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Background: The literature on associations of circulating concentrations of minerals and vitamins with risk of colorectal cancer is limited and inconsistent. Evidence from randomized controlled trials (RCTs) to support the efficacy of dietary modification or nutrient supplementation for colorectal cancer prevention is also limited., Objectives: To complement observational and RCT findings, we investigated associations of genetically predicted concentrations of 11 micronutrients (β-carotene, calcium, copper, folate, iron, magnesium, phosphorus, selenium, vitamin B-6, vitamin B-12, and zinc) with colorectal cancer risk using Mendelian randomization (MR)., Methods: Two-sample MR was conducted using 58,221 individuals with colorectal cancer and 67,694 controls from the Genetics and Epidemiology of Colorectal Cancer Consortium, Colorectal Cancer Transdisciplinary Study, and Colon Cancer Family Registry. Inverse variance-weighted MR analyses were performed with sensitivity analyses to assess the impact of potential violations of MR assumptions., Results: Nominally significant associations were noted for genetically predicted iron concentration and higher risk of colon cancer [ORs per SD (ORSD): 1.08; 95% CI: 1.00, 1.17; P value = 0.05] and similarly for proximal colon cancer, and for vitamin B-12 concentration and higher risk of colorectal cancer (ORSD: 1.12; 95% CI: 1.03, 1.21; P value = 0.01) and similarly for colon cancer. A nominally significant association was also noted for genetically predicted selenium concentration and lower risk of colon cancer (ORSD: 0.98; 95% CI: 0.96, 1.00; P value = 0.05) and similarly for distal colon cancer. These associations were robust to sensitivity analyses. Nominally significant inverse associations were observed for zinc and risk of colorectal and distal colon cancers, but sensitivity analyses could not be performed. None of these findings survived correction for multiple testing. Genetically predicted concentrations of β-carotene, calcium, copper, folate, magnesium, phosphorus, and vitamin B-6 were not associated with disease risk., Conclusions: These results suggest possible causal associations of circulating iron and vitamin B-12 (positively) and selenium (inversely) with risk of colon cancer., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Background: The Western dietary pattern (WD) is positively associated with risk of coronary artery disease (CAD) and cancer, whereas the Prudent dietary pattern (PD) may be protective. Foods may influence metabolite concentrations as well as oxidative stress and lipid dysregulation, biological mechanisms associated with CAD and cancer., Objective: The aim was to assess the association of 2 derived dietary pattern scores with serum metabolites and identify metabolic pathways associated with the metabolites., Methods: We evaluated the cross-sectional association between each dietary pattern (WD, PD) and metabolites in 2199 Women's Health Initiative (WHI) participants. With FFQ and factor analysis, we determined 2 dietary patterns consistent with WD and PD. Metabolites were measured with LC-tandem MS. Metabolite discovery among 904 WHI Observational Study (WHI-OS) participants was replicated among 1295 WHI Hormone Therapy Trial (WHI-HT) participants. We analyzed each of 495 metabolites with each dietary score (WD, PD) in linear regression models., Results: The PD included higher vegetables and fruit intake compared with the WD with higher saturated fat and meat intake. Independent of energy intake, BMI, physical activity, and other confounding variables, 45 overlapping metabolites were identified (WHI-OS) and replicated (WHI-HT) with an opposite direction of associations for the WD compared with the PD [false discovery rate (FDR) P < 0.05]. In metabolite set enrichment analyses, phosphatidylethanolamine (PE) plasmalogens were positively enriched for association with WD [normalized enrichment score (NES) = 2.01, P = 0.001, FDR P = 0.005], and cholesteryl esters (NES = -1.77, P = 0.005, FDR P = 0.02), and phosphatidylcholines (NES = -1.72, P = 0.01, P = 0.03) were negatively enriched for WD. PE plasmalogens were positively correlated with saturated fat and red meat. Phosphatidylcholines and cholesteryl esters were positively correlated with fatty fish., Conclusions: Distinct metabolite signatures associated with Western and Prudent dietary patterns highlight the positive association of mitochondrial oxidative stress and lipid dysregulation with a WD and the inverse association with a PD., (Copyright © The Author(s) on behalf of the American Society for Nutrition 2020.)

Background: Previous studies have shown mixed results on the association between carbohydrate intake and insomnia. However, any influence that refined carbohydrates have on risk of insomnia is likely commensurate with their relative contribution to the overall diet, so studies are needed that measure overall dietary glycemic index (GI), glycemic load, and intakes of specific types of carbohydrates., Objective: We hypothesized that higher GI and glycemic load would be associated with greater odds of insomnia prevalence and incidence., Methods: This was a prospective cohort study with postmenopausal women who participated in the Women's Health Initiative Observational Study, investigating the relations of GI, glycemic load, other carbohydrate measures (added sugars, starch, total carbohydrate), dietary fiber, and specific carbohydrate-containing foods (whole grains, nonwhole/refined grains, nonjuice fruits, vegetables, dairy products) with odds of insomnia at baseline (between 1994 and 1998; n = 77,860) and after 3 y of follow-up (between 1997 and 2001; n = 53,069)., Results: In cross-sectional and longitudinal analyses, higher dietary GI was associated with increasing odds of prevalent (fifth compared with first quintile OR: 1.11; CI: 1.05, 1.16; P-trend = 0.0014) and incident (fifth compared with first quintile OR: 1.16; CI: 1.08, 1.25; P-trend < 0.0001) insomnia in fully adjusted models. Higher intakes of dietary added sugars, starch, and nonwhole/refined grains were each associated with higher odds of incident insomnia. By contrast, higher nonjuice fruit and vegetable intakes were significantly associated with lower odds of incident insomnia. Also, higher intakes of dietary fiber, whole grains, nonjuice fruit, and vegetables were significantly associated with lower odds of prevalent insomnia., Conclusions: The results suggest that high-GI diets could be a risk factor for insomnia in postmenopausal women. Substitution of high-GI foods with minimally processed, whole, fiber-rich carbohydrates should be evaluated as potential treatments of, and primary preventive measures for, insomnia in postmenopausal women., (Copyright © The Author(s) 2019.)

Background: Contemporary energy expenditure data are crucial to inform and guide nutrition policy in older adults to optimize nutrition and health., Objective: The aim was to determine the optimal method of estimating total energy expenditure (TEE) in adults (aged ≥65 y) through 1) establishing which published predictive equations have the closest agreement between measured resting metabolic rate (RMR) and predicted RMR and 2) utilizing the RMR equations with the best agreement to predict TEE against the reference method of doubly labeled water (DLW)., Methods: A database consisting of international participant-level TEE data from DLW studies was developed to enable comparison with energy requirements estimated by 17 commonly used predictive equations. This database included 31 studies comprising 988 participant-level RMR data and 1488 participant-level TEE data. Mean physical activity level (PAL) was determined for men (PAL = 1.69, n = 320) and women (PAL = 1.66, n = 668). Bland-Altman plots assessed agreement of measured RMR and TEE with predicted RMR and TEE in adults aged ≥65 y, and subgroups of 65-79 y and ≥80 y. Linear regression assessed proportional bias., Results: The Ikeda, Livingston, and Mifflin equations most closely agreed with measured RMR and TEE in all adults aged ≥65 y and in the 65-79 y and ≥80 y subgroups. In adults aged ≥65 y, the Ikeda and Livingston equations overestimated TEE by a mean ± SD of 175 ± 1362 kJ/d and 86 ± 1344 kJ/d, respectively. The Mifflin equation underestimated TEE by a mean ± SD of 24 ± 1401 kJ/d. Proportional bias was present as energy expenditure increased., Conclusions: The Ikeda, Livingston, or Mifflin equations are recommended for estimating energy requirements of older adults. Future research should focus on developing predictive equations to meet the requirements of the older population with consideration given to body composition and functional measures., (Copyright © American Society for Nutrition 2019.)

Background: The influence of a low-fat dietary pattern on the cardiovascular health of postmenopausal women continues to be of public health interest. Objective: This report evaluates low-fat dietary pattern influences on cardiovascular disease (CVD) incidence and mortality during the intervention and postintervention phases of the Women's Health Initiative Dietary Modification Trial. Design: Participants comprised 48,835 postmenopausal women aged 50-79 y; 40% were randomly assigned to a low-fat dietary pattern intervention (target of 20% of energy from fat), and 60% were randomly assigned to a usual diet comparison group. The 8.3-y intervention period ended in March 2005, after which >80% of surviving participants consented to additional active follow-up through September 2010; all participants were followed for mortality through 2013. Breast and colorectal cancer were the primary trial outcomes, and coronary heart disease (CHD) and overall CVD were additional designated outcomes. Results: Incidence rates for CHD and total CVD did not differ between the intervention and comparison groups in either the intervention or postintervention period. However, CHD HRs comparing these groups varied strongly with baseline CVD and hypertension status. Participants without prior CVD had an intervention period CHD HR of 0.70 (95% CI: 0.56, 0.87) or 1.04 (95% CI: 0.90, 1.19) if they were normotensive or hypertensive, respectively ( P -interaction = 0.003). The CHD benefit among healthy normotensive women was partially offset by an increase in ischemic stroke risk. Corresponding HRs in the postintervention period were close to null. Participants with CVD at baseline (3.4%) had CHD HRs of 1.47 (95% CI: 1.12, 1.93) and 1.61 (95% CI: 1.02, 2.55) in the intervention and postintervention periods, respectively. However, various lines of evidence suggest that results in women with CVD or hypertension at baseline are confounded by postrandomization use of cholesterol-lowering medications. Conclusions: CVD risk in postmenopausal women appears to be sensitive to a change to a low-fat dietary pattern and, among healthy women, includes both CHD benefit and stroke risk. This trial was registered at clinicaltrials.gov as NCT00000611., (© 2017 American Society for Nutrition.)

Background: Although studies to date have confirmed the association between nutrition and frailty, the impact of dietary intake and dietary patterns on survivorship in those with frailty is yet to be examined in a well-powered cohort with validated frailty status. Moreover, previous studies were limited by measurement error from dietary self-reports. Objective: We derived biomarker-calibrated dietary energy and protein intakes to address dietary self-report error. Using these data, we then evaluated the association of mortality in older women with frailty and dietary intake and healthy diet indexes, such as the alternate Mediterranean Diet (aMED), the Dietary Approaches to Stop Hypertension (DASH) score, and the Dietary Inflammatory Index (DII). Design: The analytic sample included 10,034 women aged 65-84 y with frailty and complete dietary data from the Women's Health Initiative Observational Study. Frailty was assessed with modified Fried's criteria. Dietary data were collected by food-frequency questionnaire. Results: Over a mean follow-up period of 12.4 y, 3259 (31%) deaths occurred. The HRs showed progressively decreased rates of mortality in women with higher calibrated dietary energy intakes ( P- trend = 0.003), higher calibrated dietary protein intakes ( P- trend = 0.03), higher aMED scores ( P- trend = 0.006), and higher DASH scores ( P- trend = 0.02). Although the adjusted point estimates of HRs (95% CIs) for frail women scoring in the second, third, and fourth quartiles on DII measures were 1.15 (1.03, 1.27), 1.28 (1.15, 1.42), and 1.24 (1.12, 1.38), respectively, compared with women in the first quartile, no overall effect was observed across quartiles ( P- trend = 0.35). Subgroup analyses by chronic morbidity or smoking status or by excluding women with early death did not substantially change these findings. Conclusions: The current study highlights the importance of nutrition in older, frail women. Diet quality and quantity should be considered in managing persons with frailty., (© 2017 American Society for Nutrition.)

Background: The effects of dietary protein on bone health are controversial., Objective: We examined the relation between protein intake with fracture and bone mineral density (BMD) within the Women's Health Initiative (WHI)., Design: This prospective analysis included 144,580 women aged 50-79 y at baseline in the WHI clinical trials (CTs) and observational study (OS) that recruited participants in 1993-1998 with follow-up through 2011. Self-reported clinical fractures were collected semiannually through the original end of the trials (WHI CTs) and annually (WHI OS) by questionnaires. Hip fracture was adjudicated by a central review of radiology reports. BMDs for total body, hip, and spine were measured at baseline and 3 and 6 y in 9062 women at 3 WHI clinics by using dual-energy X-ray absorptiometry. Protein intake was assessed via food-frequency questionnaire and calibrated by using biomarkers of energy and protein intakes. Associations between protein intake and fracture were estimated by using Cox proportional hazards regression, and the relation between protein intake and BMD was estimated by using linear regression., Results: Median biomarker-calibrated protein intake was 15% of energy intake. Per 20% increase in calibrated protein intake (percentage of energy), there was no significant association with total fracture (HR: 0.99; 95% CI: 0.97, 1.02) or hip fracture (HR: 0.91; 95% CI: 0.84, 1.00), but there was an inverse association with forearm fracture (HR: 0.93; 95% CI: 0.88, 0.98). Each 20% increase in calibrated protein intake was associated with a significantly higher BMD for total body (mean 3-y change: 0.003 g/cm²; 95% CI: 0.001, 0.005 g/cm²) and hip (mean 3-y change: 0.002 g/cm²; 95% CI: 0.001, 0.004 g/cm²)., Conclusions: Higher biomarker-calibrated protein intake within the range of usual intake was inversely associated with forearm fracture and was associated with better maintenance of total and hip BMDs. These data suggest higher protein intake is not detrimental to bone health in postmenopausal women.

Background: The Women's Health Initiative Dietary Modification (DM) Trial was a randomized controlled trial that compared the effects of a low-fat (≤20% of total energy) or a usual diet in relation to chronic disease risk in postmenopausal women., Objective: We characterized long-term body-composition changes associated with the DM trial and potential modifiers of these associations., Design: In the DM trial, 48,835 women aged 50-79 y were randomly assigned to intervention (40%) or comparison (60%) groups. We studied a subset with whole-body dual-energy X-ray absorptiometry scans at baseline and during follow-up. Changes in fat mass (FM), lean mass (LM), and percentage body fat between the intervention (n = 1580) and comparison (n = 2731) groups at years 1, 3, and 6 were compared. By using generalized estimating equations, we calculated overall differences between groups and tested for interactions with age, diabetes, race-ethnicity (white, black, and Hispanic), body mass index (BMI), and hormone therapy (HT)., Results: The intervention women experienced significantly greater reductions in percentage body fat, FM, and LM at years 1 and 3 than did women in the comparison group (all P < 0.05). At year 6, only the FM change was significantly different between groups. Overall, the intervention was associated with reductions in percentage body fat (-0.8%; 95% CI: -1.0%, -0.6%), FM (-1.1 kg; 95% CI: -1.3, -0.8 kg), and LM (-0.17 kg; 95% CI: -0.28, -0.06 kg) during follow-up (all P < 0.003). Intervention associations varied by race-ethnicity, BMI, diabetes, and HT and remained significant after adjustment for physical activity., Conclusion: This intervention was associated with modest long-term body-composition changes; the findings were more robust in years 1 and 3. This trial was registered at clinicaltrials.gov as NCT00000611.

Background: Fatty acids (FAs) may be important dietary components that modulate osteoporotic fracture risk., Objective: The objective was to examine FA intake in relation to osteoporotic fractures., Design: The participants were postmenopausal women enrolled in the Women's Health Initiative (n = 137,486). Total fractures were identified by self-report; hip fractures were confirmed by medical record review. FA intake was estimated from baseline food-frequency questionnaires and standardized to total caloric intake. No data on omega-3 (n-3) FA supplements were available. Cox proportional hazard models were constructed to estimate risk of fracture., Results: Higher saturated FA consumption was associated with higher hip fracture risk [quartile 4 multivariate-adjusted hazard ratio (HR): 1.31; 95% CI: 1.11, 1.55; P for trend = 0.001]. Lower total fracture risk was associated with a higher monounsaturated FA intake (quartile 3 HR: 0.94; 95% CI: 0.89, 0.98; P for trend = 0.050) and polyunsaturated FA intake (quartile 4 HR: 0.95; 95% CI: 0.90, 0.99; P for trend = 0.019). Unexpectedly, higher consumption of marine n-3 FAs was associated with greater total fracture risk (quartile 4 HR: 1.07; 95% CI: 1.02, 1.12; P for trend = 0.010), whereas a higher n-6 FA intake was associated with a lower total fracture risk (quartile 4 HR: 0.94; 95% CI: 0.89, 0.98; P for trend 0.009)., Conclusions: These results suggest that saturated FA intake may significantly increase hip fracture risk, whereas monounsaturated and polyunsaturated FA intakes may decrease total fracture risk. In postmenopausal women with a low intake of marine n-3 FAs, a higher intake of n-6 FAs may modestly decrease total fracture risk. This trial was registered at clinicaltrials.gov as NCT00000611.