the colon (based on increased levels of IL6, CRP, and TNFRSF1B in peripheral blood) contributes to impairment of the mucosal barrier and altered immune cell responses, affecting the composition of the intestinal microbiota. Colonization by Fusobacterium nucleatum has been associated with the presence and features of colorectal adenocarcinoma. We investigated the association between diets that promote inflammation (based on EDIP score) and colorectal cancer subtypes classified by level of F nucleatum in the tumor microenvironment., Methods: We calculated EDIP scores based on answers to food frequency questionnaires collected from participants in the Nurses' Health Study (through June 1, 2012) and the Health Professionals Follow-up Study (through January 31, 2012). Participants in both cohorts reported diagnoses of rectal or colon cancer in biennial questionnaires; deaths from unreported colorectal cancer cases were identified through the National Death Index and next of kin. Colorectal tumor tissues were collected from hospitals where the patients underwent tumor resection and F nucleatum DNA was quantified by a polymerase chain reaction assay. We used multivariable duplication-method Cox proportional hazard regression to assess the associations of EDIP scores with risks of colorectal cancer subclassified by F nucleatum status., Results: During 28 years of follow-up evaluation of 124,433 participants, we documented 951 incident cases of colorectal carcinoma with tissue F nucleatum data. Higher EDIP scores were associated with increased risk of F nucleatum-positive colorectal tumors (P trend  = .03); for subjects in the highest vs lowest EDIP score tertiles, the hazard ratio for F nucleatum-positive colorectal tumors was 1.63 (95% CI, 1.03-2.58). EDIP scores did not associate with F nucleatum-negative tumors (P trend  = .44). High EDIP scores associated with proximal F nucleatum-positive colorectal tumors but not with proximal F nucleatum-negative colorectal tumors (P heterogeneity  = .003)., Conclusions: Diets that may promote intestinal inflammation, based on EDIP score, are associated with increased risk of F nucleatum-positive colorectal carcinomas, but not carcinomas that do not contain these bacteria. These findings indicate that diet-induced intestinal inflammation alters the gut microbiome to contribute to colorectal carcinogenesis; nutritional interventions might be used in precision medicine and cancer prevention., (Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Objective: Although evidence suggests an inverse association between calcium intake and the risk of colorectal cancer, the mechanisms remain unclear. The calcium-sensing receptor (CASR) is expressed abundantly in normal colonic epithelium and may influence carcinogenesis. We hypothesized that calcium intake might be associated with lower risk of CASR-positive, but not CASR-negative, colorectal cancer., Design: We assessed tumour CASR protein expression using immunohistochemistry in 779 incident colon and rectal cancer cases that developed among 136 249 individuals in the Nurses' Health Study and Health Professionals Follow-Up Study. Duplication method Cox proportional hazards regression analysis was used to assess associations of calcium intake with incidence of colorectal adenocarcinoma subtypes by CASR status., Results: Total calcium intake was inversely associated with the risk of developing colorectal cancer (p trend =0.01, comparing ≥1200 vs <600 mg/day: multivariable HR=0.75, 95% CI 0.60 to 0.95). For the same comparison, higher total calcium intake was associated with a lower risk of CASR-positive tumours (p trend =0.003, multivariable HR=0.67, 95% CI 0.51 to 0.86) but not with CASR-negative tumours (p trend =0.67, multivariable HR=1.15, 95% CI 0.75 to 1.78; p heterogeneity =0.06 between the CASR subtypes). The stronger inverse associations of calcium intake with CASR-positive but not CASR-negative tumours generally appeared consistent regardless of sex, tumour location and source of calcium., Conclusions: Our molecular pathological epidemiology data suggest a causal relationship between higher calcium intake and lower colorectal cancer risk, and a potential role of CASR in mediating antineoplastic effect of calcium., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background & Aims: Dietary patterns affect systemic and local intestinal inflammation, which have been linked to colorectal carcinogenesis. Chronic inflammation can interfere with the adaptive immune response. We investigated whether the association of a diet that promotes intestinal inflammation with risk of colorectal carcinoma was stronger for tumors with lower lymphocytic reactions than tumors with higher lymphocytic reactions., Methods: We collected data from the molecular pathological epidemiology databases of 2 prospective cohort studies: the Nurses' Health Study (since 1976) and the Health Professionals Follow-Up Study (since 1986). We used duplication-method time-varying Cox proportional cause-specific hazards regression to assess the association of empirical dietary inflammatory pattern (EDIP) score (derived from food frequency questionnaire data) with colorectal carcinoma subtype. Foods that contribute to high EDIP scores include red and processed meats, refined grains, carbonated beverages, and some vegetables; foods that contribute to low EDIP scores include beer, wine, coffee, tea, yellow and leafy vegetables, and fruit juice. Colorectal tissue samples were analyzed histologically for patterns of lymphocytic reactions (Crohn's-like lymphoid reaction, peritumoral lymphocytic reaction, intratumoral periglandular reaction, and tumor-infiltrating lymphocytes)., Results: During follow-up of 124,433 participants, we documented 1311 incident colon and rectal cancer cases with available tissue data. The association between the EDIP and colorectal cancer risk was significant (P trend  = .02), and varied with degree of peritumoral lymphocytic reaction (P heterogeneity < .001). Higher EDIP scores were associated with increased risk of colorectal cancer with an absent or low peritumoral lymphocytic reaction (highest vs lowest EDIP score quintile hazard ratio, 2.60; 95% confidence interval, 1.60-4.23; P trend < .001), but not risk of tumors with intermediate or high peritumoral lymphocytic reaction (P trend > .80)., Conclusions: In 2 prospective cohort studies, we associated inflammatory diets with a higher risk of colorectal cancer subtype that contains little or no peritumoral lymphocytic reaction. These findings suggest that diet-related inflammation might contribute to development of colorectal cancer, by suppressing the adaptive anti-tumor immune response., (Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Importance: Marine ω-3 polyunsaturated fatty acids (PUFAs), including eicosapentaenoic acid, docosahexaenoic acid, and docosapentaenoic acid, possess potent immunomodulatory activity and may protect against cancer development. However, evidence relating marine ω-3 PUFAs to colorectal cancer (CRC) risk remains inconclusive., Objective: To test the hypothesis that marine ω-3 PUFA intake may be associated with lower risk of CRC subsets characterized by immune infiltrate., Design, Setting, and Participants: This prospective cohort study was conducted among participants in the Nurses' Health Study (1984-2010) and Health Professionals Follow-up Study (1986-2010)., Exposures: Intake of marine ω-3 PUFAs., Main Outcomes and Measures: Incidence of CRC characterized by CD3+, CD8+, CD45RO (PTPRC)+, or FOXP3+ T-cell densities in tumor tissue, measured by immunohistochemical and computer-assisted image analysis., Results: Among 173 229 predominantly white participants, 125 172 with 2 895 704 person-years of follow-up provided data about marine ω-3 PUFA intake every 4 years through a validated food frequency questionnaire and followed up for incident CRC evaluation. Of 2504 CRC cases, we documented 614 (252 men, 362 women) from which we could assess T-cell infiltration in the tumor microenvironment. The inverse association of marine ω-3 PUFAs intake with CRC risk differed according to FOXP3+ T-cell infiltration: compared with intake of less than 0.15 g/d of marine ω-3 PUFAs, intake of at least 0.35 g/d was associated with a multivariable hazard ratio (HR) of 0.57 (95% CI, 0.40-0.81; P < .001 for trend) for FOXP3+ T-cell-high tumors. In contrast, the HR for FOXP3+ T-cell-low tumors was 1.14 (95% CI, 0.8-1.60) (P = .77 for trend; P = .01 for heterogeneity). No statistically significant differential association was found for high-density tumors (compared with low-density tumors) according to CD3+, CD8+, or CD45RO+ cell density (P ≥ .34 for heterogeneity for all comparisons). In functional assays, the suppressive activity of regulatory T cells was approximately 2-fold lower (T-effector-cell proliferation, ≥64% vs 38%) when preincubated with docosahexaenoic acid at 50μM, 100μM, and 200μM concentrations than without docosahexaenoic acid (P < .001 for all comparisons)., Conclusions and Relevance: High marine ω-3 PUFA intake was associated with lower risk of CRC with high-level, but not low-level, FOXP3+ T-cell density, suggesting a potential role of ω-3 PUFAs in cancer immunoprevention through modulation of regulatory T cells., Competing Interests: Disclosures: Andrew T. Chan previously served as a consultant for Bayer Healthcare, Pozen Inc, and Pfizer Inc. for work unrelated to the topic of this manuscript. This study was not funded by Bayer Healthcare, Pozen Inc, or Pfizer Inc. No other conflict of interest exists.

Background: Higher intake of certain vitamins may protect against cochlear damage from vascular compromise and oxidative stress, thereby reducing risk of acquired hearing loss, but data are limited., Objective: We prospectively examined the relation between carotenoids, vitamin A, vitamin C, vitamin E, and folate intake and risk of self-reported hearing loss in women., Design: This prospective cohort study followed 65,521 women in the Nurses' Health Study II from 1991 to 2009. Baseline and updated information obtained from validated biennial questionnaires was used in Cox proportional hazards regression models to examine independent associations between nutrient intake and self-reported hearing loss., Results: After 1,084,598 person-years of follow-up, 12,789 cases of incident hearing loss were reported. After multivariable adjustment, we observed modest but statistically significant inverse associations between higher intake of β-carotene and β-cryptoxanthin and risk of hearing loss. In comparison with women in the lowest quintile of intake, the multivariable-adjusted RR of hearing loss among women in the highest quintile was 0.88 (95% CI: 0.81, 0.94; P-trend < 0.001) for β-carotene and 0.90 (95% CI: 0.84, 0.96; P-trend < 0.001) for β-cryptoxanthin. In comparison with women with folate intake 200-399 μg/d, very low folate intake (<200 μg/d) was associated with higher risk (RR: 1.19; 95% CI: 1.01, 1.41), and higher intake tended to be associated with lower risk (P-trend = 0.04). No significant associations were observed for intakes of other carotenoids or vitamin A. Higher vitamin C intake was associated with higher risk; in comparison with women with intake <75 mg/d, the RR among women with vitamin C intake ≥1000 mg/d (mainly supplemental) was 1.22 (95% CI: 1.06, 1.42; P-trend = 0.02). There was no significant trend between intake of vitamin E intake and risk., Conclusion: Higher intakes of β-carotene, β-cryptoxanthin, and folate, whether total or from diet, are associated with lower risk of hearing loss, whereas higher vitamin C intake is associated with higher risk., (© 2015 American Society for Nutrition.)

Although the association between red meat consumption and colorectal cancer (CRC) is well established, the association across subsites of the colon and rectum remains uncertain, as does time of consumption in relation to cancer development. As these relationships are key for understanding the pathogenesis of CRC, they were examined in two large cohorts with repeated dietary measures over time, the Nurses' Health Study (n = 87,108 women, 1980-2010) and Health Professionals Follow-up Study (n = 47,389 men, 1986-2010). Cox proportional hazards regression models generated hazard ratios (HRs) and 95% confidence intervals (CIs), which were pooled by random-effects meta-analysis. In combined cohorts, there were 2,731 CRC cases (1,151 proximal colon, 816 distal colon, and 589 rectum). In pooled analyses, processed red meat was positively associated with CRC risk (per 1 serving/day increase: HR = 1.15, 95% CI: 1.01-1.32; P for trend 0.03) and particularly with distal colon cancer (per 1 serving/day increase; HR = 1.36; 95% CI: 1.09-1.69; P for trend 0.006). Recent consumption of processed meat (within the past 4 years) was not associated with distal cancer. Unprocessed red meat was inversely associated with risk of distal colon cancer and a weak non-significant positive association between unprocessed red meat and proximal cancer was observed (per 1 serving/day increase: distal HR = 0.75; 95% CI: 0.68-0.82; P for trend <0.001; proximal HR = 1.14, 95% CI: 0.92-1.40; P for trend 0.22). Thus, in these two large cohorts of US health professionals, processed meat intake was positively associated with risk of CRC, particularly distal cancer, with little evidence that higher intake of unprocessed red meat substantially increased risk of CRC. Future studies, particularly those with sufficient sample size to assess associations by subsites across the colon are needed to confirm these findings and elucidate potentially distinct mechanisms underlying the relationship between processed meat and subtypes of unprocessed red meat with CRC.

Background: Regular milk consumption during childhood and adolescence is recommended for bone health. However, milk consumption increases circulating insulin-like growth factor I concentrations, and may also accelerate puberty., Objective: We prospectively investigated the association between milk consumption and age at menarche in the Growing Up Today Study., Methods: Study participants were 5583 US girls who were premenarcheal and ages 9-14 y in 1996. Girls were followed through 2001, at which time 97% of noncensored participants had reported menarche. Frequency of milk and meat consumption was calculated with the use of annual youth/adolescent food frequency questionnaires from 1996-1998. Intake of related nutrients was also measured. Age at menarche was self-reported annually through 2001., Results: During follow-up, 5227 girls attained menarche over 10,555 accrued person-years. In models adjusted for dietary and sociodemographic predictors of menarche, frequency of milk consumption did not predict age at onset of menarche (for >3 glasses of milk/d vs. 1.1-4 glasses/wk, HR: 0.93; 95% CI: 0.83, 1.04). After additional adjustment for body size, premenarcheal girls consuming >3 glasses of milk daily were 13% less likely (95% CI: -3%, -23%; P-trend: <0.01) to attain menarche in the next month relative to those consuming 1.1-4 glasses/wk. Neither total meat nor red meat consumption was associated with age at menarche., Conclusions: Our findings suggest that regular consumption of milk in girls aged ≥9 y is unlikely to substantially affect age at onset of menarche. Studies assessing associations between diet in early childhood and pubertal timing may be more illuminating., (© 2015 American Society for Nutrition.)

Background: Use of multivitamin supplements during the pre-HAART era has been found to reduce viral load, enhance immune response, and generally improve clinical outcomes among HIV-infected adults. However, immune reconstitution is incomplete and significant mortality and opportunistic infections occur in spite of HAART. There is insufficient research information on whether multivitamin supplementation may be beneficial as adjunct therapy for HIV-infected individuals taking HAART. We propose to evaluate the efficacy of a single recommended daily allowance (RDA) of micronutrients (including vitamins B-complex, C, and E) in slowing disease progression among HIV-infected adults receiving HAART in Uganda., Methods/design: We are using a randomized, double-blind, placebo-controlled trial study design. Eligible patients are HIV-positive adults aged at least 18 years, and are randomized to receive either a placebo; or multivitamins that include a single RDA of the following vitamins: 1.4 mg B1, 1.4 mg B2, 1.9 mg B6, 2.6 mcg B12, 18 mg niacin, 70 mg C, 10 mg E, and 0.4 mg folic acid. Participants are followed for up to 18 months with evaluations at baseline, 6, 12 and 18 months. The study is primarily powered to examine the effects on immune reconstitution, weight gain, and quality of life. In addition, we will examine the effects on other secondary outcomes including the risks of development of new or recurrent disease progression event, including all-cause mortality; ARV regimen change from first- to second-line therapy; and other adverse events as indicated by incident peripheral neuropathy, severe anemia, or diarrhea., Discussions: The conduct of this trial provides an opportunity to evaluate the potential benefits of this affordable adjunct therapy (multivitamin supplementation) among HIV-infected adults receiving HAART in a developing country setting., Trial Registration: Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01228578.

Background: Certain dietary patterns can elicit systemic and intestinal inflammatory responses, which may influence adaptive anti‐tumor immune responses and tumor behavior. We hypothesized that pro‐inflammatory diets might be associated with higher colorectal cancer mortality and that the association might be stronger for tumors with lower immune responses. Methods: We calculated an empirical dietary inflammatory pattern (EDIP) score in 2829 patients among 3988 incident rectal and colon carcinoma cases in the Nurses' Health Study and Health Professionals Follow‐up Study. Using Cox proportional hazards regression analyses, we examined the prognostic association of EDIP scores and whether it might be modified by histopathologic immune reaction (in 1192 patients with available data). Results: Higher EDIP scores after colorectal cancer diagnosis were associated with worse survival, with multivariable‐adjusted hazard ratios (HRs) for the highest versus lowest tertile of 1.41 (95% confidence interval [CI]: 1.13–1.77; Ptrend = 0.003) for 5‐year colorectal cancer‐specific mortality and 1.44 (95% CI, 1.19‐1.74; Ptrend = 0.0004) for 5‐year all‐cause mortality. The association of post‐diagnosis EDIP scores with 5‐year colorectal cancer‐specific mortality differed by degrees of tumor‐infiltrating lymphocytes (TIL; Pinteraction =.002) but not by three other lymphocytic reaction patterns. The multivariable‐adjusted, 5‐year colorectal cancer‐specific mortality HRs for the highest versus lowest EDIP tertile were 1.59 (95% CI: 1.01–2.53) in TIL‐absent/low cases and 0.48 (95% CI: 0.16–1.48) in TIL‐intermediate/high cases. Conclusions: Pro‐inflammatory diets after colorectal cancer diagnosis were associated with increased mortality, particularly in patients with absent or low TIL. [ABSTRACT FROM AUTHOR]

Healthy maternal diets during pregnancy are an important protective factor for pregnancy‐related outcomes, including gestational weight gain (GWG) and birth outcomes. We prospectively examined the associations of maternal dietary diversity and diet quality, using Minimum Dietary Diversity for Women (MDD‐W) and Prime Diet Quality Score (PDQS), with GWG and birth outcomes among women enrolled in a trial in Tanzania (n = 1190). MDD‐W and PDQS were derived from a baseline food frequency questionnaire. Women were monthly followed until delivery, during which weight was measured. GWG was classified based on the 2009 Institute of Medicine guidelines. Adverse birth outcomes were classified as low birth weight (LBW), small for gestational age, large for gestational age, and preterm birth. 46.2% participants had MDD‐W ≥ 5. Mean score of PDQS was 23.3. Maternal intakes of nuts, poultry, and eggs were low, whereas intakes of sugar‐sweetened beverages and refined grains were high. MDD‐W was not associated with GWG or birth outcomes. For PDQS, compared to the lowest tertile, women in the highest tertile had lower risk of inappropriate GWG (risk ratio [RR] = 0.93, 95% confidence interval [CI]: 0.87–1.00). Women in the middle tertile group of PDQS (RR = 0.72, 95% CI: 0.51–1.00) had lower risk of preterm birth. After excluding women with prior complications, higher PDQS was associated with lower risk of LBW (middle tertile: RR = 0.55, 95% CI: 0.31–0.99, highest tertile: RR = 0.52, 95% CI: 0.29–0.94; continuous per SD: RR = 0.77, 95% CI: 0.60–0.99). Our findings support continuing efforts to improve maternal diet quality for optimal GWG and infant outcomes among Tanzanian women. Key messages: •Maternal diets are a key modifiable determinant of gestational weight gain (GWG) and birth outcomes.•We observed suboptimal intakes of healthy proteins and fats and high intakes of refined grains and sugar‐containing foods among well‐nourished pregnant women in urban Tanzania.•This study found that higher‐quality maternal diets were associated with lower risks of inappropriate GWG, low birth weight, and preterm birth.•This study supports the importance of high maternal diet quality and continuing efforts to promote well‐balanced maternal diets with avoiding both under‐ and over‐nutrition for optimal pregnancy outcomes among Tanzanian populations. [ABSTRACT FROM AUTHOR]

Background Diet quality scores (DQSs) are frequently used to study diet–disease relations but the validity of these scores derived from FFQs has rarely been evaluated. Objectives To evaluate the validity and reproducibility of 6 commonly used DQSs derived from the FFQ, including the Alternate Healthy Eating Index–2010, Dietary Approaches to Stop Hypertension Trial score, alternative Mediterranean diet score, and 3 plant-based diet indices (overall, healthful, and unhealthful). Methods This analysis included 1394 participants from the Men's Lifestyle Validation Study (N = 652) and the Women's Lifestyle Validation Study (N = 742). Participants completed a 152-item FFQ at the beginning of the study and 1 y later, as well as completed 2 weighed 7-d dietary records (7DDRs) and donated 2 blood samples 6 mo apart between FFQ assessments. The reproducibility of the FFQs was evaluated by rank intraclass correlation coefficients (ICCs). The validity was assessed by comparing FFQ-derived DQSs with those from the average of two 7DDRs using Spearman rank correlation coefficients deattenuated for random measurement error in the 7DDRs (r s). Furthermore, we calculated the correlations between DQSs and plasma biomarkers of diet, including fatty acids, folate, carotenoids, retinol, and α- and γ-tocopherol. Results Six FFQ-derived DQSs demonstrated moderate to high reproducibility (energy-adjusted ICCs: 0.61–0.84) and validity (energy-adjusted, deattenuated r s = 0.56–0.80) in both men and women. We consistently observed expected correlations between FFQ-derived DQSs with plasma fatty acids, including long-chain n–3 (ω-3) and trans fatty acids, most carotenoids, and γ-tocopherol (r s > 0.2). Conclusions Our study demonstrates the validity of the FFQ to evaluate overall diet quality using 6 commonly used DQSs. In addition, these DQSs have qualitatively demonstrated biological relevance, as indicated by their correlations with circulating biomarkers. [ABSTRACT FROM AUTHOR]

Background Epidemiologic studies examining the relations between dairy product and calcium intakes and breast cancer have been inconclusive, especially for tumor subtypes. Objective To evaluate the associations between intakes of specific dairy products and calcium and risk of breast cancer overall and for subtypes defined by estrogen receptor (ER) status. Method We pooled the individual-level data of over 1 million women who were followed for a maximum of 8–20 years across studies. Associations were evaluated for dairy product and calcium intakes and risk of incident invasive breast cancer overall (n  = 37,861 cases) and by subtypes defined by ER status. Study-specific multivariable hazard ratios (HRs) were estimated and then combined using random-effects models. Results Overall, no clear association was observed between the consumption of specific dairy foods, dietary (from foods only) calcium, and total (from foods and supplements) calcium, and risk of overall breast cancer. Although each dairy product showed a null or very weak inverse association with risk of overall breast cancer (P , test for trend >0.05 for all), differences by ER status were suggested for yogurt and cottage/ricotta cheese with associations observed for ER-negative tumors only (pooled HR = 0.90, 95% CI: 0.83, 0.98 comparing ≥60 g/d with <1 g/d of yogurt and 0.85, 95% CI: 0.76, 0.95 comparing ≥25 g/d with <1 g/d of cottage/ricotta cheese). Dietary calcium intake was only weakly associated with breast cancer risk (pooled HR = 0.98, 95% CI: 0.97, 0.99 per 350 mg/d). Conclusion Our study shows that adult dairy or calcium consumption is unlikely to associate with a higher risk of breast cancer and that higher yogurt and cottage/ricotta cheese intakes were inversely associated with the risk of ER-negative breast cancer, a less hormonally dependent subtype with poor prognosis. Future studies on fermented dairy products, earlier life exposures, ER-negative breast cancer, and different racial/ethnic populations may further elucidate the relation. [ABSTRACT FROM AUTHOR]

Growth faltering in early childhood is prevalent in many low resource countries. Poor maternal dietary diversity during pregnancy has been linked with increased risk of fetal growth failure and adverse birth outcomes but may also influence subsequent infant growth. Our aim is to assess the role of prenatal maternal dietary diversity in infant growth in rural Uganda. Data from 3291 women and infant pairs enrolled in a birth cohort from 2014 to 2016 were analysed (NCT04233944). Maternal diets were assessed using dietary recall in the second or third trimesters of pregnancy. Maternal dietary diversity scores (DDS) were calculated using the FAO Minimum Dietary Diversity for Women (MDD‐W). Cox regression models were used to evaluate associations of the DDS with the incidence of underweight, stunting and wasting in infants from 3 to 12 months, adjusting for confounding factors. The median DDS for women was low, at 3.0 (interquartile range 3.0–4.0), relative to the threshold of consuming five or more food groups daily. Infants of women in highest quartile of DDS (diverse diets) were less likely to be underweight (adjusted hazard ratio: 0.70, 95% confidence interval: 0.61, 0.80) compared with infants of women in Quartile 1 (p for trend <0.001) in models controlling for maternal factors. There was no significant association between DDS and stunting or wasting. Our findings suggest a relationship between higher maternal dietary diversity and lower risk of underweight in infancy. These findings suggest that programmes to improve infant growth could additionally consider strengthening prenatal dietary diversity to improve child outcomes globally. [ABSTRACT FROM AUTHOR]

Purpose: Although a growing body of evidence supports an early-life contribution to prostate cancer (PCa) development, few studies have investigated early-life diet, and only three have examined early-life dairy product intake, a promising candidate risk factor because of its known/suspected influence on insulin-like growth factor levels and height. Methods: We used recalled dietary data from 162,816 participants in the NIH-AARP Diet and Health Study to investigate associations for milk, cheese, ice cream, total dairy, and calcium intake at ages 12–13 years with incident total (n = 17,729), advanced (n = 2,348), and fatal PCa (n = 827) over 14 years of follow-up. We calculated relative risks (RRs) and 95% confidence intervals (CIs) by Cox proportional hazards regression. Results: We observed suggestive positive trends for milk, dairy, and calcium intake with total and/or advanced PCa (p-trends = 0.016–0.148). These trends attenuated after adjustment for additional components of adolescent diet, particularly red meat and vegetables/potatoes. In contrast, suggestive inverse trends were observed for cheese and ice cream intake with total and/or advanced PCa (p-trends = 0.043–0.153), and for milk, dairy, and calcium intake with fatal PCa (p-trend = 0.045–0.117). Conclusion: Although these findings provide some support for a role of adolescent diet in increasing PCa risk, particularly for correlates of milk intake or overall dietary patterns, our protective findings for cheese and ice cream intake with PCa risk and mortality, and for all dairy products with PCa mortality, suggest alternative explanations, such as the influence of early-life socioeconomic status, and increased PCa screening, earlier detection, and better PCa care. [ABSTRACT FROM AUTHOR]

We conducted a prospective study of dietary patterns and longitudinal change in audiometric hearing thresholds among 3,135 women (mean age = 59 years) in the Nurses' Health Study II (2012–2018). Diet adherence scores for the Dietary Approaches to Stop Hypertension (DASH) and Alternate Mediterranean (AMED) diets and the Alternate Healthy Eating Index 2010 (AHEI-2010) were calculated using validated food-frequency questionnaires. Baseline and 3-year follow-up hearing sensitivities were assessed by pure-tone audiometry at 19 US sites. We used multivariable-adjusted logistic regression models to examine independent associations between diet adherence scores and risk of ≥5 dB elevation in the pure-tone average (PTA) of low-frequency (LPTA0.5,1,2 kHz), mid-frequency (MPTA3,4 kHz), and high-frequency (HPTA6,8 kHz) hearing thresholds. Higher adherence scores were associated with lower risk of hearing loss. Compared with the lowest quintile of DASH score, the multivariable-adjusted odds ratios for mid-frequency and high-frequency threshold elevation in the highest quintile were 0.71 (95% confidence interval (CI): 0.55, 0.92; P for trend = 0.003) and 0.75 (95% CI: 0.59, 0.96; P for trend = 0.02); for AMED and AHEI scores, for mid-frequency threshold elevation, they were 0.77 (95% CI: 0.60, 0.99; P for trend = 0.02) and 0.72 (95% CI: 0.57, 0.92; P for trend = 0.002). Nonsignificant inverse associations were observed for high-frequency threshold elevation. There were no significant associations between adherence scores and low-frequency threshold elevation. Our findings indicate that eating a healthy diet might reduce the risk of acquired hearing loss. [ABSTRACT FROM AUTHOR]

Background: Interindividual differences in the bioavailability of potentially carcinogenic estrogen and estrogen metabolites (EMs) may play a role in the risk of breast cancer. Objective: We examined whether dietary intakes of fiber and fat influence premenopausal EM profiles through effects on estrogen synthesis, metabolism, or excretion. Methods: We conducted a cross-sectional analysis of 598 premenopausal women who participated in a reproducibility study (n = 109) or served as controls in a nested case-control study of breast cancer (n = 489) within the Nurses' Health Study II. Dietary intakes of fiber and fat were assessed via semiquantitative food frequency questionnaires in 1995 and 1999. Midluteal urine samples were collected between 1996 and 1999 and EMs were quantified with the use of HPLC-tandem mass spectrometry. Linear mixed models were used to estimate creatinine-adjusted geometric means for individual EMs and their pathway groups across categories of dietary intake while controlling for total energy intake and potential confounders. Results: Higher total dietary fiber intake (>25 g/d vs. ≤15 g/d) was associated with significantly higher concentrations of 4-methoxyestradiol (50% difference, P-difference = 0.01, P-trend = 0.004) and lower concentrations of 17-epiestriol (227% difference, P-difference = 0.03, P-trend = 0.03), but was not associated with any other EMs. The associations did not vary by fiber intake from different sources. Total fat intake (>35% energy vs. ≤25% energy) was suggestively positively associated with 17-epiestriol (22.6% difference, P-difference = 0.14, P-trend = 0.06); the association was significant for polyunsaturated fatty acid (37%difference, P-difference = 0.01, P-trend = 0.01) and trans fat (36.1% difference, P-difference = 0.01, P-trend = 0.01) intakes. Conclusion: Fiber and fat intakes were not strongly associated with patterns of estrogen metabolism in premenopausal women. Our data suggest estrogen metabolism is not a major mechanism through which dietary fiber and fat may affect breast or other hormone-related cancer risks. [ABSTRACT FROM AUTHOR]

Background: Acquired hearing loss is common and often disabling, yet limited prospective data exist on potentially modifiable risk factors. Evidence suggests that higher intake of fish and long-chain omega-3 (n23) polyunsaturated fatty acids (PUFAs) may be associated with a lower risk of hearing loss, but prospective information on these relations is limited. Objective: We prospectively examined the independent associations between consumption of total and specific types of fish, long-chain omega-3 PUFAs, and self-reported hearing loss in women. Design: Data were from the Nurses' Health Study II, a prospective cohort study. The independent associations between consumption of fish and long-chain omega-3 PUFAs and self-reported hearing loss were examined in 65,215 women followed from 1991 to 2009. Baseline and updated information was obtained from validated biennial questionnaires. Cox proportional hazards regression models were used to estimate multivariable-adjusted RRs and 95% CIs. Results: After 1,038,093 person-years of follow-up, 11,606 cases of incident hearing loss were reported. Consumption of 2 or more servings of fish per week was associated with a lower risk of hearing loss. In comparison with women who rarely consumed fish (<1 serving/mo), the multivariable-adjusted RR for hearing loss among women who consumed 2-4 servings of fish per week was 0.80 (95% CI: 0.74, 0.88) (P-trend < 0.001). When examined individually, higher consumption of each specific fish type was inversely associated with risk (P-trend ≤ 0.04). Higher intake of long-chain omega-3 PUFAs was also inversely associated with risk of hearing loss. In comparison with women in the lowest quintile of intake of long-chain omega-3 PUFAs, the multivariable-adjusted RR for hearing loss among women in the highest quintile was 0.85 (95% CI: 0.80, 0.91) and among women in the highest decile was 0.78 (95% CI: 0.72, 0.85) (P-trend < 0.001). Conclusion: Regular fish consumption and higher intake of long-chain omega-3 PUFAs are associated with lower risk of hearing loss in women. [ABSTRACT FROM AUTHOR]

Background We examined the role of the insulinemic potential of diet and lifestyle in the development of cancers of the digestive system, using two plasma C-peptide-based indices: the empirical dietary index for hyperinsulinemia (EDIH) and empirical lifestyle index for hyperinsulinemia (ELIH). Methods We used Cox regression to analyze data on 45 816 men (Health Professionals Follow-up Study, 1986–2012) and 74 191 women (Nurses' Health Study, 1984–2012) to examine associations between EDIH and ELIH scores and digestive system cancers. We computed the diet-only score (EDIH) from food-frequency questionnaires administered every 4 years. The lifestyle score (ELIH) included diet, body mass index, and physical activity. Outcomes included incident cancer of the digestive system (mouth, throat, esophagus, stomach, small intestine, and colorectum) and its accessory organs (pancreas, gallbladder, and liver). P values were two-sided. Results We found direct associations between higher insulinemic potential of diet or lifestyle and risk of developing digestive system cancers in both men and women. The pooled multivariable hazard ratios (HRs) for participants comparing the highest to lowest EDIH quintile were: HR = 1.27, 95% confidence interval (CI) = 1.15 to 1.40, P trend < .001 for digestive system cancers; HR = 1.30, 95% CI = 1.17 to 1.45, P trend <.001 for digestive tract cancers (excluding accessory organs); and HR = 1.15, 95% CI = 0.93 to 1.41, P trend =.48 for digestive accessory organ cancers. The same associations were stronger with the lifestyle score: HR = 1.47, 95% CI = 1.23 to 1.76, P trend <.001 for digestive system cancers; HR = 1.49, 95% CI = 1.14 to 1.95, P trend =.001 for digestive tract cancers; and HR = 1.43, 95% CI = 1.17 to 1.73, P trend <.001 for digestive accessory organ cancers. Conclusions The findings suggest that interventions to reduce the insulinemic potential of diet and lifestyle may be a means of preventing digestive system cancer. [ABSTRACT FROM AUTHOR]