To evaluate racial variation in umbilical cord blood concentration of vitamin D and to explore its correlation with markers of the insulin-like growth factor axis (IGFs) and sex steroid hormones in white and black male neonates.
In 2004/2005 venous umbilical cord blood samples were collected from 75 black and 38 white male neonates, along with maternal and birth characteristics from two hospitals in Maryland, US. 25-hydroxyvitamin D [25(OH)D], and 1,25-dihydroxyvitamin D [1,25(OH)2D] were measured by radioimmunoassay (RIA), testosterone, estradiol and sex hormone binding globulin (SHBG) by immunoassay and IGF-1, IGF-2, and IGF-binding protein-3 (IGFBP-3) by ELISA. Crude and multivariable-adjusted geometric mean concentrations were computed.
Mean 25(OH)D levels were lower in black than in white neonates (11.44; 95% CI 10.10–12.95 ng/mL vs. 18.24; 95% CI 15.32–21.72 ng/mL; p<0.0001). Black neonates were at higher risk of suboptimal vitamin D levels [25(OH)D < 20 ng/mL] than whites (84% vs. 63%). 25(OH)D concentrations varied by season in whites but not in blacks and were significantly inversely correlated with mother’s parity (number of live births) in blacks but not in whites. Mean concentration of 1,25(OH)2D did not differ by race. 25(OH)D and 1,25(OH)2D did not correlate with IGFs, sex steroid hormones and SHBG.
Suboptimal vitamin D levels were prevalent especially in blacks and influenced by mother’s parity and by season. The observed vitamin D differences between black and white neonates warrant further evaluation of the etiology of the disparity in chronic diseases in adulthood.
Vitamin D; umbilical cord blood; black and white Americans
vitamin D; 25-hydroxyvitamin D; 1,25-dihydroxyvitamin D; calcidiol; calcitriol
Control of tuberculosis worldwide depends on our understanding of human immune mechanisms, which combat the infection. Acquired T cell responses are critical for host defense against microbial pathogens, yet the mechanisms by which they act in humans remain unclear. We report that T cells, by the release of interferon-γ (IFN-γ), induce autophagy, phagosomal maturation, the production of antimicrobial peptides such as cathelicidin, and antimicrobial activity against Mycobacterium tuberculosis in human macrophages via a vitamin D–dependent pathway. IFN-γ induced the antimicrobial pathway in human macrophages cultured in vitamin D–sufficient sera, but not in sera from African-Americans that have lower amounts of vitamin D and who are more susceptible to tuberculosis. In vitro supplementation of vitamin D–deficient serum with 25-hydroxyvitamin D3 restored IFN-γ–induced antimicrobial peptide expression, autophagy, phagosome-lysosome fusion, and antimicrobial activity. These results suggest a mechanism in which vitamin D is required for acquired immunity to overcome the ability of intracellular pathogens to evade macrophage-mediated antimicrobial responses. The present findings underscore the importance of adequate amounts of vitamin D in all human populations for sustaining both innate and acquired immunity against infection.
The need, safety and effectiveness of vitamin D supplementation during pregnancy remain controversial.
In this randomized controlled trial, women with a singleton pregnancy at 12–16 weeks’ gestation received 400, 2000 or 4000 IU vitamin D3/day until delivery. The primary outcome was maternal/neonatal circulating 25(OH)D at delivery, with secondary outcomes 25(OH)D ≥80 nmol/L achieved and 25(OH)D concentration required to achieve maximal 1,25(OH)2D production.
Of the 494 women enrolled, 350 women continued until delivery: Mean 25(OH)D by group at delivery and 1-month before delivery were significantly different (p<0.0001), and percent who achieved sufficiency was significantly different by group, greatest in 4000 IU group (p<0.0001). The relative risk (RR) for achieving ≥80 nmol/L within one month of delivery was significantly different between 2000 vs. 400 IU (RR 1.52 [CI 1.24–1.86]); 4000 vs. 400 (RR 1.60 [CI 1.32–1.95]), but not between 4000 vs. 2000 (RR 1.06 [CI 0.93–1.19]). Circulating 25(OH)D had a direct influence on circulating 1,25(OH)2D concentrations throughout pregnancy (p<0.0001) with maximal production of 1,25(OH)2D in all strata in the 4000 IU group. There were no differences between groups on any safety measure. Not a single adverse event was attributed to vitamin D supplementation or circulating 25(OH)D levels.
Vitamin D supplementation of 4,000 IU/day for pregnant women was safe and most effective in achieving sufficiency in all women and their neonates regardless of race while the current estimated average requirement was comparatively ineffective at achieving adequate circulating 25(OH)D, especially in African Americans.
Human in vivo models of primary hyperparathyroidism (HPT), humoral hypercalcemia of malignancy (HHM) or lactational bone mobilization for more than 48 hours have not been described previously. We therefore developed seven-day continuous infusion models using hPTH(1–34) and hPTHrP(1–36) in healthy human adult volunteers. Study subjects developed sustained mild increases in serum calcium (10.0 mg/dl), with marked suppression of endogenous PTH(1–84). The maximal tolerated infused doses over a seven-day period (2 and 4 pmol/kg/hr, for PTH and PTHrP, respectively) were far lower than in prior, briefer human studies (8–28 pmol/kg/hr). In contrast to prior reports using higher PTH and PTHrP doses, both 1,25(OH)2D and TmP/GFR remained unaltered with these low doses, despite achievement of hypercalcemia and hypercalciuria. As expected, bone resorption increased rapidly, and reversed promptly with cessation of the infusion. However, in contrast to events in primary HPT, bone formation was suppressed by 30–40% for the seven days of the infusions. With cessation of PTH and PTHrP infusion, bone formation markers abruptly rebounded upward, confirming that bone formation is suppressed by continuous PTH or PTHrP infusion. These studies demonstrate that continuous exposure of the human skeleton to PTH or PTHrP in vivo recruits and activates the bone resorption program, but causes sustained arrest in the osteoblast maturation program. These events would most closely mimic and model events in HHM. Although not a perfect model for lactation, the increase in resorption and the rebound increase in formation with cessation of the infusions is reminiscent of the maternal skeletal calcium mobilization and reversal that occur following lactation. The findings also highlight similarities and differences between the model and HPT.
Parathyroid Hormone; PTH-Related Protein; Humoral Hypercalcemia of Malignancy; Hyperparathyroidism; Lactation
It remains unknown whether increased risk with low levels of vitamin D is present for colon and/or rectal cancer. To investigate the association between circulating vitamin D levels and colon and rectal cancer, we examined the associations between plasma levels of 25-hydroxyvitamin D (25(OH)D) and 1,25-dihydroxyvitamin D (1,25(OH)2D) and colon and rectal cancer in the Physicians’ Health Study and then conducted a meta-analysis of eight prospective studies of circulating levels of 25-hydroxyvitamin D (25(OH)D) and colon and rectal cancers, including the Physicians’ Health Study. Study-specific odds ratios (ORs) and 95% confidence intervals (CIs) were pooled using a random-effects model. A total of 1822 colon and 868 rectal cancers were included in the meta-analysis. We observed a significant inverse association for colorectal cancer (OR = 0.66; 95% CI = 0.54–0.81), comparing top versus bottom quantiles of circulating 25(OH)D levels. The inverse association was stronger for rectal cancer (OR = 0.50 for top versus bottom quantiles; 95% CI = 0.28–0.88) than colon cancer (OR = 0.77; 95% CI = 0.56–1.07; P for difference between colon and rectal cancer = 0.20). These data suggest an inverse association between circulating 25(OH)D levels and colorectal cancer, with a stronger association for rectal cancer.
Recently vitamin D deficiency has been associated with increased risks for preeclampsia and diagnosis of early-onset, severe preeclampsia (EOSPE). The purpose of this investigation was to examine the association between vitamin D levels and small for gestational age (SGA) in patients with EOSPE.
Patients with EOSPE were recruited and demographics, outcomes, and plasma were collected. 25-hydroxy-vitamin D (25-OH-D) was assessed by radioimmunoassay and reported in ng/mL. Results were analyzed by Mann Whitney U test and Spearman correlation and reported as median (Q1–Q3).
In patients with EOSPE (n=56), 25-OH-D was lower in patients with SGA (16.8 ng/mL [8.9–23]) verses normal fetal growth (25.3 ng/mL [16–33]) (p=0.02). 25-OH-D was significantly correlated with percentile growth at delivery (ρ = 0.31, p=0.02).
Vitamin D is lower among patients with SGA in EOSPE than those without growth retardation. We suspect that vitamin D may impact fetal growth through placental mechanisms.
25-hydroxyvitamin D; fetal growth restriction; preeclampsia; Vitamin D; small for gestational age (SGA)
Previous studies have suggested that higher plasma 25-hydroxyvitamin D3 [25(OH)D] levels are associated with decreased colorectal cancer risk and improved survival, but the prevalence of vitamin D deficiency in advanced colorectal cancer and its influence on outcomes are unknown.
Patients and Methods
We prospectively measured plasma 25(OH)D levels in 515 patients with stage IV colorectal cancer participating in a randomized trial of chemotherapy. Vitamin D deficiency was defined as 25(OH)D lower than 20 ng/mL, insufficiency as 20 to 29 ng/mL, and sufficiency as ≥ 30 ng/mL. We examined the association between baseline 25(OH)D level and selected patient characteristics. Cox proportional hazards models were used to calculate hazard ratios (HR) for death, disease progression, and tumor response, adjusted for prognostic factors.
Among 515 eligible patients, 50% of the study population was vitamin D deficient, and 82% were vitamin D insufficient. Plasma 25(OH)D levels were lower in black patients compared to white patients and patients of other race (median, 10.7 v 21.1 v 19.3 ng/mL, respectively; P < .001), and females compared to males (median, 18.3 v 21.7 ng/mL, respectively; P = .0005). Baseline plasma 25(OH)D levels were not associated with patient outcome, although given the distribution of plasma levels in this cohort, statistical power for survival analyses were limited.
Vitamin D deficiency is highly prevalent among patients with stage IV colorectal cancer receiving first-line chemotherapy, particularly in black and female patients.
Despite its discovery a hundred years ago, vitamin D has emerged as one of the most controversial nutrients and prohormones of the 21st century. Its role in calcium metabolism and bone health is undisputed but its role in immune function and long-term health is debated. There are clear indicators from in vitro and animal in vivo studies that point to vitamin D’s indisputable role in both innate and adaptive immunity; however, the translation of these findings to clinical practice, including the care of the pregnant woman, has not occurred. Until recently, there has been a paucity of data from randomized controlled trials to establish clear cut beneficial effects of vitamin D supplementation during pregnancy. An overview of vitamin metabolism, states of deficiency, and the results of recent clinical trials conducted in the U.S. are presented with an emphasis on what is known and what questions remain to be answered.
vitamin D; cholecalciferol; calcitriol; pregnancy; neonate
Vitamin D deficiency has been linked to adverse pregnancy outcomes. The purpose of this investigation was to assess total 25-hydroxyvitamin D (25-OH-D) levels at diagnosis of early-onset severe preeclampsia (EOSPE).
Following IRB approval, subjects with EOSPE (< 34 weeks gestation with severe preeclampsia) were enrolled in this case-control investigation in a 1:2 ratio with gestation matched, contemporaneous controls. Demographic and outcome information was collected for each subject. Plasma total 25-OH-D levels were determined by radioimmunoassay and reported in ng/mL. Results were analyzed by Mann-Whitney U and multivariable regression.
Subjects with EOSPE (n=50) were noted to have decreased total 25-OH-D levels relative to healthy controls (n=100; p<0.001). This difference in total 25-OH-D remained significant after controlling for potential confounders.
Total 25-OH-D is decreased at diagnosis of EOSPE. Further study is needed to understand the impact of vitamin D deficiency on pregnancy outcomes.
25-hydroxyvitamin D; adverse pregnancy outcome; preeclampsia; Vitamin D
African Americans generally have lower circulating levels of 25 hydroxyvitamin D (25(OH)D) than whites, attributed to skin pigmentation and dietary habits. Little is known about the genetic determinants of 25(OH)D levels, nor whether the degree of African ancestry associates with circulating 25(OH)D.
Using a panel of 276 ancestry informative genetic markers, we estimated African and European admixture for a sample of 758 African American and non-Hispanic white Southern Community Cohort Study participants. For African Americans, cutpoints of <85%, 85%–95%, and ≥95% defined “low”, “medium”, and “high” African ancestry. We estimated the association between African ancestry and 25(OH)D, and also explored whether vitamin D exposure (sunlight, diet) had varying effects on 25(OH)D levels dependent on ancestry level.
Mean serum 25(OH)D levels among whites and among African Americans of low, medium, and high African ancestry were 27.2, 19.5, 18.3, and 16.5ng/mL, respectively. Serum 25(OH)D was estimated to decrease by 1.0–1.1ng/mL per 10% increase in African ancestry. The effect of high vitamin D exposure from sunlight and diet was 46% lower among African Americans with high African ancestry than among those with low/medium ancestry.
We found novel evidence that the level of African ancestry may play a role in clinical vitamin D status.
This is the first study to describe how 25(OH)D levels vary in relation to genetic estimation of African ancestry. Further study is warranted to replicate these findings and uncover the potential pathways involved.
vitamin D; African Americans; health status disparities; genetics; epidemiology
Asthma exacerbations, most often due to respiratory tract infections, are the leading causes of asthma morbidity and comprise a significant proportion of asthma-related costs. Vitamin D status may play a role in preventing asthma exacerbations.
To assess the relationship between serum vitamin D levels and subsequent severe asthma exacerbations.
We measured 25-hydroxyvitamin D (25(OH)D) levels in serum collected from 1,024 mild to moderate persistent asthmatic children at the time of enrollment in a multi-center clinical trial of children randomized to receiving budesonide, nedocromil, or placebo (as-needed beta-agonists), the Childhood Asthma Management Program. Using multivariable modeling we examined the relationship between baseline vitamin D level and the odds of any hospitalization or emergency department (ED) visit over the 4 years of the trial.
35% of all subjects were vitamin D insufficient, as defined by a level ≤ 30 ng/ml 25(OH)D. Mean vitamin D levels were lowest in African-American subjects, and highest in whites. After adjusting for age, sex, BMI, income, and treatment group, insufficient vitamin D status was associated with a higher odds of any hospitalization or ED visit (odds ratio [OR] 1.5 [95% confidence interval [CI]: 1.1 – 1.9] P =0.01).
Vitamin D insufficiency is common in this population of North American children with mild to moderate persistent asthma, and is associated with higher odds of severe exacerbation over a four year period.
Asthma; Vitamin D; inhaled corticosteroids; asthma exacerbations
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.
We conducted a prospective nested case-control study within the Nurses' 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.
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).
Circulating 25(OH)D levels were not significantly associated with breast cancer risk in this predominantly premenopausal population.
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)2vitamin D [1,25(OH)2D] 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)2D 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 (Ptrend = 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)2D 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.
Experimental evidence suggests that vitamin D has anti-carcinogenic properties; however, a nested case-control study conducted in a population of male Finnish smokers found that higher 25-hydroxyvitamin D [25(OH)D], the best indicator of vitamin D status as determined by the sun and diet, was associated with a significant 3-fold increased risk for pancreatic cancer. We conducted a nested case-control study in the Prostate, Lung, Colorectal, and Ovarian Screening Trial cohort of men and women 55 to 74 years of age at baseline to test whether prediagnostic serum 25(OH)D concentrations were associated with pancreatic cancer risk. Between 1994 and 2006, 184 incident cases of pancreatic adenocarcinoma occurred (follow-up to 11.7 years). Two controls (n = 368) who were alive at the time the case was diagnosed were selected for each case and matched by age, race, sex, and calendar date of blood draw (to control for seasonal variation). We calculated odds ratios (OR) and 95% confidence intervals (95% CI) using conditional logistic regression, adjusting for smoking and body mass index. Vitamin D concentrations were not associated with pancreatic cancer overall (highest versus lowest quintile, >82.3 versus <45.9 nmol/L: OR, 1.45; 95% CI, 0.66–3.15; P trend = 0.49). However, positive associations were observed among subjects with low estimated annual residential solar UBV exposure, but not among those with moderate to high annual exposure (P interaction = 0.015). We did not confirm the previous strong positive association between 25(OH)D and pancreatic cancer; however, the increased risk among participants with low residential UVB exposure is similar.
Vitamin D influences cellular proliferation and proliferation-related breast tissue characteristics, such as mammographic breast density. Little is known about vitamin D status, assessed by serum [25(OH)D], and its relationship to breast density in breast cancer survivors.
Participants were 426 postmenopausal breast cancer survivors from the HEAL (Health, Eating, Activity and Lifestyle) Study. Women from New Mexico, Los Angeles and western Washington were enrolled post-diagnosis. Data for this report are from an examination conducted 24 months post-enrollment. Participants completed health-related questionnaires, gave fasting blood samples and completed height and weight measurements. Serum [25(OH)D] was assayed by radioimmunoabsorbant (RIA) assay. Breast dense area and percent density were measured from post-diagnosis digitized mammograms. Multivariate linear regression tested associations of serum [25(OH)D] with mammographic breast density measures.
Of the 426 participants, 22.8% were African-American, 11.3% were Hispanic and 62.8% were non-Hispanic white. We observed no associations of serum [25(OH)D] with either breast density or breast dense area. Among women with vitamin D deficiency (serum [25(OH)D] <16.0 ng/ml) (n=103), mean percent breast density was 8.0% and among those with sufficient status (n=99) (serum [25(OH)D] ≥ 32.0 ng/ml) mean percent density was 8.5%. Breast dense area averaged 27.2 and 26.2 cm2 for women with vitamin D deficiency and sufficiency, respectively.
Data from this multiethnic cohort of breast cancer survivors do not support the hypothesis that serum vitamin D, [25(OH)D], is associated with breast density in cancer survivors.
Vitamin D; mammography; breast cancer
Objective: Determine prevalence of vitamin D deficiency (VDD) in a diverse group of women presenting for obstetrical care at two community health centers in South Carolina at latitude 32°N. Methods and Design: Any pregnant woman presenting for care at 2 community health centers was eligible to participate. Sociodemographic and clinical history were recorded. A single blood sample was taken to measure circulating 25(OH)D as indicator of vitamin D status [25(OH)D < 20 ng/mL (50 nmol/L deficiency; <32 ng/mL (80 nmol/L) insufficiency]. Total serum calcium, phosphorus, creatinine, and intact parathyroid hormone also were measured. Results: 559 women, [mean age 25.0 ± 5.4 (range 14–43) years] participated: African American (48%), Hispanic (38%), Caucasian/Other (14%). Mean gestational age was 18.5 ± 8.4 (median 14.6, range 6.4–39.6) weeks' gestation. 48% were VDD; an additional 37% insufficient. Greatest degree was in the African American women (68% deficient; 94% insufficient). In multivariable regression, 25(OH)D retained a significant negative association with PTH (P < .001). Conclusions: VDD was high in a diverse group of women, greatest in those of darker pigmentation. The negative correlation between 25(OH)D and PTH confirms their corroborative use as biomarkers of VDD. These findings raise the issue of adequacy of current vitamin D recommendations for pregnant women.
Little is known about vitamin D status in breast cancer survivors. This issue is important since vitamin D influences pathways related to carcinogenesis.
The objective of this report is to describe and understand vitamin D status in a breast cancer survivor cohort.
Data are from the HEAL (Health, Eating, Activity and Lifestyle) Study. Using a cross-sectional design, we examined serum concentrations of [25(OH)D] in 790 breast cancer survivors from western Washington, New Mexico and Los Angeles County. Cancer treatment data were obtained from SEER (Surveillance Epidemiology and End Results) registries and medical records. Fasting blood, anthropometry and lifestyle-habits were collected post-diagnosis and treatment. We examined distributions of [25(OH)D] by race/ethnicity, season, geography and clinical characteristics. Multivariate regression tested associations between [25(OH)D] and stage of disease.
597 (75.6%) of women had low serum [25(OH)D] suggesting vitamin D insufficiency or frank deficiency. The overall mean (SD) was 24.8 (10.4) ng/ml, but lower for African-Americans [18.1 (8.7) ng/ml] and Hispanics [22.1 (9.2) ng/ml]. Women with localized (n=424) or regional (n=182) breast cancer had lower serum [25(OH)D] than women with in situ disease (n=184), (p = 0.03 and p = 0.02, respectively). Multivariate regression models controlled for age, BMI, race/ethnicity, geography, season, physical activity, diet and cancer treatments demonstrated that stage of disease independently predicted serum [25(OH)D] (p=0.02).
In these breast cancer survivors, the prevalence of vitamin D insufficiency was high. Clinicians might consider monitoring vitamin D status in breast cancer patients, together with appropriate treatments, if necessary.
Vitamin D; breast cancer; 25(OH)D; vitamin D insufficiency; ethnicity
To assess the frequency of vitamin D deficiency among men with prostate cancer, as considerable epidemiological, in vitro, in vivo and clinical data support an association between vitamin D deficiency and prostate cancer outcome.
Patients, subjects and methods
The study included 120 ambulatory men with recurrent prostate cancer and 50 with clinically localized prostate cancer who were evaluated and serum samples assayed for 25-OH vitamin D levels. Then 100 controls (both sexes), matched for age and season of serum sample, were chosen from a prospective serum banking protocol. The relationship between age, body mass index, disease stage, Eastern Cooperative Oncology Group performance status, season and previous therapy on vitamin D status were evaluated using univariate and multivariate analyses.
The mean 25-OH vitamin D level was 25.9 ng/mL in those with recurrent disease, 27.5 ng/mL in men with clinically localized prostate cancer and 24.5 ng/mL in controls. The frequency of vitamin D deficiency (< 20 ng/mL) and insufficiency (20–31 ng/mL) was 40% and 32% in men with recurrent prostate; 28% had vitamin D levels that were normal (32–100 ng/mL). Among men with localized prostate cancer, 18% were deficient, 50% were insufficient and 32% were normal. Among controls, 31% were deficient, 40% were insufficient and 29% were normal. Metastatic disease (P = 0.005) and season of blood sampling (winter/spring; P = 0.01) were associated with vitamin D deficiency in patients with prostate cancer, while age, race, performance status and body mass index were not.
Vitamin D deficiency and insufficiency were common among men with prostate cancer and apparently normal controls in the western New York region.
prostate cancer; 25-hydroxy vitamin D; deficiency; season
Rationale: Maternal vitamin D intake during pregnancy has been inversely associated with asthma symptoms in early childhood. However, no study has examined the relationship between measured vitamin D levels and markers of asthma severity in childhood.
Objectives: To determine the relationship between measured vitamin D levels and both markers of asthma severity and allergy in childhood.
Methods: We examined the relation between 25-hydroxyvitamin D levels (the major circulating form of vitamin D) and markers of allergy and asthma severity in a cross-sectional study of 616 Costa Rican children between the ages of 6 and 14 years. Linear, logistic, and negative binomial regressions were used for the univariate and multivariate analyses.
Measurements and Main Results: Of the 616 children with asthma, 175 (28%) had insufficient levels of vitamin D (<30 ng/ml). In multivariate linear regression models, vitamin D levels were significantly and inversely associated with total IgE and eosinophil count. In multivariate logistic regression models, a log10 unit increase in vitamin D levels was associated with reduced odds of any hospitalization in the previous year (odds ratio [OR], 0.05; 95% confidence interval [CI], 0.004–0.71; P = 0.03), any use of antiinflammatory medications in the previous year (OR, 0.18; 95% CI, 0.05–0.67; P = 0.01), and increased airway responsiveness (a ≤8.58-μmol provocative dose of methacholine producing a 20% fall in baseline FEV1 [OR, 0.15; 95% CI, 0.024–0.97; P = 0.05]).
Conclusions: Our results suggest that vitamin D insufficiency is relatively frequent in an equatorial population of children with asthma. In these children, lower vitamin D levels are associated with increased markers of allergy and asthma severity.
Studies indicate that higher sun exposure, especially in the recent past, is associated with reduced risk of non-Hodgkin lymphoma (NHL). Ultraviolet radiation-derived vitamin D may be protective against lymphomagenesis. We examined the relationship between pre-diagnostic serum 25-hydroxyvitamin D (25(OH)D) and lymphoid cancer risk in a case-control study nested within the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study cohort (1985–2002) of 29,133 Finnish male smokers (ages 50 to 69). We identified 270 incident lymphoid cancer cases and matched them individually with 538 controls by birth-year and month of fasting blood draw at baseline. In conditional logistic regression models for 10nmol/L increments or tertile comparisons, serum 25(OH)D was not associated with the risk of overall lymphoid cancers, NHL (N = 208), or multiple myeloma (N = 41). Odds ratios (OR) for NHL for higher tertiles were 0.75 (95% confidence interval (CI), 0.50, 1.14) and 0.82 (95% CI, 0.53, 1.26). The 25(OH)D-NHL association, however, differed by follow-up duration at diagnosis. Cases diagnosed less than 7 years from the baseline showed an inverse association (OR for highest versus lowest tertile = 0.43; 95% CI: 0.23, 0.83; p for trend = 0.01), but not later diagnoses (OR = 1.52; 95% CI: 0.82, 2.80; p for trend = 0.17). The inverse association found for close exposure to diagnosis was not confounded by other risk factors for lymphoma or correlates of 25(OH)D. Although our findings suggest that circulating 25(OH)D is not likely associated with overall lymphoid cancer, they indicate a potentially protective effect on short-term risk of NHL.
25-hydroxyvitamin D; diet; lymphoid neoplasms; nested case-control studies; non-Hodgkin lymphoma; vitamin D
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.
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.
We showed previously that in early-stage non–small-cell lung cancer (NSCLC), serum vitamin D levels and VDR polymorphisms were associated with survival. We hypothesized that vitamin D levels and VDR polymorphisms may also affect survival among patients with advanced NSCLC.
Patients and Methods
We evaluated the relationship between circulating 25-hydroxyvitamin D levels; VDR polymorphisms, including Cdx-2 G>A (rs11568820), FokI C>T (rs10735810), and BsmI C>T (rs144410); and overall survival among patients with advanced NSCLC. Analyses of survival outcomes were performed using the log-rank test and Cox proportional hazards models, adjusting for sex, stage, and performance status.
There were 294 patients and 233 deaths, with median follow-up of 42 months. We found no difference in survival by circulating vitamin D level. The C/C genotype of the FokI polymorphism was associated with improved survival: median survival for C/C was 21.4 months, for C/T was 12.1 months, and for T/T was 15.6 months (log-rank P = .005). There were no significant effects on survival by the Cdx-2 or BsMI polymorphism. However, having increasing numbers of protective alleles was associated with improved survival (adjusted hazard ratio for two or more v zero to one protective alleles, 0.57; 95% CI, 0.41 to 0.79; P = .0008). On haplotype analysis, the G-T-C (Cdx-2-FokI-BsmI) haplotype was associated with worse survival compared with the most common haplotype of G-C-T (adjusted hazard ratio, 1.61; 95% CI, 1.21 to 2.14; P = .001).
There was no main effect of vitamin D level on overall survival in the advanced NSCLC population. The T allele of the VDR FokI>T polymorphism and the G-T-C (Cdx-2-FokI-BsmI) haplotype were associated with worse survival.
Vitamin D has emerged from obscurity, and its effects on various organ systems throughout the body down to the cellular level are being discovered. What was once thought to be a simple hormone affecting only bone and calcium metabolism has shifted. We no longer see vitamin D as a “vitamin” important only in childhood, but as a complex hormone that is involved not only in calcium homeostasis but also in the integrity of the innate immune system. Vitamin D deficiency is linked to inflammatory and long-latency diseases such as multiple sclerosis, rheumatoid arthritis, tuberculosis, diabetes, and various cancers, to name a few. In this review, we trace how we came to view vitamin D and how that view led to one of the largest epidemics of nutrient deficiency beginning in the late 20th century. We then discuss the needs of vitamin D in the context of the breastfeeding mother and her infant and child, why breastfed infants are particularly at risk, and what to do about it.