African-Americans have significantly higher rates of hypertension than whites, and lower circulating levels of 25-hydroxyvitamin D. There are few data about the effect of vitamin D3 (cholecalciferol) supplementation on blood pressure in African-Americans. During two winter periods from 2008–2010, 283 African-Americans (median age, 51 years) were randomized into a four-arm, double-blind trial for three months of placebo, 1,000, 2,000, or 4,000 international units of cholecalciferol per day. At baseline, three months, and six months, systolic and diastolic pressure and 25-hydroxyvitamin D were measured. The 3-month follow-up was completed in 250 (88%) participants. The difference in systolic pressure between baseline and 3 months was +1.7 mmHg for those receiving placebo, −0.66 mmHg for 1,000 units/day, −3.4 mmHg for 2,000 units/day, and −4.0 mmHg for 4,000 units/day of cholecalciferol (−1.4 mmHg for each additional 1000 units/day of cholecalciferol; p=0.04). For each 1 ng/mL increase in plasma 25-hydroxyvitamin D, there was a significant 0.2 mmHg reduction in systolic pressure (p = 0.02). There was no effect of cholecalciferol supplementation on diastolic pressure (p=0.37). Within an unselected population of African-Americans, three months of oral vitamin D3 supplementation significantly, yet modestly, lowered systolic pressure. Future trials of vitamin D supplementation on blood pressure are needed to confirm these promising results, particularly among African-Americans, a population for whom vitamin D deficiency may play a more specific mechanistic role in the pathogenesis of hypertension.

Lipids were associated with total, lung, and colorectal cancer risks in women. Lifestyle interventions for heart-disease prevention, which reduce apo B-100 or raise HDL cholesterol, may be associated with reduced cancer risk. The Women's Health Study was registered at clinicaltrials.gov as NCT00000479.

Rationale Circulating glycoprotein N-acetyl glucosamine residues have recently been associated with incident cardiovascular disease (CVD) and diabetes mellitus. Objective Using a plasma glycan biosignature (GlycA) to identify circulating N-acetyl glycan groups, we examined the longitudinal association between GlycA and mortality among initially-healthy individuals. Methods and Results We quantified GlycA by 400 MHz 1H nuclear magnetic resonance (NMR) spectroscopy in 27,524 participants in the Women's Health Study (WHS; NCT00000479). The primary outcome was all-cause mortality. We replicated the findings in an independent cohort of 12,527 individuals in the JUPITER trial (NCT00239681). We also undertook secondary examination of CVD and cancer mortality in WHS. In WHS, during 524,515 person-years of follow-up (median 20.5 years) there were 3,523 deaths. Risk-factor adjusted multivariable Cox proportional hazard ratio (95% confidence interval) per standard deviation increment in GlycA for all-cause mortality was significantly increased at 5-years (1.21 [1.06, 1.40]) and during maximal follow-up (1.14 [1.09, 1.16]). Similar risk for all-cause mortality was observed in the replication cohort (1.33 [1.21, 1.45]). In WHS, risk of CVD mortality was increased at 5-years (1.43 [1.05, 1.95]) and during maximal follow-up (1.15 [1.04, 1.26]); and of cancer mortality at 5-years (1.23 [1.02, 1.47]) and during maximal follow-up (1.08 [1.01, 1.16]). Examination of correlations and mortality associations adjusted for hsCRP, fibrinogen, and ICAM-1, suggested that GlycA reflects summative risk related to multiple pathways of systemic inflammation. Conclusions Among initially-healthy individuals, elevated baseline circulating glycoprotein N-acetyl methyl groups were associated with longitudinal risk of all-cause, cardiovascular, and cancer mortality.

Within African Americans, an estimated 1640 IU vitamin D₃/d was required to achieve concentrations of plasma 25(OH)D recommended by the Institute of Medicine, whereas 4000 IU/d was needed to reach concentrations predicted to reduce cancer and cardiovascular disease risk in prospective observational studies. These results may be helpful for informing future trials of disease prevention.

IMPORTANCEEpidemiologic and trial data suggest that vitamin D supplementation may reduce metastatic cancer and cancer mortality, reflecting shared biological pathways. OBJECTIVE To follow up on the possible reduction in cancer death in the Vitamin D and Omega-3 Trial (VITAL) with an evaluation of whether vitamin D reduces the incidence of advanced (metastatic or fatal) cancer and an examination possible effect modification by body mass index. DESIGN, SETTING, AND PARTICIPANTS VITAL is a randomized, double-blind, placebo-controlled, 2 × 2 factorial clinical trial of vitamin D 3 (cholecalciferol, 2000 IU/d) and marine omega-3 fatty acids (1 g/d). This multicenter clinical trial was conducted in the United States; participants included men

Chronic inflammation may be a risk factor for the development and progression of breast cancer, yet it is unknown which inflammatory biomarkers and pathways are especially relevant. The present study included 27,071 participants (mean age = 54.5 years) in the Women's Health Study who were free of cancer and cardiovascular disease at enrollment (1992-1995), with baseline measures of 4 inflammatory biomarkers: high-sensitivity C-reactive protein, fibrinogen, N-acetyl side-chains of acute phase proteins, and soluble intercellular adhesion molecule-1. We used Cox proportional hazards regression models to evaluate associations between baseline concentrations of biomarkers and incident breast cancer, and adjusted for baseline and time-varying factors such as age and body mass index. Self-reported invasive breast cancer was confirmed against medical records for 1,497 incident cases (90% postmenopausal). We observed different patterns of risk depending on the inflammatory biomarker. There was a significant direct association between fibrinogen and breast cancer risk (for quintile 5 vs. quintile 1, adjusted hazard ratio = 1.25, 95% confidence interval: 1.03, 1.51; P for trend = 0.01). In contrast, soluble intercellular adhesion molecule-1 was inversely associated with breast cancer (for quintile 5 vs. quintile 1, adjusted hazard ratio = 0.79, 95% confidence interval: 0.66, 0.94; P for trend = 0.02). N-acetyl side-chains of acute phase proteins and high-sensitivity C-reactive protein were not associated with breast cancer. The complex association of chronic inflammation and breast cancer may be considered when formulating anti-inflammatory cancer prevention or intervention strategies.

African-Americans have a disproportionate burden of inflammation-associated chronic diseases such as cancer and lower circulating levels of 25-hydroxyvitamin D [25(OH)D]. The effect of vitamin D3 (cholecalciferol) supplementation on inflammatory markers is uncertain. We conducted a randomized, double-blind, placebo-controlled trial of supplemental oral vitamin D (Placebo; 1,000; 2,000; or 4,000 IU/day of vitamin D3 orally for 3 months) in 328 African-Americans (median age, 51 years) of public housing communities in Boston, MA who were enrolled over 3 consecutive winter periods (2007–2010). Change from 0 to 3 months of plasma levels of 25(OH)D, high-sensitivity C-reactive protein (CRP), interleukin (IL)-6, interleukin (IL)-10, and soluble tumor necrosis factor alpha receptor type 2 (sTNF-R2) in 292 (89%) participants were measured. Overall, no statistically significant changes in CRP, IL-6, IL-10, and sTNF-R2 were observed after vitamin D supplementation period. Baseline CRP was significantly inversely associated with baseline 25(OH)D level (p<0.001) in unadjusted and adjusted models. An interaction between baseline 25(OH)D and vitamin D supplementation was observed for outcome change in log CRP (Month 3-Month 0) (p for interaction=0.04). Within an unselected population of African-Americans, short-term exposure to vitamin D supplementation produced no change in circulating inflammatory markers. This study confirms the strong independent association of CRP with 25(OH)D status even after adjusting for BMI. Future studies of longer supplemental vitamin D3 duration are necessary to examine the complex influence of vitamin D3 on CRP and other chronic inflammatory cytokines for possible reduction of cancer health disparities in African-Americans.

Objective Assess vitamin D supplementation alone or with calcium alters adiposity measures. Methods Systematic search (1966-March 2014) of MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials for randomized clinical trials (RCTs) with >50 participants aged ≥18 years at baseline and at least 12 weeks of treatment. Primary end points were changes in weight, body mass index (BMI), or fat mass (FM). Results Of 953 trials identified, 26 RCTs (12:Vitamin D alone; 10: Vitamin D plus calcium versus calcium control; 4:Vitamin D plus calcium versus placebo) met the inclusion criteria; 42,430 participants (median duration: 12 months). Vitamin D supplementation alone versus placebo: no significant change in BMI (weighted mean difference (WMD): −0.06 kg/m2, 95% CI: −0.14,0.03), weight (WMD: −0.05 kg, 95% CI:−0.32,0.23) or FM (WMD: −0.43 kg, 95% CI: −1.69,0.84). Vitamin D plus calcium versus calcium control: no significant reduction in BMI (WMD: 0.02 kg/m2, 95% CI: −0.11, 0.14), weight (WMD: 0.12 kg, 95% CI: −0.24, 0.49), or FM (WMD: 0.12 kg, 95% CI: −0.22, 0.45); no significant heterogeneity. Conclusions Vitamin D showed no effect on adiposity measures in adults.