Analyzing Adherence to Prenatal Supplement: Does Pill Count Measure Up?

Objective. To determine if adherence as measured by pill count would show a significant association with serum-based measures of adherence. Methods. Data were obtained from a prenatal vitamin D supplementation trial where subjects were stratified by race and randomized into three dosing groups: 400 (control), 2000, or 4000 IU vitamin D3/day. One measurement of adherence was obtained via pill counts remaining compared to a novel definition for adherence using serum 25-hydroxy-vitamin D (25-OH-D) levels (absolute change in 25(OH)D over the study period and the subject's steady-state variation in their 25(OH)D levels). A multivariate logistic regression model examined whether mean percent adherence by pill count was significantly associated with the adherence measure by serum metabolite levels. Results. Subjects' mean percentage of adherence by pill count was not a significant predictor of adherence by serum metabolite levels. This finding was robust across a series of sensitivity analyses. Conclusions. Based on our novel definition of adherence, pill count was not a reliable predictor of adherence to protocol, and calls into question how adherence is measured in clinical research. Our findings have implications regarding the determination of efficacy of medications under study and offer an alternative approach to measuring adherence of long half-life supplements/medications

Plasma 25-hydroxyvitamin D and risk of breast cancer in the Nurses' Health Study II

Introduction Experimental evidence indicates vitamin D may play an important role in breast cancer etiology but epidemiologic evidence to date is inconsistent. Vitamin D comes from dietary intake and sun exposure and plasma levels of 25-hydroxyvitamin D (25(OH)D) are considered the best measure of vitamin D status. Methods We conducted a prospective nested case-control study within the Nurses\u27 Health Study II (NHSII). Plasma samples collected in 1996 to 1999 were assayed for 25(OH)D in 613 cases, diagnosed after blood collection and before 1 June 2007, and in 1,218 matched controls. Multivariate relative risks (RR) and 95% confidence intervals (CI) were calculated by conditional logistic regression, adjusting for several breast cancer risk factors. Results No significant association was observed between plasma 25(OH)D levels and breast cancer risk (top vs. bottom quartile multivariate RR = 1.20, 95% CI (0.88 to 1.63), P-value, test for trend = 0.32). Results were similar when season-specific quartile cut points were used. Results did not change when restricted to women who were premenopausal at blood collection or premenopausal at diagnosis. Results were similar between estrogen receptor (ER)+/progesterone receptor (PR)+ and ER-/PR- tumors (P-value, test for heterogeneity = 0.51). The association did not vary by age at blood collection or season of blood collection, but did vary when stratified by body mass index (P-value, test for heterogeneity = 0.01). Conclusions Circulating 25(OH)D levels were not significantly associated with breast cancer risk in this predominantly premenopausal population

Vitamin D Status Relative to Diet, Lifestyle, Injury, and Illness in College Athletes

Vitamin D deficiency is endemic in the general population; however, there is much to be learned about the vitamin D status of athletes. Purpose: The purposes of this study were to assess the prevalence of vitamin D insufficiency in collegiate athletes and to determine whether 25(OH)D concentrations are related to vitamin D intake, sun exposure, body composition, and risk for illness or athletic injury. Methods: 25(OH) vitamin D concentrations were measured in 41 athletes (18 men/23 women, 12 indoor/29 outdoor athletes) throughout the academic year. Dietary intake and lifestyle habits were assessed via questionnaire, bone density was measured by dual energy x-ray absorptiometry, and injury and illness were documented as part of routine care. Results: The 25(OH)D concentrations changed across time (P = 0.001) and averaged 49.0 T 16.6, 30.5 T 9.4, and 41.9 T 14.6 ngImLj1 (mean T SD) in the fall, winter, and spring, respectively, and were higher in outdoor versus indoor athletes in the fall (P G 0.05). Using 40 ngImLj1 as the cutoff for optimal status, 75.6%, 15.2%, and 36.0% of athletes had optimal status in the fall, winter, and spring, respectively. 25(OH)D concentrations were significantly (P G 0.05) correlated with multivitamin intake in the winter (r = 0.39) and tanning bed use in the spring (r = 0.48); however, status was otherwise not related to intake, lifestyle factors, or body composition. 25(OH)D concentrations in the spring (r = j0.40, P = 0.048) was correlated with frequency of illness. Conclusions: Our results suggest that collegiate athletes can maintain sufficient status during the fall and spring but would benefit from supplementation during the winter to prevent seasonal decreases in 25(OH)D concentrations. Results further suggest that insufficient vitamin D status may increase risk for frequent illness. Future research is needed to identify whether vitamin D status influences injury risk during athletic training or competition

Circulating 25-Hydroxyvitamin D Levels in Fully Breastfed Infants on Oral Vitamin D Supplementation

Objective. To examine the effectiveness of oral vitamin D3 (400 IU) supplementation on the nutritional vitamin D status of breastfeeding infants. Design. As part of a larger ongoing vitamin D RCT trial of lactating women, infants of mothers assigned to control received 1 drop of 400 IU vitamin D3/day starting at one month of age. Infant 25(OH)D levels (mean ± S.D.) were measured by RIA at visits 1, 4, and 7. Results. The infant mean ± S.D. 25(OH)D at baseline was 16.0 ±9.3 ng/mL (range 1.0–40.8; n = 33); 24 (72.7%) had baseline levels <20 ng/mL (consistent with deficiency). The mean levels increased to 43.6 ±14.1 (range 18.2–69.7) at 4 months and remained relatively unchanged at month 7: 42.5 ±12.1 ng/mL (range 18.9–67.2). The change in values between 1 and 4 months and 1 and 7 months was statistically significant (P ≤ .0001), and despite a decrease in dose per kilogram, values were not significantly different between months 4 and 7 (P = .66). Conclusions. Oral vitamin D3 supplementation as an oil emulsion was associated with significant and sustained increases in 25(OH)D from baseline in fully breastfeeding infants through 7 months

Prediagnostic Plasma Vitamin D Metabolites and Mortality among Patients with Prostate Cancer

Laboratory evidence suggests that vitamin D might influence prostate cancer prognosis.We examined the associations between prediagnostic plasma levels of 25(OH)vitamin D [25(OH)D] and 1,25(OH)(2) vitamin D [1,25(OH)(2)D] and mortality among 1822 participants of the Health Professionals Follow-up Study and Physicians' Health Study who were diagnosed with prostate cancer. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) of total mortality (n = 595) and lethal prostate cancer (death from prostate cancer or development of bone metastases; n = 202). In models adjusted for age at diagnosis, BMI, physical activity, and smoking, we observed a HR of 1.22 (95% CI: 0.97, 1.54) for total mortality, comparing men in the lowest to the highest quartile of 25(OH)D. There was no association between 1,25(OH)(2)D and total mortality. Men with the lowest 25(OH)D quartile were more likely to die of their cancer (HR: 1.59; 95% CI: 1.06, 2.39) compared to those in the highest quartile (P(trend) = 0.006). This association was largely explained by the association between low 25(OH)D levels and advanced cancer stage and higher Gleason score, suggesting that these variables may mediate the influence of 25(OH)D on prognosis. The association also tended to be stronger among patients with samples collected within five years of cancer diagnosis. 1,25(OH)(2)D levels were not associated with lethal prostate cancer.Although potential bias of less advanced disease due to more screening activity among men with high 25(OH)D levels cannot be ruled out, higher prediagnostic plasma 25(OH)D might be associated with improved prostate cancer prognosis

Premature atherosclerosis is associated with hypovitaminosis d and angiotensin-converting enzyme inhibitor non-use in lupus patients

The ultimate goal is to identify and target modifiable risk factors that will reduce major cardiovascular events in African American lupus patients. As a first step toward achieving this goal, this study was designed to explore risk factor models of preclinical atherosclerosis in a predominantly African American group of patients with systemic lupus erythematosus (SLE) using variables historically associated with endothelial function in nonlupus populations. Fifty-one subjects with SLE but without a history of clinical cardiovascular events were enrolled. At entry, a Framingham risk factor history and medication list were recorded. Sera and plasma samples were analyzed for lipids, lupus activity markers and total 25-hydroxyvitamin D (25 OH)D) levels. Carotid ultrasound measurements were performed to determine total plaque area (TPA) in both carotids. Cases had TPA values above age-matched controls from a vascular prevention clinic population. Logistic regression and machine learning analyses were performed to create predictive models. 25(OH)D levels were significantly lower, and SLE disease duration was significantly higher in cases. 25(OH)D levels inversely correlated with age-adjusted TPA. Angiotensin-converting enzyme (ACE) inhibitor nonuse associated with case status. Logistic regression models containing ACE inhibitor use, 25(OH)D levels and low-density lipoprotein levels had a diagnostic accuracy of 84% for predicting accelerated atherosclerosis. Similar results were obtained with machine learning models, but hydroxychlo-roquine use associated with controls in these models. This is the first study to demonstrate an association between atherosclerotic burden and 25(OH)D insufficiency or ACE inhibitor nonuse in lupus patients. These findings provide strong rationale for the study of ACE inhibitors and vitamin D replenishment as preventive therapies in this high-risk population. © Copyright 2012 Southern Society for Clinical Investigation

Reduction of parathyroid hormone with vitamin D supplementation in blacks: A randomized controlled trial

BACKGROUND: Response of parathyroid hormone (PTH) to vitamin D supplementation is determined by the baseline PTH level and change in vitamin D status. Conflicting reports in Blacks exist on the PTH response to vitamin D to supplementation. METHODS: During 3 winters from 2007-2010, 328 healthy Blacks (median age, 51 years) living in Boston, MA were randomized into a 4-arm, double-blind trial for 3 months of placebo, 1000, 2000, or 4000 IU of vitamin D3. PTH was measured in 254 participants at baseline and at the end of vitamin D supplementation period. RESULTS: The differences in PTH between baseline and 3 months were 3.93 pg/mL for those receiving placebo, -3.37 pg/mL for those receiving 1000 IU/d, -6.76 pg/mL for those receiving 2000 IU/d, and -8.99 pg/mL for those receiving 4000 IU/d ( -2.98 pg/mL for each additional 1000 IU/d of vitamin D3; p<0.001). CONCLUSION: We found a significant decrease in PTH with increasing doses of vitamin D supplementation up to intakes of 4000 IU/d in Blacks. Clinical Trials.gov: NCT0058563

A Prospective Study of Plasma Vitamin D Metabolites, Vitamin D Receptor Polymorphisms, and Prostate Cancer

BACKGROUND: Vitamin D insufficiency is a common public health problem nationwide. Circulating 25-hydroxyvitamin D(3) (25[OH]D), the most commonly used index of vitamin D status, is converted to the active hormone 1,25 dihydroxyvitamin D(3) (1,25[OH](2)D), which, operating through the vitamin D receptor (VDR), inhibits in vitro cell proliferation, induces differentiation and apoptosis, and may protect against prostate cancer. Despite intriguing results from laboratory studies, previous epidemiological studies showed inconsistent associations of circulating levels of 25(OH)D, 1,25(OH)(2)D, and several VDR polymorphisms with prostate cancer risk. Few studies have explored the joint association of circulating vitamin D levels with VDR polymorphisms. METHODS AND FINDINGS: During 18 y of follow-up of 14,916 men initially free of diagnosed cancer, we identified 1,066 men with incident prostate cancer (including 496 with aggressive disease, defined as stage C or D, Gleason 7–10, metastatic, and fatal prostate cancer) and 1,618 cancer-free, age- and smoking-matched control participants in the Physicians' Health Study. We examined the associations of prediagnostic plasma levels of 25(OH)D and 1,25(OH)(2)D, individually and jointly, with total and aggressive disease, and explored whether relations between vitamin D metabolites and prostate cancer were modified by the functional VDR FokI polymorphism, using conditional logistic regression. Among these US physicians, the median plasma 25(OH)D levels were 25 ng/ml in the blood samples collected during the winter or spring and 32 ng/ml in samples collected during the summer or fall. Nearly 13% (summer/fall) to 36% (winter/spring) of the control participants were deficient in 25(OH)D (<20 ng/ml) and 51% (summer/fall) and 77% (winter/spring) had insufficient plasma 25(OH)D levels (<32 ng/ml). Plasma levels of 1,25(OH)(2)D did not vary by season. Men whose levels for both 25(OH)D and 1,25(OH)(2)D were below (versus above) the median had a significantly increased risk of aggressive prostate cancer (odds ratio [OR] = 2.1, 95% confidence interval [CI] 1.2–3.4), although the interaction between the two vitamin D metabolites was not statistically significant (p (interaction) = 0.23). We observed a significant interaction between circulating 25(OH)D levels and the VDR FokI genotype (p (interaction) < 0.05). Compared with those with plasma 25(OH)D levels above the median and with the FokI FF or Ff genotype, men who had low 25(OH)D levels and the less functional FokI ff genotype had increased risks of total (OR = 1.9, 95% CI 1.1–3.3) and aggressive prostate cancer (OR = 2.5, 95% CI 1.1–5.8). Among men with plasma 25(OH)D levels above the median, the ff genotype was no longer associated with risk. Conversely, among men with the ff genotype, high plasma 25(OH)D level (above versus below the median) was related to significant 60%∼70% lower risks of total and aggressive prostate cancer. CONCLUSIONS: Our data suggest that a large proportion of the US men had suboptimal vitamin D status (especially during the winter/spring season), and both 25(OH)D and 1,25(OH)(2)D may play an important role in preventing prostate cancer progression. Moreover, vitamin D status, measured by 25(OH)D in plasma, interacts with the VDR FokI polymorphism and modifies prostate cancer risk. Men with the less functional FokI ff genotype (14% in the European-descent population of this cohort) are more susceptible to this cancer in the presence of low 25(OH)D status