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Author(s): J A Greenberg [sup.1] , J E Manson [sup.2] , L Tinker [sup.3] , M L Neuhouser [sup.3] , L Garcia [sup.4] , M Z Vitolins [sup.5] , L [...], Background/Objectives: Recent long-term prospective cohort studies found inverse associations between chocolate consumption and the risk of type 2 diabetes, but provided conflicting evidence on the nature of the association among women. To assess this association in a large cohort of American women. Subjects/Methods: Multivariable Cox regression was used with the data from 92 678 postmenopausal women in the prospective Women's Health Initiative study. Chocolate intake was assessed by food frequency questionnaire. Incidence of type 2 diabetes was determined by self-report of the first treatment with oral medication or insulin. Results: Among women free of diabetes at baseline, there were 10 804 cases, representing an incidence rate of 11.7% during 13.1 years and 1 164 498 person-years of follow-up. There was no significant linear association between long-term chocolate intake and type 2 diabetes risk, but there was significantly reduced risk at moderate levels of intake. Compared to women who ate 1 oz. of chocolate Conclusions: We only found an inverse association between chocolate consumption and type 2 diabetes at moderate levels of consumption in two subgroups of postmenopausal women in the Women's Health initiative cohort.

An objective measure of energy intake is needed in epidemiologic studies to evaluate random and systematic error associated with dietary self-report tools. Total energy expenditure in weight-stable humans is accepted as a measure of energy intake, but doubly labeled water remains cost prohibitive for large studies. Our purpose was to develop a practical indirect calorimetry (IC) protocol for estimating resting metabolic rate (RMR) in free-living, postmenopausal women. We conducted duplicate IC measures 1 wk apart using a canopy system on 102 women ages 50-79 y from the Seattle area. We compared RMR for 0-5, 5-10, 5-15, 5-20, 5-25, 5-30, and 0- to 30-min IC segments and segments meeting stability criteria. The mean RMR for the first 5 min was significantly higher than other time segments (P = 0.001). Correlation coefficients between duplicate measures were high (r = 0.90). Use of defined stability criteria produced RMR measures that were 10-30 kcal (42-126 kJ) higher than the 5- to 10-min RMR measures and 40-60% of subjects did not achieve these stability criteria. For protocols including IC to assess RMR as a component of total energy expenditure in free-living, postmenopausal women, a single 10-min canopy study, excluding the first 5 min of data, produces reliable results with minimal subject burden. [ABSTRACT FROM AUTHOR]

An important part of understanding the functions of vitamin A, vitamin E and the carotenoids in nutritional status assessment, health promotion and disease prevention is knowledge of factors that influence their distribution in human tissues. Our objective was to examine serum concentrations of these nutrients and compounds in a sample of 285 healthy participants, 12-17 y old, from three U. S. cities. Pearson correlations between diet measured with a food frequency questionnaire and serum nutrient concentrations among these adolescents (adjusted for total serum cholesterol, age, sex, race and body mass index) were as follows: retinol, 0.23; alpha-tocopherol, 0.16; alpha-carotene, 0.31; beta-carotene, 0.15; beta-cryptoxanthin, 0.38; lycopene, 0.08; and lutein + zeaxanthin, 0.25. Multivariate linear regression modeled associations of demographic, dietary and physiologic variables with serum concentrations of these nutrients. African-American participants had significantly lower concentrations of serum retinol (P < 0.001), alpha-tocopherol (P < 0.01) and alpha-carotene (P < 0.02), but higher concentrations of lutein + zeaxanthin (P = 0.001) compared with Caucasians. Obese participants had serum nutrient concentrations that were 2-10% (P < 0.05) lower than normal weight participants. Dietary intake was a significant predictor of all serum analytes (P < 0.01) except lycopene. These models explained 20% of the variability in serum retinol, 28% of the variability in serum alpha-tocopherol, and 14-24% of the variability in serum carotenoids. [ABSTRACT FROM AUTHOR]

In 1996, the U.S. Food and Drug Administration approved olestra, a fat substitute, for use in snack foods. Previous studies had shown that olestra consumption could reduce absorption of carotenoids and fat-soluble vitamins. To determine the association between consumption of olestra-containing snack foods and serum concentrations of carotenoids and fat-soluble vitamins in a free-living population, we interviewed independent population-based cross-sectional samples of 1043 adults before olestra was available and 933 adults 9 mo after olestra snacks were introduced into the marketplace in Marion County, IN, the first major test market for olestra. A cohort composed of 403 adults from the first survey, oversampling those most frequently reporting olestra consumption during follow-up telephone interviews, completed a second survey. We assessed diet, lifestyle factors and olestra consumption, and collected blood for assays for the serum concentrations of six carotenoids, four fat-soluble vitamins and lipids. Nine months after the introduction of olestra into the marketplace, 15.5% of Marion County residents reported consuming an olestra-containing snack in the previous month, with a median frequency among consumers of 3.0 times per month. There were no significant associations or consistent trends for decreased serum carotenoids or fat-soluble vitamins associated with olestra consumption, although cohort members consuming >/=2 g/d of olestra had adjusted total serum carotenoids 15% lower compared with baseline. There were increases in serum vitamin K concentrations associated with olestra consumption (P = 0.03 in the cross section and P = 0.06 in the cohort). In summary, there was no statistically significant evidence in this free-living population of associations between olestra consumption and decreased serum concentrations of carotenoids and fat-soluble vitamins. [ABSTRACT FROM AUTHOR]

Biochemical measures of nutrients or other dietary constituents can be an important component of nutritional assessment and monitoring. However, accurate interpretation of the nutrient concentration is dependent on knowledge of the determinants of the body pool measured. The purpose of this study was to identify the determinants of serum carotenoid and fat-soluble vitamin concentrations in a large, community-based sample (n = 1042). Multiple linear regression analysis was used to examine effects of demographic characteristics (age, sex, race/ethnicity, education), health-related behavior (exercise, sun exposure, smoking, alcohol consumption), and intake (diet, supplements) on serum retinol, 25-hydroxyvitamin D, alpha-tocopherol, phylloquinone, and carotenoid concentrations. Age, sex, race/ethnicity, vitamin A intake, and alcohol consumption were found to be determinants of serum retinol concentration. Race/ethnicity, vitamin D intake, body mass index, smoking status, and sun exposure were determinants of serum 25-hydroxyvitamin D concentration. Determinants of serum alpha-tocopherol were age, sex, race/ethnicity, alpha-tocopherol intake, serum cholesterol, percentage of energy from fat (inversely related), supplement use, and body mass index. Age, sex, phylloquinone intake, serum triglycerides, and supplement use were determinants of serum phylloquinone concentration. Primary determinants of serum carotenoids were age, sex, race/ethnicity, carotenoid intake, serum cholesterol, alcohol consumption, body mass index, and smoking status. Overall, the demographic, dietary, and other lifestyle factors explained little of the variability in serum concentrations of retinol (R2 = 0.20), 25-hydroxyvitamin D (R2 = 0.24), and the carotenoids (R2 = 0.15-0.26); only modest amounts of the variability in serum phylloquinone concentration (R2 = 0.40); and more substantial amounts of the variability in serum alpha-tocopherol concentration (R2 = 0.62). [ABSTRACT FROM AUTHOR]

Abstract Background C-reactive protein (CRP) and Serum amyloid A protein (SAA) increases with systemic inflammation and are related to worse survival for breast cancer survivors. This study examines the association between percent body fat and SAA and CRP and the potential interaction with NSAID use and weight change. Methods Participants included 134 non-Hispanic white and Hispanic breast cancer survivors from the Health, Eating, Activity, and Lifestyle Study. Body fat percentage, measured with Dual Energy X-ray Absorptiometer (DEXA), and circulating levels of CRP and SAA were obtained 30 months after breast cancer diagnosis. Results Circulating concentrations of CRP and SAA were associated with increased adiposity as measured by DEXA after adjustment for age at 24-months, race/ethnicity, dietary energy intake, weight change, and NSAID use. Survivors with higher body fat ≥35% had significantly higher concentrations of CRP (2.01 mg/l vs. 0.85 mg/l) and SAA (6.21 mg/l vs. 4.21 mg/l) compared to non-obese (body fat Conclusions Breast cancer survivors with higher body fat had higher mean concentrations of CRP and SAA than women with lower body fat. Further assessment of NSAID use and weight control in reducing circulating inflammatory markers among survivors may be worthwhile to investigate in randomized intervention trials as higher inflammatory markers are associated with worse survival.

Abstract Background It remains unclear whether estrogenic botanical supplement (EBS) use influences breast cancer survivors' health-related outcomes. Methods We examined the associations of EBS use with health-related quality of life (HRQOL), with fatigue, and with 15 hormone-related symptoms such as hot flashes and night sweats among 767 breast cancer survivors participating in the Health, Eating, Activity, and Lifestyle (HEAL) Study. HRQOL was measured by the Medical Outcomes Study short form-36 physical and mental component scale summary score. Fatigue was measured by the Revised-Piper Fatigue Scale score. Results Neither overall EBS use nor the number of EBS types used was associated with HRQOL, fatigue, or hormone-related symptoms. However, comparisons of those using each specific type of EBS with non-EBS users revealed the following associations. Soy supplements users were more likely to have a better physical health summary score (odds ratio [OR] = 1.66, 95% confidence interval [CI] = 1.02-2.70). Flaxseed oil users were more likely to have a better mental health summary score (OR = 1.76, 95% CI = 1.05-2.94). Ginseng users were more likely to report severe fatigue and several hormone-related symptoms (all ORs ≥ 1.7 and all 95% CIs exclude 1). Red clover users were less likely to report weight gain, night sweats, and difficulty concentrating (all OR approximately 0.4 and all 95% CIs exclude 1). Alfalfa users were less likely to experience sleep interruption (OR = 0.28, 95% CI = 0.12-0.68). Dehydroepiandrosterone users were less likely to have hot flashes (OR = 0.33, 95% CI = 0.14-0.82). Conclusions Our findings indicate that several specific types of EBS might have important influences on a woman's various aspects of quality of life, but further verification is necessary.

There is considerably greater variation in metabolic rates between men than between women, in terms of basal, activity and total (daily) energy expenditure (EE). One possible explanation is that EE is associated with male sexual characteristics (which are known to vary more than other traits) such as musculature and athletic capacity. Such traits might be predicted to be most prominent during periods of adolescence and young adulthood, when sexual behaviour develops and peaks. We tested this hypothesis on a large dataset by comparing the amount of male variation and female variation in total EE, activity EE and basal EE, at different life stages, along with several morphological traits: height, fat free mass and fat mass. Total EE, and to some degree also activity EE, exhibit considerable greater male variation (GMV) in young adults, and then a decreasing GMV in progressively older individuals. Arguably, basal EE, and also morphometrics, do not exhibit this pattern. These findings suggest that single male sexual characteristics may not exhibit peak GMV in young adulthood, however total and perhaps also activity EE, associated with many morphological and physiological traits combined, do exhibit GMV most prominently during the reproductive life stages.

Background: Advanced prostate cancer etiology is poorly understood. Few studies have examined associations of anthropometric factors (e.g. early adulthood obesity) with advanced prostate cancer risk., Patients and Methods: We carried out pooled analyses to examine associations between body fatness, height, and prostate cancer risk. Among 830 772 men, 51 734 incident prostate cancer cases were identified, including 4762 advanced (T4/N1/M1 or prostate cancer deaths) cases, 2915 advanced restricted (same as advanced, but excluding localized cancers that resulted in death) cases, 9489 high-grade cases, and 3027 prostate cancer deaths. Cox proportional hazards models were used to calculate study-specific hazard ratios (HR) and 95% confidence intervals (CI); results were pooled using random effects models., Results: No statistically significant associations were observed for body mass index (BMI) in early adulthood for advanced, advanced restricted, and high-grade prostate cancer, and prostate cancer mortality. Positive associations were shown for BMI at baseline with advanced prostate cancer (HR = 1.30, 95% CI = 0.95-1.78) and prostate cancer mortality (HR = 1.52, 95% CI = 1.12-2.07) comparing BMI ≥35.0 kg/m 2 with 21-22.9 kg/m 2 . When considering early adulthood and baseline BMI together, a 27% higher prostate cancer mortality risk (95% CI = 9% to 49%) was observed for men with BMI <25.0 kg/m 2 in early adulthood and BMI ≥30.0 kg/m 2 at baseline compared with BMI <25.0 kg/m 2 in early adulthood and BMI <30.0 kg/m 2 at baseline. Baseline waist circumference, comparing ≥110 cm with <90 cm, and waist-to-hip ratio, comparing ≥1.00 with <0.90, were associated with significant 14%-16% increases in high-grade prostate cancer risk and suggestive or significant 20%-39% increases in prostate cancer mortality risk. Height was associated with suggestive or significant 33%-56% risks of advanced or advanced restricted prostate cancer and prostate cancer mortality, comparing ≥1.90 m with <1.65 m., Conclusion: Our findings suggest that height and total and central adiposity in mid-to-later adulthood, but not early adulthood adiposity, are associated with risk of advanced forms of prostate cancer. Thus, maintenance of healthy weight may help prevent advanced prostate cancer., (Copyright © 2019 European Society for Medical Oncology. All rights reserved.)

Objective: To examine the associations of dietary and supplemental magnesium (Mg) as assessed by a semi-quantitative food frequency questionnaire with cognitive outcomes among ageing women., Design: This work conducts a prospective cohort study of participants enrolled in the Women's Health Initiative Memory Study (WHIMS), which was subsequently extended and named WHIMS-Epidemiology of Cognitive Health., Setting: Forty clinical centres in the USA., Participants: Postmenopausal women aged 65-79 years without dementia on enrolment., Main Outcome Measures: Physician-adjudicated mild cognitive impairment (MCI) and/or probable dementia (PD)., Results: Participants were excluded (n=1006) if they had extreme values of dietary energy intake, had missing or extreme body mass index values, with prevalent MCI/PD at baseline, received only one cognitive assessment or had been followed up for <1 year. During >20 years of follow-up, 765 (11.8%) out of 6473 participants developed MCI/PD. For MCI/PD and MCI, the risks tended to be lower among participants in quintiles Q2-Q5 of Mg consumption compared with those in the lowest quintile. Participants in Q3 had a significantly lower risk of MCI/PD (HR 0.69, 95% CI 0.53 to 0.91) and MCI (HR 0.63, 95% CI 0.45 to 0.87) after multivariate adjustments. No significant association was observed between total Mg intake and PD. The association between total Mg intake, MCI/PD and MCI was non-linear as suggested by the likelihood test., Conclusions: Total Mg intake between the estimated average requirement and the recommended dietary allowances may associate with a lower risk of MCI/PD and MCI., Trial Registration Number: NCT00685009., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Observational studies have reported an inverse association between vitamin D intake and breast cancer risk. We examined whether vitamin D supplementation in high-risk premenopausal women reduces mammographic density (MD), an established breast cancer risk factor. We conducted a multicenter randomized double-blind placebo-controlled trial in premenopausal women at high risk for breast cancer [5-year risk ≥ 1.67%, lifetime risk ≥ 20%, lobular carcinoma in situ , prior stage 0-II breast cancer, hereditary breast cancer syndrome, or high MD (heterogeneously/extremely dense)], with a baseline serum 25-hydroxyvitamin D [25(OH)D] ≤ 32 ng/mL. Participants were randomized to 12 months of vitamin D3 20,000 IU/week or matching placebo. The primary endpoint was change in MD from baseline to 12 months using the Cumulus technique. Secondary endpoints included serial blood biomarkers [25(OH)D, 1,25-dihydroxyvitamin D (1,25(OH)D), insulin-like growth factor (IGF)-1, IGF-binding protein-3] and MD change at 24 months. Among 208 women randomized, median age was 44.6 years, 84% were white, 33% had baseline 25(OH)D < 20 ng/mL, and 78% had high baseline MD. Comparing the active and placebo groups at 12 months, MD changes were small and did not significantly differ. Mean MD changes at 12 and 24 months were -0.3% and -1.2%, respectively, in the active arm and +1.5% and +1.6% with placebo ( P > 0.05). We observed a mean change in serum 25(OH)D of +18.9 versus +2.8 ng/mL ( P < 0.01) and IGF-1 of -9.8 versus -1.8 ng/mL ( P = 0.28), respectively. At 12 months, MD was positively correlated with serum IGF-1 and IGF-1/IGFBP-3 ( P < 0.01). This trial does not support the use of vitamin D supplementation for breast cancer risk reduction., (©2019 American Association for Cancer Research.)

Excess body weight is a poor prognostic factor in women with early breast cancer, but the effect of weight loss on the risk of breast cancer recurrence and mortality in women who are overweight or obese at the time of breast cancer diagnosis has not been evaluated. The Alliance for Clinical Trials in Oncology Breast Cancer Weight Loss trial, also known as A011401, is testing the impact of a telephone-based weight loss program on invasive disease-free survival in 3136 women with a body mass index ≥27 kg/m 2 who have recently been diagnosed with stage II-III, HER-2 negative breast cancer. Secondary outcomes of the trial include the impact of the weight loss intervention on overall survival, body weight, physical activity, dietary intakes, incidence of comorbidities, serum biomarkers and patient reported outcomes. Participants are randomized 1:1 to a 2-year, telephone-based weight loss intervention or to an education control group. The intervention is delivered through 42 telephone calls, delivered by health coaches based at the Dana-Farber Cancer Institute. Calls are supplemented by an intervention workbook, as well as a number of tools to help facilitate weight loss. Intervention goals include loss of 10% of baseline body weight, achieved through caloric restriction and increased physical activity. This large-scale study testing the impact of purposeful weight loss after cancer diagnosis on the risk of breast cancer recurrence and mortality has the potential to make weight loss programs a standard part of breast cancer treatment.

Genome-wide association studies (GWAS) of obesity measures have identified associations with single nucleotide polymorphisms (SNPs). However, no large-scale evaluation of gene-environment interactions has been performed. We conducted a search of gene-environment (G × E) interactions in post-menopausal African-American and Hispanic women from the Women's Health Initiative SNP Health Association Resource GWAS study. Single SNP linear regression on body mass index (BMI) and waist-to-hip circumference ratio (WHR) adjusted for multidimensional-scaling-derived axes of ancestry and age was run in race-stratified data with 871,512 SNPs available from African-Americans (N = 8,203) and 786,776 SNPs from Hispanics (N = 3,484). Tests of G × E interaction at all SNPs for recreational physical activity (m h/week), dietary energy intake (kcal/day), alcohol intake (categorical), cigarette smoking years, and cigarette smoking (ever vs. never) were run in African-Americans and Hispanics adjusted for ancestry and age at interview, followed by meta-analysis of G × E interaction terms. The strongest evidence for concordant G × E interactions in African-Americans and Hispanics was for smoking and marker rs10133840 (Q statistic P = 0.70, beta = -0.01, P = 3.81 × 10(-7)) with BMI as the outcome. The strongest evidence for G × E interaction within a cohort was in African-Americans with WHR as outcome for dietary energy intake and rs9557704 (SNP × kcal = -0.04, P = 2.17 × 10(-7)). No results exceeded the Bonferroni-corrected statistical significance threshold.

Low-folate status and genetic polymorphisms in folate metabolism have been linked to several cancers. Possible biological mechanisms for this association include effects on purine and thymidine synthesis, DNA methylation, or homocysteine concentrations. The influence of genetic variation in folate metabolism on these putative mechanisms or biomarkers of cancer risk has been largely unexplored. We used a mathematical model that simulates folate metabolism biochemistry to predict (a) the effects of polymorphisms with defined effects on enzyme function (MTHFR and TS) and (b) the effects of potential, as-of-yet-unidentified polymorphisms in a comprehensive set of folate-metabolizing enzymes on biomarkers and mechanisms related to cancer risk. The model suggests that there is substantial robustness in the pathway. Our predictions were consistent with measured effects of known polymorphisms in MTHFR and TS on biomarkers. Polymorphisms that alter enzyme function of FTD, FTS, and MTCH are expected to affect purine synthesis, FTS more so under a low-folate status. In addition, MTCH polymorphisms are predicted to influence thymidine synthesis. Polymorphisms in methyltransferases should affect both methylation rates and thymidylate synthesis. Combinations of polymorphisms in MTHFR, TS, and SHMT are expected to affect nucleotide synthesis in a nonlinear fashion. These investigations provide information on effects of genetic polymorphisms on biomarkers, including those that cannot be measured well, and highlight robustness and sensitivity in this complex biological system with regard to genetic variability. Although the proportional changes in biomarkers of risk with individual polymorphisms are frequently small, they may be quite relevant if present over an individual's lifetime.

Accurate assessment of fruit and vegetable intakes is critical for cancer control research and public health surveillance. This report examines the bias and precision of two commonly used food frequency questionnaire methods to assess fruit and vegetable intakes: (a) the 5 A Day method, based on seven items; and (b) the summation method, based on adding total servings of all fruit and vegetable items on a comprehensive (100+ item) food frequency questionnaire. Data are from three studies in which 24-h dietary recalls, food records, or serum carotenoid concentrations could be used as criterion measures (n = 260, 1031, and 342). Studies differed markedly in distributions of participants' age, race/ethnicity, sex, and socioeconomic status. Mean intakes of total fruit and vegetables based on the 5 A Day method were consistently lower than those from either the summation method (3.11 versus 4.06), 24-h recalls (3.32 versus 4.07), or food records (3.11 versus 3.46; all P < 0.01), and this was due primarily to underestimates of vegetable intake. Correlations of the 5 A Day and summation measures with all criterion measures were similar and were consistently higher for fruit (range, 0.33-0.57) than for vegetables (range, 0.24-0.32). These results, which were consistent across diverse participant samples, suggest that the 5 A Day method yields both biased and imprecise measures of vegetable intake and that research to improve this measure is needed.