Baseline Serum 25-hydroxyvitamin Research Articles

Vitamin D3 supplementation in patients with chronic obstructive pulmonary disease (ViDiCO): a multicentre, double-blind, randomised controlled trial

Patients with chronic obstructive pulmonary disease (COPD) often have vitamin D deficiency, which is associated with increased susceptibility to upper respiratory infection-a major precipitant of exacerbation. Multicentre trials of vitamin D supplementation for prevention of exacerbation and upper respiratory infection in patients with COPD are lacking. We therefore investigated whether vitamin D3 (colecalciferol) supplementation would reduce the incidence of moderate or severe COPD exacerbations and upper respiratory infections. We did a randomised, double-blind, placebo-controlled trial of vitamin D3 supplementation in adults with COPD in 60 general practices and four Acute National Health Service Trust clinics in London, UK. Patients were allocated to receive six 2-monthly oral doses of 3 mg vitamin D3 or placebo over 1 year in a 1:1 ratio using computer-generated permuted block randomisation. Participants and study staff were masked to treatment assignment. Coprimary outcomes were time to first moderate or severe exacerbation and first upper respiratory infection. Analysis was by intention to treat. A prespecified subgroup analysis was done to assess whether effects of the intervention on the coprimary outcomes were modified by baseline vitamin D status. This trial is registered with ClinicalTrials.gov, number NCT00977873. 240 patients were randomly allocated to the vitamin D3 group (n=122) and placebo group (n=118). Vitamin D3 compared with placebo did not affect time to first moderate or severe exacerbation (adjusted hazard ratio 0·86, 95% CI 0·60-1·24, p=0·42) or time to first upper respiratory infection (0·95, 0·69-1·31, p=0·75). Prespecified subgroup analysis showed that vitamin D3 was protective against moderate or severe exacerbation in participants with baseline serum 25-hydroxyvitamin D concentrations of less than 50 nmol/L (0·57, 0·35-0·92, p=0·021), but not in those with baseline 25-hydroxyvitamin D levels of at least 50 nmol/L (1·45, 0·81-2·62, p=0·21; p=0·021 for interaction between allocation and baseline serum 25-hydroxyvitamin D status). Baseline vitamin D status did not modify the effect of the intervention on risk of upper respiratory infection (pinteraction=0·41). Vitamin D3 supplementation protected against moderate or severe exacerbation, but not upper respiratory infection, in patients with COPD with baseline 25-hydroxyvitamin D levels of less than 50 nmol/L. Our findings suggest that correction of vitamin D deficiency in patients with COPD reduces the risk of moderate or severe exacerbation. UK National Institute for Health Research.

Adequate Vitamin D Status May Prevent Subsequent Tooth Loss

Article Title and Bibliographic Information Prospective study of serum 25-hydroxy vitamin D and tooth loss. Zhan Y, Samietz S, Holtfreter B, Hannemann A, Meisel P, Nauck M, Volzke H, Wallaschofski H, Dietrich T, Kocher T. J Dent Res 2014;93(7):639-44. Reviewer Amy E. Millen, PhD Purpose/Question The authors analyzed data from a prospective, population-based study in northeast Germany to examine the association between baseline serum 25-hydroxyvitamin D (25[OH)]D) concentrations, a marker of vitamin D status, and the occurrence of tooth loss and the progression of periodontal disease and caries status over a mean 5.9 years of follow-up. Source of Funding German Federal Ministry of Education and Research (BMBF; grant 01ZZ96030, 01ZZ0701). The Ministry of Education, Research, and Cultural Affairs, and the Ministry of Social Affairs of the Federal State of Mecklenburg-West Pomerania (Government). Rheumatoid Arthritis and Periodontal Inflammatory Disease (grant 290246), Seventh Framework Programme of the European Union (Government). GABA, Switzerland, Immunodiagnostic Systems (Industry) Type of Study/Design Cohort study (prospective) Level of Evidence Level 2: Limited-quality, patient-oriented evidence Strength of Recommendation Grade Not applicable

S104 Double-blind Multi-centre Randomised Controlled Trial Of Vitamin D3 Supplementation In Copd (vidico)

Introduction and objectives Inadequate vitamin D status is common in patients with COPD, and it associates with susceptibility to upper respiratory infection (URI) – a major precipitant of exacerbation. Multi-centre trials of vitamin D supplementation for prevention of exacerbation and URI in COPD are lacking. We therefore conducted a multi-centre double-blind randomised placebo-controlled trial of vitamin D supplementation for the prevention of moderate/severe exacerbation and URI in adults with COPD. Methods Two hundred and forty patients were allocated to receive a 2-monthly oral dose of 3 mg vitamin D 3 or placebo for one year. Co-primary outcomes were time to first moderate/severe exacerbation and time to first URI. Secondary outcomes included peak severity and area under the curve for exacerbation symptoms. A pre-specified sub-group analysis was conducted to determine whether effects of the intervention on co-primary outcomes were modified by baseline vitamin D status. This trial is registered with ClinicalTrials.gov (NCT00977873). Results 122 participants were allocated to the intervention arm of the trial, and 118 to the control arm. Vitamin D supplementation did not influence time to first exacerbation (HR 0.86, 95% CI 0.60–1.24, p = 0.42) or time to first URI (HR 0.95, 95% CI 0.69–1.31, p = 0.75) in the study population as a whole, but it did reduce peak severity (p = 0.042) and area under the curve (p = 0.032) for exacerbation symptoms. Pre-specified sub-group analysis revealed that vitamin D supplementation was protective against moderate/severe exacerbation among the 148 participants with baseline serum 25-hydroxyvitamin D (25[OH]D) concentration Conclusions Vitamin D supplementation protected against moderate/severe exacerbation, but not upper respiratory infection, in COPD patients with baseline 25(OH)D

25-Hydroxyvitamin D levels and survival in advanced pancreatic cancer: findings from CALGB 80303 (Alliance).

Data from animal and cell-line models suggest that vitamin D metabolism plays an important role in pancreatic tumor behavior. Although vitamin D deficiency has been implicated in numerous cancers, the vitamin D status of patients with advanced pancreatic cancer and the effect of baseline vitamin D levels on survival are unknown. Participants in this correlative study (CALGB 151006) were enrolled in CALGB 80303, which was a randomized trial of patients with advanced pancreatic cancer that demonstrated no difference in overall survival (OS) among patients treated with gemcitabine plus placebo vs gemcitabine plus bevacizumab. We measured baseline serum 25-hydroxyvitamin D (25[OH]D) levels and examined associations between baseline 25(OH)D levels and progression-free survival and OS using the Cox rank score test. All statistical tests were two-sided. Of 256 patients with available serum, the median 25(OH)D level was 21.7ng/mL (range 4 to 77). 44.5% of patients were vitamin D deficient (25[OH]D <20ng/mL), and 32.4% were insufficient (25[OH]D ≥20 and <30ng/mL). 25(OH)D levels were lower in black patients compared with white patients, and patients of other/undisclosed race (10.7 vs 22.4 vs 20.9ng/mL, P < .001). Baseline 25(OH)D levels were not associated with PFS (HR = 1.00, 95% CI = 0.99 to 1.01, P = .60) or OS (HR = 1.00, 95% CI = 0.99 to 1.01, P = .95). Vitamin D deficiency was highly prevalent among patients with a new diagnosis of advanced pancreatic cancer. Black patients had statistically significantly lower 25(OH)D levels than white patients. In this cohort of patients with advanced pancreatic cancer receiving gemcitabine-based chemotherapy, baseline 25(OH)D levels were not associated with PFS or OS.

25-hydroxyvitamin D and increased all-cause mortality in very old women: the Newcastle 85+ study.

ObjectiveTo investigate the associations between low and high concentrations of baseline serum 25-hydroxyvitamin D [25(OH)D] and all-cause mortality in very old (≥85 years) men and women over 6 years.Design, setting and subjectsProspective mortality data from 775 participants in the Newcastle 85+ Study were analysed for survival in relation to 25(OH)D (season-specific quartiles and predefined cut-off values) and sex using Cox proportional hazards models. The models were fitted to the entire and restricted (nonusers of vitamin D-containing supplements and medication) cohorts.ResultsFor the entire cohort, mortality was higher in both the lowest and highest 25(OH)D season-specific quartiles [SQ1: hazard ratio (HR) 1.31, 95% confidence interval (CI) 1.01–1.69, P = 0.04; SQ4: HR 1.44, 95% CI 1.12–1.85, P = 0.004] compared with the combined middle quartiles (SQ2 + SQ3), after adjustment for sociodemographic factors. The increased risk for the highest quartile remained significant after further adjustment for lifestyle variables (SQ4: HR 1.37, 95% CI 1.06–1.77, P = 0.02) and was seen only in women in sex-specific analyses. Similarly, in sensitivity analyses with predefined 25(OH)D cut-off values, the highest 25(OH)D concentration (≥75 nmol L−1) was associated with a 2.4-fold increased risk of mortality in women (restricted cohort) after adjusting for all covariates.ConclusionLow and high season-specific 25(OH)D quartiles were associated with increased risks of mortality over 6 years in the very old; this effect was particularly noticeable in women, including those who reported taking vitamin D-containing supplements/medication.

Baseline Serum 25-Hydroxyvitamin D Levels in Men Undergoing Radical Prostatectomy: Is There An Association With Adverse Pathologic Features?

Introduction/BackgroundThe purpose of this study was to evaluate the prevalence of vitamin D (VitD) deficiency in men undergoing radical prostatectomy and determine whether an association exists between preoperative VitD levels and adverse pathologic features. Patients and MethodsPatients scheduled to undergo radical prostatectomy for clinically localized disease from January to August 2012 were prospectively followed and those with available preoperative serum 25-hydroxyvitamin D levels were included. Men with a known diagnosis of VitD deficiency or taking VitD supplementation were excluded. Cox regression analysis was performed to determine whether preoperative VitD level is predictive of adverse pathologic outcomes. ResultsOne hundred consecutive men were included. Mean age was 62 (range, 42-79) years and mean VitD level was 26 (range, 6-57) ng/mL. Overall, 65 men (65%) had suboptimal levels of VitD (< 30 ng/mL), and 32 (32%) had deficiency (< 20 ng/mL). There was no significant correlation between VitD and age (P = .5). In logistic regression analysis, VitD level was not predictive of pathologic Gleason (P = .11), pathologic stage (P = .7), or positive margin status (P = .8). ConclusionThe association between VitD and prostate cancer has been controversial and data suggesting an increased risk of aggressive cancer in men with low levels of VitD have been inconsistent. We found that baseline preoperative VitD level was not associated with any adverse pathologic features. However, VitD deficiency is a common finding in this population, although unrelated to patient age. These results represent the first time the correlation between VitD and prostate cancer has been evaluated in a cohort of men undergoing radical prostatectomy.

Changes in blood pressure and lipid levels in young women consuming a vitamin D-fortified skimmed milk: a randomised controlled trial.

Vitamin D exerts a variety of extra-skeletal functions. Aim: to know the effects of the consumption of a vitamin D-fortified skimmed milk on glucose, lipid profile, and blood pressure in young women. Methods: a randomised, placebo-controlled, double-blind parallel-group trial of 16 weeks duration was conducted in young women with low iron stores who consumed a skimmed milk fortified with iron and 200 IU/day (5 μg) of vitamin D (D-fortified group, n = 55), or a placebo without vitamin D (D-placebo group, n = 54). A reference group (n = 56) of iron-sufficient women was also recruited. Results: baseline serum 25-hydroxyvitamin D was inversely correlated with total-cholesterol (r = −0.176, p = 0.023) and low density lipoprotein-cholesterol (LDL-chol) (r = −0.176, p = 0.024). During the assay, LDL-cholesterol increased in the D-placebo group (p = 0.005) while it tended to decrease in the D-fortified group (p = 0.07). Neither group displayed changes in total-cholesterol, high density lipoprotein-cholesterol (HDL-chol), triglycerides or glucose levels. Systolic (p = 0.017) and diastolic (p = 0.010) blood pressure decreased during the assay in the D-fortified group without significant differences compared to the D-placebo. Conclusion: consumption of a dairy product fortified with vitamin D reduces systolic and diastolic blood pressure but does not change lipid levels in young women.

Effects of vitamin D supplements on bone mineral density: a systematic review and meta-analysis

Findings from recent meta-analyses of vitamin D supplementation without co-administration of calcium have not shown fracture prevention, possibly because of insufficient power or inappropriate doses, or because the intervention was not targeted to deficient populations. Despite these data, almost half of older adults (older than 50 years) continue to use these supplements. Bone mineral density can be used to detect biologically significant effects in much smaller cohorts. We investigated whether vitamin D supplementation affects bone mineral density. We searched Web of Science, Embase, and the Cochrane Database, from inception to July 8, 2012, for trials assessing the effects of vitamin D (D3 or D2, but not vitamin D metabolites) on bone mineral density. We included all randomised trials comparing interventions that differed only in vitamin D content, and which included adults (average age >20 years) without other metabolic bone diseases. We pooled data with a random effects meta-analysis with weighted mean differences and 95% CIs reported. To assess heterogeneity in results of individual studies, we used Cochran's Q statistic and the I(2) statistic. The primary endpoint was the percentage change in bone mineral density from baseline. Of 3930 citations identified by the search strategy, 23 studies (mean duration 23·5 months, comprising 4082 participants, 92% women, average age 59 years) met the inclusion criteria. 19 studies had mainly white populations. Mean baseline serum 25-hydroxyvitamin D concentration was less than 50 nmol/L in eight studies (n=1791). In ten studies (n=2294), individuals were given vitamin D doses less than 800 IU per day. Bone mineral density was measured at one to five sites (lumbar spine, femoral neck, total hip, trochanter, total body, or forearm) in each study, so 70 tests of statistical significance were done across the studies. There were six findings of significant benefit, two of significant detriment, and the rest were non-significant. Only one study showed benefit at more than one site. Results of our meta-analysis showed a small benefit at the femoral neck (weighted mean difference 0·8%, 95% CI 0·2-1·4) with heterogeneity among trials (I(2)=67%, p<0·00027). No effect at any other site was reported, including the total hip. We recorded a bias toward positive results at the femoral neck and total hip. Continuing widespread use of vitamin D for osteoporosis prevention in community-dwelling adults without specific risk factors for vitamin D deficiency seems to be inappropriate. Health Research Council of New Zealand.

Vitamin D3 Supplementation and Upper Respiratory Tract Infections in a Randomized, Controlled Trial

Randomized controlled trials testing the association between vitamin D status and upper respiratory tract infection (URTI) have given mixed results. During a multicenter, randomized controlled trial of colorectal adenoma chemoprevention, we tested whether 1000 IU/day vitamin D(3) supplementation reduced winter episodes and duration of URTI and its composite syndromes, influenza-like illness (ILI; fever and ≥2 of sore throat, cough, muscle ache, or headache) and colds (no fever, and ≥2 of runny nose, nasal congestion, sneezing, sore throat, cough, swollen or tender neck glands). The 2259 trial participants were aged 45-75, in good health, had a history of colorectal adenoma, and had a serum 25-hydroxyvitamin D level ≥12 ng/mL. They were randomized to vitamin D(3) (1000 IU/day), calcium (1200 mg/day), both, or placebo. Of these, 759 participants completed daily symptom diaries. Secondary data included semiannual surveys of all participants. Among those who completed symptom diaries, supplementation did not significantly reduce winter episodes of URTI (rate ratio [RR], 0.93; 95% confidence interval [CI], .79-1.09) including colds (RR, 0.93; 95% CI, .78-1.10) or ILI (RR, 0.95; 95% CI, .62-1.46), nor did it reduce winter days of illness (RR, 1.13; 95% CI, .90-1.43). There was no significant benefit according to adherence, influenza vaccination, body mass index, or baseline vitamin D status. Semiannual surveys of all participants (N = 2228) identified no benefit of supplementation on ILI (odds ratio [OR], 1.14; 95% CI, .84-1.54) or colds (OR, 1.03; 95% CI, .87-1.23). Supplementation with 1000 IU/day vitamin D(3) did not significantly reduce the incidence or duration of URTI in adults with a baseline serum 25-hydroxyvitamin D level ≥12 ng/mL.

Vitamin D, Muscle Function, and Falls in Older Adults: Does Reduced Deposition of Intramuscular Adipose Tissue Influence the Relationship?

In addition to its established role in bone and mineral homeostasis, there is growing evidence for a role of vitamin D in skeletal muscle physiology. Vitamin D deficiency has long been implicated in muscle function. Observational studies report an increase in muscle weakness and falls in vitamin D deficiency. Clinical trials also suggest that vitamin D supplementation may improve muscle strength and balance and reduce risk of falls in those with vitamin D deficiency; however, there is controversy regarding these effects because the current evidence base is restricted by highly heterogeneous studies (1). Vitamin D deficiency may be associated with preferential atrophy of type II muscle fibers, and this potentially explains the association of vitamin D with reduced strength and increased risk of falls. However, vitamin Dassociated improvements in skeletal muscle function are unlikely to be explained by muscle hypertrophy alone. For example, we have previously reported that spanning almost 3 years in a population-based study of older adults, higher baseline serum 25-hydroxyvitamin D (25OHD) was associated with improved maintenance of lower-limb strength but not appendicular lean mass assessed by dualenergy x-ray absorptiometry (2). If vitamin D exerts a direct effect on human skeletal muscle, it follows that vitamin D receptors (VDRs) should be located in the skeletal muscle. Research has indicated that 1,25-dihydroxyvitamin D3 (1,25OH2D3) binds to a nuclear receptor in muscle and promotes de novo protein synthesis, and in support of this, VDR-knockout mice exhibit reduced muscle fiber size and poor vestibular function. Studies using several different antibodies have reported that the VDR is expressed in adult muscle tissue, but this is currently controversial; the VDR was reported to be undetectable in normal and mature mouse, rat, and human skeletal muscle tissue using a highly sensitive and specific VDR antibody (3). The present questions surrounding the VDR are whether the VDR is indeed expressed in skeletal muscle in vivo and whether it exists in fully differentiated adult muscle or only in immature muscle cells as suggested by in vitro studies (1). A recent Endocrine Society Scientific Statement has concluded that there is controversy regarding the role of vitamin D in skeletal muscle function but that there is evidence that effects of vitamin D on muscle function may be both direct and indirect. The statement suggests that the effects of vitaminDonmuscle functionmaybeexplainedbyvitamin D-related changes in calcium absorption, as reported by Ebeling et al (4), rather than a direct interaction with skeletal muscle VDR (3). We propose there may be an additional mechanism through which vitamin D exerts an indirect effect, which may be unrelated to a skeletal muscle VDR; reductions in intraand intermuscular adipose tissue (IMAT) deposition. A characteristic of aging skeletal muscle is increased deposition of adipose tissue within and between muscle fibers, and IMAT appears to have independent and deleterious outcomes for skeletal muscle function. It has been proposed that IMAT may contribute to declines in muscle function by altering the orientation and hence force production capabilities of skeletal muscle and by secreting inflammatory cytokines leading to systemic low-level inflammation that has been associated with reduced force production (5). Observational studies have reported an association between IMAT and functional decline in older adults. Among well-functioning participants of the U.S. Health, Aging and Body Composition study, IMAT at the

Effect of short-term vitamin D supplementation on markers of vascular health in South Asian women living in the UK – A randomised controlled trial

ObjectiveLow vitamin D levels and risk factors for vascular disease are both common in South Asian women. This trial evaluated whether vitamin D supplementation could improve markers of vascular health in South Asian women with low 25-hydroxyvitamin D levels. MethodsParallel-group, double-blind, randomised placebo-controlled trial. Healthy South Asian women with baseline serum 25-hydroxyvitamin D levels of <75 nmol/L were randomised to receive a single dose of 100,000 units oral vitamin D3 or matching placebo. Outcomes were measured at baseline, 4 and 8 weeks. The primary outcome was change in endothelial function measured using brachial artery flow-mediated dilatation. Secondary outcomes included blood pressure, arterial stiffness, microvascular function measured using laser Doppler iontophoresis, insulin resistance, serum lipids, circulating markers of inflammation, thrombosis and adipokines. Results50 women were randomised, 25 to each group. Mean age was 41 years; mean baseline 25-hydroxyvitamin D level was 27 nmol/L. 25-Hydroxyvitamin D levels rose in the vitamin D group relative to the placebo group by 4 weeks (16 nmol/L, 95% CI 11 to 21, p < 0.001). There was no improvement in flow-mediated dilatation in the vitamin D group relative to placebo at 4 weeks (0.1%, 95% CI −0.9 to 1.1, p = 0.84) or 8 weeks (0.0%, 95% CI −1.4 to 1.4, p = 0.98). There was no improvement in cholesterol, insulin resistance or markers of inflammation. Both platelet activation inhibitor-1 and tissue plasminogen activator levels fell significantly in the vitamin D group relative to placebo at 8 weeks. ConclusionA single large dose of vitamin D3 did not improve blood pressure or endothelial function in South Asian women with low baseline 25-hydroxyvitamin D levels. Trial registrationISRCTN75081811.

Abstract 2196: Genetic correlates of serum 25-hydroxyvitamin D levels and response to vitamin D supplementation.

Abstract Epidemiological studies indicate that vitamin D has antineoplastic effects in the colorectum and suggest that vitamin D supplementation may be a promising chemopreventative approach to reduce risk of colorectal cancer. Thus, it is important to consider how genetic factors may modify vitamin D status and response to vitamin D supplementation. We investigated this question among 2,259 participants randomized in the Vitamin D/Calcium Polyp Prevention Study, an on-going, double-blind, placebo-controlled clinical trial of supplementation with vitamin D3 (1000 IU/day) and/or calcium carbonate (1200 mg elemental calcium/day) for the prevention of colorectal adenomas. Candidate single nucleotide polymorphisms (SNPs) were genotyped in or near seven genes involved in vitamin D or calcium metabolism, transport or signaling. Excluding SNPs with MAF&amp;lt;5% and r2&amp;gt;0.8, 23 SNPs were analyzed in vitamin D binding protein (GC), 25-hydroxylase (CYP2R1), 24-hydroxylase (CYP24A1), 1-hydroxylase (CYP27B1), 7-dehydrocholesterol reductase (DHCR7), vitamin D receptor (VDR), and calcium-sensing receptor (CaSR). These included 5 SNPs previously associated with circulating 25-hydroxyvitamin D levels in genome-wide association studies (GWAS): rs2282679, rs12785878, rs3829251, rs10741657 and rs6013897. Linear regression was used to estimate associations with baseline serum 25-hydroxyvitamin D levels and with levels of 25-hydroxyvitamin D achieved after approximately one year of vitamin D supplementation in the trial after adjusting for baseline levels. Analyses were restricted to non-Hispanic white participants (82%) to avoid population stratification and additive genetic models were used. Baseline 25-hydroxyvitamin D was statistically significantly associated with genotype at 3 GWAS hits in GC, DHCR7 and CYP2R1 and at 5 other SNPs in GC, CYP2R1 and CYP24A1. When response to supplementation was investigated, compliance with pill taking was taken into account by restricting analyses to optimally compliant subjects. Genotype at 3 SNPs in VDR, CYP2R1, and CYP24A1 statistically significantly modified the 25-hydroxyvitamin D level achieved with vitamin D supplementation. In conclusion, we have identified variation in or near key vitamin D and calcium pathway genes that modify serum 25-hydroxyvitamin D status and the response to supplementation with vitamin D. This research may identify individuals at risk for poor response to vitamin D supplementation. The public health significance of this work is substantial due to the prevalence of vitamin D insufficiency and the high incidence of colorectal cancer, osteoporosis, and other common diseases associated with poor vitamin D status. Citation Format: Elizabeth L. Barry, Leila A. Mott, Janet L. Peacock, Judith R. Rees, John A. Baron. Genetic correlates of serum 25-hydroxyvitamin D levels and response to vitamin D supplementation. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2196. doi:10.1158/1538-7445.AM2013-2196

Supplementation with 1000 IU vitamin D/d leads to parathyroid hormone suppression, but not increased fractional calcium absorption, in 4–8-y-old children: a double-blind randomized controlled trial

The effects of vitamin D supplementation in healthy prepubertal children on physiologic outcomes have not been investigated. The objective was to evaluate the effects of supplementation with 1000 IU vitamin D(3)/d on calcium absorption. In a double-blind, placebo-controlled trial, we randomly assigned 64 children to 1000 IU vitamin D(3)/d (n = 32) or placebo (n = 32) for 8 wk. Stable isotopes were used to assess calcium absorption. The main outcome measure was calcium absorption before and after supplementation. All of the data are shown as means ± SDs. At baseline, vitamin D intake was 221 ± 79 IU/d and calcium intake was 830 ± 197 mg/d. Baseline serum 25-hydroxyvitamin D [25(OH)D] was not significantly correlated with fractional or total calcium absorption. After 8 wk, with baseline values used as a covariate, no differences were seen in fractional or total calcium absorption based on supplementation group (P = 0.75 and 0.36, respectively). Supplemented children had a significant increase in 25(OH)D concentrations (from 27.7 ± 7.4 to 36.0 ± 10.3 ng/mL; P < 0.0001) and a decrease in parathyroid hormone (from 21.4 ± 10.4 to 12.9 ± 7.1 pg/mL; P < 0.001); no significant changes in the placebo group were observed. No adverse side effects were noted in either group. Vitamin D(3) supplementation at 1000 IU/d increases 25(OH)D and decreases parathyroid hormone in children with average vitamin D intakes below the dietary recommendations of the Institute of Medicine. However, no significant effects of this change on calcium absorption occurred. This trial was registered at clinicaltrials.gov as NCT 00868738.

Memory, Mood, and Vitamin D in Persons with Parkinson's Disease

Research in recent years has suggested a role of vitamin D in the central nervous system. The final converting enzyme and the vitamin D receptor are found throughout the human brain. From animal studies vitamin D appears important in neurodevelopment, up-regulation of neurotrophic factors, stabilization of mitochondrial function, and antioxidation. To examine the relationship between serum vitamin D and neuropsychiatric function in persons with Parkinson's disease (PD). This is an add-on study to a longitudinal study following neuropsychiatric function in persons with PD. Baseline neuropsychiatric performance and serum 25-hydroxyvitamin D were examined for 286 participants with PD. Measures of global cognitive function (MMSE, MOCA, Mattis Dementia Scale), verbal memory (Hopkins Verbal Learning Test), fluency (animals, vegetables, and FAS words), visuospatial function (Benton Line Orientation), executive function (Trails Making Test and Digit-Symbol Substitution), PD severity (Hoehn & Yahr and Unified Parkinson's Disease Rating Scale) and depression (Geriatric Depression Scale (GDS)) were administered. Multivariate linear regression assessed the association between vitamin D concentration and neuropsychiatric function, in the entire cohort as well as the non-demented and demented subsets. Using a multivariate model, higher vitamin D concentrations were associated with better performance on numerous neuropsychiatric tests in the non-demented subset of the cohort. Significant associations were specifically found between vitamin D concentration and verbal fluency and verbal memory (t = 4.31, p < 0.001 and t = 3.04, p = 0.0083). Vitamin D concentrations also correlated with depression scores (t = -3.08, p = 0.0083) in the non-demented subset. Higher plasma vitamin D is associated with better cognition and better mood in this sample of PD patients without dementia. Determination of causation will require a vitamin D intervention study.

Serum 25-Hydroxyvitamin D Levels and Incident Asthma in Adults: The HUNT Study

The impact of low vitamin D status on asthma development is unclear. The authors investigated the relation between the baseline serum 25-hydroxyvitamin D (25(OH)D) level and incident asthma in adults, including possible effect modification by allergy status, using allergic rhinitis as a proxy measure. A cohort of 25,616 Norwegian adults aged 19-55 years participated in 2 surveys of the Nord-Trøndelag Health Study known as HUNT 2 (1995-1997) and HUNT 3 (2006-2008). Of this cohort, a nested case-control study included 584 new-onset asthma cases and 1,958 nonasthma controls whose baseline serum 25(OH)D levels were measured. After adjustment for potential asthma risk factors, the baseline serum level of 25(OH)D (<50 nmol/L) was not significantly associated with asthma in either women (adjusted odds ratio = 0.94, 95% confidence interval (CI): 0.67, 1.32) or men (adjusted odds ratio = 1.47, 95% CI: 0.93, 2.32). In men, allergic rhinitis modified the association with the adjusted odds ratio being 0.87 (95% CI: 0.36, 2.06) among men with allergic rhinitis and 2.32 (95% CI: 1.06, 5.10) among men without allergic rhinitis. The serum 25(OH)D level was not associated with incident asthma in women, regardless of allergy status. Low vitamin D status was not significantly associated with incident asthma in most adults, but it may have increased risk among men without allergy.

Prospective Study of Serum 25-Hydroxyvitamin D Concentration and Mortality in a Chinese Population

Prospective epidemiologic data on the association between vitamin D and mortality are limited, particularly in Asian populations. Among subjects in Linxian, China, the authors aimed to test whether baseline serum 25-hydroxyvitamin D (25(OH)D) concentrations in a prospective cohort were associated with all-cause mortality and cause-specific mortality rates over 24 years of follow-up (1986-2010). Serum 25(OH)D concentrations were measured in 1,101 subjects using an immunoassay. Hazard ratios and 95% confidence intervals were calculated using Cox regression models that were adjusted for age, sex, tobacco smoking, alcohol drinking, and hypertension. The 25th, 50th, and 75th percentile concentrations of 25(OH)D were 19.6, 31.9, and 48.4 nmol/L, respectively. During follow-up, 793 subjects died, including 279 who died of cerebrovascular accident, 217 who died of cancer, and 200 cardiovascular disease deaths. All-cause mortality was not associated with 25(OH)D concentrations using continuous models (for every 15 nmol/L, hazard ratio = 1.01, 95% confidence interval: 0.97, 1.05) or quartile models (fourth vs. first quartiles, hazard ratio = 1.06, 95% confidence interval: 0.87, 1.30; P for trend = 0.731). The authors also found no association with the cause-specific mortality outcomes. Results were similar for men and women. This study showed that prediagnostic serum 25(OH)D concentrations were not associated with all-cause or cause-specific mortality rates in this Chinese population who had low levels of vitamin D.

The Effects of Supraphysiologic Doses of Vitamin D3 in Conjunction With Teriparatide on Bone Mineral Density in Two Postmenopausal Females With Severe Osteoporosis

Teriparatide was approved by the FDA in 2002 for the treatment of osteoporosis in postmenopausal women who are at high risk for fractures. Previous studies involving the use of teriparatide in conjunction with vitamin D and calcium supplementation have suggested that sufficient vitamin D levels may not be a requirement to achieve an effective response to teriparatide. We present a case of two postmenopausal females with severe osteoporosis who were treated with teriparatide along with calcium and supraphysiologic doses of vitamin D, as illustrated by an increase from their baseline serum 25-hydroxyvitamin D concentrations. Both patients experienced an increase in bone mineral density that was significantly higher than what has been seen in prior studies of teriparatide administration in conjunction with physiologic doses of vitamin D. These findings suggest that administering supraphysiologic doses of vitamin D may in fact potentiate the effects of teriparatide in postmenopausal females with osteoporosis, resulting in larger increases in bone mineral density than would otherwise be expected. doi:10.4021/jem104 w

Vitamin D deficiency and changes in serum vitamin D levels with treatment among tuberculosis patients in South Korea

Vitamin D deficiency has been reported to be associated with the development of active tuberculosis (TB), but many discrepancies exist among studies. The aims of this study were to compare the frequency of vitamin D deficiency in a Korean population of TB patients and control subjects, and to monitor the changes in vitamin D levels during TB treatment. Patients with newly diagnosed TB were prospectively enrolled. In addition, healthy volunteers or patients with diseases other than TB were enrolled as controls. Baseline serum 25-hydroxyvitamin D (25-OHD) levels were measured in both groups and compared. In the TB patients, measurements of serum 25-OHD were repeated 1 month after the initiation of treatment and again after completion of treatment. In total, 116 patients with TB and 86 control subjects were recruited. The median 25-OHD concentration was not different in TB patients at diagnosis (13.9 ng/mL; interquartile range (IQR) 8.80-21.8) compared with control subjects (13.2 ng/mL; IQR 9.6-19.3) (P = 0.97). The frequency of vitamin D deficiency (≤ 10 ng/mL) was also not different in TB patients (36.2%) compared with controls (27.3%) (P = 0.21). In TB patients, the median 25-OHD concentration decreased significantly during treatment, to 12.5 ng/mL at 1 month and 11.0 ng/mL on completion of treatment (P = 0.01). Vitamin D levels do not appear to be associated with the development of TB in the Korean population. The median 25-OHD concentration decreased after treatment for TB.

No change in calcium absorption in adult Pakistani population before and after vitamin D administration using strontium as surrogate

Vitamin D, parathyroid hormone levels and calcium absorption was assessed before and after cholecalciferol using Strontium as a surrogate. Increase in 25OHD, lowering of iPTH with no effect on Sr absorption was seen, suggesting the possibility that maximal Ca absorption had already been achieved in these volunteers. This paper discusses the determination of calcium (Ca) absorption, using strontium (Sr) as a surrogate, before and after a single IM injection of vitamin D(3) (600,000 IU). Baseline serum 25-hydroxyvitamin D (25OHD), Sr, Ca, P, and intact parathyroid hormone (iPTH) were determined in 53 fasting volunteers, followed by administrating (PO) 0.03 mM (4.8 mg/kg) SrCl(2) and collecting blood at 0.5, 1 and 4 h to determine the absorption (AUC(0 → t )) of Sr. Following the initial absorption test, volunteers received a single IM injection of 600,000 IU vitamin D(3). Two months later, the fasting serum and the Sr absorption test were repeated, as described above. The IM injection of vitamin D(3) caused a significant increase in fasting 25OHD (from 43.5 ± 19 to 66.1 ± 19.1 nmol/L (p < 0.001)) and a trend toward lower serum iPTH (from 59.8 ± 27.8 to 53 ± 31 ng/L). Fasting serum Ca and P remained unchanged. A higher 25OHD level failed (p = 0.32) to translate into a higher rate of Sr absorption. AUC(0 → 4 h) were almost identical before and after the IM injection of vitamin D(3). A single vitamin D(3) injection of 600,000 IU significantly increase mean 25OHD concentration and tended to lower iPTH concentrations in volunteers with initially low 25OHD status, suggesting to utilize this simple form of treatment to improve vitamin D status and to have a possible biological effect on Ca homeostasis. However, we found no obvious effect on Sr absorption, suggesting the possibility that maximal vitamin D-dependent Ca absorption had already been achieved in these volunteers at a lower vitamin D status.

Effect of supplementation with cholecalciferol and calcium on 2-y bone mass accrual in HIV-infected children and adolescents: a randomized clinical trial

Skeletal abnormalities have been reported in HIV-infected children and adolescents. Although the etiology is not well understood, vitamin D deficiency may be involved. The study objective was to evaluate the effect of vitamin D and calcium supplementation on bone mass accrual in HIV-infected youth. Perinatally HIV-infected children were randomly assigned to receive vitamin D (100,000 IU cholecalciferol given every 2 mo) and calcium (1 g/d) (supplemented group) or double placebo (placebo group) for 2 y. The total-body bone mineral content (TBBMC), total-body bone mineral density (TBBMD), spine bone mineral content (SBMC), and spine bone mineral density (SBMD) were assessed by using dual-energy X-ray absorptiometry at baseline and at 2 annual follow-up visits. Fifty-nine participants, aged 6-16 y, were randomly assigned to either the supplemented (n = 30) or the placebo (n = 29) group. At enrollment, supplemented and placebo groups did not differ with respect to age, sex, dietary intakes of vitamin D and calcium, mean baseline serum 25-hydroxyvitamin D [25(OH)D] concentration, TBBMC, TBBMD, SBMC, or SBMD. Significant increases in serum 25(OH)D were observed in the supplemented group but not in the placebo group. TBBMC, TBBMD, SBMC, and SBMD increased significantly at 1 and 2 y in both groups. No between-group differences were observed at any time before or after adjustment for stage of sexual maturation by mixed linear model analysis. One gram of calcium per day and oral cholecalciferol at a dosage of 100,000 IU every 2 mo administered to HIV-infected children and adolescents did not affect bone mass accrual despite significant increases in serum 25(OH)D concentrations. This trial was registered at clinicaltrials.gov as NCT00724178.