Dietary Fats and All-cause and Breast Cancer-specific Mortality among Women with Breast Cancer: The Western New York Exposures and Breast Cancer Study.

BACKGROUND: Study results of prediagnostic dietary fat intake and breast cancer mortality have been inconclusive. While dietary fat subtypes [saturated (SFA), polyunsaturated (PUFA), and monounsaturated (MUFA) fatty acids] may have different biological effects, there is little evidence regarding the association of dietary fat and fat subtype intake with mortality after breast cancer diagnosis. METHODS: Women with incident, pathologically confirmed invasive breast cancer and complete dietary data (n = 793) were followed in a population-based study, the Western New York Exposures and Breast Cancer study. Usual intake before diagnosis of total fat and subtypes were estimated from a food frequency questionnaire completed at baseline. HRs and 95% confidence intervals (CI) for all-cause and breast cancer-specific mortality were estimated with Cox proportional hazards models. Interactions by menopausal status, estrogen receptor (ER) status, and tumor stage were examined. RESULTS: Median follow-up time was 18.75 years; 327 (41.2%) participants had died. Compared with lower intake, greater intake of total fat (HR, 1.05; 95% CI, 0.65-1.70), SFA (1.31; 0.82-2.10), MUFA (0.99; 0.61-1.60), and PUFA (0.99; 0.56-1.75) was not associated with breast cancer-specific mortality. There was also no association with all-cause mortality. Results did not vary by menopausal status, ER status, or tumor stage. CONCLUSIONS: Prediagnostic intake of dietary fat and fat subtypes was not associated with either all-cause or breast cancer mortality in a population-based cohort of breast cancer survivors. IMPACT: Understanding factors affecting survival among women diagnosed with breast cancer is critically important. Dietary fat intake prior to diagnosis may not impact that survival.

Red blood cell fatty acids and age-related macular degeneration in postmenopausal women.

PURPOSE: To evaluate the relationship between red blood cell (RBC) polyunsaturated fatty acid (PUFA) levels, and dietary PUFA and fish intake, with prevalent and incident age-related macular degeneration (AMD) in a US cohort of postmenopausal women. METHODS: This analysis included 1456 postmenopausal women from the Women's Health Initiative (WHI) Clinical Trials. RBC PUFAs were measured from fasting serum samples collected at WHI baseline. Dietary PUFAs and fish intake were assessed via food frequency questionnaires at baseline. There were 240 women who had prevalent AMD and 138 who self-reported AMD development over 9.5 years. Adjusted odds ratios and 95% confidence intervals were estimated for prevalent AMD by RBC PUFA levels, dietary PUFA intake, and frequency of fish consumption. Adjusted hazard ratios and 95% confidence intervals were estimated for incident AMD. A p-for-trend was estimated for continuous measures of dietary PUFA and fish intake. RESULTS: No significant association was found between prevalent or incident AMD and RBC docosahexaenoic acid (DHA) + eicosapentaenoic acid (EPA), EPA, DHA, alpha-linolenic acid (ALA), linoleic acid (LA), or arachidonic acid (AA). A positive association was found between dietary intake of AA and odds of prevalent AMD (p-for-trend for continuous AA intake = 0.02) and between intake of LA/ALA and incident AMD (p-for-trend for continuous ratio of LA/ALA intake = 0.03). No statistically significant associations were found between AMD and dietary intake of PUFAs or fish. CONCLUSIONS: RBC PUFAs were not associated with AMD in this cohort. Overall, dietary analyses of PUFAs supported this, excepting dietary AA intake and intake of LA in proportion to ALA of which there were trends of increased risk.

Clinical and Lifestyle-Related Prognostic Indicators among Esophageal Adenocarcinoma Patients Receiving Treatment at a Comprehensive Cancer Center.

PURPOSE: The incidence of esophageal adenocarcinoma (EAC) has risen substantially in recent decades, while the average 5-year survival remains only ~20%. Disease stage and treatment are the strongest prognostic factors. The role of lifestyle factors in relation to survival remains uncertain, with a handful of studies to date investigating associations with obesity, smoking, physical activity, diet, or medications. METHODS: This study included patients diagnosed with primary adenocarcinoma of the esophagus, gastroesophageal junction, or cardia (N = 371) at Roswell Park Comprehensive Cancer Center between 2003 and 2019. Leveraging extensive data abstracted from electronic medical records, epidemiologic questionnaires, and a tumor registry, we analyzed clinical, behavioral, and environmental exposures and evaluated stage-specific associations with survival. Survival distributions were visualized using Kaplan-Meier curves. Cox proportional hazards regression models adjusted for age, sex, stage, treatment, and comorbidities were used to estimate the association between each exposure and all-cause or cancer-specific mortality. RESULTS: Among patients presenting with localized/regional tumors (stages I-III), current smoking was associated with increased overall mortality risk (HR = 2.5 [1.42-4.53], p = 0.002), while current physical activity was linked to reduced risk (HR = 0.58 [0.35-0.96], p = 0.035). Among patients with stage IV disease, individuals reporting pre-diagnostic use of statins (HR = 0.62 [0.42-0.92], p = 0.018) or NSAIDs (HR = 0.61 [0.42-0.91], p = 0.016) had improved overall survival. Exploratory analyses suggested that high pre-diagnostic dietary consumption of broccoli, carrots, and fiber correlated with prolonged overall survival in patients with localized/regional disease. CONCLUSION: Our data suggest that lifestyle exposures may be differentially associated with EAC survival based on disease stage. Future investigation of larger, diverse patient cohorts is essential to validate these findings. Our results may help inform the development of lifestyle-based interventions to improve EAC prognosis and quality of life.

Associations of dietary intakes and serum levels of folate and vitamin B-12 with methylation of inorganic arsenic in Uruguayan children: Comparison of findings and implications for future research.

BACKGROUND: In the human body, inorganic arsenic (iAs) is methylated via the one-carbon cycle to form monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA). Lower proportions of iAs and MMA, and higher proportions of DMA in urine indicate efficient methylation; formation of DMA is thought to detoxify iAs and MMA. Studies on folate, vitamin B-12 and iAs methylation yield mixed findings, depending on whether folate and vitamin B-12 were assessed from diet, supplements, or using a blood biomarker. OBJECTIVE: First, to compare the associations of serum concentrations and estimated intake of folate and vitamin B-12 with indicators of iAs methylation. Second, to highlight the implications of these different B-vitamin assessment techniques on the emerging evidence of the impact of dietary modifications on iAs methylation. METHODS: The study was conducted among ~7-year-old children from Montevideo, Uruguay. Serum folate and vitamin B-12 levels were measured on the Horiba ABX Pentra 400 analyzer; urinary arsenic was measured using High-Performance Liquid Chromatography on-line with Inductively Coupled Plasma Mass Spectrometry. Dietary intakes were assessed using the average of two 24-h dietary recalls. Linear regressions assessed the associations of serum levels, and dietary intakes of folate (n = 237) and vitamin B-12 (n = 217) with indicators of iAs methylation. Models were adjusted for age, sex, body mass index, total urinary arsenic, and rice intake. RESULTS: Serum folate and vitamin B-12 levels were above the adequacy threshold for 99% of the participants. No associations were observed between serum folate, serum vitamin B-12, or vitamin B-12 intake and iAs methylation. Folate intake was inversely associated with urinary %MMA [ß (95% confidence interval): -1.04 (-1.89, -0.18)]. CONCLUSION: Additional studies on the role of B-vitamins in iAs methylation are needed to develop a deeper understanding of the implications of assessing folate and vitamin B-12 intake compared to the use of biomarkers. Where possible, both methods should be employed because they reflect different exposure windows and inherent measurement error, and if used individually, will likely continue to contribute to lack of consensus.

Could Vitamin D influence risk for Periodontal Disease - to "D" or not to "D"?

PURPOSE OF REVIEW: The purpose of this review is to discuss the literature on associations between vitamin D and periodontal disease, including its strengths and weaknesses. Future direction for continued work in this area is provided. RECENT FINDINGS: Research in cross-sectional cohorts, surveys, and case-control studies provide support for a role of vitamin D in periodontal disease, especially using clinical indicators such as bleeding on probing and clinical attachment loss. However, these studies have a number of limitations. They cannot establish temporality of these associations. Most case-control studies have been limited in sample size and have inconsistent findings. A number of cross-sectional studies are restricted to select populations (e.g., persons with HIV, diabetes, rheumatoid arthritis) limiting extrapolation of findings to the general aging population.Fewer prospective studies have been conducted, and only three have examined associations using a biomarker for vitamin D that reflects exposure from all its sources (sunlight, diet and supplements). One study is limited by using self-reported measures of disease outcomes, and only two used measures of alveolar crestal height. However, of the prospective studies published, there is a suggestion that vitamin D might prevent against tooth loss. Only two randomized controlled trials have examined these associations, and they support the effects of vitamin D supplementation on prevention of tooth loss and gingival bleeding. SUMMARY: We strongly suggest that new research should focus on prospective study designs with followup of participants longer than a decade and long-term clinical trials. Such studies should incorporate measures of alveolar bone loss and tooth loss with indication for reason for tooth loss. Such clinical trials should be designed to examine both the influence of vitamin D supplementation alone as well as with other nutrients (e.g., calcium) or therapeutic medications (e.g., bisphosphonates). Currently, there is no strong evidence to suggest that vitamin D protects against development of periodontal disease.

Associations between adiposity measures and 25-hydroxyvitamin D among police officers.

OBJECTIVE: Studies show that serum levels of 25-hydroxyvitamin D (25(OH)D), a biomarker for vitamin D status, are lower in persons with higher adiposity levels and that police officers have been found to have a high prevalence of obesity. The purpose of this study was to examine relationships between several adiposity measures and 25(OH)D, and also compare those measures to determine the best one that predicts insufficiency of 25(OH)D (<20 ng/mL) among police officers in the Northeast area of the United States. METHODS: Participants were 281 police officers (71.5% men) from the Buffalo Cardio-Metabolic Occupational Police Stress Study (2011-2016). Associations of body mass index (BMI), abdominal height (AbHt), waist circumference (WC), WC-to-height ratio (WCHtR), percent body fat (PBF), and fat mass index (FMI) with 25(OH)D were obtained using multiple regression models after adjustment for age, race/ethnicity, season, multivitamin supplement use, and high-density lipoprotein cholesterol. The area under the curve (AUC) was used to evaluate the predictive ability of each adiposity measure to identify insufficient 25(OH)D concentrations. RESULTS: The prevalence of obesity (BMI ≥ 30) was 50.7% in men and 21.3% in women. Mean levels of 25(OH)D were 32.4 ng/mL in men and 34.4 ng/mL in women. After adjustment for covariates, PBF and FMI among men were inversely associated with 25(OH)D: PBF (ß ± SE = -2.40 ± 1.01, P = .018); FMI (-2.21 ± 0.93, .018). Among women, no adiposity measure was associated with 25(OH)D. PBF was the best predictor of insufficient 25(OH)D concentrations regardless of gender (AUC = 0.878). CONCLUSION: Adiposity measures were inversely associated with 25(OH)D, but differed between female and male officers.

Adequate vitamin D status is associated with the reduced odds of prevalent diabetic retinopathy in African Americans and Caucasians.

BACKGROUND: Vitamin D status has been hypothesized to protect against development of diabetic retinopathy via its anti-inflammatory and anti-angiogenic properties. Additionally, in vitro and in vivo studies suggest vitamin D favorably influences blood pressure and blood glucose control, strong risk factors for diabetic retinopathy. We examined the association between vitamin D status and prevalent diabetic retinopathy in participants with diabetes from a population-based cohort. METHODS: Among participants in the Atherosclerosis Risk in Communities (ARIC) study with diabetes at visit 3 (1993-1995), 1339 (906 Caucasians, 433 African Americans) had serum 25-hydroxyvitamin (25[OH]D) concentrations assessed at visit 2 (1989-1992) and nonmydriatic retinal photographs taken at visit 3. Dietary intake of vitamin D was assessed at visit 1 (1987-1989). Logistic regression was used to estimate odds ratios (ORs) and 95 % confidence intervals (CIs) for diabetic retinopathy by categories of season-adjusted 25(OH)D (<30 [referent], 30-<50, 50-<75 and ≥75 nmol/L), by quartile of vitamin D intake (IU/day), and use of vitamin D or fish oil supplements (yes/no). P for trend was estimated using continuous 25(OH)D or vitamin D intake. ORs were adjusted for race, and duration of diabetes. We further adjusted for HBA1c and hypertension to examine if 25(OH)D influenced diabetic retinopathy via its effects on either glycemic control or blood pressure. RESULTS: ORs (95 % CIs) for retinopathy, adjusted for race and duration, were 0.77 (0.45-1.32), 0.64 (0.37-1.10), and 0.39 (0.20-0.75), p for trend = 0.001, for participants with 25(OH)D of 30-<50, 50-<75, and ≥75 nmol/L, respectively. Further adjustment for hypertension minimally influenced results (data not show), but adjustment for HBA1c attenuated the OR among those with 25(OH)D ≥75 (0.47 [0.23-0.96], p for trend = 0.030). No statistically significant association was observed between vitamin D intake from foods or supplements and retinopathy. CONCLUSIONS: 25(OH)D concentrations ≥75 nmol/L were associated with lower odds of any retinopathy assessed 3 years later. We speculate this may be due in part to vitamin D's influence on blood glucose control.

Associations of intakes of magnesium and calcium and survival among women with breast cancer: results from Western New York Exposures and Breast Cancer (WEB) Study.

Magnesium (Mg) and calcium (Ca) antagonizes each other in (re) absorption, cell cycle regulation, inflammation, and many other physiologic activities. However, few studies have investigated the association between magnesium and calcium intakes and breast cancer survival, and the interaction between calcium and magnesium intake. In a cohort of 1,170 women with primary, incident, and histologically confirmed breast cancer from Western New York State, we examined the relationship between intakes of these two minerals and survival. Cox regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI). Mean follow-up time was 87.4 months after breast cancer diagnosis; there were 170 deaths identified. After adjustment for known prognostic factors, and intakes of energy, total vitamin D and total calcium, higher dietary intake of magnesium was inversely associated with risk of all-cause mortality (HR = 0.50, 95% CI, 0.28-0.90 for highest vs. lowest tertile; p trend = 0.02). Likewise, a marginal association was found for total Magnesium intake from foods and supplements combined (HR = 0.58, 95% CI, 0.31-1.08; p trend = 0.09). The inverse association of higher total magnesium intake with all-cause mortality was primarily presented among postmenopausal women and was stronger among women who had a high Ca:Mg intake ratio (>2.59). There were no clear associations for prognosis with intake of calcium. We found that magnesium intake alone may improve overall survival following breast cancer, and the association may be stronger among those with high Ca:Mg intake ratio.

Vitamin D intake determines vitamin d status of postmenopausal women, particularly those with limited sun exposure.

Few detailed data are available on the wide range of determinants of vitamin D status among postmenopausal women, and it is also unclear whether there may be undiscovered determinants. The objective of this study was to comprehensively evaluate determinants of serum 25-hydroxyvitamin D [25(OH)D] concentrations in a large cohort of postmenopausal women. Data from a subset of the Women's Health Initiative Observational Study were analyzed (50-79 y; n = 3345). Information on diet, lifestyle behaviors, secondhand smoke, use of dietary supplements and medication, chronic diseases, and anthropometry was collected at baseline (1993-1998) and on sun exposure at year 4 follow-up. Linear regression was performed to estimate regression coefficients (ß). Significant determinants were total vitamin D intake (food plus supplements per 100 IU/d, ß = 2.08), years of supplemental vitamin D use (ß = 0.15), total fat intake (grams per day, ß = -0.03), smoking status (ß = -2.64, current vs. never), regional solar irradiance (ß = 6.26, 475-500 vs. 300-325 Langleys), daylight time spent outdoors in summer (ß = 5.15, >2 h vs. <30 min/d), recreational physical activity (metabolic equivalent task per hour per week, ß = 0.13), waist circumference (centimeters, ß = -0.26), and race/ethnicity (ß = -11.94, black vs. white). Total vitamin D intake (partial R(2) = 0.09) explained the most variance in serum 25(OH)D concentrations (total R(2) = 0.29). The association between total vitamin D intake and serum 25(OH)D concentrations was stronger among participants who spent less rather than more daylight time outdoors in summer (P-interaction = 0.026). History and medications for hypertension, hyperlipidemia, and type 2 diabetes and secondhand smoke exposure were not associated with serum 25(OH)D. In conclusion, dietary factors and sun exposure remain important determinants of vitamin D status in postmenopausal women. Vitamin D intake should be emphasized for those with limited sun exposure.

Changes in vitamin D supplement use and baseline plasma 25-hydroxyvitamin D concentration predict 5-y change in concentration in postmenopausal women.

Few studies have prospectively examined predictors of change in plasma concentrations of 25-hydroxyvitamin D [25(OH)D]. We sought to determine the predictors of 5-y change in 25(OH)D. Plasma 25(OH)D concentrations were assessed at baseline (1997-2000) and 5 y later (2002-2005) in 668 postmenopausal women enrolled in the Osteoporosis and Periodontal Disease Study. Baseline and changes in demographic, dietary, lifestyle, and health-related factors were tested as predictors of change in 25(OH)D concentrations by using multivariable linear regression. The mean 5-y change in 25(OH)D (mean ± SD) was 7.7 ± 0.7 nmol/L (P < 0.001). In our predictive model (n = 643), predictors explained 31% of the variance in change in 25(OH)D concentrations and included baseline 25(OH)D, baseline and change in vitamin D supplementation and physical activity, change in season of blood draw, BMI, whole-body T score, and baseline hormone therapy use. Baseline 25(OH)D and change in vitamin D supplementation explained the most variation (25%) in 25(OH)D. Exploratory analyses showed a borderline significant interaction between tertiles of baseline 25(OH)D and change in vitamin D supplementation over time (P = 0.06). The greatest mean increase in 25(OH)D (22.9 ± 16.8 nmol/L), with adjustment for other statistically significant predictors, occurred in women whose baseline 25(OH)D concentration was ≤51.0 nmol/L (tertile 1) and who increased supplementation use over time. These results confirm the importance of supplementation in increasing 25(OH)D concentrations in aging women, even after other statistically significant predictors are controlled for. These data also suggest that this is especially true among aging women with inadequate 25(OH)D (e.g., <50 nmol/L).

Vitamin D supplementation and depression in the women's health initiative calcium and vitamin D trial.

While observational studies have suggested that vitamin D deficiency increases risk of depression, few clinical trials have tested whether vitamin D supplementation affects the occurrence of depression symptoms. The authors evaluated the impact of daily supplementation with 400 IU of vitamin D(3) combined with 1,000 mg of elemental calcium on measures of depression in a randomized, double-blinded US trial comprising 36,282 postmenopausal women. The Burnam scale and current use of antidepressant medication were used to assess depressive symptoms at randomization (1995-2000). Two years later, women again reported on their antidepressant use, and 2,263 completed a second Burnam scale. After 2 years, women randomized to receive vitamin D and calcium had an odds ratio for experiencing depressive symptoms (Burnam score ≥0.06) of 1.16 (95% confidence interval: 0.86, 1.56) compared with women in the placebo group. Supplementation was not associated with antidepressant use (odds ratio = 1.01, 95% confidence interval: 0.92, 1.12) or continuous depressive symptom score. Results stratified by baseline vitamin D and calcium intake, solar irradiance, and other factors were similar. The findings do not support a relation between supplementation with 400 IU/day of vitamin D(3) along with calcium and depression in older women. Additional trials testing higher doses of vitamin D are needed to determine whether this nutrient may help prevent or treat depression.

Intraindividual variation in plasma 25-hydroxyvitamin D measures 5 years apart among postmenopausal women.

BACKGROUND: Current literature examining associations between vitamin D and chronic disease generally use a single assessment of 25-hydroxyvitamin D [25(OH)D], assuming the 25(OH)D concentration of an individual is consistent over time. METHODS: We investigated the intraindividual variability between two measures of plasma 25(OH)D concentrations collected approximately five years apart (1997-2000 to 2002-2005) in 672 postmenopausal women participating in the Women's Health Initiative. Plasma 25(OH)D was assessed using the DiaSorin LIAISON® chemiluminescence immunoassay. The within-pair coefficient of variation (CV) was 4.9% using blinded quality control samples. Mean and SDs of 25(OH)D at the two time points were compared using a paired t test. An intraindividual CV and intraclass correlation coefficient (ICC) were used to assess intraindividual variability. A Spearman correlation coefficient (r) assessed the strength of the association between the two measures, and concordance in vitamin D status at two time points was compared. RESULTS: Mean 25(OH)D concentrations (nmol/L) significantly increased over time from 60.0 (SD = 22.2) to 67.8 (SD = 22.2; P < 0.05). The CV was 24.6%, the ICC [95% confidence interval (CI)] was 0.59 (0.54-0.64), and the Spearman r was 0.61 (95% CI = 0.56-0.66). Greater concordance over five years was observed in participants with sufficient compared with deficient or inadequate baseline 25(OH)D concentrations (weighted kappa = 0.39). Reliability measures were moderately influenced by season of blood draw and vitamin D supplement use. CONCLUSION: There is moderate intraindividual variation in 25(OH)D concentrations over approximately five years. IMPACT: These data support the use of a one-time measure of blood 25(OH)D in prospective studies with ≤ five years of follow-up.

Vitamin D intake from foods and supplements and depressive symptoms in a diverse population of older women.

BACKGROUND: Vitamin D may plausibly reduce the occurrence of depression in postmenopausal women; however, epidemiologic evidence is limited, and few prospective studies have been conducted. OBJECTIVE: We conducted a cross-sectional and prospective analysis of vitamin D intake from foods and supplements and risk of depressive symptoms. DESIGN: Study participants were 81,189 members of the Women's Health Initiative (WHI) Observational Study who were aged 50-79 y at baseline. Vitamin D intake at baseline was measured by food-frequency and supplement-use questionnaires. Depressive symptoms at baseline and after 3 y were assessed by using the Burnam scale and current antidepressant medication use. RESULTS: After age, physical activity, and other factors were controlled for, women who reported a total intake of ≥800 IU vitamin D/d had a prevalence OR for depressive symptoms of 0.79 (95% CI: 0.71, 0.89; P-trend < 0.001) compared with women who reported a total intake of <100 IU vitamin D/d. In analyses limited to women without evidence of depression at baseline, an intake of ≥400 compared with <100 IU vitamin D/d from food sources was associated with 20% lower risk of depressive symptoms at year 3 (OR: 0.80; 95% CI: 0.67, 0.95; P-trend = 0.001). The results for supplemental vitamin D were less consistent, as were the results from secondary analyses that included as cases women who were currently using antidepressant medications. CONCLUSIONS: Overall, our findings support a potential inverse association of vitamin D, primarily from food sources, and depressive symptoms in postmenopausal women. Additional prospective studies and randomized trials are essential in establishing whether the improvement of vitamin D status holds promise for the prevention of depression, the treatment of depression, or both.

The effect of calcium plus vitamin D on risk for invasive cancer: results of the Women's Health Initiative (WHI) calcium plus vitamin D randomized clinical trial.

In the Women's Health Initiative (WHI) trial of calcium plus vitamin D (CaD), we examined the treatment effect on incidence and mortality for all invasive cancers. Postmenopausal women (N = 36,282) were randomized to 1,000 mg of elemental calcium with 400 IU vitamin D3 or placebo. Cox models estimated risk of cancer incidence and mortality. After 7.0 yr, 1,306 invasive cancers were diagnosed in the supplement and 1,333 in the placebo group [hazard ratio (HR) = 0.98; CI = 0.90, 1.05, unweighted P = 0.54]. Mortality did not differ between supplement (315, annualized% = .26) and placebo [(347, 0.28%; P = 0.17; HR = 0.90 (0.77, 1.05)]. Significant treatment interactions on incident cancer were found for family history of cancer, personal total intake of vitamin D, smoking, and WHI dietary trial randomized group. Calcium/vitamin D supplementation did not reduce invasive cancer incidence or mortality. Supplementation lowered cancer risk in the WHI healthy diet trial arm and in women without a first-degree relative with cancer. The interactions are only suggestive given multiple testing considerations. The low vitamin D dose provided, limited adherence, and lack of serum 25(OH)D values should be considered when interpreting these findings.

Vitamin D status and early age-related macular degeneration in postmenopausal women.

OBJECTIVE: The relationship between serum 25-hydroxyvitamin D (25[OH]D) concentrations (nmol/L) and the prevalence of early age-related macular degeneration (AMD) was investigated in participants of the Carotenoids in Age-Related Eye Disease Study. METHODS: Stereoscopic fundus photographs, taken from 2001 to 2004, assessed AMD status. Baseline (1994-1998) serum samples were available for 25(OH)D assays in 1313 women with complete ocular and risk factor data. Odds ratios (ORs) and 95% confidence intervals (CIs) for early AMD (n = 241) of 1287 without advanced disease were estimated with logistic regression and adjusted for age, smoking, iris pigmentation, family history of AMD, cardiovascular disease, diabetes, and hormone therapy use. RESULTS: In multivariate models, no significant relationship was observed between early AMD and 25(OH)D (OR for quintile 5 vs 1, 0.79; 95% CI, 0.50-1.24; P for trend = .47). A significant age interaction (P = .002) suggested selective mortality bias in women aged 75 years and older: serum 25(OH)D was associated with decreased odds of early AMD in women younger than 75 years (n = 968) and increased odds in women aged 75 years or older (n = 319) (OR for quintile 5 vs 1, 0.52; 95% CI, 0.29-0.91; P for trend = .02 and OR, 1.76; 95% CI, 0.77-4.13; P for trend = .05, respectively). Further adjustment for body mass index and recreational physical activity, predictors of 25(OH)D, attenuated the observed association in women younger than 75 years. Additionally, among women younger than 75 years, intake of vitamin D from foods and supplements was related to decreased odds of early AMD in multivariate models; no relationship was observed with self-reported time spent in direct sunlight. CONCLUSIONS: High serum 25(OH)D concentrations may protect against early AMD in women younger than 75 years.

Pretreatment serum concentrations of 25-hydroxyvitamin D and breast cancer prognostic characteristics: a case-control and a case-series study.

BACKGROUND: Results from epidemiologic studies on the relationship between vitamin D and breast cancer risk are inconclusive. It is possible that vitamin D may be effective in reducing risk only of specific subtypes due to disease heterogeneity. METHODS AND FINDINGS: In case-control and case-series analyses, we examined serum concentrations of 25-hydroxyvitamin D (25OHD) in relation to breast cancer prognostic characteristics, including histologic grade, estrogen receptor (ER), and molecular subtypes defined by ER, progesterone receptor (PR) and HER2, among 579 women with incident breast cancer and 574 controls matched on age and time of blood draw enrolled in the Roswell Park Cancer Institute from 2003 to 2008. We found that breast cancer cases had significantly lower 25OHD concentrations than controls (adjusted mean, 22.8 versus 26.2 ng/mL, p<0.001). Among premenopausal women, 25OHD concentrations were lower in those with high- versus low-grade tumors, and ER negative versus ER positive tumors (p≤0.03). Levels were lowest among women with triple-negative cancer (17.5 ng/mL), significantly different from those with luminal A cancer (24.5 ng/mL, p = 0.002). In case-control analyses, premenopausal women with 25OHD concentrations above the median had significantly lower odds of having triple-negative cancer (OR = 0.21, 95% CI = 0.08-0.53) than those with levels below the median; and every 10 ng/mL increase in serum 25OHD concentrations was associated with a 64% lower odds of having triple-negative cancer (OR = 0.36, 95% CI = 0.22-0.56). The differential associations by tumor subtypes among premenopausal women were confirmed in case-series analyses. CONCLUSION: In our analyses, higher serum levels of 25OHD were associated with reduced risk of breast cancer, with associations strongest for high grade, ER negative or triple negative cancers in premenopausal women. With further confirmation in large prospective studies, these findings could warrant vitamin D supplementation for reducing breast cancer risk, particularly those with poor prognostic characteristics among premenopausal women.

Healthy diets and the subsequent prevalence of nuclear cataract in women.

OBJECTIVE: To assess the association between healthy diet scores and prevalence of nuclear cataract in women. METHODS: The association between healthy diet scores, which reflect adherence to the US dietary guidelines, and prevalence of nuclear cataract determined 4 to 7 years later was assessed in a sample of Women's Health Initiative Observational Study participants (aged 50-79 years) residing in Iowa, Wisconsin, and Oregon. Scores on the 1995 Healthy Eating Index, which reflect adherence to 1990 guidelines, were assigned from responses to food frequency questionnaires at the Women's Health Initiative baseline (1994-1998). Presence of nuclear cataract was determined from slitlamp photographs and self-reports of cataract extractions were assessed from May 1, 2001, to January 31, 2004, in 1808 women participating in the Carotenoids in Age-Related Eye Disease Study. RESULTS: Having a high 1995 Healthy Eating Index score was the strongest modifiable predictor of low prevalence of nuclear cataract among numerous risk factors investigated in this sample. The multivariate-adjusted odds ratio for high vs low quintile for diet score was 0.63 (95% confidence interval, 0.43-0.91). Higher prevalence of nuclear cataract was also associated with other modifiable factors (smoking and marked obesity) and nonmodifiable factors (having brown eyes, myopia, and high pulse pressure). Vitamin supplement use was not related to cataract. CONCLUSION: These data add to the body of evidence suggesting that eating foods rich in a variety of vitamins and minerals may contribute to postponing the occurrence of the most common type of cataract in the United States.

Predictors of serum 25-hydroxyvitamin D concentrations among postmenopausal women: the Women's Health Initiative Calcium plus Vitamin D clinical trial.

BACKGROUND: It is unclear how well surrogate markers for vitamin D exposure (eg, oral intake of vitamin D and estimates of sunlight exposure), with and without consideration of other potential predictors of 25-hydroxyvitamin D [25(OH)D] concentrations, similarly rank individuals with respect to 25(OH)D blood concentrations. OBJECTIVE: The objective was to determine how much variation in serum 25(OH)D concentrations (nmol/L) could be explained by a predictive model with the use of different vitamin D surrogate markers (latitude of residence, mean annual regional solar irradiance estimates, and oral sources) and other individual characteristics that might influence vitamin D status. DESIGN: A random sample of 3055 postmenopausal women (aged 50-70 y) participating in 3 nested case-control studies of the Women's Health Initiative Calcium plus Vitamin D Clinical Trial was used. Serum 25(OH)D values, assessed at year 1 (1995-2000), and potential predictors of 25(OH)D concentrations, assessed at year 1 or Women's Health Initiative baseline (1993-1998), were used. RESULTS: More than half of the women (57.1%) had deficient (<50 nmol/L) concentrations of 25(OH)D. Distributions of 25(OH)D concentrations by level of latitude of residence, mean annual regional solar irradiance, and intake of vitamin D varied considerably. The predictive model for 25(OH)D explained 21% of the variation in 25(OH)D concentrations. After adjustment for month of blood draw, breast cancer status, colorectal cancer status, fracture status, participation in the hormone therapy trial, and randomization to the dietary modification trial, the predictive model included total vitamin D intake from foods and supplements, waist circumference, recreational physical activity, race-ethnicity, regional solar irradiance, and age. CONCLUSIONS: Surrogate markers for 25(OH)D concentrations, although somewhat correlated, do not adequately reflect serum vitamin D measures. These markers and predictive models of blood 25(OH)D concentrations should not be given as much weight in epidemiologic studies of cancer risk.

Vitamin D assessment in population-based studies: a review of the issues.

In the past decade, research on the relation between vitamin D exposure and disease in population-based studies has increased exponentially. These studies have involved measurement of vitamin D exposure by means of several methods: blood assays, self-reported dietary and supplemental intakes, and sunlight exposure questionnaires or diaries. As with all exposure measurements, researchers must consider the validity of their assessment tools for capturing vitamin D exposure. The purpose of this article is to summarize our current understanding of the various approaches to measuring vitamin D status within populations as reviewed at the 2007 Experimental Biology symposium, "Assessment of Vitamin D in Population-Based Studies." In summary, serum 25-hydroxyvitamin D is the accepted biomarker for short-term vitamin D status, but estimates of long-term dietary and supplemental intakes of vitamin D and long-term sunlight exposure may be the most logistically feasible indicators of lifetime vitamin D exposure in population-based studies. Also discussed are issues investigators should consider when analyzing relations between vitamin D exposure and disease outcomes in population-based studies as well as research avenues that need further exploration. The best method for assessing vitamin D status in population-based studies will depend primarily on the research question asked and the critical window of vitamin D exposure hypothesized to be most important.

Association between vitamin D and age-related macular degeneration in the Third National Health and Nutrition Examination Survey, 1988 through 1994.

OBJECTIVE: To evaluate the associations between levels of vitamin D (25-hydroxyvitamin D) in serum and prevalent age-related macular degeneration (AMD). METHODS AND DESIGN: Cross-sectional associations of serum vitamin D and early and advanced AMD, assessed from nonmydriatic fundus photographs, were evaluated in the third National Health and Nutrition Examination Survey, a multistage nationally representative probability sample of noninstitutionalized individuals (N = 7752; 11% with AMD). RESULTS: Levels of serum vitamin D were inversely associated with early AMD but not advanced AMD. The odds ratio (OR) and 95% confidence interval (CI) for early AMD among participants in the highest vs lowest quintile of serum vitamin D was 0.64 (95% CI, 0.5-0.8; P trend <.001). Exploratory analyses were conducted to evaluate associations with important food and supplemental sources of vitamin D. Milk intake was inversely associated with early AMD (OR, 0.75; 95% CI, 0.6-0.9). Fish intake was inversely associated with advanced AMD (OR, 0.41; 95% CI, 0.2-0.9). Consistent use vs nonuse of vitamin D from supplements was inversely associated with early AMD only in individuals who did not consume milk daily (early AMD: OR, 0.67; 95% CI, 0.5-0.9). CONCLUSION: This study provides evidence that vitamin D may protect against AMD. Additional studies are needed to confirm these findings.