Publications by authors named "Marian L Neuhouser"

332 Publications

Novel application of nutritional biomarkers from a controlled feeding study and observational study toward dietary pattern characterization in postmenopausal women.

Am J Epidemiol 2021 Jun 18. Epub 2021 Jun 18.

Division of Public Health Sciences. Fred Hutchinson Cancer Research Center, Seattle, WA.

Dietary guidance emphasizes healthy dietary patterns, but supporting evidence comes from measurement-error prone self-reported diet. We explored whether nutritional biomarkers from the Women's Health Initiative Nutrition and Physical Activity Assessment Study Feeding Study (n=153; 2010-2014) and the WHI-NPAAS Observational Study (NPAAS-OS; n=450; 2006-2009) could identify biomarker signatures of dietary patterns for development of corresponding regression calibration equations to help mitigate measurement error. Fasting blood was assayed for a specific panel of vitamins, carotenoids and phospholipid fatty acids; 24-hour urine was assayed for nitrogen, sodium and potassium. NPAAS Feeding Study intake records were used to calculate participant Healthy Eating Index-2010 (HEI-2010), Alternative Healthy Eating Index-2010, Alternative Mediterranean Diet (aMED) and Dietary Approaches to Stop Hypertension scores. Scores were regressed on blood and urine nutritional measures for discovery of dietary pattern biomarkers using a cross-validated model R2> 36% criterion (stage one). Next, stepwise models (p<0.10 for entry, removal) using NPAAS-OS regressed stage one dietary pattern biomarkers on NPAAS-OS self-reported dietary pattern scores using food frequency questionnaire, four-day food record and 24-hour recall (stage two). HEI-2010 and aMED analyses achieved cross-validated R2>36% in stage one; while Alternative Healthy Eating Index-2010 and Dietary Approaches to Stop Hypertension analyses did not. R2 for HEI-2010 stage two calibration equations were: food frequency questionnaire: 63.5%, four-day food record: 83.1% and 24-hour recall: 77.8%; while stage 2 aMED R2 were 34.9-46.8%. Dietary pattern biomarkers have potential for calibrating self-report to enhance diet-disease association studies.
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http://dx.doi.org/10.1093/aje/kwab171DOI Listing
June 2021

Change to a Higher Carbohydrate Diet and Energy Expenditure among Postmenopausal Women.

J Nutr 2021 Jun;151(6):1673-1674

Department of Medicine, Georgetown University Medical Center, and MedStar Health Research Institute, Hyattsville MD, USA.

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http://dx.doi.org/10.1093/jn/nxab095DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8169807PMC
June 2021

Self-reported symptoms of arm lymphedema and health-related quality of life among female breast cancer survivors.

Sci Rep 2021 May 21;11(1):10701. Epub 2021 May 21.

Department of Population Sciences, Beckman Research Institute, City of Hope, Duarte, CA, USA.

We examined cross-sectional associations between arm lymphedema symptoms and health-related quality of life (HRQoL) in the Health, Eating, Activity and Lifestyle (HEAL) Study. 499 women diagnosed with localized or regional breast cancer at ages 35-64 years completed a survey, on average 40 months after diagnosis, querying presence of lymphedema, nine lymphedema-related symptoms, e.g., tension, burning pain, mobility loss, and warmth/redness, and HRQoL. Analysis of covariance models were used to assess HRQoL scores in relation to presence of lymphedema and lymphedema-related symptoms. Lymphedema was self-reported by 137 women, of whom 98 were experiencing lymphedema at the time of the assessment. The most common symptoms were heaviness (52%), numbness (47%), and tightness (45%). Perceived physical health was worse for women reporting past or current lymphedema than those reporting no lymphedema (P-value < 0.0001). No difference was observed for perceived mental health (P-value = 0.31). Perceived physical health, stress, and lymphedema-specific HRQoL scores worsened as number of symptoms increased (P-values ≤ 0.01). Women reporting tension in the arm had lower physical health (P-value = 0.01), and those experiencing burning pain, tension, heaviness, or warmth/redness in the arm had lower lymphedema-specific HRQoL (P-values < 0.05). Treatment targeting specific lymphedema-related symptoms in addition to size/volume reduction may improve some aspects of HRQoL among affected women.
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http://dx.doi.org/10.1038/s41598-021-89055-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8139966PMC
May 2021

Low-fat dietary pattern and breast cancer mortality by metabolic syndrome components: a secondary analysis of the Women's Health Initiative (WHI) randomised trial.

Br J Cancer 2021 May 18. Epub 2021 May 18.

Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.

Background: In the Women's Health Initiative (WHI) dietary modification (DM) randomised trial, the low-fat dietary intervention reduced deaths from breast cancer (P = 0.02). Extending these findings, secondary analysis examined dietary intervention influence on breast cancer mortality by metabolic syndrome (MS) components.

Methods: In total, 48,835 postmenopausal women with no prior breast cancer were randomised to a low-fat dietary intervention or comparison groups. Four MS components were determined at entry in 45,833 participants: (1) high waist circumference, (2) high blood pressure, (3) high cholesterol and (4) diabetes history. Forest plots of hazard ratios (HRs) were generated with P-values for interaction between randomisation groups and MS component score. Primary outcome was death from breast cancer by metabolic syndrome score.

Results: HRs and 95% confidence intervals (CI) for dietary intervention influence on death from breast cancer were with no MS components (n = 10,639), HR 1.09, 95% CI 0.63-1.87; with 1-2 MS components (n = 30,948), HR 0.80, 95% CI 0.62-1.02; with 3-4 MS components (n = 4,246), HR 0.31, 95% CI 0.14-0.69 (interaction P = 0.01).

Conclusions: While postmenopausal women with 3-4 MS components were at higher risk of death from breast cancer, those randomised to a low-fat dietary intervention more likely had reduction in this risk.

Registry: ClinicalTrials.gov (NCT00000611).
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http://dx.doi.org/10.1038/s41416-021-01379-wDOI Listing
May 2021

Evaluation of potential metabolomic-based biomarkers of protein, carbohydrate and fat intakes using a controlled feeding study.

Eur J Nutr 2021 May 15. Epub 2021 May 15.

Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.

Purpose: Objective biomarkers of dietary exposure are needed to establish reliable diet-disease associations. Unfortunately, robust biomarkers of macronutrient intakes are scarce. We aimed to assess the utility of serum, 24-h urine and spot urine high-dimensional metabolites for the development of biomarkers of daily intake of total energy, protein, carbohydrate and fat, and the percent of energy from these macronutrients (%E).

Methods: A 2-week controlled feeding study mimicking the participants' habitual diets was conducted among 153 postmenopausal women from the Women's Health Initiative (WHI). Fasting serum metabolomic profiles were analyzed using a targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay for aqueous metabolites and a direct-injection-based quantitative lipidomics platform. Urinary metabolites were analyzed using H nuclear magnetic resonance (NMR) spectroscopy at 800 MHz and by untargeted gas chromatography-mass spectrometry (GC-MS). Variable selection was performed to build prediction models for each dietary variable.

Results: The highest cross-validated multiple correlation coefficients (CV-R) for protein intake (%E) and carbohydrate intake (%E) using metabolites only were 36.3 and 37.1%, respectively. With the addition of established dietary biomarkers (doubly labeled water for energy and urinary nitrogen for protein), the CV-R reached 55.5% for energy (kcal/d), 52.0 and 45.0% for protein (g/d, %E), 55.9 and 37.0% for carbohydrate (g/d, %E).

Conclusion: Selected panels of serum and urine metabolites, without the inclusion of doubly labeled water and urinary nitrogen biomarkers, give a reliable and robust prediction of daily intake of energy from protein and carbohydrate.
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http://dx.doi.org/10.1007/s00394-021-02577-1DOI Listing
May 2021

Indices of Diet Quality and Risk of Lung Cancer in the Women's Health Initiative Observational Study.

J Nutr 2021 Jun;151(6):1618-1627

Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, State University of New York (SUNY) at Buffalo, Buffalo, NY, USA.

Background: Prospective evidence on associations between diet quality indices and lung cancer risk is limited, particularly among older women.

Objectives: We investigated associations between 4 diet quality indices [Healthy Eating Index-2015 (HEI-2015), Alternate Healthy Eating Index 2010 (AHEI-2010), alternate Mediterranean Diet (aMED), and Dietary Approaches to Stop Hypertension (DASH)] and lung cancer incidence and mortality in the Women's Health Initiative Observational Study.

Methods: Postmenopausal women aged 50-79 y at baseline (1993-1998) self reported their diet intake and information on relevant covariates. We used Cox proportional hazards regression models to estimate HRs and 95% CIs after controlling for age, smoking, and other relevant covariates.

Results: During ∼17 y of follow-up among 86,090 participants, 1491 lung cancer cases and 1393 lung cancer deaths were documented. Dietary indices were not associated with overall lung cancer incidence but were protective against squamous cell carcinoma (12.8% of total lung cancer) cases (HEI-2015: HR: 0.85; 95% CI: 0.76, 0.96; AHEI-2010: HR: 0.87; 95% CI: 0.78, 0.98; aMED: HR: 0.90; 95% CI: 0.81, 0.99; DASH: HR: 0.87; 95% CI: 0.77, 0.98). Among the indices, only HEI-2015 showed an inverse trend (P-trend = 0.02) with overall lung cancer mortality. Smoking status or participant age at baseline did not modify the association between dietary indices and lung cancer incidence or mortality.

Conclusions: After comprehensive control of smoking exposure, we found that diet quality was not associated with overall lung cancer among postmenopausal women. However, a high-quality diet was inversely related to incident lung cancer of the squamous cell subtype. Future studies in populations with diverse age, smoking history, and dietary intake may further elucidate the relation between diet quality indices and lung cancer, especially by histological subtype.
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http://dx.doi.org/10.1093/jn/nxab033DOI Listing
June 2021

Dairy foods, calcium, and risk of breast cancer overall and for subtypes defined by estrogen receptor status: a pooled analysis of 21 cohort studies.

Am J Clin Nutr 2021 May 8. Epub 2021 May 8.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD, USA.

Background: Epidemiologic studies examining the relations between dairy product and calcium intakes and breast cancer have been inconclusive, especially for tumor subtypes.

Objective: To evaluate the associations between intakes of specific dairy products and calcium and risk of breast cancer overall and for subtypes defined by estrogen receptor (ER) status.

Method: We pooled the individual-level data of over 1 million women who were followed for a maximum of 8-20 years across studies. Associations were evaluated for dairy product and calcium intakes and risk of incident invasive breast cancer overall (n = 37,861 cases) and by subtypes defined by ER status. Study-specific multivariable hazard ratios (HRs) were estimated and then combined using random-effects models.

Results: Overall, no clear association was observed between the consumption of specific dairy foods, dietary (from foods only) calcium, and total (from foods and supplements) calcium, and risk of overall breast cancer. Although each dairy product showed a null or very weak inverse association with risk of overall breast cancer (P, test for trend >0.05 for all), differences by ER status were suggested for yogurt and cottage/ricotta cheese with associations observed for ER-negative tumors only (pooled HR = 0.90, 95% CI: 0.83, 0.98 comparing ≥60 g/d with <1 g/d of yogurt and 0.85, 95% CI: 0.76, 0.95 comparing ≥25 g/d with <1 g/d of cottage/ricotta cheese). Dietary calcium intake was only weakly associated with breast cancer risk (pooled HR = 0.98, 95% CI: 0.97, 0.99 per 350 mg/d).

Conclusion: Our study shows that adult dairy or calcium consumption is unlikely to associate with a higher risk of breast cancer and that higher yogurt and cottage/ricotta cheese intakes were inversely associated with the risk of ER-negative breast cancer, a less hormonally dependent subtype with poor prognosis. Future studies on fermented dairy products, earlier life exposures, ER-negative breast cancer, and different racial/ethnic populations may further elucidate the relation.
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http://dx.doi.org/10.1093/ajcn/nqab097DOI Listing
May 2021

Biomarker-Calibrated Macronutrient Intake and Chronic Disease Risk among Postmenopausal Women.

J Nutr 2021 Apr 20. Epub 2021 Apr 20.

Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.

Background: Knowledge about macronutrient intake and chronic disease risk has been limited by the absence of objective macronutrient measures. Recently, we proposed novel biomarkers for protein, protein density, carbohydrate, and carbohydrate density, using established biomarkers and serum and urine metabolomics profiles in a human feeding study.

Objectives: We aimed to use these biomarkers to develop calibration equations for macronutrient variables using dietary self-reports and personal characteristics and to study the association between biomarker-calibrated intake estimates and cardiovascular disease, cancer, and diabetes risk in Women's Health Initiative (WHI) cohorts.

Methods: Prospective disease association analyses are based on WHI cohorts of postmenopausal US women aged 50-79 y when enrolled at 40 US clinical centers (n = 81,954). We used biomarker intake values in a WHI nutritional biomarker study (n = 436) to develop calibration equations for each macronutrient variable, leading to calibrated macronutrient intake estimates throughout WHI cohorts. We then examined the association of these intakes with chronic disease incidence over a 20-y (median) follow-up period using HR regression methods.

Results: In analyses that included doubly labeled water-calibrated total energy, HRs for cardiovascular diseases and cancers were mostly unrelated to calibrated protein density. However, many were inversely related to carbohydrate density, with HRs (95% CIs) for a 20% increment in carbohydrate density of 0.81 (0.69, 0.95) and 0.83 (0.74, 0.93), respectively, for primary outcomes of coronary heart disease and breast cancer, as well as 0.74 (0.60, 0.91) and 0.87 (0.81, 0.93) for secondary outcomes of heart failure and total invasive cancer. Corresponding HRs (95% CIs) for type 2 diabetes incidence in relation to protein density and carbohydrate density were 1.17 (1.09, 1.75) and 0.73 (0.66, 0.80), respectively.

Conclusions: At specific energy intake, a diet high in carbohydrate density is associated with substantially reduced risk of major chronic diseases in a population of US postmenopausal women. This trial was registered at clinicaltrials.gov as NCT00000611.
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http://dx.doi.org/10.1093/jn/nxab091DOI Listing
April 2021

Nutritional epidemiology and the Women's Health Initiative: a review.

Am J Clin Nutr 2021 05;113(5):1083-1092

Lundquist Institute for Innovative Biomedical Research at Harbor-UCLA Medical Center, Torrance, CA, USA.

The dietary modification (DM) clinical trial, within the Women's Health Initiative (WHI), studied a low-fat dietary pattern intervention that included guidance to increase vegetables, fruit, and grains. This study was motivated in part from uncertainty about the reliability of observational studies examining the association between dietary fat and chronic disease risk by using self-reported dietary data. In addition to this large trial, which had breast and colorectal cancer as its primary outcomes, a substantial biomarker research effort was initiated midway in the WHI program to contribute to nutritional epidemiology research more broadly. Here we review and update findings from the DM trial and from the WHI nutritional biomarker studies and examine implications for future nutritional epidemiology research. The WHI included the randomized controlled DM trial (n = 48,835) and a prospective cohort observational (OS) study (n = 93,676), both among postmenopausal US women, aged 50-79 y when enrolled during 1993-1998. Also reviewed is a nutrition and physical activity assessment study in a subset of 450 OS participants (2007-2009) and a related controlled feeding study among 153 WHI participants (2010-2014). Long-term follow-up in the DM trial provides evidence for intervention-related reductions in breast cancer mortality, diabetes requiring insulin, and coronary artery disease in the subset of normotensive healthy women, without observed adverse effects or changes in all-cause mortality. Studies of intake biomarkers, and of biomarker-calibrated intake, suggest important associations of total energy intake and macronutrient dietary composition with the risk for major chronic diseases among postmenopausal women. Collectively these studies argue for a nutrition epidemiology research agenda that includes major efforts in nutritional biomarker development, and in the application of biomarkers combined with self-reported dietary data in disease association analyses. We expect such efforts to yield novel disease association findings and to inform disease prevention approaches for potential testing in dietary intervention trials. This trial was registered at clinicaltrials.gov as NCT00000611.
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http://dx.doi.org/10.1093/ajcn/nqab091DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120331PMC
May 2021

Discovery and fine-mapping of height loci via high-density imputation of GWASs in individuals of African ancestry.

Am J Hum Genet 2021 04 12;108(4):564-582. Epub 2021 Mar 12.

The Charles R. Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

Although many loci have been associated with height in European ancestry populations, very few have been identified in African ancestry individuals. Furthermore, many of the known loci have yet to be generalized to and fine-mapped within a large-scale African ancestry sample. We performed sex-combined and sex-stratified meta-analyses in up to 52,764 individuals with height and genome-wide genotyping data from the African Ancestry Anthropometry Genetics Consortium (AAAGC). We additionally combined our African ancestry meta-analysis results with published European genome-wide association study (GWAS) data. In the African ancestry analyses, we identified three novel loci (SLC4A3, NCOA2, ECD/FAM149B1) in sex-combined results and two loci (CRB1, KLF6) in women only. In the African plus European sex-combined GWAS, we identified an additional three novel loci (RCCD1, G6PC3, CEP95) which were equally driven by AAAGC and European results. Among 39 genome-wide significant signals at known loci, conditioning index SNPs from European studies identified 20 secondary signals. Two of the 20 new secondary signals and none of the 8 novel loci had minor allele frequencies (MAF) < 5%. Of 802 known European height signals, 643 displayed directionally consistent associations with height, of which 205 were nominally significant (p < 0.05) in the African ancestry sex-combined sample. Furthermore, 148 of 241 loci contained ≤20 variants in the credible sets that jointly account for 99% of the posterior probability of driving the associations. In summary, trans-ethnic meta-analyses revealed novel signals and further improved fine-mapping of putative causal variants in loci shared between African and European ancestry populations.
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http://dx.doi.org/10.1016/j.ajhg.2021.02.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8059339PMC
April 2021

A standard calculation methodology for human doubly labeled water studies.

Cell Rep Med 2021 Feb 16;2(2):100203. Epub 2021 Feb 16.

Maastricht University, Maastricht, the Netherlands.

The doubly labeled water (DLW) method measures total energy expenditure (TEE) in free-living subjects. Several equations are used to convert isotopic data into TEE. Using the International Atomic Energy Agency (IAEA) DLW database (5,756 measurements of adults and children), we show considerable variability is introduced by different equations. The estimated rCO is sensitive to the dilution space ratio (DSR) of the two isotopes. Based on performance in validation studies, we propose a new equation based on a new estimate of the mean DSR. The DSR is lower at low body masses (<10 kg). Using data for 1,021 babies and infants, we show that the DSR varies non-linearly with body mass between 0 and 10 kg. Using this relationship to predict DSR from weight provides an equation for rCO over this size range that agrees well with indirect calorimetry (average difference 0.64%; SD = 12.2%). We propose adoption of these equations in future studies.
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http://dx.doi.org/10.1016/j.xcrm.2021.100203DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7897799PMC
February 2021

Association of Serum Carotenoids and Retinoids with Intraprostatic Inflammation in Men without Prostate Cancer or Clinical Indication for Biopsy in the Placebo Arm of the Prostate Cancer Prevention Trial.

Nutr Cancer 2021 Jan 29:1-8. Epub 2021 Jan 29.

Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.

Non-supplemental carotenoids and retinol may potentiate antioxidant and anti-inflammatory mechanisms. Chronic intraprostatic inflammation is linked to prostate carcinogenesis. We investigated the association of circulating carotenoids and retinol with intraprostatic inflammation in benign tissue. We included 235 men from the Prostate Cancer Prevention Trial placebo arm who had a negative end-of-study biopsy, most (92.8%) done without clinical indication. α-carotene, β-carotene, β-cryptoxanthin, lycopene, and retinol were assessed by high-performance liquid chromatography using pooled year 1 and 4 serum. Presence and extent of intraprostatic inflammation in benign tissue was assessed in 3 (of 6-10) biopsy cores. Logistic (any core with inflammation vs none) and polytomous logistic (some or all cores with inflammation vs none) regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) of intraprostatic inflammation by concentration tertile adjusting for age, race, prostate cancer family history, and serum cholesterol. None of the carotenoids or retinol was associated with intraprostatic inflammation, except β-cryptoxanthin, which appeared to be positively associated with any core with inflammation [vs none, T2: OR (95% CI) = 2.67 (1.19, 5.99); T3: 1.80 (0.84, 3.82), -trend = 0.12]. These findings suggest that common circulating carotenoids and retinol are not useful dietary intervention targets for preventing prostate cancer via modulating intraprostatic inflammation.
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http://dx.doi.org/10.1080/01635581.2021.1879879DOI Listing
January 2021

Protein Intake by Source and Breast Cancer Incidence and Mortality: The Women's Health Initiative.

JNCI Cancer Spectr 2020 Dec 7;4(6):pkaa101. Epub 2020 Nov 7.

Lundquist Institute for Biomedical Innovation at Harbor, UCLA Medical Center, Torrance, CA, USA.

Background: Prior studies of dietary protein intake and breast cancer have been mixed and were limited by dietary self-report measurement error.

Methods: Biomarker-calibrated total protein intake and estimated vegetable protein and animal protein intake were determined from baseline food frequency questionnaires in 100 024 Women's Health Initiative participants. Associations between total, animal, and vegetable protein intake and breast cancer incidence, deaths from breast cancer, and deaths after breast cancer were estimated using Cox proportional hazards regression. Breast cancers were verified by medical record review and survival outcomes enhanced by National Death Index queries. All statistical tests were 2-sided.

Results: After 14 years of follow-up, there were 6340 incident breast cancers, 764 deaths from breast cancer, and 2059 deaths after breast cancer. In multivariable analyses, higher calibrated total protein intake was not associated with breast cancer incidence or deaths from or after breast cancer. Vegetable protein intake was associated with statistically significantly lower breast cancer incidence (hazard ratio [HR] = 0.98, 95% confidence interval [CI] = 0.96 to 0.99, = .006) and statistically significantly lower risk of death after breast cancer (HR = 0.93, 95% CI = 0.91 to 0.97 < .001) but not with deaths from breast cancer. In contrast, higher animal protein intake was associated with statistically significantly higher breast cancer incidence (HR = 1.03, 95% CI = 1.01 to 1.06, = .02) but not with deaths from or after breast cancer.

Conclusions: Calibrated total protein intake was not associated with breast cancer incidence or mortality. Higher vegetable protein intake was associated with lower breast cancer incidence and lower risk of death after breast cancer. Higher animal protein intake was associated with higher breast cancer incidence.
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http://dx.doi.org/10.1093/jncics/pkaa101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7768926PMC
December 2020

Risk of metabolic syndrome and metabolic phenotypes in relation to biomarker-calibrated estimates of energy and protein intakes: an investigation from the Women's Health Initiative.

Am J Clin Nutr 2021 03;113(3):706-715

Biobehavioral Nursing and Health Informatics, University of Washington School of Nursing, Seattle, WA, USA.

Background: Metabolic syndrome (MetS) is associated with increased mortality independent of BMI, resulting in discordant metabolic phenotypes, such as metabolically healthy obese and metabolically unhealthy normal-weight individuals. Studies investigating dietary intake in MetS have reported mixed results, due in part to the limitations of self-reported measures.

Objectives: To investigate the role of biomarker-calibrated estimates of energy and protein in MetS and metabolic phenotypes.

Methods: Postmenopausal participants from the Women's Health Initiative (WHI) study who were free of MetS at baseline, had available data from FFQs at baseline, and had components of MetS at Year 3 (n = 3963) were included. Dietary energy and protein intakes were estimated using biomarker calibration methods. MetS was defined as 3 or more of the following: elevated serum triglycerides (≥150 mg/dL), low HDL cholesterol (<50 mg/dL), hypertension [systolic blood pressure (BP) ≥130 or diastolic BP ≥85 mmHg], elevated serum glucose (>100 mg/dL), and abdominal adiposity (waist circumference > 89 cm). Models were adjusted for age, WHI study component, race/ethnicity, education, income, smoking, recreational physical activity, disease history, and parity.

Results: For every 10% increment in total calibrated energy intake, women were at a 1.37-fold elevated risk of MetS (95% CI, 1.15-1.63); a 10% increment in calibrated total protein intake was associated with a 1.21-fold elevated risk of MetS (95% CI, 1.00-1.47). Specifically, animal protein intake was associated with MetS (OR, 1.08; 95% CI, 1.02-1.14), whereas vegetable protein intake was not (OR, 0.99; 95% CI, 0.95-1.03). No differences were seen when examining metabolic phenotypes.

Conclusions: We found that higher calibrated total energy, total protein, and total animal protein intakes were strongly associated with MetS. If replicated in clinical trials, these results will have implications for the promotion of energy and animal protein restrictions for the reduction of MetS risks.
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http://dx.doi.org/10.1093/ajcn/nqaa334DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7948844PMC
March 2021

Diet quality indices and risk of metabolic syndrome among postmenopausal women of Mexican ethnic descent in the Women's Health Initiative Observational Study.

Nutr Healthy Aging 2020 Nov 3;5(4):261-272. Epub 2020 Nov 3.

Cancer Prevention Program, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.

Background: The prevalence of metabolic syndrome is higher among minority populations, including individuals of Mexican ethnic descent. Whether alignment to healthy dietary patterns is associated with lower risk of metabolic syndrome in this population is largely unknown.

Objective: To prospectively evaluate the associations between diet quality scores and risk of metabolic syndrome and its components among postmenopausal women of Mexican ethnic descent.

Methods: A total of 334 women of Mexican ethnic descent who participated in the Women's Health Initiative (WHI) observational study without metabolic syndrome or diabetes at baseline (1993-1998) were included. Baseline diets were scored with the Alternate Mediterranean Diet (aMED), the Dietary Approaches to Stop Hypertension (DASH), the Healthy Eating Index (HEI-2010), the Mediterranean Diet Score (MDS), and the traditional Mexican Diet (MexD) score. Multivariable linear and logistic regression models were used to test the associations between baseline diet quality and risk of metabolic syndrome and its individual components at follow-up (2012-2013).

Results: Approximately 16% of women met the criteria for metabolic syndrome at follow-up. None of the diet quality indices were associated with risk of metabolic syndrome. However, higher vs lower DASH scores were associated with lower waist circumference (85.2 vs 88.0 cm) and glucose concentrations (90.0 vs 95.1 mg/dL), and higher HDL cholesterol (62.6 vs 59.0 mg/dL), while higher vs lower HEI-2010 scores were associated with lower waist circumference (83.9 vs 88.1 cm), triglycerides (103 vs 117 mg/dL) and glucose concentrations (89.5 vs 94.4 mg/dL), and higher HDL cholesterol levels (63.9 vs 58.5 mg/dL).

Conclusions: Diet quality was not associated with risk of metabolic syndrome in this population. However, the results suggest that alignment to DASH and HEI-2010 recommendations may be beneficial for reducing some individual components of metabolic syndrome among postmenopausal women of Mexican descent.
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http://dx.doi.org/10.3233/NHA-190076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7745721PMC
November 2020

Hysterectomy, Oophorectomy, and Risk of Renal Cell Carcinoma.

Cancer Epidemiol Biomarkers Prev 2021 Mar 17;30(3):499-506. Epub 2020 Dec 17.

Department of Environmental and Occupational Health, School of Public Health, Indiana University, Bloomington, Indiana.

Background: Female hormones may play roles during renal cell carcinoma (RCC) carcinogenesis. The aims of this study were to investigate associations between hysterectomy, oophorectomy, and risk of RCC and to assess whether the associations were modified by exogenous estrogen, commonly used among women who have undergone hysterectomy.

Methods: Postmenopausal women ( = 144,599) ages 50-79 years at enrollment (1993-1998) in the Women's Health Initiative were followed for a mean of 15.9 years. Hysterectomy and oophorectomy were self-reported. Incident RCC cases were confirmed by physician review of medical records and pathology reports. Multivariable Cox proportional hazards modeling was used to estimate hazard ratios (HR) and 95% confidence intervals (CI), adjusting for potential confounders.

Results: A total of 583 women developed RCC during follow-up. We observed that hysterectomy, regardless of oophorectomy status, was significantly associated with an increased risk of RCC (HR, 1.28; 95% CI, 1.03-1.60). The association appeared to be more pronounced in women with age at hysterectomy younger than 40 years (HR, 1.34; 95% CI, 1.01-1.80) or older than 55 years (HR, 1.52; 95% CI, 1.01-2.29). Oophorectomy was not significantly associated with risk of RCC. There was no evidence that exogenous estrogen use modified the association between hysterectomy and risk of RCC.

Conclusions: In this large prospective study, we showed that women with a history of hysterectomy had 28% increased risk of RCC, and this finding was not modified by exogenous hormone use.

Impact: If our findings are confirmed, women should be made aware of increased risk of RCC when considering hysterectomy.
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http://dx.doi.org/10.1158/1055-9965.EPI-20-1373DOI Listing
March 2021

Dietary cholesterol and egg intake in relation to incident cardiovascular disease and all-cause and cause-specific mortality in postmenopausal women.

Am J Clin Nutr 2021 04;113(4):948-959

Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA.

Background: The potential cardiovascular impact of dietary cholesterol intake has been actively debated for decades.

Objectives: We aimed to evaluate associations of dietary cholesterol and egg intakes with incident cardiovascular disease (CVD) and all-cause and cause-specific mortality.

Methods: We included 96,831 US postmenopausal women aged 50-79 y without known CVD or cancer during baseline enrollment (1993-1998) of the Women's Health Initiative. Dietary information was collected using a validated FFQ. Incident CVD [i.e., ischemic heart disease (IHD) and stroke] and all-cause and cause-specific mortality were ascertained and adjudicated through February 2018.

Results: A total of 9808 incident CVD cases and 19,508 all-cause deaths occurred during a median follow-up of 17.8 y and 18.9 y, respectively. After multivariable adjustment for traditional risk factors and key dietary nutrients including dietary saturated fat, there were modest associations of dietary cholesterol intake with incident CVD (HRQ5versusQ1: 1.12; 95% CI: 1.03, 1.21; P-trend < 0.001) and all-cause mortality (HRQ5versusQ1: 1.09; 95% CI: 1.02, 1.15; P-trend < 0.001). Significant positive associations were also observed between dietary cholesterol and incident IHD (P-trend = 0.007), incident ischemic stroke (P-trend = 0.002), and CVD mortality (P-trend = 0.002), whereas there was an inverse association for incident hemorrhagic stroke (P-trend = 0.037) and no association for mortality from cancer, Alzheimer disease/dementia, respiratory diseases, or other causes (P-trend > 0.05). Higher egg consumption was also associated with modestly higher risk of incident CVD (P-trend = 0.004) and all-cause mortality (P-trend < 0.001), with HRs of 1.14 (95% CI: 1.04, 1.25) and 1.14 (95% CI: 1.07, 1.22), respectively, when comparing ≥1 egg/d with <1 egg/wk.

Conclusions: Both higher dietary cholesterol intake and higher egg consumption appeared to be associated with modestly elevated risk of incident CVD and all-cause mortality in US postmenopausal women.
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http://dx.doi.org/10.1093/ajcn/nqaa353DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8023834PMC
April 2021

Alignment of Dietary Patterns With the Dietary Guidelines for Americans 2015-2020 and Risk of All-Cause and Cause-Specific Mortality in the Women's Health Initiative Observational Study.

Am J Epidemiol 2021 05;190(5):886-892

Poor diet quality is a leading risk factor for death in the United States. We examined the association between Healthy Eating Index-2015 (HEI-2015) scores and death from all causes, cardiovascular disease (CVD), cancer, Alzheimer disease, and dementia not otherwise specified (NOS) among postmenopausal women in the Women's Health Initiative Observational Study (1993-2017). This analysis included 59,388 participants who completed a food frequency questionnaire and were free of cancer, CVD, and diabetes at enrollment. Stratified Cox proportional hazards models were fit using person-years from enrollment as the underlying time metric. We estimated multivariable adjusted hazard ratios and 95% confidence intervals for risk of death associated with HEI-2015 quintiles, with higher scores reflecting more optimal diet quality. Over a median of 18.2 years, 9,679 total deaths 3,303 cancer deaths, 2,362 CVD deaths, and 488 deaths from Alzheimer disease and dementia NOS occurred. Compared with those with lower scores, women with higher HEI-2015 scores had an 18% lower risk of all-cause death and 21% lower risk of cancer death. HEI-2015 scores were not associated with death due to CVD, Alzheimer disease, and dementia NOS. Consuming a diet aligned with 2015-2020 US dietary guidelines may have beneficial impacts for preventing overall causes of death and death from cancer.
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http://dx.doi.org/10.1093/aje/kwaa268DOI Listing
May 2021

Plasma lipidomic profiles after a low and high glycemic load dietary pattern in a randomized controlled crossover feeding study.

Metabolomics 2020 11 20;16(12):121. Epub 2020 Nov 20.

Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, Seattle, WA, USA.

Background: Dietary patterns low in glycemic load are associated with reduced risk of cardiometabolic diseases. Improvements in serum lipid concentrations may play a role in these observed associations.

Objective: We investigated how dietary patterns differing in glycemic load affect clinical lipid panel measures and plasma lipidomics profiles.

Methods: In a crossover, controlled feeding study, 80 healthy participants (n = 40 men, n = 40 women), 18-45 y were randomized to receive low-glycemic load (LGL) or high glycemic load (HGL) diets for 28 days each with at least a 28-day washout period between controlled diets. Fasting plasma samples were collected at baseline and end of each diet period. Lipids on a clinical panel including total-, VLDL-, LDL-, and HDL-cholesterol and triglycerides were measured using an auto-analyzer. Lipidomics analysis using mass-spectrometry provided the concentrations of 863 species. Linear mixed models and lipid ontology enrichment analysis were implemented.

Results: Lipids from the clinical panel were not significantly different between diets. Univariate analysis showed that 67 species on the lipidomics panel, predominantly in the triacylglycerol class, were higher after the LGL diet compared to the HGL (FDR < 0.05). Three species with FA 17:0 were lower after LGL diet with enrichment analysis (FDR < 0.05).

Conclusion: In the context of controlled eucaloric diets with similar macronutrient distribution, these results suggest that there are relative shifts in lipid species, but the overall pool does not change. Further studies are needed to better understand in which compartment the different lipid species are transported in blood, and how these shifts are related to health outcomes. This trial was registered at clinicaltrials.gov as NCT00622661.
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http://dx.doi.org/10.1007/s11306-020-01746-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8116047PMC
November 2020

Cardiometabolic risk factors and survival after cancer in the Women's Health Initiative.

Cancer 2021 Feb 5;127(4):598-608. Epub 2020 Nov 5.

Department of Oncology, Barbara Ann Karmanos Cancer Institute at Wayne State University, Detroit, Michigan.

Background: Cardiometabolic abnormalities are a leading cause of death among women, including women with cancer.

Methods: This study examined the association between prediagnosis cardiovascular health and total and cause-specific mortality among 12,076 postmenopausal women who developed local- or regional-stage invasive cancer in the Women's Health Initiative (WHI). Cardiovascular risk factors included waist circumference, hypertension, high cholesterol, and type 2 diabetes. Obesity-related cancers included breast cancer, colorectal cancer, endometrial cancer, kidney cancer, pancreatic cancer, ovarian cancer, stomach cancer, liver cancer, and non-Hodgkin lymphoma. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) adjusted for important predictors of survival.

Results: After a median follow-up of 10.0 years from the date of the cancer diagnosis, there were 3607 total deaths, with 1546 (43%) due to cancer. Most participants (62.9%) had 1 or 2 cardiometabolic risk factors, and 8.1% had 3 or 4. In adjusted models, women with 3 to 4 risk factors (vs none) had a higher risk of all-cause mortality (HR, 1.99; 95% CI, 1.73-2.30), death due to cardiovascular disease (CVD) (HR, 4.01; 95% CI, 2.88-5.57), cancer-specific mortality (HR, 1.37; 95% CI, 1.1-1.72), and other-cause mortality (HR, 2.14; 95% CI, 1.70-2.69). A higher waist circumference was associated with greater all-cause mortality (HR, 1.17; 95% CI, 1.06-1.30) and cancer-specific mortality (HR, 1.22; 95% CI, 1.04-1.42).

Conclusions: Among postmenopausal women diagnosed with cancer in the WHI, cardiometabolic risk factors before the cancer diagnosis were associated with greater all-cause, CVD, cancer-specific, and other-cause mortality. These results raise hypotheses regarding potential clinical intervention strategies targeting cardiometabolic abnormalities that require future prospective studies for confirmation.

Lay Summary: This study uses information from the Women's Health Initiative (WHI) to find out whether cardiac risk factors are related to a greater risk of dying among older women with cancer. The WHI is the largest study of medical problems faced by older women in this country. The results show that women who have 3 or 4 risk factors are more likely to die of any cause, heart disease, or cancer in comparison with women with no risk factors. It is concluded that interventions to help to lower the burden of cardiac risk factors can have an important impact on survivorship among women with cancer.
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http://dx.doi.org/10.1002/cncr.33295DOI Listing
February 2021

Body size and weight change over adulthood and risk of breast cancer by menopausal and hormone receptor status: a pooled analysis of 20 prospective cohort studies.

Eur J Epidemiol 2021 Jan 30;36(1):37-55. Epub 2020 Oct 30.

Epidemiology and Prevention Group, Research Center for Cancer Prevention and Screening, National Cancer Center, Tokyo, Japan.

Associations between anthropometric factors and breast cancer (BC) risk have varied inconsistently by estrogen and/or progesterone receptor (ER/PR) status. Associations between prediagnostic anthropometric factors and risk of premenopausal and postmenopausal BC overall and ER/PR status subtypes were investigated in a pooled analysis of 20 prospective cohorts, including 36,297 BC cases among 1,061,915 women, using multivariable Cox regression analyses, controlling for reproductive factors, diet and other risk factors. We estimated dose-response relationships and tested for nonlinear associations using restricted cubic splines. Height showed positive, linear associations for premenopausal and postmenopausal BC risk (6-7% RR increase per 5 cm increment), with stronger associations for receptor-positive subtypes. Body mass index (BMI) at cohort baseline was strongly inversely associated with premenopausal BC risk, and strongly positively-and nonlinearly-associated with postmenopausal BC (especially among women who never used hormone replacement therapy). This was primarily observed for receptor-positive subtypes. Early adult BMI (at 18-20 years) showed inverse, linear associations for premenopausal and postmenopausal BC risk (21% and 11% RR decrease per 5 kg/m, respectively) with stronger associations for receptor-negative subtypes. Adult weight gain since 18-20 years was positively associated with postmenopausal BC risk, stronger for receptor-positive subtypes, and among women who were leaner in early adulthood. Women heavier in early adulthood generally had reduced premenopausal BC risk, independent of later weight gain. Positive associations between height, baseline (adult) BMI, adult weight gain and postmenopausal BC risk were substantially stronger for hormone receptor-positive versus negative subtypes. Premenopausal BC risk was positively associated with height, but inversely with baseline BMI and weight gain (mostly in receptor-positive subtypes). Inverse associations with early adult BMI seemed stronger in receptor-negative subtypes of premenopausal and postmenopausal BC.
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http://dx.doi.org/10.1007/s10654-020-00688-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7847460PMC
January 2021

Feasibility of a behavioral intervention using mobile health applications to reduce cardiovascular risk factors in cancer survivors: a pilot randomized controlled trial.

J Cancer Surviv 2020 Oct 10. Epub 2020 Oct 10.

Fred Hutchinson Cancer Research Center, PO Box 19024, Mailstop M4-C308, Seattle, WA, 98109, USA.

Purpose: Determine the feasibility of a remotely delivered mobile health (mHealth)-supported intervention to improve diet and physical activity in hematologic malignancy survivors.

Methods: Pilot randomized controlled trial of a 16-week intervention for improving diet and physical activity: individualized goal-setting (daily steps, sodium, saturated fat, added sugar intake) per feedback from mHealth trackers (Fitbit for activity; Healthwatch360 for diet), supplemented by a Facebook peer support group. Controls accessed the trackers without goal-setting or peer support. Everyone received standardized survivorship counseling with tailored advice from a clinician. Actigraphy and food frequency questionnaires assessed activity and diet at baseline and follow-up.

Results: Forty-one participants (51.2% male; median age 45.1 years; 7.0 years from treatment) were randomized (24 intervention; 17 control). Fitbit and Healthwatch360 use were more common among intervention versus control participants (75.0% versus 70.6% and 50.0% versus 17.7% of eligible days, respectively). Most intervention participants (66.7%) engaged with Facebook; overall, 91.7% interacted with the study's mHealth applications. While no comparisons in activity or dietary outcomes between intervention versus control group met statistical significance, the intervention was associated with greater reductions in the targeted dietary factors and improvements in Healthy Eating Index-2015 score, moderate-vigorous physical activity time, and daily steps. Participant retention at 6 months was 90.2%.

Conclusions: An intervention for cardiovascular risk reduction based on individualized goal-setting enhanced by mHealth and social media peer support was feasible and acceptable among cancer survivors.

Implications For Cancer Survivors: Effective and easily disseminated strategies that improve diet and physical activity in this population are needed.

Trial Registration: Registered in ClinicalTrials.gov (NCT03574012) on June 29, 2018.
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http://dx.doi.org/10.1007/s11764-020-00949-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8035343PMC
October 2020

Associations between Plasma Choline Metabolites and Genetic Polymorphisms in One-Carbon Metabolism in Postmenopausal Women: The Women's Health Initiative Observational Study.

J Nutr 2020 11;150(11):2874-2881

Huntsman Cancer Institute, Salt Lake City, UT, USA.

Background: Choline plays an integral role in one-carbon metabolism in the body, but it is unclear whether genetic polymorphisms are associated with variations in plasma choline and its metabolites.

Objectives: This study aimed to evaluate the association of genetic variants in choline and one-carbon metabolism with plasma choline and its metabolites.

Methods: We analyzed data from 1423 postmenopausal women in a case-control study nested within the Women's Health Initiative Observational Study. Plasma concentrations of choline, betaine, dimethylglycine (DMG), and trimethylamine N-oxide were determined in 12-h fasting blood samples collected at baseline (1993-1998). Candidate and tagging single-nucleotide polymorphisms (SNPs) were genotyped in betaine-homocysteine S-methyltransferase (BHMT), BHMT2, 5,10-methylenetetrahydrofolate reductase (MTHFR), methylenetetrahydrofolate dehydrogenase (NADP+ dependent 1) (MTHFD1), 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR), and 5-methyltetrahydrofolate-homocysteine methyltransferase reductase (MTRR). Linear regression was used to derive percentage difference in plasma concentrations per variant allele, adjusting for confounders, including B-vitamin biomarkers. Potential effect modification by plasma vitamin B-12, vitamin B-6, and folate concentrations and folic-acid fortification periods was examined.

Results: The candidate SNP BHMT R239Q (rs3733890) was associated with lower concentrations of plasma betaine and DMG concentrations (-4.00% and -6.75% per variant allele, respectively; both nominal P < 0.05). Another candidate SNP, BHMT2 rs626105 A>G, was associated with higher plasma DMG concentration (13.0%; P < 0.0001). Several tagSNPs in these 2 genes were associated with plasma concentrations after correction for multiple comparisons. Vitamin B-12 status was a significant effect modifier of the association between the genetic variant BHMT2 rs626105 A>G and plasma DMG concentration.

Conclusions: Genetic variations in metabolic enzymes were associated with plasma concentrations of choline and its metabolites. Our findings contribute to the knowledge on the variation in blood nutrient concentrations in postmenopausal women.
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http://dx.doi.org/10.1093/jn/nxaa266DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7675024PMC
November 2020

Associations of Number of Daily Eating Occasions with Type 2 Diabetes Risk in the Women's Health Initiative Dietary Modification Trial.

Curr Dev Nutr 2020 Aug 21;4(8):nzaa126. Epub 2020 Jul 21.

Canyon Ranch Center for Prevention & Health Promotion, Mel & Enid Zuckerman College of Public Health, University of Arizona, Tucson, AZ, USA.

Background: Over 23 million Americans have type 2 diabetes (T2D). Eating habits such as breakfast consumption, time-restricted eating, and limiting daily eating occasions have been explored as behaviors for reducing T2D risk, but prior evidence is inconclusive.

Objectives: Our objectives were to examine associations between number of daily eating occasions and T2D risk in the Women's Health Initiative Dietary Modification Trial (WHI-DM) and whether associations vary by BMI, age, or race/ethnicity.

Methods: Participants were postmenopausal women in the WHI-DM who comprised a 4.6% subsample completing 24-h dietary recalls (24HRs) at years 3 and 6 as part of trial adherence activities ( = 2159). Numbers of eating occasions per day were obtained from the year 3 24HRs, and participants were grouped into approximate tertiles as 1-3 ( = 795), 4 ( = 713), and ≥5 ( = 651) daily eating occasions as the exposure. Incident diabetes was self-reported on semiannual questionnaires as the outcome.

Results: Approximately 15% (15.4%,  = 332) of the WHI-DM 24HR cohort reported incident diabetes at follow-up. Cox proportional hazards regression tested associations of eating occasions with T2D adjusted for neighborhood socioeconomic status, BMI, waist circumference, race/ethnicity, family history of T2D, recreational physical activity, Healthy Eating Index-2005, 24HR energy intake, and WHI-DM arm. Compared with women reporting 1-3 meals/d, those consuming 4 meals/d had a T2D HR = 1.38 (95% CI: 1.03, 1.84) without further increases in risk for ≥5 meals/d. In stratified analyses, associations for 4 meals/d compared with 1-3 meals/d were stronger in women with BMI <30.0 kg/m (HR = 1.55; 95% CI: 1.00, 2.39) and women aged ≥60 (HR = 1.61; 95% CI: 1.11, 2.33).

Conclusions: Four meals per day compared with 1-3 meals/d was associated with increased risk of T2D in postmenopausal women, but no dose-response effect was observed for additional eating occasions. Further studies are needed to understand eating occasions in relation to T2D risk.
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http://dx.doi.org/10.1093/cdn/nzaa126DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7431012PMC
August 2020

Impact of a sweetened beverage tax on beverage prices in Seattle, WA.

Econ Hum Biol 2020 12 23;39:100917. Epub 2020 Jul 23.

University of Washington, School of Public Health, Department of Epidemiology, USA; Public Health-Seattle & King County, Assessment, Policy, Development and Evaluation Division, Seattle, WA, USA.

Seattle's Sweetened Beverage Tax is an excise tax of 1.75 cents per ounce on sugar-sweetened beverages and is one of the highest beverage taxes in the U.S. This study examined the impact of Seattle's tax on the prices of beverages. We conducted audits of 407 retail food stores and eating places (quick service restaurants and coffee shops) before and 6 months after the tax was implemented in Seattle and in a comparison area. Ordinary least squares difference-in-differences models with store fixed effects were used to estimate the effect of the tax on prices, stratified by beverage type and store type. In secondary analyses, we assessed the effect of the tax on the price of non-taxed beverages and foods. Results from the adjusted difference-in-differences models indicated the tax was associated with an average increase of 1.58 cents per ounce among Seattle retailers, representing 90 % of the price of the tax. By store type, price increases were highest in smaller grocery stores and drug stores. By beverage type, price increases were highest for energy beverages and soda and lowest for bottled coffee and juice drinks. Prices of some non-taxed beverages also increased while the prices of select healthy foods generally did not. The sweetened beverage tax in Seattle is higher than beverage taxes in most other cities, and nearly the full cost of the tax is being passed through to consumers for many beverage types and stores types.
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http://dx.doi.org/10.1016/j.ehb.2020.100917DOI Listing
December 2020

Barriers to eating are associated with poor physical function in older women.

Prev Med 2020 10 12;139:106234. Epub 2020 Aug 12.

Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, M4B402, Seattle, WA 98109-1024, USA. Electronic address:

Older adults have physical and social barriers to eating but whether this affects functional status is unknown. We examined associations between eating barriers and physical function in the Women's Health Initiative (WHI). In 2012-14, a subset of alive and participating women (n = 5910) completed an in-home examination including the Short Physical Performance Battery (SPPB) (grip strength, balance, timed walking speed, chair stand). WHI participants complete annual mailed questionnaires; the 2013-14 questionnaire included items on eating alone, eating < two meals/day, dentition problems affecting eating, physical difficulties with cooking/shopping and monetary resources for food. Linear regression tested associations of these eating barriers with SPPB, adjusting for BMI, age, race/ethnicity, and medical multimorbidities. Over half (56.8%) of participants were ≥ 75 years, 98.8% had a BMI ≥ 25.0 kg/m and 66% had multimorbidities. Eating barriers, excluding eating alone, were associated with significantly lower total (all p < .001) and component-specific, multivariate-adjusted SPPB scores (all p < .05). Compared to no barriers, eating < two meals/day (7.83 vs. 8.38, p < .0002), dentition problems (7.69 vs. 8.38, p < .0001), inability to shop/prepare meals (7.74 vs. 8.38, p < .0001) and insufficient resources (7.84 vs. 8.37 p < .001) were significantly associated with multivariate-adjusted mean SPPB score < 8. Models additionally adjusting for Healthy Eating Index-2010 had little influence on scores. As barriers increased, scores declined further for grip strength (16.10 kg for 4-5 barriers, p = .001), timed walk (0.58 m/s for 4-5 barriers, p = .001) and total SPPB (7.27 for 4-5 barriers, p < .0001). In conclusion, in this WHI subset, eating barriers were associated with poor SPPB scores.
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http://dx.doi.org/10.1016/j.ypmed.2020.106234DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7494579PMC
October 2020

Chocolate Candy and Incident Invasive Cancer Risk in the Women's Health Initiative: An Observational Prospective Analysis.

J Acad Nutr Diet 2021 Feb 4;121(2):314-326.e4. Epub 2020 Aug 4.

Background: Laboratory and animal studies suggest an inverse association between chocolate consumption and the risk of cancer. Epidemiological studies have yielded inconsistent evidence.

Objective: To assess the association of chocolate candy consumption with incident, invasive total, breast, colorectal, and lung cancers in a large cohort of postmenopausal American women.

Design: Prospective cohort study with a mean 14.8-year follow-up. Chocolate candy intake was assessed by food frequency questionnaire. Invasive cancer events were assessed by physician adjudication.

Participants/setting: The Women's Health Initiative Study enrolled 161,808 postmenopausal women at 40 clinical centers nationwide between 1993 and 1998. Of these women, 114,281 with plausible food frequency or biometric data and no missing data on chocolate candy exposure were selected for analysis.

Main Outcome Measures: Cancer risk in quartiles of chocolate candy consumption with the first quartile as referent.

Statistical Analyses: Multivariable Cox regression was used to calculate hazard ratios and 95% confidence intervals.

Results: There were 16,164 documented incident invasive cancers, representing an incidence rate of 17.0 per 100 participants and 12.3 per 1000 person years during follow-up among participants without any preexisting cancers or missing outcome data. There were no statistically significant associations for total invasive cancer (P-linear = .47, P-curvature = .14), or invasive breast cancer (P-linear = .77, P-curvature = .26). For colorectal cancer P-linear was .02, P-curvature was .03, and compared with women eating a 1 oz (28.4 g) chocolate candy serving <1 time per month, the hazard ratio for ≥1.5 times/wk was 1.18 (95% confidence interval: 1.04-1.35). This result may be attributable to the excess adiposity associated with frequent chocolate candy consumption.

Conclusions: In the Women's Health Initiative, there was no significant association between chocolate candy consumption and invasive total or breast cancer. There was a modest 18% higher risk of invasive colorectal cancer for women who ate chocolate candy at least 1.5 times/wk. These results require confirmation.
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http://dx.doi.org/10.1016/j.jand.2020.06.014DOI Listing
February 2021

The Carbon Isotope Ratios of Serum Amino Acids in Combination with Participant Characteristics can be Used to Estimate Added Sugar Intake in a Controlled Feeding Study of US Postmenopausal Women.

J Nutr 2020 10;150(10):2764-2771

Center for Alaska Native Health Research, Institute of Arctic Biology, Department of Biology and Wildlife, University of Alaska Fairbanks, Fairbanks, AK, USA.

Background: The carbon isotope ratio (CIR) is a proposed biomarker for added sugar (AS) intake in the United States; however, because the CIR is also associated with meat intake in most populations the need for specificity remains. The CIR of amino acids (AAs) has the potential to differentiate sugars from meat intakes, because essential AAs must derive from dietary protein whereas certain nonessential AAs can be synthesized from sugars.

Objectives: We tested whether serum CIR-AAs in combination with participant characteristics could meet a prespecified biomarker criterion for AS intake in the Nutrition and Physical Activity Assessment Study Feeding Study (NPAAS-FS) of the Women's Health Initiative, a population in which the whole-serum CIR was not associated with AS intake.

Methods: Postmenopausal women (n = 145) from Seattle, WA, were provided with individualized diets that approximated their habitual food intakes for 2 wk. Dietary intakes from consumed foods were characterized over the feeding period using the Nutrition Data System for Research. The CIR of 7 AAs-Ala, Gly, Val, Leu, Ile, Pro, and Phe-were measured in fasting serum collected at the end of the 2-wk feeding period, using gas chromatography-combustion isotope ratio mass spectrometry. Biomarker models were evaluated using regression R2 ≥ 0.36 as a major biomarker criterion, based on the benchmark R2 values of well-established recovery biomarkers in the NPAAS-FS.

Results: AS intake was associated with CIR-Ala (ρ = 0.32; P < 0.0001). A model of AS intake based on CIR-Ala, CIR-Gly, CIR-Ile, smoking, leisure physical activity, and body weight met the biomarker criterion (R2 = 0.37). Biomarker-estimated AS intake was not associated with meat or animal protein intake.

Conclusions: Results support serum CIR-AAs in combination with participant characteristics as potential biomarkers of AS intake in US populations, including those with low AS intake.The Women's Health Initiative is registered at clinicaltrials.gov (NCT00000611).
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http://dx.doi.org/10.1093/jn/nxaa195DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7549297PMC
October 2020

Small changes in glucose variability induced by low and high glycemic index diets are not associated with changes in β-cell function in adults with pre-diabetes.

J Diabetes Complications 2020 08 18;34(8):107586. Epub 2020 Apr 18.

Public Health Sciences Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, Seattle, WA 98109, USA. Electronic address:

Oscillating glucose levels can increase oxidative stress and may contribute to β-cell dysfunction. We tested the hypothesis that increased glycemic variability contributes to β-cell dysfunction by experimentally altering glucose variability with controlled diets varying in glycemic index (GI). Fifty-two adults with prediabetes received a 2-week moderate GI (GI = 55-58) control diet followed by randomization to a four-week low GI (LGI: GI < 35) or high GI (HGI HI > 70) diet. Those on the HGI diet were randomized to placebo or the antioxidant N-acetylcysteine (NAC). Participants underwent blinded CGMS, fasting oxidative stress markers and an intravenous glucose tolerance test to estimate β-cell function (disposition index: DI). On the control diet, DI was inversely correlated with SD glucose (r = -0.314, p = 0.03), but neither DI nor glucose variability were associated with oxidative stress markers. The LGI diet decreased SD glucose (Control 0.96 ± 0.08 vs. LGI 0.79 ± 0.06, p = 0.02) while the HGI diet increased it (Control 0.88 ± 0.06 vs. HGI 1.06 ± 0.07, p = 0.03). Neither DI nor oxidative stress markers changed after the LGI or HGI diets. NAC had no effect on DI, glucose variability or oxidative stress markers. We conclude small changes in glucose variability induced by dietary GI in adults with pre-diabetes are unlikely to contribute to β-cell dysfunction.
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http://dx.doi.org/10.1016/j.jdiacomp.2020.107586DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7583355PMC
August 2020

Associations between reproductive factors and biliary tract cancers in women from the Biliary Tract Cancers Pooling Project.

J Hepatol 2020 10 11;73(4):863-872. Epub 2020 May 11.

Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA.

Background & Aims: Gallbladder cancer (GBC) is known to have a female predominance while other biliary tract cancers (BTCs) have a male predominance. However, the role of female reproductive factors in BTC etiology remains unclear.

Methods: We pooled data from 19 studies of >1.5 million women participating in the Biliary Tract Cancers Pooling Project to examine the associations of parity, age at menarche, reproductive years, and age at menopause with BTC. Associations for age at menarche and reproductive years with BTC were analyzed separately for Asian and non-Asian women. Hazard ratios (HRs) and 95% CIs were estimated using Cox proportional hazards models, stratified by study.

Results: During 21,681,798 person-years of follow-up, 875 cases of GBC, 379 of intrahepatic bile duct cancer (IHBDC), 450 of extrahepatic bile duct cancer (EHBDC), and 261 of ampulla of Vater cancer (AVC) occurred. High parity was associated with risk of GBC (HR ≥5 vs. 0 births 1.72; 95% CI 1.25-2.38). Age at menarche (HR per year increase 1.15; 95% CI 1.06-1.24) was associated with GBC risk in Asian women while reproductive years were associated with GBC risk (HR per 5 years 1.13; 95% CI 1.04-1.22) in non-Asian women. Later age at menarche was associated with IHBDC (HR 1.19; 95% CI 1.09-1.31) and EHBDC (HR 1.11; 95% CI 1.01-1.22) in Asian women only.

Conclusion: We observed an increased risk of GBC with increasing parity. Among Asian women, older age at menarche was associated with increased risk for GBC, IHBDC, and EHBDC, while increasing reproductive years was associated with GBC in non-Asian women. These results suggest that sex hormones have distinct effects on cancers across the biliary tract that vary by geography.

Lay Summary: Our findings show that the risk of gallbladder cancer is increased among women who have given birth (especially women with 5 or more children). In women from Asian countries, later age at menarche increases the risk of gallbladder cancer, intrahepatic bile duct cancer and extrahepatic bile duct cancer. We did not see this same association in women from Western countries. Age at menopause was not associated with the risk of any biliary tract cancers.
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http://dx.doi.org/10.1016/j.jhep.2020.04.046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7901003PMC
October 2020