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1.  Optimism and Diet Quality in the Women’s Health Initiative 
doi:10.1016/j.jand.2013.12.018
PMCID: PMC4071123  PMID: 24556429
diet quality; psychosocial factors; Alternate Healthy Eating Index; psychological attitudes; diet; dietary behavior
2.  Physical Activity and Cancer Survivorship 
There has been an increase in the cancer survivor population in the United States over the past several decades primarily due to improvements in early detection of first malignancies and effective treatment modalities. A wealth of evidence has demonstrated that regular physical activity is associated with a lower risk of death, all-cause mortality, cancer recurrence, and several chronic diseases, including type 2 diabetes and cardiovascular disease, common comorbid conditions in people who have survived cancer. Physical activity also is a central component of weight management.
Methods
This review summarizes the current physical activity recommendations and the evidence linking physical activity to improvements in weight management, physiological effects, and psychological health outcomes for cancer survivors.
Results
The available literature suggests physical activity is safe and is positively associated with weight management, cardiorespiratory fitness, muscular strength and endurance, quality of life, fatigue, and other psychosocial factors in cancer survivors. Yet relationships related to specific cancer diagnoses, treatments, and underlying cardiometabolic mechanisms associated with survival have not been thoroughly examined in randomized controlled trials. Furthermore, factors that influence adherence to physical activity behaviors must be identified to develop effective exercise programs. The use of objective measures of physical activity and the standardization of reporting outcome measures within intervention trials are needed to complement this effort.
Conclusions
Healthcare providers should consider individual differences among cancer survivors and tailor physical activity programs to meet the individual needs of the patient to assist in the adoption and maintenance of a physically active lifestyle.
doi:10.1177/0884533614551969
PMCID: PMC4470419  PMID: 25335787
survival; neoplasms; exercise; obesity; cancer
3.  Comparison between Dietary Assessment Methods for Determining Associations between Nutrient Intakes and Bone Mineral Density in Postmenopausal 
It is important to identify the role of nutrition in the treatment and prevention of osteoporosis. The goal of this study is to compare the equivalency of nutrient intakes assessed by diet records (DR) and the Arizona Food Frequency Questionnaire (AFFQ) and the associations of these nutrients with bone mineral density (BMD). This is a secondary analysis of cross-sectional data that was analyzed from 6 cohorts (Fall 1995–Fall 1997) of postmenopausal women (n=244; 55.7±4.6 years) participating in a 12 month, block-randomized, clinical trial. One-year dietary intakes were assessed using eight days of DR and the AFFQ. Participant’s BMD was measured at the lumbar spine (L2–L4), femur trochanter, femur neck, Ward's triangle and total body using dual energy X-ray absorptiometry. Linear regression analyses (p≤0.05) were adjusted for the effects of exercise, hormone therapy use, body weight at one year, years post menopause and total energy intake. Significant correlations (r=0.30–0.70, p≤0.05) between dietary assessment methods were found with all dietary intake variables. Iron and magnesium were consistently and significantly positively associated with BMD at all bone sites regardless of the dietary assessment method. Zinc, dietary calcium, phosphorous, potassium, total calcium, and fiber intakes were positively associated with BMD at three or more of the same bone sites regardless of the dietary assessment method. Protein, alcohol, caffeine, sodium, and vitamin E did not have any similar BMD associations. The DR and AFFQ are acceptable dietary tools used to determine the associations of particular nutrients and BMD sites in healthy postmenopausal women.
doi:10.1016/j.jada.2009.02.008
PMCID: PMC4414039  PMID: 19394478
osteoporosis; bone mineral density; postmenopausal; diet
4.  A Pilot Feasibility Study of Whole-systems Ayurvedic Medicine and Yoga Therapy for Weight Loss 
Objective:
To develop and test the feasibility of a whole-systems lifestyle intervention for obesity treatment based on the practices of Ayurvedic medicine/ Yoga therapy.
Design:
A pre-post weight loss intervention pilot study using conventional and Ayurvedic diagnosis inclusion criteria, tailored treatment within a standardized treatment algorithm, and standardized data collection instruments for collecting Ayurvedic outcomes.
Participants:
A convenience sample of overweight/obese adult community members from Tucson, Arizona interested in a “holistic weight loss program” and meeting predetermined inclusion/exclusion criteria.
Intervention:
A comprehensive diet, activity, and lifestyle modification program based on principles of Ayurvedic medicine/yoga therapy with significant self-monitoring of lifestyle behaviors. The 3-month program was designed to change eating and activity patterns and to improve self-efficacy, quality of life, well-being, vitality, and self-awareness around food choices, stress management, and barriers to weight loss.
Primary Outcome Measures:
Changes in body weight, body mass index; body fat percentage, fat/lean mass, waist/hip circumference and ratio, and blood pressure.
Secondary Outcome Measures:
Diet and exercise self-efficacy scales; perceived stress scale; visual analog scales (VAS) of energy, appetite, stress, quality of life, well-being, and program satisfaction at all time points.
Results:
Twenty-two adults attended an in-person Ayurvedic screening; 17 initiated the intervention, and 12 completed the 3-month intervention. Twelve completed follow-up at 6 months and 11 completed follow-up at 9 months. Mean weight loss at 3 months was 3.54 kg (SD 4.76); 6 months: 4.63 kg, (SD 6.23) and 9 months: 5.9 kg (SD 8.52). Self-report of program satisfaction was more than 90% at all time points.
Conclusions:
An Ayurveda-/yoga-based lifestyle modification program is an acceptable and feasible approach to weight management. Data collection, including self-monitoring and conventional and Ayurvedic outcomes, did not unduly burden participants, with attrition similar to that of other weight loss studies.
doi:10.7453/gahmj.2013.084
PMCID: PMC3921615  PMID: 24753993
Obesity; integrative medicine; Ayurveda; yoga; whole systems; behavior change
5.  Regression Calibration in Nutritional Epidemiology: Example of Fat Density and Total Energy in Relationship to Postmenopausal Breast Cancer 
American Journal of Epidemiology  2013;178(11):1663-1672.
Regression calibration using biomarkers provides an attractive approach to strengthening nutritional epidemiology. We consider this approach to assessing the relationship of fat and total energy consumption with postmenopausal breast cancer. In analyses that included fat density data, biomarker-calibrated total energy was positively associated with postmenopausal breast cancer incidence in cohorts of the US Women's Health Initiative from 1994–2010. The estimated hazard ratio for a 20% increment in calibrated food frequency questionnaire (FFQ) energy was 1.22 (95% confidence interval (CI): 1.15, 1.30). This association was not evident without biomarker calibration, and it ceased to be apparent following control for body mass index (weight (kg)/height (m)2), suggesting that the association is mediated by body fat deposition over time. The hazard ratio for a corresponding 40% increment in FFQ fat density was 1.05 (95% CI: 1.00, 1.09). A stronger fat density association, with a hazard ratio of 1.19 (95% CI: 1.00, 1.41), emerged from analyses that used 4-day food records for dietary assessment. FFQ-based analyses were also carried out by using a second dietary assessment in place of the biomarker for calibration. This type of calibration did not correct for systematic bias in energy assessment, but may be able to accommodate the “noise” component of dietary measurement error. Implications for epidemiologic applications more generally are described.
doi:10.1093/aje/kwt198
PMCID: PMC3842904  PMID: 24064741
bias; biological markers; breast cancer; dietary assessment; dietary energy; dietary fat; postmenopausal women
6.  AN EXPLORATORY STUDY OF RESPIRATORY QUOTIENT CALIBRATION AND ASSOCIATION WITH POSTMENOPAUSAL BREAST CANCER 
Background
The respiratory quotient (RQ), defined as the ratio of carbon dioxide exhaled to oxygen uptake, reflects substrate utilization when energy is expended. Fat and alcohol have RQ values of about 0.7, compared to 1.0 for carbohydrate, and about 0.8 for protein. Here, the association between RQ and postmenopausal breast cancer risk is studied.
Methods
Paired RQ measurements were obtained, separated by about 6 months, for women in the reliability subset of a Women’s Health Initiative (WHI) Nutrition and Physical Activity Assessment Study. Linear regression of the average of the paired log RQ assessments on a corresponding log food quotient (FQ) average and other study subject characteristics, including age, body mass index, race, and education, yielded calibration equations for predicting RQ.
Results
Calibration equations, using any of food frequency, food record, or dietary recall data, explained an appreciable fraction of measured log RQ variation, and these were used to compute calibrated RQ estimates throughout WHI cohorts. Calibrated RQ estimates using four-day food record data related inversely (P=0.004) to (invasive) breast cancer risk in the WHI Dietary Modification trial comparison group, and corresponding RQ estimates using food frequency data related inversely (P=0.002) to breast cancer incidence in this cohort combined with the larger WHI Observational Study.
Conclusion
Though preliminary, these analyses suggest a substantially higher postmenopausal breast cancer risk among women having relatively low RQ.
Impact
RQ elevation could provide a novel target for breast cancer risk reduction.
doi:10.1158/1055-9965.EPI-13-0511
PMCID: PMC3864792  PMID: 24108790
breast cancer; dietary assessment; food quotient; indirect calorimetry; postmenopausal women; respiratory quotient; substrate utilization
7.  The role of dietary protein intake in the prevention of sarcopenia of aging 
Sarcopenia is defined as age-related decrease in muscle mass and performance. Several consensus definitions of sarcopenia exist, each providing different cut points and methodologies for assessing muscle mass and muscle strength. Thus, wide variation in the prevalence of sarcopenia has been reported, generally ranging up to 45% for men and 26% for women. Risk factors for sarcopenia include age, malnutrition, and physical inactivity. Additional evidence suggests a protective role for protein supplementation in older adults in order to preserve lean body mass and prevent frailty, accepted intervention targets for reducing the risk of sarcopenia. Protein supplements vary widely in their composition, and small trials of heterogeneous study designs have made it difficult to extrapolate findings to develop data-driven, evidence-based recommendations for protein supplementation in sarcopenia prevention. Short-term randomized, controlled trials of muscle protein synthesis have demonstrated that whey protein increases synthesis more so than casein or soy isolates. Studies also suggest that essential amino acids stimulate muscle protein synthesis to a greater extent than non-essential amino acids. This review summarizes the epidemiological and clinical trial evidence establishing the current definitions for sarcopenia and provides an overview of the state of the evidence for protein supplementation to prevent and/or mitigate sarcopenia.
doi:10.1177/0884533613507607
PMCID: PMC3928027  PMID: 24163319
Sarcopenia; diet; protein; amino acids; aging
8.  Short sleep duration is associated with decreased serum leptin, increased energy intake, and decreased diet quality in postmenopausal women 
Obesity (Silver Spring, Md.)  2014;22(5):E55-E61.
Objective
Short sleep duration induces hormonal perturbations contributing to hyperphagia, insulin resistance, and obesity. The majority of these studies are conducted in young adults. This analysis in a large (n= 769) sample of postmenopausal women (median age 63 y) sought to 1) confirm that sleep duration and sleep quality are negatively correlated with circulating leptin concentrations and 2) to examine the relationship between self-reported sleep, dietary energy intake, and diet quality, as well as, investigate the role of leptin in these associations.
Design and Methods
Sleep duration/quality, insomnia, and dietary intake were determined via self-report. Blood samples were collected following an overnight fast to assess serum leptin concentration. All analyses were adjusted for total body fat mass.
Results
Women reporting ≤6h sleep/night had lower serum leptin concentrations than those reporting ≥8h sleep (P= 0.04). Furthermore, those with ≤6h sleep/night reported higher dietary energy intake (p=0.01) and lower diet quality (P= 0.04) than the reference group (7h sleep/night). Women sleeping ≥8h also reported lower diet quality than the reference group (P= 0.02). Importantly, serum leptin did not confound these associations.
Conclusions
These results provide evidence that sleep duration is inversely associated with serum leptin and dietary energy intake in postmenopausal women.
doi:10.1002/oby.20683
PMCID: PMC4008703  PMID: 24347344
obesity; sleep duration; sleep quality; leptin; energy intake; diet quality
9.  Biomarker-Calibrated Protein Intake and Physical Function in the Women’s Health Initiative 
OBJECTIVES
Preserving physical function with aging may be partially met through modification in dietary protein intake.
DESIGN
Women’s Health Initiative Clinical Trials (CT) and Observational Study (OS).
SETTING & PARTICIPANTS
Women age 50–79 y (n=134,961) with dietary data and ≥ 1 physical function measure.
MEASUREMENTS
Physical function was assessed by short form RAND-36 at baseline and annually beginning in 2005 for all WHI participants, and at closeout for CT participants (average ~7 y after baseline). In a subset of 5346 participants, physical performance measures (grip strength, number of chair stands in 15 seconds, and timed 6-meter walk) were assessed at baseline and years 1, 3, and 6. Calibrated energy and protein intake were derived from regression equations using baseline food frequency questionnaire data collected on the entire cohort and doubly labeled water and 24-hour urinary nitrogen collected from a representative sample as reference measures. Associations between calibrated protein intake and each of the physical function measures were assessed using generalized estimating equations.
RESULTS
Calibrated protein intake ranged from 6.6 to 22.3% energy. Higher calibrated protein intake at baseline was associated with higher self-reported physical function [quintile (Q) 5 vs. Q1: 85.6 (95% CI, 81.9 to 87.5) vs. 75.4 (73.2 to 78.5), Ptrend=0.002] and a slower rate of functional decline [Q5 vs. Q1 annualized change: −0.47 (−0.63 to −0.39) vs. −0.98 (−1.18 to −0.75), Ptrend=0.022]. Women with higher calibrated protein intake also had higher grip strength at baseline [Q5 vs. Q1: 24.7 (24.3 to 25.2) vs. 24.1 (23.6 to 24.5), Ptrend=0.036] and showed slower declines in grip strength [Q5 vs. Q1 annualized change: −0.45 kg (−0.39 to −0.63) vs. −0.59 kg (−0.50 to −0.66), Ptrend=0.028]. Additionally, women with higher calibrated protein intake completed more chair stands at baseline [Q5 vs. Q1: 7.11 (6.91 to 7.26) vs. 6.61 (6.46 to 6.76), Ptrend=0.002].
CONCLUSION
Higher calibrated protein intake is associated with greater physical function and performance and slower rates of decline in postmenopausal women.
doi:10.1111/jgs.12503
PMCID: PMC3928025  PMID: 24219187
dietary protein intake; physical performance; physical function; grip strength
10.  The Women’s Health Initiative Hormone Therapy Trials: Update and Overview of Health Outcomes During the Intervention and Post-Stopping Phases 
IMPORTANCE
Menopausal hormone therapy continues in clinical use but questions remain regarding its risks and benefits for chronic disease prevention.
OBJECTIVE
To provide a comprehensive, integrated overview of findings from the two Women’s Health Initiative (WHI) hormone therapy (HT) trials with extended post-intervention follow up.
DESIGN, SETTING, PARTICIPANTS, AND INTERVENTIONS
27,347 postmenopausal women, age 50–79 years, were enrolled at 40 US centers. Interventions were conjugated equine estrogens (CEE, 0.625 mg/day) with medroxyprogesterone acetate (MPA, 2.5 mg/day) for women with an intact uterus (N = 16,608) and CEE alone for women with hysterectomy (N= 10,739), or their placebos. Intervention continued for 5.6 and 7.2 years (median), respectively, with cumulative follow-up of 13 years through September 30, 2010.
MAIN OUTCOMES AND MEASURES
The primary efficacy and safety outcomes were coronary heart disease (CHD) and invasive breast cancer, respectively. A global index also included stroke, pulmonary embolism, colorectal cancer, endometrial cancer, hip fracture, and deaths. Secondary and quality-of-life outcomes were also assessed.
RESULTS
During the intervention phase for CEE+MPA, the hazard ratio (HR) for CHD was 1.18 (95% confidence interval [CI] 0.95–1.45) and overall risks outweighed benefits, with increases in invasive breast cancer, stroke, pulmonary embolism, and the global index. Other risks included increased dementia (in women >65 years), gallbladder disease, and urinary incontinence, while benefits included decreased hip fractures, diabetes, and vasomotor symptoms. Post-intervention, most risks and benefits dissipated, although some elevation in breast cancer risk persisted (cumulative hazard ratio [HR] =1.28; 95% confidence interval, 1.11–1.48). During intervention for CEE alone, risks and benefits were more balanced, with a HR for CHD of 0.94 (0.78–1.14), increased stroke and venous thrombosis, decreased hip fractures and diabetes, and over cumulative follow-up, decreased breast cancer (HR=0.79 [0.65–0.97]). Neither regimen affected all-cause mortality. With CEE, younger women (50–59 years) had more favorable results for all-cause mortality, myocardial infarction, and the global index (nominal P values for trend by age <0.05), but not for stroke and venous thrombosis. Absolute risks of adverse events (measured by the global index) per 10,000 women per year on CEE+MPA ranged from 12 excess cases for age 50–59 to 38 for age 70–79 and, for CEE, from 19 fewer cases for age 50–59 to 51 excess cases for age 70–79. Results for quality of life outcomes in both trials were mixed.
CONCLUSIONS AND RELEVANCE
Menopausal hormone therapy has a complex pattern of risks and benefits. While appropriate for symptom management in some women, its use for chronic disease prevention is not supported by the WHI randomized trials.
TRIAL REGISTRATION
clinical trials.gov Identifier: NCT00000611
doi:10.1001/jama.2013.278040
PMCID: PMC3963523  PMID: 24084921
11.  Nutrition and Physical Activity Cancer Prevention Guidelines, Cancer Risk, and Mortality in the Women's Health Initiative 
Healthy lifestyle behaviors are recommended to reduce cancer risk and overall mortality. Adherence to cancer-preventive health behaviors and subsequent cancer risk has not been evaluated in a diverse sample of postmenopausal women. We examined the association between the American Cancer Society (ACS) Nutrition and Physical Activity Cancer Prevention Guidelines score and risk of incident cancer, cancer-specific mortality, and all-cause mortality in 65,838 postmenopausal women enrolled in the Women’s Health Initiative Observational Study. ACS guidelines scores (0–8 points) were determined from a combined measure of diet, physical activity, body mass index (current and at age 18 years), and alcohol consumption. After a mean follow-up of 12.6 years, 8,632 incident cancers and 2,356 cancer deaths were identified. The highest ACS guidelines scores compared with the lowest were associated with a 17% lower risk of any cancer [HR, 0.83; 95% confidence interval (CI), 0.75–0.92], 22% lower risk of breast cancer (HR, 0.78; 95% CI, 0.67–0.92), 52% lower risk of colorectal cancer (HR, 0.48; 95% CI, 0.32–0.73), 27% lower risk of all-cause mortality, and 20% lower risk of cancer-specific mortality (HR, 0.80; 95% CI, 0.71–0.90). Associations with lower cancer incidence and mortality were generally strongest among Asian, black, and Hispanic women and weakest among non-Hispanic whites. Behaviors concordant with Nutrition and Physical Activity Cancer Prevention Guidelines were associated with lower risk of total, breast, and colorectal cancers and lower cancer-specific mortality in postmenopausal women.
doi:10.1158/1940-6207.CAPR-13-0258
PMCID: PMC4090781  PMID: 24403289
12.  Genome-wide association analysis of red blood cell traits in African Americans: the COGENT Network 
Human Molecular Genetics  2013;22(12):2529-2538.
Laboratory red blood cell (RBC) measurements are clinically important, heritable and differ among ethnic groups. To identify genetic variants that contribute to RBC phenotypes in African Americans (AAs), we conducted a genome-wide association study in up to ∼16 500 AAs. The alpha-globin locus on chromosome 16pter [lead SNP rs13335629 in ITFG3 gene; P < 1E−13 for hemoglobin (Hgb), RBC count, mean corpuscular volume (MCV), MCH and MCHC] and the G6PD locus on Xq28 [lead SNP rs1050828; P < 1E − 13 for Hgb, hematocrit (Hct), MCV, RBC count and red cell distribution width (RDW)] were each associated with multiple RBC traits. At the alpha-globin region, both the common African 3.7 kb deletion and common single nucleotide polymorphisms (SNPs) appear to contribute independently to RBC phenotypes among AAs. In the 2p21 region, we identified a novel variant of PRKCE distinctly associated with Hct in AAs. In a genome-wide admixture mapping scan, local European ancestry at the 6p22 region containing HFE and LRRC16A was associated with higher Hgb. LRRC16A has been previously associated with the platelet count and mean platelet volume in AAs, but not with Hgb. Finally, we extended to AAs the findings of association of erythrocyte traits with several loci previously reported in Europeans and/or Asians, including CD164 and HBS1L-MYB. In summary, this large-scale genome-wide analysis in AAs has extended the importance of several RBC-associated genetic loci to AAs and identified allelic heterogeneity and pleiotropy at several previously known genetic loci associated with blood cell traits in AAs.
doi:10.1093/hmg/ddt087
PMCID: PMC3658166  PMID: 23446634
13.  Correlates of 25-hydroxyvitamin D and breast cancer stage in the Women’s Healthy Eating and Living Study 
Nutrition and cancer  2013;65(2):188-194.
Inverse associations between circulating 25-hydroxyvitamin D [25(OH)D] and breast cancer stage have been reported, thus it is critical to understand the variables that contribute to 25(OH)D levels among women with breast cancer. Among 904 women in the Women’s Healthy Eating and Living Study, plasma 25(OH)D concentrations were measured and data on demographic characteristics, diet, physical activity, and tumor characteristics were collected at study entry. Statistically significant associations with 25(OH)D concentrations were observed for body mass index (BMI), body surface area (BSA), height, smoking, total vitamin D intake, physical activity, and race or ethnicity. Of the correlates of 25(OH)D, BMI, BSA, height, physical activity, and study site were associated with stage of breast cancer; however, concentrations of 25(OH)D were not significantly related to stage. In fully adjusted logistic regression models, the ORs (95% CIs) for the association between vitamin D deficiency and Stage II and III cancers were 0.85 (0.59-1.22) and 1.23 (0.71-2.15), respectively (p-trend=0.59), compared to Stage I. This study confirms previous work regarding the correlates of 25(OH)D concentrations but does not provide support for an association between vitamin D status and breast cancer stage.
doi:10.1080/01635581.2013.756531
PMCID: PMC4041275  PMID: 23441606
14.  Frequency of private spiritual activity and cardiovascular risk in postmenopausal women: the Women’s Health Initiative 
Annals of epidemiology  2013;23(5):239-245.
Purpose
Spirituality has been associated with better cardiac autonomic balance, but its association with cardiovascular risk is not well studied. We examined whether more frequent private spiritual activity was associated with reduced cardiovascular risk in postmenopausal women enrolled in the Women’s Health Initiative Observational Study.
Methods
Frequency of private spiritual activity (prayer, Bible reading, and meditation) was self-reported at year 5 of follow-up. Cardiovascular outcomes were centrally adjudicated, and cardiovascular risk was estimated from proportional hazards models.
Results
Final models included 43,708 women (mean age, 68.9 ± 7.3 years; median follow-up, 7.0 years) free of cardiac disease through year 5 of follow-up. In age-adjusted models, private spiritual activity was associated with increased cardiovascular risk (hazard ratio [HR], 1.16; 95% confidence interval [CI], 1.02–1.31 for weekly vs. never; HR, 1.25; 95% CI, 1.11–1.40 for daily vs. never). In multivariate models adjusted for demographics, lifestyle, risk factors, and psychosocial factors, such association remained significant only in the group with daily activity (HR, 1.16; 95% CI, 1.03–1.30). Subgroup analyses indicate this association may be driven by the presence of severe chronic diseases.
Conclusions
Among aging women, higher frequency of private spiritual activity was associated with increased cardiovascular risk, likely reflecting a mobilization of spiritual resources to cope with aging and illness.
doi:10.1016/j.annepidem.2013.03.002
PMCID: PMC3741666  PMID: 23621989
Women’s health; Cardiovascular diseases; Spirituality
15.  Variants in the Dopamine-4-Receptor Gene Promoter Are Not Associated with Sensation Seeking in Skiers 
PLoS ONE  2014;9(4):e93521.
Sensation seeking is a personality trait that has been associated with disinhibited behaviours including substance use and gambling, but also with high-risk sport practices including skydiving, paragliding, and downhill skiing. Twin studies have shown that sensation seeking is moderately heritable, and candidate genes encoding components involved in dopaminergic transmission have been investigated as contributing to this type of behaviour. To determine whether variants in the regulatory regions of the dopamine-4-receptor gene (DRD4) influenced sport-specific sensation seeking, we analyzed five polymorphisms (−1106T/C, −906T/C, −809G/A, −291C/T, 120-bp duplication) in the promoter region of the gene in a cohort of skiers and snowboarders (n = 599) that represented a broad range of sensation seeking behaviours. We grouped subjects by genotype at each of the five loci and compared impulsive sensation seeking and domain-specific (skiing) sensation seeking between groups. There were no significant associations between genotype(s) and general or domain-specific sensation seeking in the skiers and snowboarders, suggesting that while DRD4 has previously been implicated in sensation seeking, the promoter variants investigated in this study do not contribute to sensation seeking in this athlete population.
doi:10.1371/journal.pone.0093521
PMCID: PMC3972116  PMID: 24691022
16.  Physical Activity Assessment: Biomarkers and Self-Report of Activity-Related Energy Expenditure in the WHI 
American Journal of Epidemiology  2013;177(6):576-585.
We used a biomarker of activity-related energy expenditure (AREE) to assess measurement properties of self-reported physical activity and to determine the usefulness of AREE regression calibration equations in the Women's Health Initiative. Biomarker AREE, calculated as the total energy expenditure from doubly labeled water minus the resting energy expenditure from indirect calorimetry, was assessed in 450 Women's Health Initiative participants (2007–2009). Self-reported AREE was obtained from the Arizona Activity Frequency Questionnaire (AAFQ), the 7-Day Physical Activity Recall (PAR), and the Women's Health Initiative Personal Habits Questionnaire (PHQ). Eighty-eight participants repeated the protocol 6 months later. Reporting error, measured as log(self-report AREE) minus log(biomarker AREE), was regressed on participant characteristics for each instrument. Body mass index was associated with underreporting on the AAFQ and PHQ but overreporting on PAR. Blacks and Hispanics underreported physical activity levels on the AAFQ and PAR, respectively. Underreporting decreased with age for the PAR and PHQ. Regressing logbiomarker AREE on logself-reported AREE revealed that self-report alone explained minimal biomarker variance (R2 = 7.6, 4.8, and 3.4 for AAFQ, PAR, and PHQ, respectively). R2 increased to 25.2, 21.5, and 21.8, respectively, when participant characteristics were included. Six-month repeatability data adjusted for temporal biomarker variation, improving R2 to 79.4, 67.8, and 68.7 for AAFQ, PAR, and PHQ, respectively. Calibration equations “recover” substantial variation in average AREE and valuably enhance AREE self-assessment.
doi:10.1093/aje/kws269
PMCID: PMC3626043  PMID: 23436896
biomakers; measurement error; physical activity; postmenopausal women
17.  A Comparison of Mediterranean-Style and MyPyramid Diets on Weight Loss and Inflammatory Biomarkers in Postpartum Breastfeeding Women 
Journal of Women's Health  2013;22(1):48-57.
Abstract
Background
Of postpartum women, 15%–20% retain≥5 kg of their gestational weight gain, increasing risk for adult weight gain. Postpartum women are also in a persistent elevated inflammatory state. Both factors could increase the risk of obesity-related chronic disease. We hypothesized that breastfeeding women randomized to a Mediterranean-style (MED) diet for 4 months would demonstrate significantly greater reductions in body weight, body fat, and inflammation than women randomized to the U.S. Department of Agriculture's (USDA) MyPyramid diet for Pregnancy and Breastfeeding (comparison diet).
Methods
A randomized, controlled dietary intervention trial was conducted in 129 overweight (body mass index [BMI] 27.2±4.9 kg/m2), mostly exclusively breastfeeding (73.6%) women who were a mean 17.5 weeks postpartum. Dietary change was assessed using a validated Food Frequency Questionnaire (FFQ) before and after intervention as well as plasma fatty acid measures (gas chromatography/flame ionization detector [GC/FID]). Anthropometric measurements and biomarkers of inflammation, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), also were assessed at baseline and 4 months via enzyme-linked immunosorbent assay (ELISA).
Results
Participants in both diet groups demonstrated significant (p<0.001) reductions in body weight (−2.3±3.4 kg and −3.1±3.4 kg for the MED and comparison diets, respectively) and significant (p≤0.002) reductions in all other anthropometric measurements; no significant between-group differences were shown as hypothesized. A significant decrease in TNF-α but not IL-6 was also demonstrated in both diet groups, with no significant between-group difference.
Conclusions
Both diets support the promotion of postpartum weight loss and reduction in inflammation (TNF-α) in breastfeeding women.
doi:10.1089/jwh.2012.3707
PMCID: PMC3546415  PMID: 23276189
18.  MULTIVITAMIN USE AND RISK OF CANCER AND CARDIOVASCULAR DISEASE IN THE WOMEN’S HEALTH INITIATIVE COHORTS 
Archives of internal medicine  2009;169(3):10.1001/archinternmed.2008.540.
Context
Millions of postmenopausal women use multivitamins, often believing that supplements prevent chronic diseases such as cancer and cardiovascular disease.
Objective
To examine associations between multivitamin use and risk of cancer, cardiovascular disease and mortality in postmenopausal women.
Design, Setting and Participants
161,808 participants from the Women’s Health Initiative Clinical Trials (n=68,132 in three overlapping trials of hormone therapy, dietary modification and calcium-vitamin D) or Observational Study (n=93,676). Detailed data were collected on multivitamin use at baseline and follow-up time points. Study enrollment occurred between 1993–1998; women were followed for a median of 8.0 years in the clinical trials and 7.9 years in the observational study. Disease endpoints were collected through 2005.
Outcome Measures
Cancers of the breast (invasive), colon/rectum, endometrium, kidney, bladder, stomach, ovary and lung; cardiovascular disease (myocardial infarction, stroke, venous thrombosis); and total mortality.
Results
41.5% of participants used multivitamins. After a median of 8.0 years of follow-up in the CT and 7.9 years in the OS, 9,619 cases of breast, colorectal, endometrium, kidney, bladder, stomach lung or ovary cancer; 8,751 CVD events and 9,865 deaths were reported. Multivariate-adjusted analyses revealed no association of multivitamins with risk of cancer (breast HR=0.98, 95%CI 0.91–1.05; colorectal HR = 0.99, 95% CI 0.88–1.11; endometrial HR = 1.05, 95%CI= 0.90–1.21; lung HR = 1.0, 95% CI=0.88–1.13; ovary HR = 1.07, 95%CI =0.88–1.29); CVD (MI HR= 0.96, 95%CI= 0.89–1.03; stroke HR = 0.99, 95%CI =0.91–1.07; VT HR = 1.05, 95%CI =0.85–1.29); or mortality (HR = 1.02, 95% CI=0.97–1.07).
Conclusion
After a median follow-up of 8.0 and 7.9 years in the CT and OS, respectively, the WHI cohorts provide convincing evidence that multivitamin use has little or no influence on the risk of common cancers, cardiovascular disease or total mortality in postmenopausal women.
Clinical Trial Registration
clinicaltrials.gov identifier: NCT00000611
doi:10.1001/archinternmed.2008.540
PMCID: PMC3868488  PMID: 19204221
dietary supplements; vitamins; minerals; breast cancer; lung cancer; colon cancer; myocardial infarction; stroke
19.  Weight Loss Is Associated With Increased Serum 25-Hydroxyvitamin D in Overweight or Obese Women 
Obesity (Silver Spring, Md.)  2012;20(11):10.1038/oby.2012.57.
Low circulating concentrations of vitamin D metabolites have been associated with increased risk for several diseases and clinical conditions. Large observational studies and surveys have shown that obesity is independently associated with lower serum 25-hydroxyvitamin D (25(OH)D) concentration. Few studies have examined the effect of weight loss on serum 25(OH)D concentration. The purpose of this study was to prospectively examine the effect of weight loss on serum 25(OH)D concentration. Data were collected from 383 overweight or obese women who participated in a 2-year clinical trial of a weight-loss program, in which 51% (N = 195) lost at least 5% of baseline weight by 24 months, 18% (N = 67) lost 5–10%, and 33% (N = 128) lost >10%. Women who did not lose weight at 24 months had an increase in serum 25(OH)D of 1.9 (9.7) ng/ml (mean (SD)); 25(OH)D increased by 2.7 (9.1) ng/ml for those who lost 5–10% of baseline weight; and 25(OH)D increased by 5.0 (9.2) ng/ml for those who lost >10% of baseline weight (P = 0.014). At baseline, 51% (N = 197) of participants met or exceeded the recommended serum concentration of 20 ng/ml. By study end, 64% (N = 230) of overweight or obese women met this goal, as well as 83% (N = 20) of those whose weight loss achieved a normal BMI. These findings suggest that weight loss, presumably associated with a reduction in body fat, is associated with increased serum 25(OH)D concentration in overweight or obese women.
doi:10.1038/oby.2012.57
PMCID: PMC3849029  PMID: 22402737
20.  VITAMIN C AND ZINC INTAKES ARE RELATED TO BONE MACRO-ARCHITECTURAL STRUCTURE AND STRENGTH IN PREPUBESCENT GIRLS 
Calcified tissue international  2012;91(6):430-439.
Background
The extent to which nutrient intake may influence bone structure and strength during maximum rates of skeletal growth remains uncertain.
Objective
To examine the relationship of dietary intake of micronutrients and bone macro-architectural structure in young girls.
Design
This cross-sectional analysis included baseline data from 363 4th and 6th grade girls enrolled in the Jump-In study. Nutrient intake was assessed using the Harvard Youth/Adolescent Food Frequency Questionnaire. Volumetric BMD (vBMD), bone geometry and strength were measured by peripheral quantitative computed tomography (pQCT). Correlations and regression modeling assessed relations between usual nutrient intake and bone parameters.
Results
In 4th grade girls, metaphyseal and diaphyseal area and circumferences, and diaphyseal strength were associated with vitamin C intake (r = 0.15–0.19; p<0.05). Zinc intake was correlated with diaphyseal vBMD (r = 0.15–0.16; p<0.05). Using multiple linear regression to adjust for important covariates, we observed significant independent associations for vitamin C and zinc with bone parameters. For every mg/d of vitamin C intake trabecular area increased by 11%, cortical strength improved by 14%; and periosteal and endosteal circumferences increased by 5% and 8.6%, respectively. For every mg/d of zinc intake, cortical vBMD increased by <1%. No significant associations were observed in 6th-grade girls.
Conclusion
Results of this study suggests that vitamin C and zinc intake are positively associated with objective measures of bone geometry, size and strength in 4th-grade girls. This indicates potential differences in micronutrient and bone associations at various age-associated stages of bone maturation perhaps indicative of competing hormonal influences.
doi:10.1007/s00223-012-9656-8
PMCID: PMC3496253  PMID: 23076447
peripheral quantitative computed tomography (pQCT); preadolescence; bone mineral density (BMD); bone strength; micronutrient intake; vitamin C
21.  Recreational physical activity, body mass index and survival in women with colorectal cancer 
Cancer causes & control : CCC  2012;23(12):1939-1948.
Background and purpose
Previous studies have shown that physical inactivity and obesity are risk factors for the development of colorectal cancer. However, controversy exists regarding the influence of these factors on survival in colorectal cancer patients. We evaluated the impact of recreational physical activity and body mass index (BMI) before and after colorectal cancer diagnosis on disease-specific mortality and all-cause mortality.
Patients and Methods
This prospective cohort study included 1339 women enrolled in the Women’s Health Initiative study who were diagnosed with colorectal cancer subsequent to study enrolment. BMI and recreational physical activity were measured before cancer diagnosis at study entry (pre-diagnostic) and after diagnosis at study follow-up interviews (post-diagnostic). We used Cox regression to estimate the association between pre- and post-diagnostic exposures and survival after colorectal cancer diagnosis.
Results
Among women diagnosed with colorectal cancer, 265 (13%) deaths occurred during a median study follow-up of 11.9 years, of which 171 (65%) were attributed to colorectal cancer. Compared with women reporting no pre-diagnostic recreational physical activity, those reporting activity levels of ≥18 MET-hours/week had significantly lower colorectal cancer-specific mortality (hazard ratio (HR)=0.68; 95% confidence interval (CI): 0.41–1.13) and all-cause mortality (HR=0.63; 95% CI: 0.42–0.96). Similar inverse associations were seen for post-diagnostic recreational physical activity. Neither pre- nor post-diagnostic BMI were associated with mortality after colorectal cancer diagnosis.
Conclusion
Recreational physical activity before and after CR colorectal cancer C diagnosis, but not BMI, is associated with more favourable survival.
doi:10.1007/s10552-012-0071-2
PMCID: PMC3499635  PMID: 23053793
Physical activity; body mass index; colorectal cancer; survival; postmenopausal
22.  Predictors of Improvement in Cardiometabolic Risk Factors With Weight Loss in Women 
Background
Weight loss is associated with improvements in cardiometabolic risk factors, including serum glucose, insulin, C‐reactive protein, and blood lipids. Few studies have evaluated the long‐term (>18 months) effect of weight loss on these risk factors or sought to identify factors associated with sustained improvements in these measures.
Methods and Results
In 417 overweight/obese women (mean [SD] age, 44 [10] years) participating in a weight loss trial, we sought to identify predictors of weight loss–associated cardiometabolic risk factors after 12 and 24 months of intervention. Total cholesterol (TC), low‐density lipoprotein (LDL)–cholesterol (LDL‐C), high‐density lipoprotein (HDL)–cholesterol, non‐HDL‐cholesterol, triglycerides (TG), insulin, glucose, C‐reactive protein (CRP), and cardiopulmonary fitness were measured at baseline and at 12 and 24 months. After 24 months, significant reductions in body weight, waist circumference, CRP, TC, HDL‐cholesterol, and non‐HDL‐cholesterol were observed (P<0.01). After 24 months, mean TC and non‐HDL‐cholesterol were reduced regardless of the amount of weight lost, whereas reductions in LDL–cholesterol, CRP, insulin, and TG were observed only in those who lost ≥10% body weight. Step‐test performance improved only in those who lost ≥10% body weight after 24 months. Change in weight demonstrated a positive predictive value for change in cholesterol, insulin, glucose, and triglycerides. Baseline level of the biomarker showed the greatest predictive value for follow‐up measures for insulin, cholesterol, glucose, and triglycerides.
Conclusions
Our data extend the results from short‐term weight loss trials and suggest that the magnitude of weight loss and baseline values for risk factors are associated with improvements in cardiometabolic risk factors even after 24 months.
Clinical Trials Registration Information
URL: http://www.clinicaltrials.gov/. Unique identifier: NCT00640900.
doi:10.1161/JAHA.113.000152
PMCID: PMC3886783  PMID: 24351700
lipids; obesity; risk factors; women
23.  Safety and Feasibility of Topical Application of Limonene as a Massage Oil to the Breast 
Journal of cancer therapy  2012;3(5A):10.4236/jct.2012.325094.
Background
Limonene, a major component in citrus oil, has demonstrated anti-cancer effects in preclinical mammary cancer models. However, the effective oral dose translates to a human dose that may not be feasible for chronic dosing. We proposed to evaluate topical application of limonene to the breast as an alternative dosing strategy.
Materials and Methods
We conducted a mouse disposition study to determine whether limonene would be bio available in the mammary tissue after topical application. SKH-1 mice received topical or oral administration of limonene in the form of orange oil every day for 4 weeks. Plasma and mammary pads were collected 4 hrs after the final dosing. We also conducted an exploratory clinical study to evaluate the safety and feasibility of topically applied limonene in the form of orange oil to the breast. Healthy women were recruited to apply orange oil containing massage oil to their breasts daily for four weeks. Safety and feasibility were assessed by reported adverse events, clinical labs, and usage compliance. Pre and post-intervention nipple aspirate fluid (NAF) and plasma were collected for limonene concentration determination.
Results
The mouse disposition study showed that topical and oral orange oil administration resulted in similar mammary tissue disposition of limonene with no clinical signs of toxicity. In the clinical study, the topical application of limonene containing massage oil to the breast was found to be safe with high levels of usage compliance for daily application, although NAF and plasma limonene concentrations were not significantly changed after the massage oil application.
Conclusions
Our studies showed that limonene is bio available in mammary tissue after topical orange oil application in mice and this novel route of administration to the breast is safe and feasible in healthy women.
doi:10.4236/jct.2012.325094
PMCID: PMC3824622  PMID: 24236248
Limonene; Topical Application; Safety
24.  A low-fat dietary pattern and risk of metabolic syndrome in postmenopausal women: The Women’s Health Initiative 
Metabolism: clinical and experimental  2012;61(11):1572-1581.
Objective
Nutrition plays an important role in metabolic syndrome etiology. We examined whether the Women’s Health Initiative (WHI) Dietary Modification Trial influenced metabolic syndrome risk.
Materials/Methods
48,835 postmenopausal women aged 50–79 years were randomized to a low-fat (20% energy from fat) diet (intervention) or usual diet (comparison) for a mean of 8.1 years. Blood pressure, waist circumference and fasting blood measures of glucose, HDL-cholesterol and triglycerides were measured on a subsample (n= 2816) at baseline and years 1, 3 and 6 post-randomization. Logistic regression estimated associations of the intervention with metabolic syndrome risk and use of cholesterol-lowering and hypertension medications. Multivariate linear regression tested associations between the intervention and metabolic syndrome components.
Results
At year 3, but not years 1 or 6, women in the intervention group (vs. comparison) had a non-statistically significant lower risk of metabolic syndrome (OR=0.83, 95% CI 0.59–1.18). Linear regression models simultaneously modeling the five metabolic syndrome components revealed significant associations of the intervention with metabolic syndrome at year 1 (p<0.0001), but not years 3 (p=0.19) and 6 (p=0.17). Analyses restricted to intervention-adherent participants strengthened associations at years 3 (p=0.05) and 6 (p=0.06). Cholesterol-lowering and hypertension medication use was 19% lower at year 1 for intervention vs. comparison group women (OR=0.81, 95% CI 0.60–1.09). Over the entire trial, fewer intervention vs. comparison participants used these medications (26.0% vs. 29.9%), although results were not statistically significant (p=0.89).
Conclusions
The WHI low-fat diet may influence metabolic syndrome risk and decrease use of hypertension and cholesterol-lowering medications. Findings have potential for meaningful clinical translation.
doi:10.1016/j.metabol.2012.04.007
PMCID: PMC3430820  PMID: 22633601
clinical trials; aging; dietary fat; metabolic syndrome
25.  Racial Differences in Colorectal Cancer Incidence and Mortality in the Women’s Health Initiative 
Background
Colorectal cancer (CRC) incidence and mortality rates are higher in African–Americans as compared with other racial/ethnic groups. The women’s health initiative (WHI) study sample was used to determine whether differences in CRC risk factors explain racial/ethnic differences in incidence and mortality.
Methods
The WHI is a longitudinal study of postmenopausal women recruited from 40 centers. Baseline questionnaires were used to collect sociodemographic and health status information. All CRC diagnoses were centrally adjudicated. Cox regression models were used to compute hazard ratios (HRs) and 95% confidence intervals (CIs) for invasive CRC by race/ethnicity.
Results
The study sample included 131,481 (83.7%) White, 14,323 (9.1%) African–American, 6,362 (4.1%) Hispanic, 694 (0.4%) Native American and 4,148 (2.6%) Asian/Pacific Islanders. After a mean follow-up of 10.8 years (SD 2.9), CRC incidence was the highest in African–Americans (annualized rate = 0.14%), followed by Whites and Native Americans (0.12% each), Asian/Pacific Islanders (0.10%), and Hispanics (0.08%). After adjustment for age and trial assignment, Hispanics had a lower risk compared with Whites, HR 0.73 (95% CI: 0.54–0.97) (P = 0.03), and African–Americans had a marginally greater risk, HR 1.16 (95% CI: 0.99–1.34), P = 0.06. Multivariable adjustment attenuated the difference in incidence between African–Americans and Whites (HR 0.99, 95% CI: 0.82–1.20), while strengthening the lower HR for Hispanics (HR 0.68, 95% CI: 0.48–0.97).
Conclusions
African–American/White differences in CRC risk are likely due to sociodemographic/cultural factors other than race.
Impact
A number of modifiable exposures could be a focus for reducing CRC risk in African–Americans.
doi:10.1158/1055-9965.EPI-11-0027
PMCID: PMC3784999  PMID: 21602308

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