Vitamin D
IVitamin D has several important roles e.g. it helps control the amount of calcium and phosphate in your body, which are needed to keep your bones and teeth healthy. Having too little vitamin D (a deficiency) can damage the way your body absorbs calcium and phosphorus. In children, this can lead to rickets, a condition that can cause bone deformities, such as bowed legs. In adults, vitamin D deficiency can cause osteomalacia (weak bones), which can make bones painful and tender. Where do I get vitamin D? You get most of your vitamin D from sunlight on your skin. This is because the vitamin forms under the skin in reaction to sunlight -10 and 15 minutes in the UK summer sun, without sunscreen several times a week is probably a safe balance between adequate vitamin D levels and any risk of skin cancer”. Vitamin D is also found in a small number of foods, including: oily fish, eggs, fortified foods that have had vitamin D added to them, such as margarine, breakfast cereals and powdered milk
Safety and tolerability of Vitamin D3 5000 IU/day in epilepsy Christopher M.DeGiorgio Dieter Hertling Ashley Curtis Diana Murray Daniela Markovic Abstract Purpose: Preclinical and early clinical research indicates that Vitamin D3 may reduce seizures in both animal models and open-label clinical trials. Methods: This is an initial report of an ongoing pilot study of oral Vitamin D3 5000 IU/day in subjects with drugresistant epilepsy. After Institutional Review Board (IRB) approval and informed consent, subjects with ;less than one focal onset or generalized tonic–clonic seizure per month were enrolled. Subjects entered a 4-week baseline, followed by a 12-week treatment period. Serum 25, OH Vitamin D3, Blood Urea Nitrogen (BUN), creatinine, and calcium levels were monitored at baseline and at 6 and 12 weeks. Results: High-dose Vitamin D3 5000 IU/day was well tolerated. Serum 25, OH Vitamin D3 levels increased significantly at six and twelve weeks. Vitamin D insufficiency, defined as a 25, OH Vitamin D3 level of <20 ng/ml normalized in all subjects with insufficient vitamin D levels. Median seizure frequency declined from 5.18 seizures per month to 3.64 seizures per month at 6 weeks and to 4.2 seizures per month at 12 weeks. The median percent change in seizure frequency was =26.9% at six weeks, and =10.7% at 12 weeks (not significant, Wilcoxon Signed Rank Test, P >0.34). Conclusions: High-dose oral Vitamin D3, 5000 IU/day was safe and well tolerated in subjects with epilepsy. Vitamin D levels increased significantly at 6 and 12 weeks but never exceeded potentially toxic levels, defined as >100 ng/ml. To reduce variability, we will now recruit subjects who only have three or more seizures per month. Source : Epilepsy & Behaviour Link to Full Article Molecular Changes in Diabetic Wound Healing following Administration of Vitamin D and Ginger Supplements: Biochemical and Molecular Experimental Study Hadeel A. Al-Rawaf,1,2 Sami A. Gabr,1 and Ahmad H. Alghadir Abstract Background. Circulating micro-RNAs are differentially expressed in various tissues and could be considered as potential regulatory biomarkers for T2DM and related complications, such as chronic wounds. Aim. In the current study, we investigated whether ginger extract enriched with [6]-gingerol-fractions either alone or in combination with vitamin D accelerates diabetic wound healing and explores underlying molecular changes in the expression of miRNA and their predicted role in diabetic wound healing. Methods. Diabetic wounded mice were treated with [6]-gingerol-fractions (GF) (25 mg/kg of body weight) either alone or in combination with vitamin D (100 ng/kg per day) for two weeks. Circulating miRNA profile, fibrogenesis markers, hydroxyproline (HPX), fibronectin (FN), and collagen deposition, diabetic control variables, FBS, HbA1c, C-peptide, and insulin, and wound closure rate and histomorphometric analyses were, respectively, measured at days 3, 6, 9, and 15 by RT–PCR and immunoassay analysis. Results. Treatment of diabetic wounds with GF and vitamin D showed significant improvement in wound healing as measured by higher expression levels of HPX, FN, collagen, accelerated wound closure, complete epithelialization, and scar formation in short periods (11-13 days, (P<0.01). On a molecular level, three circulating miRNAs, miR-155, miR-146a, and miR-15a, were identified in diabetic and nondiabetic skin wounds by PCR analysis. Lower expression in miR-155 levels and higher expression of miR-146a and miR-15a levels were observed in diabetic skin wounds following treatment with gingerols fractions and vitamin D for 15 days. The data showed that miRNAs, miR-146a, miR-155, and miR-15a, correlated positively with the expression levels of HPX, FN, and collagen and negatively with FBS, HbA1c, C-peptide, and insulin in diabetic wounds following treatment with GF and /or vitamin D, respectively. Conclusion. Treatment with gingerols fractions (GF) and vitamin D for two weeks significantly improves delayed diabetic wound healing. The data showed that vitamin D and gingerol activate vascularization, fibrin deposition (HPX, FN, and collagen), and myofibroblasts in such manner to synthesize new tissues and help in the scar formation. Accordingly, three miRNAs, miR-155, miR-146a, and miR-15, as molecular targets, were identified and significantly evaluated in wound healing process. It showed significant association with fibrin deposition, vascularization, and reepithelialization process following treatment with GF and vitamin D. It proposed having anti-inflammatory action and promoting new tissue formation via vascularization process during the wound healing. Therefore, it is very interesting to consider miRNAs as molecular targets for evaluating the efficiency of nondrug therapy in the regulation of wound healing process Source Journal Evidence Based Complementary and Alternative Medicine Link to Full Article The effects of vitamin D supplementation on ADHD (Attention Deficit Hyperactivity Disorder) in 6–13 year-old students: A randomized, double-blind, placebo-controlled study Amirmansour Alavi Naein iAkbar Hasanzadeh Forough Fasihi Mohammad Reza Ghazvini Abstract Introduction Attention Deficit Hyperactivity Disorder (ADHD) is a common mental disorder in children. Drug treatment is the most prevalent method used to control and cure it; however, considering the low efficacy and frequent side effects of current drugs, more attempts is needed to replace them with safer agents. Several studies have shown the beneficial role of micronutrients such as vitamin D in development and improving the performance of neuronal system. This research intends to study the effects of vitamin D supplementation in 6–13 year-old students with ADHD. Methods In this double-blind parallel clinical trial, the subjects were selected from among 6–13 year-old students with ADHD diagnosed by a child psychiatry specialist. Vitamin D3 supplements (1000 IU) or placebo given daily to 70 subjects for three months. ADHD symptoms were evaluated before and after the intervention using Conners Parent Questionnaire (CPQ), the Strengths and Difficulties Questionnaire Teacher Version (SDQT), the Strengths and Difficulties Questionnaire Parent Version (SDQP) and Continuous performances Test (CPT) scores. Results The mean scores of the CPQ, SDQP and SDQT showed a significant difference in the two groups after intervention (p < 0.05). The impulsivity mean scores of the CPT after intervention showed statistical significance (p = 0.002), but the attention (p = 0.11) and mean reaction time (p = 0.19) mean scores did not. Conclusions Vitamin D supplementation not only improves some behavioral problems but can prevent exacerbation in some symptoms of the disorder and reduce impulsivity. Source : European Journal of Integrative Medicine Link to Abstract Vitamin D Deficiency Is Associated with Pulmonary Exacerbations in Children with Cystic Fibrosis Laura A. McCauley1 , William Thomas2 , Theresa A. Laguna3 , Warren E. Regelmann3 , Antoinette Moran3 , and Lynda E. Polgreen3 Abstract Rationale: Recent literature suggests vitamin D has an effect on lung function and on the lung’s ability to fight infection, both important in the cystic fibrosis (CF) population as predictors of morbidity and mortality. Objectives: Our study assessed associations between vitamin D and % predicted lung function, pulmonary exacerbations, and first Pseudomonas aeruginosa infection in children with CF. We hypothesized that children with CF who have 25-hydroxy vitamin D (25-OHD) levels less than 30 mg/L would have lower % predicted lung function and more pulmonary exacerbations than those with 25-OHD greater than or equal to 30 mg/L. Methods:This retrospective longitudinal study of 130 children aged 6 to 18 years between 2000 and 2012 examined 25-OHD levels classed in three vitamin D groups: sufficient (>30 mg/L), insufficient (20–29 mg/L), and deficient (,20 mg/L). Longitudinal models followed individuals’ changing vitamin D groups over time to compare numbers of pulmonary exacerbations (defined by hospitalization), incidence of first P. aeruginosa infection, and % predicted lung function. Cross-sectional comparisons between vitamin D groups were performed at ages 8, 12, and 16 years. Measurements and Main Results: The prevalence of vitamin D deficiency and insufficiency increased slowly through adolescence. The rate of exacerbations for the deficient vitamin D group, aged 15 to 18 years, was 13.1 per 10 patient-years, significantly higher than 4.3 per 10 patient-years for the insufficient and sufficient vitamin D groups (P , 0.05), which were not significantly different There were no differences between vitamin D groups in pulmonary function or incidence of first P. aeruginosa infection, which was about 2 per 10 patient-years. Conclusions: Higher 25-OHD levels in children with CF were associated with lower rates of pulmonary exacerbations and, in adolescents, higher FEV1 Source : Ann Am Thorac Soc. Link to Full Article Association of Vitamin D Deficiency and Acute Coronary Syndrome Our Experience Mohanty Bijaya*, K Shiva Kumar and Prasad Satish Introduction Despite progress in the prevention of cardiovascular diseases, a significant proportion of first cardiovascular events occur among individuals without traditional risk factors. The advancement of pathophysiology of atherosclerotic vascular diseases has brought new insight regarding potential indicators of underlying hidden atherosclerosis and cardiovascular risk. Recently attention has been focused on various novel inflammatory markers, especially vitamin D. Particularly a growing body of evidence has identified vitamin D deficiency as a potential risk factor for acute coronary syndrome. The research revealed that vitamin D receptor (VDR) was identified in almost all human cells. Relationship between the cardiovascular system system and vitamin D status was first demonstrated in a study on a rat model deficient in vitamin D more than 20 years ago. Vitamin D has antiatherosclerotic, anti-inflammatory and direct cardio-protective actions. Studies report an inverse relationship between levels of vitamin D and atherosclerotic calcification. Also. vitamin D levels are correlated with other coronary heart disease risk factors, such as hypertension, hyperlipidemia and diabetes. So, the association between vitamin D deficiency and ischaemic heart disease may occur directly or indirectly by influencing the risk factors for ACS. Vitamin D supplementation has been shown to have a protective effect in limited studies of, but further research is needed. We have undertaken this study in our hospital with the aim to identify the relation between vitamin D levels with acute coronary syndrome. Conclusion In the current study we observed an inverse association between acute coronary syndrome and vitamin D deficiency. Since Vitamin D deficiency is a potentially modifiable risk factor people with cardiovascular risk factors should be screened and treated accordingly. Patients getting admitted with acute coronary syndrome should be evaluated for vitamin D deficiency and accordingly supplementation should be recommended. Even the family members of patients should be explained regarding vitamin D in today’s perspective. Source : Integrative Journal Of Global Health Link To Full Article Sunlight Incidence, Vitamin D Deficiency, and Alzheimer's Disease Alice Barros Câmara, Iara Dantas de Souza, and Rodrigo Juliani Siqueira Dalmolin Abstract Vitamin D (VD) deficiency is a growing problem, affecting a significant portion of the population in many countries. VD deficiency may be related to several diseases, including Alzheimer's disease (AD). This study aimed to review the relationship between VD deficiency and AD. We describe the proteins involved in AD pathogenesis and how those proteins can be influenced by VD deficiency. We also investigated a relationship between AD death rate and solar radiation and we found an increased AD death rate in countries with low sunlight. It was also observed that amyloid precursor protein, ryanodine receptor, mammalian target of rapamycin complex 1, and receptor for advanced glycation end products are associated with a worse prognosis in AD. While the Klotho protein, phosphatase and tensin homologue, and VD receptor are associated with a better prognosis in the disease. The literature suggests that decline in VD concentrations may be involved in the establishment and progression of AD. According to sunlight data, we can conclude that countries with low average sunlight have high AD death rate. Source : Journal of Medicinal Food Link to Full Article Vitamin D status is associated with uteroplacental dysfunction indicated by pre-eclampsia and small-for-gestational-age birth in a large prospective pregnancy cohort in Ireland with low vitamin D status 1,2 Mairead E Kiely,3,4* Joy Y Zhang,3 Michael Kinsella,3 Ali S Khashan,4,5 and Louise C Kenny Abstract Background: Associations between vitamin D and pregnancy outcomes have been inconsistent. Objectives: We described the distribution of 25-hydroxyvitamin D3 [25(OH)D3], 3-epi-25(OH)D3, and 25(OH)D2 in early pregnancy and investigated associations with pre-eclampsia and small-for-gestationalage (SGA) birth, which are indicative of uteroplacental dysfunction. Design: The SCOPE (Screening for Pregnancy Endpoints) Ireland prospective pregnancy cohort study included 1768 well-characterized low-risk, nulliparous women resident at 528N. Serum 25(OH)D3, 3-epi-25(OH)D3, and 25(OH)D2 were quantified at 15 wk of gestation with the use of a CDC-accredited liquid chromatography– tandem mass spectrometry method. Results: The mean 6 SD total 25(OH)D concentration was 56.7 6 25.9 nmol/L, and 17% and 44% of women had 25(OH)D concentrations , 30 and , 50 nmol/L, respectively. The prevalence of pre-eclampsia was 3.8%, and 10.7% of infants were SGA. There was a lower risk of pre-eclampsia plus SGA combined (13.6%) at 25(OH)D concentrations . 75 nmol/L (adjusted OR: 0.64; 95% CI: 0.43, 0.96). The main predictors of 25(OH)D were the use of vitamin D–containing supplements (adjusted mean difference: 20.1 nmol/L; 95% CI: 18.5, 22.7 nmol/L) and summer sampling (adjusted mean difference: 15.5 nmol/L; 95% CI: 13.4, 17.6 nmol/L). Non-Caucasian ethnicity (adjusted mean difference: 2 19.3 nmol/L; 95% CI: 2 25.4, 2 13.2 nmol/L) and smoking (adjusted mean difference: 2 7.0 nmol/L; 95% CI: 2 10.5, 2 3.6 nmol/L) were negative predictors of 25(OH)D. The mean 6 SD concentration of 3-epi-25(OH)D3, which was detectable in 99.9% of samples, was 2.6 6 1.6 nmol/L. Determinants of 3-epi-25(OH)D3 were 25(OH)D3 (adjusted mean difference: 0.052 nmol/L; 95% CI: 0.050, 0.053 nmol/L) and maternal age (adjusted mean difference: 2 0.018 nmol/L; 95% CI: 2 0.026, 2 0.009 nmol/L). The mean 6 SD concentration of 25(OH)D2 was 3.1 6 2.7 nmol/L, which was present in all samples. No adverse effects of 25(OH)D concentrations . 125 nmol/L were observed. Conclusions:In the first report to our knowledge of CDC-accredited 25(OH)D data and pregnancy outcomes from a large, clinically validated, prospective cohort study, we observed a protective association of a 25(OH)D concentration . 75 nmol/L and a reduced risk of uteroplacental dysfunction as indicated by a composite outcome of SGA and pre-eclampsia. Well-designed, adequately powered randomized controlled trials are required to verify this observation. Source : American Journal of Clinical Nutrition Link to Full Article Association of Vitamin D Levels With Multiple Sclerosis Activity and Progression in Patients Receiving Interferon Beta-1b Kathryn C. Fitzgerald, ScM1; Kassandra L. Munger, ScD1; Karl Köchert, MD2; Barry G. W. Arnason, MD3; Giancarlo Comi, MD4; Stuart Cook, MD5; Douglas S. Goodin, MD6; Massimo Filippi, MD7; Hans-Peter Hartung, MD, FRCP8; Douglas R. Jeffery, MD, PhD9; Paul O’Connor, MD10; Gustavo Suarez, MD11; Rupert Sandbrink, MD, PhD2,12; Ludwig Kappos, MD13; Christoph Pohl, MD†2,14; Alberto Ascherio, MD, DrPH1,1 Abstract Importance Low serum 25-hydroxyvitamin D (25[OH]D) levels are associated with an increased risk of multiple sclerosis (MS) as well as with increased disease activity and rate of progression in clinically isolated syndromes and early MS. Objective To assess the association between 25(OH)D and disease course and prognosis in patients with relapsing-remitting MS treated with interferon beta-1b. Design, Setting, and Participants We conducted a prospective cohort study assessing 25(OH)D levels and subsequent MS disease course and progression characterized by magnetic resonance imaging (MRI) and clinical end points. The study took place between November 2003 and June 2005; data analysis was performed between June 2013 and December 2014. The study was conducted among participants in the Betaferon Efficacy Yielding Outcomes of a New Dose (BEYOND) study, a large, phase 3, prospective, multicenter, blinded, randomized clinical trial. Patients were monitored for at least 2 years. Clinic visits were scheduled every 3 months, and MRI was performed at baseline and annually thereafter. Eligible patients included 1482 participants randomized to receive 250 μg or 500 μg of interferon-1b with at least 2 measurements of 25(OH)D obtained 6 months apart. Exposures Serum 25(OH)D measurements were performed at baseline, 6 months, and 12 months. Main Outcomes and Measures Main outcomes included cumulative number of new active lesions (T2 lesions and gadolinium acetate–enhancing lesions), change in normalized brain volume, relapse rate, and progression determined by the Expanded Disability Status Scale (EDSS). Statistical analyses were adjusted for age, sex, randomized treatment, region, disease duration, and baseline EDSS score. Results Overall, average 25(OH)D levels in 1482 patients were significantly inversely correlated with the cumulative number of new active lesions between baseline and the last MRI, with a 50.0-nmol/L increase in serum 25(OH)D levels associated with a 31% lower rate of new lesions (relative rate [RR], 0.69; 95% CI, 0.55-0.86; P = .001). The lowest rate of new lesions was observed among patients with 25(OH)D levels greater than 100.0 nmol/L (RR, 0.53; 95% CI, 0.37-0.78; P = .002). No significant associations were found between 25(OH)D levels and change in brain volume, relapse rates, or EDSS scores. Results were consistent following adjustment for HLA-DRB1*15 or vitamin D–binding protein status. Conclusions and Relevance Among patients with MS treated with interferon beta-1b, higher 25(OH)D levels were associated with lower rates of MS activity observed on MRI. Results for brain atrophy and clinical progression were more equivocal. Source : JAMA Link to Source Association of Vitamin D Status with Dual Task Physical Performance in Older Adults1. Johanna Lopez1, Adriana Campa1, John E. Lewis3, Fatma G. Ercanli-Huffman1, Juan P. Liuzzi1, Tan Li2, Ana H. Martinez3 and Serena M Ferris3 Abstract Objective To evaluate the association of vitamin D status with age-relatedchanges in mobility and higher order cognitive function using a single and dual task physical performance test. Methods After consenting, participants completed the baseline assessments that included serum levels of vitamin D, vitals, anthropometrics and body composition, as well as completing surveys to evaluate physical activity, depressive symptoms and fear of falling. Participants performed in random order the physical performance tests, which included 1) walking (single gait task); 2) counting backwards from 50 by 1 (single cognitive task); and 3) walking while counting backwards from 50 by 1 (dual task). The dual task physical performance variables measured were: 1) dual task gait velocity; 2) single task gait velocity; 3) difference in dual and single task gait velocity; 4) dual task counting rate; 5) single task counting rate; 6) difference in dual and single counting rate. Paired t-tests were used to compare single and dual task variables within the whole population andeach vitamin D status group. Spearman’s correlations, independent t-tests, repeated measures ANOVAs and multiple logistic regressions were used to examine the relationship between vitamin D insufficiency (25OHD<30ng/mL) andsufficiency (25OHD≥30ng/mL) and dual task physical performance variables. The significance level was set at α≤0.05, and statistical analyzes were performed using SPSS 21. Results The mean +/− SD of serum vitamin D levels were 30.73 +/− 8.73 ng/ml and 46% of the participants were vitamin D insufficient. Dual and single task counting rate were significantly lower in the vitamin D insufficient group compared to the sufficient group (mean difference: −0.14, P=0.018 and meandifference: −0.06, P=0.028, respectively). Using Spearman correlations, a slower single (r=0.258, P=0.011) and dual counting rate (r=0.278, P=0.006) were significantly associated with vitamin D insufficiency. Conclusions Cognitive performance for dual or single tasking were worse in thevitamin D insufficient group. Since counting backward is a mental tracking task, which is a component of executive function, our results support a relationship between vitamin D insufficiency and executive dysfunction. Source : Research Gate Link to Abstract Vitamin D and Alzheimer’s Disease: Neurocognition to Therapeutics Anindita Banerjee,1,2 Vineet Kumar Khemka,1,2 Anirban Ganguly,2 Debashree Roy,2 Upasana Ganguly,2 and Sasanka Chakrabarti1 Abstract Alzheimer’s disease (AD), the major cause of dementia worldwide, is characterized by progressive loss of memory and cognition. The sporadic form of AD accounts for nearly 90% of the patients developing this disease. The last century has witnessed significant research to identify various mechanisms and risk factors contributing to the complex etiopathogenesis of AD by analyzing postmortem AD brains and experimenting with animal and cell culture based models. However, the treatment strategies, as of now, are only symptomatic. Accumulating evidences suggested a significant association between vitamin D deficiency, dementia, and AD. This review encompasses the beneficial role of vitamin D in neurocognition and optimal brain health along with epidemiological evidence of the high prevalence of hypovitaminosis D among aged and AD population. Moreover, disrupted signaling, altered utilization of vitamin D, and polymorphisms of several related genes including vitamin D receptor (VDR) also predispose to AD or AD-like neurodegeneration. This review explores the relationship between this gene-environmental influence and long term vitamin D deficiency as a risk factor for development of sporadic AD along with the role and rationale of therapeutic trials with vitamin D. It is, therefore, urgently warranted to further establish the role of this potentially neuroprotective vitamin in preventing and halting progressive neurodegeneration in AD patients. Source : Intl Journal Alzheimer's Disease Link to Full Article Maternal/neonatal vitamin D deficiency: a risk factor for bronchopulmonary dysplasia in preterms? M Çetinkaya1, F Çekmez2, T Erener-Ercan1, G Buyukkale1, A Demirhan3, G Aydemir4 and F N Aydin5 Abstract Objective: The objective of this study was to investigate the possible association between maternal/neonatal 25-hydroxy vitamin D (25-OHD) levels and development of bronchopulmonary dysplasia. Study Design: One hundred and thirty-two preterm infants 32 weeks of gestation who were diagnosed with respiratory distress syndrome were enrolled. 25-OHD levels were determined in maternal/neonatal blood samples that were obtained at the time of admission to the neonatal intensive care unit. Result: A total of 100 infants were included and 31 (31%) developed bronchopulmonary dysplasia (BPD). Both maternal and neonatal 25-OHD levels in the BPD group were significantly lower compared with those in the no-BPD group (P=0.0001). A positive correlation was detected between maternal and neonatal 25-OHD levels. All of the infants with BPD had a 25-OHD level <10 ng ml−1, which represented severe deficiency. Univariate logistic regression analysis revealed that maternal/neonatal vitamin D levels were a significant predictor of BPD (odds ratio (OR): 0.76 and 0.61, respectively, P<0.001). Conclusion: We demonstrated for the first time that lower maternal and neonatal vitamin 25-OHD levels were associated with BPD development in preterm infants. However, further studies with larger sample sizes are needed to delineate the possible link between vitamin D deficiency and BPD. Source : Journal Perinatology Link to Abstract Circulating 25-hydroxyvitamin D and risk of lung cancer: a dose–response meta-analysis
Abstract Background Mounting experimental evidence supports a protective effect of high 25-hydroxyvitamin D (25[OH]D), a good indicator of vitamin D status, on risk of various cancers including lung cancer. However, prospective observational studies examining the 25(OH)D–lung cancer association reported inconsistent findings. A dose–response meta-analysis was carried out to elucidate the subject. Methods Potentially eligible studies were identified by searching PubMed and EMBASE databases, and by carefully reviewing the bibliographies of retrieved publications. The summary relative risks (RRs) with 95 % confidence intervals (CIs) were calculated using the random-effects model. Results Thirteen reports from ten prospective studies were included, totaling 2,227 lung cancer events. Results of the meta-analysis showed a significant 5 % (RR 0.95, 95 % CI 0.91–0.99) reduction in the risk of lung cancer for each 10 nmol/L increment in 25(OH)D concentrations. This inverse association was not significantly modified by area, study duration, sex, methods for 25(OH)D measurement, baseline 25(OH)D levels, or quality score of included studies. There was evidence of a nonlinear relationship between 25(OH)D and risk of lung cancer (p-nonlinearity = 0.02), with the greatest reductions in risk observed at 25(OH)D of nearly 53 nmol/L, and remained protective until approximately 90 nmol/L. Further increases showed no significant association with cancer risk, but scanty data were included in the analyses of high-level 25(OH)D. There was no evidence of publication bias. Conclusion This dose–response meta-analysis of prospective studies suggests that 25(OH)D may be associated with reduced risk of lung cancer, in particular among subjects with vitamin D deficiencies. Source : Journal Cancer Causes and Control Link to Abstract Association Between Vitamin D Status and Age-Related Macular Degeneration by Genetic Risk Amy E. Millen, PhD1; Kristin J. Meyers, PhD, MPH2; Zhe Liu, MS2; Corinne D. Engelman, PhD3; Robert B. Wallace, MD4; Erin S. LeBlanc, PhD5; Lesley F. Tinker, PhD6; Sudha K. Iyengar, PhD7; Jennifer G. Robinson, MD8; Gloria E. Sarto, MD, PhD9; Julie A. Mares, PhD2 Abstract Importance Deficient 25-hydroxyvitamin D (25[OH]D) concentrations have been associated with increased odds of age-related macular degeneration (AMD). Objective To examine whether this association is modified by genetic risk for AMD and whether there is an association between AMD and single-nucleotide polymorphisms of genes involved in vitamin D transport, metabolism, and genomic function. Design, Setting, and Participants Postmenopausal women (N = 913) who were participants of the Carotenoids in Age-Related Eye Disease Study (CAREDS) (aged 54 to <75 years) with available serum 25(OH)D concentrations (assessed October 1, 1993, to December 31, 1998), genetic data, and measures of AMD (n = 142) assessed at CAREDS baseline from May 14, 2001, through January 31, 2004, were studied. Main Outcomes and Measures Prevalent early or late AMD was determined from graded, stereoscopic fundus photographs. Logistic regression was used to estimate odds ratios (ORs) and 95% CIs for AMD by the joint effects of 25(OH)D (<12, ≥12 to <20, ≥20 to <30, and ≥30 ng/mL) and risk genotype (noncarrier, 1 risk allele, or 2 risk alleles). The referent group was noncarriers with adequate vitamin D status (≥30 ng/mL). Joint effect ORs were adjusted for age, smoking, iris pigmentation, self-reported cardiovascular disease, self-reported diabetes status, and hormone use. Additive and multiplicative interactions were assessed using the synergy index (SI) and an interaction term, respectively. To examine the association between AMD and variants in vitamin D–related genes, age-adjusted ORs and 95% CIs were estimated using logistic regression. Results Among the 913 women, 550 had adequate levels of vitamin D (≥20 ng/mL), 275 had inadequate levels (≥12 to <20 mg/mL), and 88 had deficient levels (<12 ng/mL). A 6.7-fold increased odds of AMD (95% CI, 1.6-28.2) was observed among women with deficient vitamin D status (25[OH]D <12 ng/mL) and 2 risk alleles for CFH Y402H (SI for additive interaction, 1.4; 95% CI, 1.1-1.7; P for multiplicative interaction = .25). Significant additive (SI, 1.4; 95% CI, 1.1-1.7) and multiplicative interactions (P = .02) were observed for deficient women with 2 high-risk CFI (rs10033900) alleles (OR, 6.3; 95% CI, 1.6-24.2). The odds of AMD did not differ by genotype of candidate vitamin D genes. Conclusions and Relevance In this study, the odds of AMD were highest in those with deficient vitamin D status and 2 risk alleles for the CFH and CFI genotypes, suggesting a synergistic effect between vitamin D status and complement cascade protein function. Limited sample size led to wide CIs. Findings may be due to chance or explained by residual confounding. Source : JAMA Opthal. Link to Abstract Vitamin D deficiency is associated with increased risk of Alzheimer’s disease and dementia: evidence from meta-analysis Liang Shen and Hong-Fang Ji* Abstract Background In recent years, the associations between vitamin D status and Alzheimer’s disease (AD) and dementia have gained increasing interests. The present meta-analysis was designed to estimate the association between vitamin D deficiency and risk of developing AD and dementia. Methods A literature search conducted until February 2015 identified 10 study populations, which were included in the meta-analysis. Pooled risk ratios (RRs) and 95 % confidence interval (CI) were calculated with a random-effect model using Stata software package. Results Results of our meta-analysis showed that subjects with deficient vitamin D status (25(OH)D level < 50 nmol/L) were at increased risk of developing AD by 21 % compared with those possessing 25(OH)D level > 50 nmol/L. Similar analysis also found a significantly increased dementia risk in vitamin D deficient subjects. There is no evidence for significant heterogeneity among the included studies. Conclusion Available data indicates that lower vitamin D status may be associated with increased risk of developing AD and dementia. More studies are needed to further confirm the associations and to evaluate the beneficial effects of vitamin D supplementation in preventing AD and dementia. Source : Nutrition Journal Link to Full Article Maternal vitamin D3 supplementation at 50 μg/d protects against low serum 25-hydroxyvitamin D in infants at 8 wk of age: a randomized controlled trial of 3 doses of vitamin D beginning in gestation and continued in lactation1
Abstract Background: Vitamin D supplementation is recommended for breastfed infants. Maternal supplementation beginning in gestation is a potential alternative, but its efficacy in maintaining infant 25-hydroxyvitamin D [25(OH)D] concentration after birth is unknown. Objectives: We determined the effect of 3 doses of maternal vitamin D supplementation beginning in gestation and continued in lactation on infant serum 25(OH)D and compared the prevalence of infant serum 25(OH)D cutoffs (>30, >40, >50, and >75 nmol/L) by dose at 8 wk of age. Design: Pregnant women (n = 226) were randomly allocated to receive 10, 25, or 50 μg vitamin D3/d from 13 to 24 wk of gestation until 8 wk postpartum, with no infant supplementation. Mother and infant blood was collected at 8 wk postpartum. Results: At 8 wk postpartum, mean [nmol/L (95% CI)] infant 25(OH)D at 8 wk was higher in the 50-μg/d [75 (67, 83)] than in the 25-μg/d [52 (45, 58)] or 10-μg/d [45 (38, 52)] vitamin D groups (P < 0.05). Fewer infants born to mothers in the 50-μg/d group had a 25(OH)D concentration <30 nmol/L (indicative of deficiency) than infants in the 25- and 10-μg/d groups, respectively (2% compared with 16% and 43%; P < 0.05). Fewer than 15% of infants in the 10- or 25-μg/d groups achieved a 25(OH)D concentration >75 nmol/L compared with 44% in the 50-μg/d group (P < 0.05). Almost all infants (∼98%, n = 44) born to mothers in the 50-μg/d group achieved a 25(OH)D concentration >30 nmol/L. At 8 wk postpartum, mean maternal 25(OH)D concentration was higher in the 50-μg/d [88 (84, 91)] than in the 25-μg/d [78 (74, 81)] or 10-μg/d [69 (66, 73)] groups (P < 0.05). Conclusions: Maternal supplementation beginning in gestation with 50 μg vitamin D3/d protects 98% of unsupplemented breastfed infants against 25(OH)D deficiency (<30 nmol/L) to at least 8 wk, whereas 10 or 25 μg vitamin D/d protects only 57% and 84% of infants, respectively. Source : American Journal of Nutrition Link to Abstract Vitamin D deficiency down-regulates Notch pathway contributing to skeletal muscle atrophy in old wistar rats Carla Domingues-Faria124, Audrey Chanet24, Jérôme Salles24, Alexandre Berry24, Christophe Giraudet24, Véronique Patrac24, Philippe Denis34, Katia Bouton24, Nicolas Goncalves-Mendes1, Marie-Paule Vasson15, Yves Boirie26 and Stéphane Walrand Abstract Background The diminished ability of aged muscle to self-repair is a factor behind sarcopenia and contributes to muscle atrophy. Muscle repair depends on satellite cells whose pool size is diminished with aging. A reduction in Notch pathway activity may explain the age-related decrease in satellite cell proliferation, as this pathway has been implicated in satellite cell self-renewal. Skeletal muscle is a target of vitamin D which modulates muscle cell proliferation and differentiation in vitro and stimulates muscle regeneration in vivo. Vitamin D status is positively correlated to muscle strength/function, and elderly populations develop a vitamin D deficiency. The aim of this study was to evaluate how vitamin D deficiency induces skeletal muscle atrophy in old rats through a reduction in Notch pathway activity and proliferation potential in muscle. Methods 15-month-old male rats were vitamin D-depleted or not (control) for 9 months (n = 10 per group). Rats were 24-month-old at the end of the experiment. Gene and/or protein expression of markers of proliferation, or modulating proliferation, and of Notch signalling pathway were studied in the tibialis anterior muscle by qPCR and western blot. An unpaired student’s t-test was performed to test the effect of the experimental conditions. Results Vitamin D depletion led to a drop in concentrations of plasma 25-hydroxyvitamin D in depleted rats compared to controls (-74%, p < 0.01). Tibialis anterior weight was decreased in D-depleted rats (-25%, p < 0.05). The D-depleted group showed -39%, -31% drops in expression of two markers known to modulate proliferation (Bmp4, Fgf-2 mRNA levels) and -56% drop in one marker of cell proliferation (PCNA protein expression) compared to controls (p < 0.05). Notch pathway activity was blunted in tibialis anterior of D-depleted rats compared to controls, seen as a down-regulation of cleaved Notch (-53%, p < 0.05) and its target Hes1 (-35%, p < 0.05). Conclusions A 9-month vitamin D depletion induced vitamin D deficiency in old rats. Vitamin D depletion induces skeletal muscle atrophy in old rats through a reduction in Notch pathway activity and proliferation potential. Vitamin D deficiency could aggravate the age-related decrease in muscle regeneration capacity. Source : Journal Nutrition and Metabolism Link to Full Article Vitamin D and type 2 diabetes: a systematic review J Mitri1, M D Muraru2 and A G Pittas1
Abstract Background/Objectives: Vitamin D may modify the risk of type 2 diabetes mellitus. The aim of this review was to examine the association between vitamin D status and incident type 2 diabetes, and the effect of vitamin D supplementation on glycemic outcomes. Methods: We performed a systematic review of English-language studies using MEDLINE through February 2011. Longitudinal cohort studies reporting associations between vitamin D status and incident type 2 diabetes, and randomized controlled trials (RCTs) of vitamin D supplementation, were included. Study characteristics and results were extracted, and study quality was assessed. Results: A total of 8 observational cohort studies and 11 RCTs were included. In meta-analyses of observational studies, vitamin D intake >500 international units (IU)/day decreased the risk of type 2 diabetes by 13%compared with vitamin D intake <200 IU/day. Individuals with the highest vitamin D status (>25 ng/ml) had a 43% lower risk of developing type 2 diabetes (95% confidence interval 24, 57%) compared with those in the lowest group (<14 ng/ml). In post hoc analyses from eight trials among participants with normal glucose tolerance at baseline and in three small underpowered (n=32–62) trials of patients with established type 2 diabetes, there was no effect of vitamin D supplementation on glycemic outcomes. In two trials among patients with baseline glucose intolerance, vitamin D supplementation improved insulin resistance. Conclusions: Vitamin D may play a role in type 2 diabetes; however, to better define the role of vitamin D in the development and progression of type 2 diabetes, high-quality observational studies and RCTs that measure blood 25-hydroxyvitamin D concentration and clinically relevant glycemic outcomes are needed. Source : European Journal of Clinical Nutrition Link to Full Article Vitamin D Receptor Protein Expression in Tumor Tissue and Prostate Cancer Progression Whitney K. Hendrickson, Richard Flavin, Julie L. Kasperzyk, Michelangelo Fiorentino, Fang Fang, Rosina Lis, Christopher Fiore, Kathryn L. Penney, Jing Ma, Philip W. Kantoff, Meir J. Stampfer, Massimo Loda, Lorelei A. Mucci and Edward Giovannucci⇓ Abstract Purpose Data suggest that circulating 25-hydroxyvitamin D [25(OH)D] interacts with the vitamin D receptor (VDR) to decrease proliferation and increase apoptosis for some malignancies, although evidence for prostate cancer is less clear. How VDR expression in tumor tissue may influence prostate cancer progression has not been evaluated in large studies. Patients and Methods We examined protein expression of VDR in tumor tissue among 841 patients with prostate cancer in relation to risk of lethal prostate cancer within two prospective cohorts, the Physicians' Health Study and Health Professionals Follow-Up Study. We also examined the association of VDR expression with prediagnostic circulating 25(OH)D and 1,25-dihydroxyvitamin D levels and with two VDR single nucleotide polymorphisms, FokI and BsmI. Results Men whose tumors had high VDR expression had significantly lower prostate-specific antigen (PSA) at diagnosis (P for trend < .001), lower Gleason score (P for trend < .001), and less advanced tumor stage (P for trend < .001) and were more likely to have tumors harboring the TMPRSS2:ERG fusion (P for trend = .009). Compared with the lowest quartile, men whose tumors had the highest VDR expression had significantly reduced risk of lethal prostate cancer (hazard ratio [HR], 0.17; 95% CI, 0.07 to 0.41). This association was only slightly attenuated after adjustment for Gleason score and PSA at diagnosis (HR, 0.33; 95% CI, 0.13 to 0.83) or, additionally, for tumor stage (HR, 0.37; 95% CI, 0.14 to 0.94). Neither prediagnostic plasma vitamin D levels nor VDR polymorphisms were associated with VDR expression. Conclusion High VDR expression in prostate tumors is associated with a reduced risk of lethal cancer, suggesting a role of the vitamin D pathway in prostate cancer progression. Source : Journal of Clinical Oncology Link to Full Article Vitamin D and Central Hypersensitivity in Patients with Chronic Pain Roland von Känel, MD,*† Veronika Müller-Hartmannsgruber, MD,* Georgios Kokinogenis, MD,* and Niklaus Egloff, MD*† Abstract Background. Low vitamin D is implicated in various chronic pain conditions with, however, inconclusive findings. Vitamin D might play an important role in mechanisms being involved in central processing of evoked pain stimuli but less so for spontaneous clinical pain. Objective. This study aims to examine the relation between low serum levels of 25-hydroxyvitamin D3 (25-OH D) and mechanical pain sensitivity. Design. We studied 174 patients (mean age 48 years, 53% women) with chronic pain. A standardized pain provocation test was applied, and pain intensity was rated on a numerical analogue scale (0–10). The widespread pain index and symptom severity score (including fatigue, waking unrefreshed, and cognitive symptoms) following the 2010 American College of Rheumatology preliminary diagnostic criteria for fibromyalgia were also assessed. Serum 25-OH D levels were measured with a chemiluminescent immunoassay. Results. Vitamin deficiency (25-OH D < 50 nmol/L) was present in 71% of chronic pain patients; another 21% had insufficient vitamin D (25-OH D < 75 nmol/ L). After adjustment for demographic and clinical variables, there was a mean ± standard error of the mean increase in pain intensity of 0.61 ± 0.25 for each 25 nmol/L decrease in 25-OH D (P = 0.011). Lower 25-OH D levels were also related to greater symptom severity (r = −0.21, P = 0.008) but not to the widespread pain index (P = 0.83) and fibromyalgia (P = 0.51). Conclusions. The findings suggest a role of low vitamin D levels for heightened central sensitivity, particularly augmented pain processing upon mechanical stimulation in chronic pain patients. Vitamin D seems comparably less important for selfreports of spontaneous chronic pain. Source : Journal Pain Medicine Link to Full Article Vitamin D hormone regulates serotonin synthesis. Part 1: relevance for autism Rhonda P. Patrick1 and Bruce N. Ames1 Nutrition and Metabolism Center, Children’s Hospital Oakland Research Institute, Oakland, California, USA Abstract Serotonin and vitamin D have been proposed to play a role in autism; however, no causal mechanism has been established. Here, we present evidence that vitamin D hormone (calcitriol) activates the transcription of the serotonin-synthesizing gene tryptophan hydroxylase 2 (TPH2) in the brain at a vitamin D response element (VDRE) and represses the transcription of TPH1 in tissues outside the blood-brain barrier at a distinct VDRE. The proposed mechanism explains 4 major characteristics associated with autism: the low concentrations of serotonin in the brain and its elevated concentrations in tissues outside the bloodbrain barrier; the low concentrations of the vitamin D hormone precursor 25-hydroxyvitamin D [25(OH)D3]; the high male prevalence of autism; and the presence of maternal antibodies against fetal brain tissue. Two peptide hormones, oxytocin and vasopressin, are also associated with autism and genes encoding the oxytocin-neurophysin I preproprotein, the oxytocin receptor, and the arginine vasopressin receptor contain VDREs for activation. Supplementation with vitamin D and tryptophan is a practical and affordable solution to help prevent autism and possibly ameliorate some symptoms of the disorder. Source : The FASEB Journal Link to Full Article Vitamin D and the omega-3 fatty acids control serotonin synthesis and action, part 2: relevance for ADHD, bipolar, schizophrenia, and impulsive behavior Rhonda P. Patrick1 and Bruce N. Ames1 Nutrition and Metabolism Center, Children’s Hospital Oakland Research Institute, Oakland, California, USA Abstract Serotonin regulates a wide variety of brain functions and behaviors. Here, we synthesize previous findings that serotonin regulates executive function, sensory gating, and social behavior and that attention deficit hyperactivity disorder, bipolar disorder, schizophrenia, and impulsive behavior all share in common defects in these functions. It has remained unclear why supplementation with omega-3 fatty acids and vitamin D improve cognitive function and behavior in these brain disorders. Here, we propose mechanisms by which serotonin synthesis, release, and function in the brain are modulated by vitamin D and the 2 marine omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Brain serotonin is synthesized from tryptophan by tryptophan hydroxylase 2, which is transcriptionally activated by vitamin D hormone. Inadequate levels of vitamin D (∼70% of the population) and omega-3 fatty acids are common, suggesting that brain serotonin synthesis is not optimal. We propose mechanisms by which EPA increases serotonin release from presynaptic neurons by reducing E2 series prostaglandins and DHA influences serotonin receptor action by increasing cell membrane fluidity in postsynaptic neurons. We propose a model whereby insufficient levels of vitamin D, EPA, or DHA, in combination with genetic factors and at key periods during development, would lead to dysfunctional serotonin activation and function and may be one underlying mechanism that contributes to neuropsychiatric disorders and depression. This model suggests that optimizing vitamin D and marine omega-3 fatty acid intake may help prevent and modulate the severity of brain dysfunction.-- Source : The FASEB Journal Link to Full Article Vitamin D supplementation for prevention of mortality in adults
Available evidence on the effects of vitamin D on mortality has been inconclusive. In a recent systematic review, we found evidence that vitamin D3 may decrease mortality in mostly elderly women. The present systematic review updates and reassesses the benefits and harms of vitamin D supplementation used in primary and secondary prophylaxis of mortality. Objectives To assess the beneficial and harmful effects of vitamin D supplementation for prevention of mortality in healthy adults and adults in a stable phase of disease. Search methods We searched The Cochrane Library, MEDLINE, EMBASE, LILACS, the Science Citation Index–Expanded and Conference Proceedings Citation Index–Science (all up to February 2012). We checked references of included trials and pharmaceutical companies for unidentified relevant trials. Selection criteria Randomised trials that compared any type of vitamin D in any dose with any duration and route of administration versus placebo or no intervention in adult participants. Participants could have been recruited from the general population or from patients diagnosed with a disease in a stable phase. Vitamin D could have been administered as supplemental vitamin D (vitamin D3 (cholecalciferol) or vitamin D2(ergocalciferol)) or as an active form of vitamin D (1α-hydroxyvitamin D (alfacalcidol) or 1,25-dihydroxyvitamin D (calcitriol)). Data collection and analysis Six review authors extracted data independently. Random-effects and fixed-effect meta-analyses were conducted. For dichotomous outcomes, we calculated the risk ratios (RRs). To account for trials with zero events, we performed meta-analyses of dichotomous data using risk differences (RDs) and empirical continuity corrections. We used published data and data obtained by contacting trial authors. To minimise the risk of systematic error, we assessed the risk of bias of the included trials. Trial sequential analyses controlled the risk of random errors possibly caused by cumulative meta-analyses. Main results We identified 159 randomised clinical trials. Ninety-four trials reported no mortality, and nine trials reported mortality but did not report in which intervention group the mortality occurred. Accordingly, 56 randomised trials with 95,286 participants provided usable data on mortality. The age of participants ranged from 18 to 107 years. Most trials included women older than 70 years. The mean proportion of women was 77%. Forty-eight of the trials randomly assigned 94,491 healthy participants. Of these, four trials included healthy volunteers, nine trials included postmenopausal women and 35 trials included older people living on their own or in institutional care. The remaining eight trials randomly assigned 795 participants with neurological, cardiovascular, respiratory or rheumatoid diseases. Vitamin D was administered for a weighted mean of 4.4 years. More than half of the trials had a low risk of bias. All trials were conducted in high-income countries. Forty-five trials (80%) reported the baseline vitamin D status of participants based on serum 25-hydroxyvitamin D levels. Participants in 19 trials had vitamin D adequacy (at or above 20 ng/mL). Participants in the remaining 26 trials had vitamin D insufficiency (less than 20 ng/mL). Vitamin D decreased mortality in all 56 trials analysed together (5,920/47,472 (12.5%) vs 6,077/47,814 (12.7%); RR 0.97 (95% confidence interval (CI) 0.94 to 0.99); P = 0.02; I2 = 0%). More than 8% of participants dropped out. 'Worst-best case' and 'best-worst case' scenario analyses demonstrated that vitamin D could be associated with a dramatic increase or decrease in mortality. When different forms of vitamin D were assessed in separate analyses, only vitamin D3 decreased mortality (4,153/37,817 (11.0%) vs 4,340/38,110 (11.4%); RR 0.94 (95% CI 0.91 to 0.98); P = 0.002; I2 = 0%; 75,927 participants; 38 trials). Vitamin D2, alfacalcidol and calcitriol did not significantly affect mortality. A subgroup analysis of trials at high risk of bias suggested that vitamin D2 may even increase mortality, but this finding could be due to random errors. Trial sequential analysis supported our finding regarding vitamin D3, with the cumulative Z-score breaking the trial sequential monitoring boundary for benefit, corresponding to 150 people treated over five years to prevent one additional death. We did not observe any statistically significant differences in the effect of vitamin D on mortality in subgroup analyses of trials at low risk of bias compared with trials at high risk of bias; of trials using placebo compared with trials using no intervention in the control group; of trials with no risk of industry bias compared with trials with risk of industry bias; of trials assessing primary prevention compared with trials assessing secondary prevention; of trials including participants with vitamin D level below 20 ng/mL at entry compared with trials including participants with vitamin D levels equal to or greater than 20 ng/mL at entry; of trials including ambulatory participants compared with trials including institutionalised participants; of trials using concomitant calcium supplementation compared with trials without calcium; of trials using a dose below 800 IU per day compared with trials using doses above 800 IU per day; and of trials including only women compared with trials including both sexes or only men. Vitamin D3 statistically significantly decreased cancer mortality (RR 0.88 (95% CI 0.78 to 0.98); P = 0.02; I2 = 0%; 44,492 participants; 4 trials). Vitamin D3 combined with calcium increased the risk of nephrolithiasis (RR 1.17 (95% CI 1.02 to 1.34); P = 0.02; I2 = 0%; 42,876 participants; 4 trials). Alfacalcidol and calcitriol increased the risk of hypercalcaemia (RR 3.18 (95% CI 1.17 to 8.68); P = 0.02; I2 = 17%; 710 participants; 3 trials). Authors' conclusions Vitamin D3 seemed to decrease mortality in elderly people living independently or in institutional care. Vitamin D2, alfacalcidol and calcitriol had no statistically significant beneficial effects on mortality. Vitamin D3 combined with calcium increased nephrolithiasis. Both alfacalcidol and calcitriol increased hypercalcaemia. Because of risks of attrition bias originating from substantial dropout of participants and of outcome reporting bias due to a number of trials not reporting on mortality, as well as a number of other weaknesses in our evidence, further placebo-controlled randomised trials seem warranted. Source : The Cochrane Library Link to Source Association of Vitamin D and Incident Statin Induced Myalgia—A Retrospective Cohort Study Ghanshyam Palamaner Subash Shantha, Julio Ramos, Linda Thomas-Hemak, Samir Bipin Pancholy Abstract Background and Objectives Evidence is conflicting with regards to the role of vitamin D in statin induced myalgia (SIM). Studies so far have assessed cross-sectional association and were limited by study sample selected predominantly from cardiology clinics. In this retrospective cohort study we assessed the association between vitamin D and SIM and attempted to establish a serum vitamin D cutoff to identify patients at risk for developing SIM. Methods Medical charts of 5526 consecutive patients from a primary care practice in Scranton, Pennsylvania from 2005–2012 were reviewed. Vitamin D level (25-hydroxy cholecalciferol) at statin initiation was considered “Exposure level”. Vitamin D levels were categorized into quartiles (≤ 10, 11–20, 21–30, >30 ng/ml). SIM was identified by patient report. Results 1160 out of 5526 patients were treated with statins. The mean age was 55.9 years. 276 (24%) developed SIM. Unadjusted 7-yr cumulative incidences of SIM for quartiles 1–4 of vitamin D were 32.3, 21.5, 18.3 and 14.6% respectively. The lowest quartile of vitamin D was independently associated with 1.21 times the hazard of the fourth quartile for developing SIM (95% CI: 1.09, 1.33; P-trend = 0.001). Vitamin D cut-off ≤15 ng/ml, showed a positive predictive value, negative predictive value, likelihood ratio (LR) + and LR- of 81, 90, 5.1 and 0.1, respectively for predicting SIM. Conclusions Low vitamin D level at statin initiation is associated with SIM, levels ≤15 ng/ml have a high predictive accuracy for SIM. Randomized controlled trials are needed to validate our results. Source : PLOS One Link to Full Article The effect of vitamin D supplementation on serum lipids in postmenopausal women with diabetes: A randomized controlled trial Paloma Muñoz-Aguirre, Mario Flores, Nayeli Macias, Amado D. Quezada, Edgar Denova-Gutiérrez, Jorge Salmerón Abstract Background & aims Dyslipidemia is a risk factor for cardiovascular disease that has become an increasing public health problem. Dyslipidemia is especially relevant in vulnerable populations such as postmenopausal women. Low serum levels of 25-hydroxyvitamin D have been associated with an unfavourable lipid profile. Due to contradictory findings from intervention trials, we investigated the effect of vitamin D supplementation on serum lipids in postmenopausal women with type 2 diabetes. Methods A total of 104 postmenopausal women with type 2 diabetes were randomly assigned in a double-blind manner to 1 of 2 groups taking a daily tablet for 6 months: a group consuming 4000 IU tablets of a vitamin D supplement (vitamin D group n = 52) or a group consuming placebo tablets (placebo group n = 52). Results The study was completed by 99 participants. However, as the analysis was based on an intention-to-treat approach, all 104 women were included in the final analysis. In the vitamin D group mean serum levels of 25(OH)D3 improved significantly at the end of the follow-up period (+25.5 nmol/L; P = <0.001). Our findings revealed no significant changes in low density lipoproteins, high density lipoproteins and total cholesterol concentrations, but did identify a greater decrease in serum triglycerides in the vitamin D group. The average effect of supplementation on the treated group was −34.24 mg/dL (P = 0.021), while the average treatment effect was −31.8 mg/dL (P = 0.023). Conclusions Our results suggest that supplementation with vitamin D (4000 IU/d) may have a beneficial effect on serum triglyceride levels without otherwise affecting levels of other lipids Source : Clinical Nutrition Link to abstract Vitamin D deficiency and depression in adults: systematic review and meta-analysis Rebecca E. S. Anglin, Zainab Samaan, Stephen D. Walter and Sarah D. McDonald Abstract Background There is conflicting evidence about the relationship between vitamin D deficiency and depression, and a systematic assessment of the literature has not been available. Aims To determine the relationship, if any, between vitamin D deficiency and depression. Method A systematic review and meta-analysis of observational studies and randomised controlled trials was conducted. Results One case–control study, ten cross-sectional studies and three cohort studies with a total of 31 424 participants were analysed. Lower vitamin D levels were found in people with depression compared with controls (SMD = 0.60, 95% CI 0.23–0.97) and there was an increased odds ratio of depression for the lowest v. highest vitamin D categories in the cross-sectional studies (OR = 1.31, 95% CI 1.0–1.71). The cohort studies showed a significantly increased hazard ratio of depression for the lowest v. highest vitamin D categories (HR = 2.21, 95% CI 1.40–3.49). Conclusions Our analyses are consistent with the hypothesis that low vitamin D concentration is associated with depression, and highlight the need for randomised controlled trials of vitamin D for the prevention and treatment of depression to determine whether this association is causal. Source : British Journal of Psychiatry Link to Full Article Vitamin D and musculoskeletal health Anne E Wolff, Andrea N Jones and Karen E Hansen University of Wisconsin School of Medicine and Public Health Summary Vitamin D is critical for calcium homeostasis. Following cutaneous synthesis or ingestion, vitamin D is metabolized to 25(OH)D and then to the active form 1,25(OH)2D. Low serum vitamin D levels are common in the general population and cause a decline in calcium absorption, leading to low serum levels of ionized calcium, which in turn trigger the release of parathyroid hormone, promoting skeletal resorption and, eventually, bone loss or osteomalacia. Vitamin D deficiency is generally defined as a serum 25(OH)D concentration <25–37 nmol/l (<10–15 ng/ml), but the definition of the milder state of vitamin D insufficiency is controversial. Three recent meta-analyses concluded that vitamin D must be administered in combination with calcium in order to substantially reduce the risk of nonvertebral fracture in adults over the age of 50 years. Fracture protection is optimal when patient adherence to medication exceeds 80% and vitamin D doses exceed 700 IU/day. In addition to disordered calcium homeostasis, low vitamin D levels might have effects on cell proliferation and differentiation and immune function. Randomized, double-blind, placebo-controlled trials are needed to clarify whether vitamin D supplementation is beneficial in cancer, autoimmune disease and infection. This Review focuses on the pathophysiology, clinical correlates, evaluation and treatment of hypovitaminosis D. Conclusions Hypovitaminosis D is common, and can cause osteomalacia, secondary hyperparathyroidism and myopathy, and contribute to the risk of falls. Recent meta-analyses report that the beneficial musculoskeletal effects of vitamin D supplementation require concomitant calcium therapy; however, the optimal serum vitamin D level for musculoskeletal health remains to be determined. Vitamin D might also have beneficial effects on immune function, potentially influencing the incidence of cancer, autoimmune diseases and/or common infections, such as tuberculosis. These data are preliminary, however, and require confirmation from randomized, placebo-controlled clinical trials. Source : Journal Nature Rheumatology Link to Full Article Meta-analysis of Vitamin D Sufficiency for Improving Survival of Patients with Breast Cancer Abstract Background/Aim: To determine whether higher serum 25-hydroxyvitamin D [25(OH)D] at diagnosis is associated with longer survival of patients with breast cancer. Materials and Methods: A meta-analysis was performed of five studies of the relationship between 25(OH)D and mortality from breast cancer. A pooled hazard ratio was calculated using a random-effects model. The Der Simonian-Laird test was used to assess homogeneity. Results: Higher serum concentrations of 25(OH)D were associated with lower case-fatality rates after diagnosis of breast cancer. Specifically, patients in the highest quintile of 25(OH)D had approximately half the death rate from breast cancer as those in the lowest. Conclusion: High serum 25(OH)D was associated with lower mortality from breast cancer. Serum 25(OH)D in all patients with breast cancer should be restored to the normal range (30-80 ng/ml), with appropriate monitoring. Clinical or field studies should be initiated to confirm that this association was not due to reverse causation. Source : Anticancer Research Link to Full Article Impact of Vitamin D Supplementation on Arterial Vasomotion, Stiffness and Endothelial Biomarkers in Chronic Kidney Disease Patients
Abstract Background Cardiovascular events are frequent and vascular endothelial function is abnormal in patients with chronic kidney disease (CKD). We demonstrated endothelial dysfunction with vitamin D deficiency in CKD patients; however the impact of cholecalciferol supplementation on vascular stiffness and vasomotor function, endothelial and bone biomarkers in CKD patients with low 25-hydroxy vitamin D [25(OH)D] is unknown, which this study investigated. Methods We assessed non-diabetic patients with CKD stage 3/4, age 17–80 years and serum 25(OH)D <75 nmol/L. Brachial artery Flow Mediated Dilation (FMD), Pulse Wave Velocity (PWV), Augmentation Index (AI) and circulating blood biomarkers were evaluated at baseline and at 16 weeks. Oral 300,000 units cholecalciferol was administered at baseline and 8-weeks. Results Clinical characteristics of 26 patients were: age 50±14 (mean±1SD) years, eGFR 41±11 ml/min/1.73 m2, males 73%, dyslipidaemia 36%, smokers 23% and hypertensives 87%. At 16-week serum 25(OH)D and calcium increased (43±16 to 84±29 nmol/L, p<0.001 and 2.37±0.09 to 2.42±0.09 mmol/L; p = 0.004, respectively) and parathyroid hormone decreased (10.8±8.6 to 7.4±4.4; p = 0.001). FMD improved from 3.1±3.3% to 6.1±3.7%, p = 0.001. Endothelial biomarker concentrations decreased: E-Selectin from 5666±2123 to 5256±2058 pg/mL; p = 0.032, ICAM-1, 3.45±0.01 to 3.10±1.04 ng/mL; p = 0.038 and VCAM-1, 54±33 to 42±33 ng/mL; p = 0.006. eGFR, BP, PWV, AI, hsCRP, von Willebrand factor and Fibroblast Growth Factor-23, remained unchanged. Conclusion This study demonstrates for the first time improvement of endothelial vasomotor and secretory functions with vitamin D in CKD patients without significant adverse effects on arterial stiffness, serum calcium or FGF-23. Source : PLOS One Link to Full Article New Analysis Claims Vitamin D Supplements Are Useless -- Here’s Why It’s Wrong Last November, researchers at the Kaiser Permanente Center for Health Research1 declared that vitamin supplements are probably useless when it comes to preventing heart disease and/or cancer. Their seriously flawed analysis (which, sadly, is being used by the US Preventive Services Task Force to update its recommendations on supplement use) was widely reported by the media.2 Now, the attack against vitamin supplements has heated up yet again—this time they're trying to quell the idea that vitamin D, specifically, has any useful purpose for the average person. Numerous media sources3, 4 have trumpeted the findings of a recent meta-analysis,5 which claims that vitamin D supplements are not only useless against heart disease, stroke and cancer, but may do more harm than good, and that further investigation into vitamin D would likely be "pointless"! According to the authors of the study: "Available evidence does not lend support to vitamin D supplementation and it is very unlikely that the results of a future6 single randomized clinical trial will materially alter the results from current meta-analyses." What's more, they also found that people taking vitamin D supplements had an increased risk for hip fracture, which prompted Professor Karl Michaëlsson, a researcher at Uppsala University in Sweden, to publish a call for stricter labeling on vitamin D supplements. In his editorial,7 which accompanied the featured analysis, he writes: "Without stringent indications -- i.e. supplementing those without true vitamin D insufficiency -- there is a legitimate fear that vitamin D supplementation might actually cause net harm." It should be noted that the dose given to the women in the study with increased fracture rates was 500,000 IU, all in one dose. This is an intake the body cannot absorb and process properly and the toxicity of the dose itself was not a surprise to the vitamin D researchers. The increased fractures were seen shortly after the huge dose but the rate declined in later months. Research Shows Vitamin D Sufficiency Is Critical for Good Health Meanwhile, a robust and rapidly growing body of research clearly shows that vitamin D is absolutely critical for good health and disease prevention, in part due to the fact that it influences about 10 percent of all your genes. Just one example of an important gene that vitamin D up-regulates is your ability to fight infections and chronic inflammation. It also produces over 200 anti-microbial peptides, the most important of which is cathelicidin, a naturally occurring broad-spectrum antibiotic. Since the early 2000s, scientific investigations into the effects of vitamin D have ballooned. By the end of 2012, there were nearly 34,000 published studies on the effects of vitamin D, and there are well over 800 references in the medical literature showing vitamin D's effectiveness against cancer alone. According to Carole Baggerly, founder of GrassrootsHealth, as much as 90 percent of ordinary breast cancer may in fact be related to vitamin D deficiency. Granted, the featured review is rebuking vitamin D supplements only. They're not trying to claim that vitamin D deficiency doesn't have any repercussions for your health. On the contrary, it supports the notion that sun exposure is your best source of vitamin D, as your skin naturally creates it in response to UV radiation. However, many people, especially those living in northern latitudes, are simply unable to get the necessary sun exposure needed to maintain clinically relevant vitamin D levels of 50-70 ng/ml year-round. Vitamin D Synthesis is Unlikely During Winter Months... The US map below shows the likelihood of vitamin D synthesis during February. My Vitamin D Resource page also contains maps showing vitamin D synthesis in various US states for the rest of the year. As you'll see, even if you live in the southernmost states, optimal vitamin D synthesis will not occur until June! I firmly believe that UVB exposure is a far healthier way to optimize your vitamin D levels, but if you can't use the sun or a safe tanning bed then it is best to use an oral supplement, but please recognize that it's an inferior choice. Vitamin D supplements are also among the least expensive, and the health impact of deficiency is so broad and detrimental that it simply makes little sense to scare people away from vitamin D supplements—unless you've got some ulterior reason for doing so. As I will discuss below, you DO benefit from taking other nutrient ratios into account when you use a vitamin D supplement though, which makes supplementation a bit more complex, compared to raising your levels through sun exposure. Vitamin D Supplements Under Fire The analysis, published in the journal Lancet Diabetes & Endocrinology,8 looked at 40 previously published randomized controlled trials of vitamin D supplements, with or without calcium, concluding that vitamin D supplements do not reduce the risk of heart attacks, strokes, cancers, or bone fractures in the general population by more than 15 percent. What's more, the researchers claim the effects of vitamin D supplementation are below a "futility threshold," (not a surprise when the average dose was 400-800 IU/day, already demonstrated to be ineffective) effectively rendering further investigations unnecessary. Attacks have been repeatedly made against nutritional supplements and the value of nutrition for disease prevention in general, but we may have reached a new low. WebProNews.com even went so far as to say that: "Further studies show unborn babies do not get any benefits from the vitamin when taken by pregnant women." The studies were not referenced so it is impossible to understand what led them to this mistake, but I'm firmly convinced that this is incorrect and may lead many mothers completely astray. Your baby will be born with approximately 60-70 percent of whatever your (the mother's) vitamin D level is. According to Dr. David Ayoub, who has testified in hundreds of cases of infantile rickets misdiagnosed as child abuse, mothers who are deficient in vitamin D, with levels around 18-19 ng/ml, have a significantly greater risk of having children with infantile rickets. Make no mistake about it: optimizing your vitamin D levels during pregnancy is absolutely CRITICAL for your baby's development. Granted, your best bet is to make sure you're getting plenty of sun exposure. Unfortunately, women in general are heavily indoctrinated to fear sun exposure, which has led to a virtual epidemic of vitamin D deficiency. Another study9 by the same New Zealand research team, published in October of last year, concluded that people with vitamin D deficiency and evidence of bone loss are the only ones that should be taking vitamin D. This too flies in the face of mounting research from premier vitamin D research organizations such as GrassrootsHealth.10 The Vitamin D Controversy Heats Up In the featured video at the top of this article, Carole Baggerly interviews Dr. Cedric Garland of UCSD Moores Cancer Center about this latest meta-review.11 Another prominent vitamin D expert and researcher, Dr. Michael F. Holick, M.D., PhD., author of The Vitamin D Solution, has also dismissed the analysis, calling it flawed and "silly." (Incidentally, Dr. Holick is the person responsible for identifying the major circulating form of vitamin D—25-hydroxyvitamin D3—which is the form of vitamin D doctors typically measure now to assess vitamin D status.) According to Dr. Garland: "This meta-analysis is nothing new and is already obsolete, since it is mainly based on old papers that used too little vitamin D to expect any effect. A New Zealand study saying we should only supplement people with vitamin D deficiency and evidence of bone loss is equally wrong. Virtually everyone in New Zealand, and most adults in the US, are vitamin D deficient by modern criteria, being below 32 ng/ml. The reality is that we now know that they are deficient with regard to extraskeletal effects of 25(OH)D if their serum level is below 40 ng/ml. These papers should be disregarded as obsolete work. We are moving into a new era of using vitamin D3 in doses no less that 4,000 IU/day for people aged 9 years and older... Studies using less than 4,000 IU/day are on the verge of obsolescence." Why the Latest Vitamin D Analysis Is Meritless Drs. Holick and Garland both point out the futility of looking at studies using subclinical doses of vitamin D—they're not going to show results, and for very obvious reasons. Robust evidence shows that 400 IUs of vitamin D per day is nowhere near enough. That's only about one-tenth of the effective dose! The authors of the analysis also did not include any epidemiological research, and completely ignored the most truly relevant randomized controlled trial on vitamin D and cancer. Research published in 2007 by Lappe et.al.12 showed that after four years of follow up, there was a 77% cancer risk reduction in women who received 1,100 IUs of vitamin D and 1,450 mg calcium per day, and, achieved a serum level of approximately 40 ng/ml. The serum level is the marker we are aiming for. The serum level of those who received either a placebo or calcium by itself was approximately 30 ng/ml. If a 77 percent risk reduction is not relevant, I don't know what is. "The Lappe et al. study and the many supportive epidemiological studies that preceded and followed it should prove to even the most ill-informed skeptic that vitamin D prevents most cancer," Dr. Garland says. "It is incredible that the authors of this review virtually disregarded all of the relevant epidemiology this randomized controlled clinical trial. Further, according to Dr. Leo Baggerly, Sr. Research Scientist at GrassrootsHealth, "the authors of this review 'reanalyzed' the results of the Lappe study in a completely invalid manner and included their 'corrected' results in their summary, while virtually disregarding the actual study results." The analysis' conclusion on vitamin D is in stark contrast to an ever growing number of studies showing that vitamin D (with or without calcium) has tremendous protective effect against cancer specifically. For example, another 2007 study published in the American Journal of Preventive Medicine13 concluded that a serum 25(OH)D level of more than 33 ng/mL was associated with a 50 percent lower risk of colorectal cancer. A recent Cochrane meta-review14 published in January of this year also concluded that even low dose vitamin D supplementation appears to reduce cancer mortality by almost 15 percent. Theories linking vitamin D deficiency to cancer have been tested and confirmed in more than 200 epidemiological studies, and understanding of its physiological basis stems from more than 2,500 laboratory studies. So, in a nutshell, there are two significant issues that render the featured analysis without merit:
"The authors argued that more trials of vitamin D are a waste of money and resources and will be negative," Dr. Cannell writes. "Luckily researchers at Harvard do not agree, as we all wait for their VITAL study results expected around 2017. It is a study of 20,000 healthy Americans, half of which will take an extra 2,000 IU/day compared to a group of 10,000 subjects getting a vitamin D placebo. The study will measure vitamin D blood levels in all subjects, so we will know if any of the placebo group started taking vitamin D. It will give us specific results for those subjects who obtained blood levels of > 40 ng/ml. The VITAL study will measure dozens of clinical endpoints with cancer and cardiovascular disease being the primary end points. I will be shocked if 2,000 IU/day has no effect on any clinical endpoint." The study that we are supporting, the D*action study run by GrassrootsHealth, is the only prospective study that actually has 1000's of subjects in the 40-60 ng/ml range. They are tracking many health outcomes such as breast cancer, pain, diabetes, as well as reporting on the dose response information. Initial publications have already been made with kidney stones (no increased risk) and a dose response relationship showing that to get approximately 97% of the population to 40 ng/ml, it will take 10,000 IU/day to achieve that. New papers are to be released soon on a very significant prevention effect with diabetes and pain levels. There is no need to wait to track your own health outcomes and achieve the benefits of the appropriate serum levels. Are You Vitamin D Deficient? Some news sources, such as the Star Tribune,16 have noted that high-risk groups such as babies, pregnant women, and the elderly are still advised to take vitamin D supplements. The thing is, a majority of people, regardless of age, sex, or nationality, are in fact low or deficient in vitamin D, and stand to benefit from raising their levels into the clinically significant levels, which is higher than the recommended "normal." (For more information, see the next section below.) Before the year 2000, very few doctors ever considered the possibility that you might be vitamin D deficient. But as the technology to measure vitamin D became inexpensive and widely available, more and more studies were done, and it became increasingly clear that vitamin D deficiency was absolutely rampant. For example:
" Both the IOM (Institute of Medicine) and the Endocrine Society acknowledge in treatment guidelines that 10,000 IU/day is considered the No Observed Adverse Effect Level (NOAEL). Most treatments to get serum levels in the 40-60 ng/ml range are likely to be below that level. GrassrootsHealth has also been looking at this issue and also recommends 40 to 60 nanograms per milliliter as the ideal level (see above)... A study was done in Maasai warriors who are outside every day. That really gives us an insight where we should all be with our blood levels of 25-hydroxyvitamin D. They were found to be around 50 nanograms per milliliter." ............ .... If you Opt for Oral Vitamin D, Remember Vitamin K2 Last but not least, if you do opt for a vitamin D supplement, you also need to take vitamin K2. The biological role of vitamin K2 is to help move calcium into the proper areas in your body, such as your bones and teeth. It also helps remove calcium from areas where it shouldn't be, such as in your arteries and soft tissues. Vitamin K2 deficiency is actually what produces the consequences similar to vitamin D toxicity, which includes inappropriate calcification that can lead to hardening of your arteries. The reason for this is because when you take vitamin D, your body creates more vitamin K2-dependent proteins that move calcium around in your body. Without vitamin K2, those proteins remain inactivated, so the benefits of those proteins remain unrealized. So remember, if you take supplemental vitamin D, you're creating an increased demand for K2. Together, these two nutrients help strengthen your bones and improve your heart health. Source : Dr. Mercola Link to Source + Graphs Higher Serum 25-Hydroxyvitamin D Concentrations Associate with a Faster Recovery of Skeletal Muscle Strength after Muscular Injury Tyler Barker 1,* , Vanessa T. Henriksen 1, Thomas B. Martins 2, Harry R. Hill 2,3, Carl R. Kjeldsberg 2,3, Erik D. Schneider 4, Brian M. Dixon 4 and Lindell K. Weaver 5 Abstract The primary purpose of this study was to identify if serum 25-hydroxyvitamin D (25(OH)D) concentrations predict muscular weakness after intense exercise. We hypothesized that pre-exercise serum 25(OH)D concentrations inversely predict exercise-induced muscular weakness. Fourteen recreationally active adults participated in this study. Each subject had one leg randomly assigned as a control. The other leg performed an intense exercise protocol. Single-leg peak isometric force and blood 25(OH)D, aspartate and alanine aminotransferases, albumin, interferon (IFN)-γ, and interleukin-4 were measured prior to and following intense exercise. Following exercise, serum 25(OH)D concentrations increased (p < 0.05) immediately, but within minutes, subsequently decreased (p < 0.05). Circulating albumin increases predicted (p < 0.005) serum 25(OH)D increases, while IFN-γ increases predicted (p < 0.001) serum 25(OH)D decreases. Muscular weakness persisted within the exercise leg (p < 0.05) and compared to the control leg (p < 0.05) after the exercise protocol. Serum 25(OH)D concentrations inversely predicted (p < 0.05) muscular weakness (i.e., control leg vs. exercise leg peak isometric force) immediately and days (i.e., 48-h and 72-h) after exercise, suggesting the attenuation of exercise-induced muscular weakness with increasing serum 25(OH)D prior to exercise. Based on these data, we conclude that pre-exercise serum 25(OH)D concentrations could influence the recovery of skeletal muscle strength after an acute bout of intense exercise Source : Nutrients Download Full Article Unrecognized vitamin D3 deficiency is common in Parkinson disease Harvard Biomarker Study Abstract Objective: To conclusively test for a specific association between the biological marker 25-hydroxy-vitamin D3, a transcriptionally active hormone produced in human skin and liver, and the prevalence and severity of Parkinson disease (PD). Methods: We used liquid chromatography/tandem mass spectrometry to establish an association specifically between deficiency of 25-hydroxy-vitamin D3 and PD in a cross-sectional and longitudinal case-control study of 388 patients (mean Hoehn and Yahr stage of 2.1 ± 0.6) and 283 control subjects free of neurologic disease nested in the Harvard Biomarker Study. Results: Plasma levels of 25-hydroxy-vitamin D3 were associated with PD in both univariate and multivariate analyses with p values = 0.0034 and 0.047, respectively. Total 25-hydroxy-vitamin D levels, the traditional composite measure of endogenous and exogenous vitamin D, were deficient in 17.6% of patients with PD compared with 9.3% of controls. Low 25-hydroxy-vitamin D3 as well as total 25-hydroxy-vitamin D levels were correlated with higher total Unified Parkinson’s Disease Rating Scale scores at baseline and during follow-up. Conclusions: Our study reveals an association between 25-hydroxy-vitamin D3 and PD and suggests that thousands of patients with PD in North America alone may be vitamin D–deficient. This finding has immediate relevance for individual patients at risk of falls as well as public health, and warrants further investigation into the mechanism underlying this association. Source : Journal Neurology Link to Abstract Vitamin D Levels, Hospital Infections Linked Preoperative vitamin D blood levels were significantly and inversely associated with risk for hospital-acquired infections after gastric bypass surgery, researchers found. Among obese patients with 25-hydroxyvitamin D levels lower than 30 ng/mL, there was a three-fold risk for a hospital-acquired infection after surgery versus patients whose vitamin D levels were 30 ng/mL or higher (adjusted odds ratio 3.05, 95% CI 1.34-6.94, according to Sadeq Quraishi, MD, of Massachusetts General Hospital (MGH) in Boston, and colleagues. This association did not "materially change" when adjusted for perioperative factors, they wrote online in JAMA Surgery. Low serum vitamin D has been tied to risk of hip osteoarthritis in older men and increased odds of heart failure versus those with normal serum levels, while elevated concentrations have been associated with decreased risk for ear infection in children. However, these associations have not supported vitamin D supplementation in most patients. The U.S. Preventive Services Task Force and the Institute of Medicine have each said that such supplementation is unnecessary. The authors noted that vitamin D insufficiency "may be as high as 70% to 80% in bariatric surgery patients," while rates of surgical site infections are as high as 10% among Roux-en-Y gastric bypass surgery patients in laparoscopic procedures and as high as 25% among open abdominal surgery. They studied the association between hospital-acquired infections and vitamin D serum concentration in a population of 770 Roux-en-Y gastric bypass surgery patients treated at MGH. Patient data was gathered through the hospital's research patient data registry. Vitamin D concentrations "are routinely measured in individuals scheduled to undergo Roux-en-Y gastric bypass surgery" at the site during a preoperative nutrition assessment, the authors stated. Hospital-acquired infections included surgical site infection, catheter-related urinary tract infection, pneumonia, and bacteremia more than 48 hours after hospital admission and within 30 days of surgery. Outcomes were adjusted for age, sex, race, body mass index, physical status, medical comorbidities, date of admission, type of surgery, use of neuraxial anesthesia, timely administration of prophylactic antibiotics, duration of general anesthesia, intraoperative fluid balance, intraoperative temperature nadir, intraoperative fraction of inspired oxygen concentration, perioperative blood transfusions, preoperative levels of nutritional markers, and preoperative daily vitamin D supplementation. Comorbidities included hypertension, diabetes, obstructive sleep apnea, and chronic obstructive pulmonary disease. Nutritional markers included hemoglobin A1c, iron, ferritin, hemoglobin, albumin, thiamine, parathyroid hormone, and calcium. The overall rate of hospital-acquired infection was 5.3%, the rate of surgical site infection was 2.6%, and the overall prevalence of low vitamin D in the cohort was 58%. There were no substantial baseline differences between patients with hospital-acquired infections and those without infection, other than vitamin D concentration and a higher rate of open Roux-en-Y gastric bypass procedures among those who developed an infection. Patients with low vitamin D also had a greater than four-fold increased risk for surgical site infection (aOR 4.14, 95% CI 1.16-14.83). Although associations were very slightly attenuated through a sensitivity analysis, odds of hospital-acquired infection were still three-fold, while odds of a surgical site infection were 3.93-fold. This changed to 2.91-fold odds (95% CI 1.25-6.76) and 4.32-fold odds (95% CI 1.16-16.17), respectively, in a fully-adjusted multivariable logistic regression analysis. The authors noted the study was limited by a lower baseline risk for surgical site infection, lower-than-average prevalence of hospital acquired infections, a population limited to obese adults undergoing gastric bypass surgery versus a random sample, and lack of association between procedure and other nosocomial infections. Additionally, the analysis was done at a single center and was conducted retrospectively. They concluded that "these results suggest that preoperative [vitamin D] levels may be a modifiable risk factor for postoperative nosocomial infections. Prospective studies must determine whether there is a potential benefit to preoperative optimization of vitamin D status." Source : Newswise Link to Source Vitamin D Does Not Contribute To Kidney Stones Increased vitamin D levels may prevent a wide range of diseases, according to recent studies. However, some previous studies led to a concern that vitamin D supplementation could increase an individual’s risk of developing kidney stones. However, a study of 2,012 participants – published in the American Journal of Public Health –found no statistically relevant association between 25-hydroxyvitamin D (25 (OH)D) serum level in the range of 20 to 100 ng/mL and the incidence of kidney stones. This study – led by Cedric F. Garland, DrPH, adjunct professor in the Division of Epidemiology, Department of Family and Preventive Medicine at the University of California, San Diego School of Medicine – used data from the nonprofit public health promotion organization GrassrootsHealth to follow more than 2,000 men and women of all ages for 19 months. Only 13 individuals self-reported a kidney stone diagnosis during the study. “Mounting evidence indicates that a Vitamin D serum level in the therapeutic range of 40 to 50 ng/mL is needed for substantial reduction in risk of many diseases, including breast and colorectal cancer,” said Garland, adding that this serum level is generally only achieved by taking vitamin supplements. “Our results may lessen concerns by individuals about taking vitamin D supplements, as no link was shown between such supplementation and an increased risk for kidney stones.” The study did show that older age, male gender and higher body mass index (BMI) were all risk factors for developing kidney stones. According to the researchers, individuals with high BMI need higher vitamin D intake than their leaner counterparts to achieve the same 25 (OH)D serum level. Source : Newswise Link to Source Model Selection Approach Suggests Causal Association between 25-Hydroxyvitamin D and Colorectal Cancer Lina Zgaga equal contributor mail, Felix Agakov equal contributor, Evropi Theodoratou, Susan M. Farrington, Albert Tenesa, Malcolm G. Dunlop,Paul McKeigue,Harry Campbell Abstract Introduction Vitamin D deficiency has been associated with increased risk of colorectal cancer (CRC), but causal relationship has not yet been confirmed. We investigate the direction of causation between vitamin D and CRC by extending the conventional approaches to allow pleiotropic relationships and by explicitly modelling unmeasured confounders. Methods Plasma 25-hydroxyvitamin D (25-OHD), genetic variants associated with 25-OHD and CRC, and other relevant information was available for 2645 individuals (1057 CRC cases and 1588 controls) and included in the model. We investigate whether 25-OHD is likely to be causally associated with CRC, or vice versa, by selecting the best modelling hypothesis according to Bayesian predictive scores. We examine consistency for a range of prior assumptions. Results Model comparison showed preference for the causal association between low 25-OHD and CRC over the reverse causal hypothesis. This was confirmed for posterior mean deviances obtained for both models (11.5 natural log units in favour of the causal model), and also for deviance information criteria (DIC) computed for a range of prior distributions. Overall, models ignoring hidden confounding or pleiotropy had significantly poorer DIC scores. Conclusion Results suggest causal association between 25-OHD and colorectal cancer, and support the need for randomised clinical trials for further confirmations. Source : PLOS One Link to Full Article Extra Vitamin D May Ease Crohn's Symptoms, Study Finds Vitamin D supplements may help those with Crohn's disease overcome the fatigue and decreased muscle strength associated with the inflammatory bowel disease, according to new research. Extra vitamin D "was associated with significantly less physical, emotional and general fatigue, greater quality of life and the ability to perform activities of daily living," said Tara Raftery, a research dietitian and doctoral candidate at Trinity College Dublin. She is scheduled to present the findings Saturday at the Digestive Disease Week meeting in Orlando, Fla. Raftery and her colleagues evaluated 27 patients who had Crohn's in remission. (Even in remission, fatigue and quality of life can be problematic.) The patients were assigned to take either 2,000 IUs (international units) of vitamin D a day or a dummy vitamin for three months. Before and after the study, the researchers measured hand-grip strength, fatigue, quality of life and blood levels of vitamin D. "Hand-grip strength is a proxy measure of muscle function," Raftery said. "Muscle function has been known to be reduced in Crohn's disease." Besides boosting bone growth and remodeling, vitamin D is thought to improve neuromuscular and immune function, reduce inflammation and help with other bodily tasks. Children and adults aged 1 year to 70 are advised to get 600 IUs a day; older adults, 800, according to the U.S. National Institutes of Health (NIH). Vitamin D is found in fatty fish such as salmon, in smaller amounts in cheese, egg yolks and beef liver, and in fortified foods such as milk. Sometimes called the sunshine vitamin, vitamin D is also produced when the sun's rays strike the skin. Crohn's can affect any part of the gastrointestinal tract, but most commonly affects the end of the small bowel and the beginning of the colon. Symptoms vary, but may include persistent diarrhea, rectal bleeding, abdominal cramps, and pain and constipation. About 700,000 Americans are affected, according to the Crohn's & Colitis Foundation of America. Its cause is not well understood, but Crohn's is thought to involve heredity and environmental factors. Experts believe that in those with Crohn's, the immune system attacks harmless intestinal bacteria, triggering chronic inflammation and, eventually, the disease symptoms. The daily vitamin D supplement benefitted participants in many ways, Raftery found. "When levels of vitamin D peaked at 30 ng/mL (75 nmol/L) or more [a level considered healthy], muscle function in both the dominant and non-dominant hands were significantly higher than in those who had levels less than 30 ng/mL," she said. Quality of life improved more for the D-supplement group, too. Using a standard measure to evaluate quality of life, the researchers found those who achieved a healthy blood level of the vitamin scored 24 points higher than those not on supplements. A 20-point difference is considered meaningful from a "real-world" perspective, Raftery said. Raftery now is testing vitamin D in a larger, year-long study of 130 Crohn's patients. The study results echo those of other researchers, including John White, professor of physiology at McGill University, Montreal. He said the research findings "show collectively that vitamin D acts in the intestine to stimulate the innate immune system to defend against pathogenic bacteria, and to enhance the barrier function of the intestinal epithelium [the lining of the intestine]." Other researchers, including Raftery, have also shown vitamin D can help improve muscle strength, he said. Vitamin D is getting a lot of attention in inflammatory bowel disease treatments, said Dr. Neera Gupta, co-chair of the Crohn's & Colitis Foundation of America's pediatric affairs committee. More study is needed to determine the benefits of maintaining vitamin D levels higher than currently recommended, she said. Gupta cautioned those with Crohn's not to self-dose with vitamin D. "Discuss your vitamin D status with your primary gastroenterologist to determine whether or not vitamin D supplementation is indicated in your particular situation," she said. White said supplements are inexpensive and safer than too much sun exposure. A daily intake of 2,000 IUs is considered safe, he said. The safe upper limit for adults is 4,000 IUs, according to the NIH. Source : Medline Link to Source Vitamin D and Chronic Lung Disease: A Review of Molecular Mechanisms and Clinical Studies 1,2James D. Finklea,3 Ruth E. Grossmann,5 and Vin Tangpricha4–6* Vitamin D is classically recognized for its role in calcium homeostasis and skeletal metabolism. Over the last few decades, vitamin D deficiency has increased in prevalence in adults and children. Potential extraskeletal effects of vitamin D have been under investigation for several diseases. Several cross-sectional studies have associated lower vitamin D status with decreased lung function. This finding has prompted investigators to examine the association of vitamin D deficiency with several chronic lung diseases. One major focus has been the link between maternal vitamin D status and childhood asthma. Vitamin D deficiency has also been associated with increased risk of respiratory infection from influenza A and Mycobacterium tuberculosis. Other chronic respiratory diseases associated with vitamin D deficiency include cystic fibrosis, interstitial lung disease, and chronic obstructive pulmonary disease. This review will examine the current clinical literature and potential mechanisms of vitamin D in various pulmonary diseases. Source : Advances in Nutrition 2011 Link to Full Article Low Vitamin D Tied to Poor Sepsis Outcomes Patients who are deficient in vitamin D had a greater risk of developing sepsis and an increased mortality risk if they do develop it, two studies showed.Those who had low serum levels of 25-hydroxyvitamin D (25(OH)D) before being admitted to the hospital were significantly more likely to develop sepsis after hospitalization than patients with normal pre-hospital vitamin D levels (OR 1.51, 95% CI 1.35 to 2.08), according to Kenneth Christopher, MD, of Brigham and Women's Hospital in Boston and colleagues. And among the patients who developed sepsis, the odds of dying within 30 days was greater for those with deficient or insufficient vitamin D levels (OR 1.55, 95% CI 1.02 to 2.34), Christopher reported at the Society of Critical Care Medicine meeting here. Another study, presented by H. Bryant Nguyen, MD, of Loma Linda University in California, revealed a similar association between deficient levels of 1,25-dihydroxyvitamin D (1,25(OH)2D) -- the active metabolite of 25(OH)D -- and a greater mortality risk in patients with sepsis. Christopher noted that interventional trials are ongoing in the U.S., Europe, and Australia to determine whether improving vitamin D status can change outcomes in critically ill patients, although he was skeptical. "I think the engine is so hot when patients become septic that I can't see a vitamin actually changing the course of that disease," he said, although he added that vitamin D supplementation might shorten recovery time. "It's hard to say that this is a magic bullet that's going to stop sepsis in its tracks," he said. "I just can't imagine that that's possible." Christopher and his colleagues examined data from 3,386 adult patients (mean age 66) who received care in the medical and surgical ICUs at one of two Boston hospitals -- Massachusetts General Hospital or Brigham and Women's Hospital -- from 1998 to 2011 and who had a serum 25(OH)D measurement in the year leading up to the hospitalization. Vitamin D deficiency was defined as a 25(OH)D level of 15 ng/mL or less. Levels greater than 15 ng/mL but less than 30 ng/mL were deemed insufficient and levels of 30 ng/mL or greater were considered sufficient. The average level was 29.4 ng/mL. While in the hospital, 17% of the patients developed sepsis. For the overall cohort, the in-hospital mortality rate was 12.2%. Within 1 year, 26% of the patients died. At each time point, the mortality rate was higher for those with sepsis, reaching 44.6% at 1 year. Pre-admission vitamin D deficiency was associated with a greater risk of sepsis whether it was defined according to diagnostic codes or (OR 1.51) to international sepsis conference guidelines (OR 2.45). The relationship remained significant after adjustment for potential confounders. Christopher acknowledged that the observational data precluded any definitive assessment of the causal relationship between vitamin D levels and either sepsis or mortality, and also that the study was limited by potential selection and ascertainment biases and confounding by unmeasured factors. But the study presented by Nguyen appeared to offer some support to the findings. Nguyen and his colleagues looked at the relationship between serum 1,25(OH)2D levels measured in the first 72 hours of hospitalization and 30-day mortality in patients with sepsis. The study included 91 adult patients who presented to the emergency department and were admitted to the ICU. The mean age of the patients was 59.1 and 53% were female. Overall, 11% of the patients died within the first 30 days. Compared with those who survived the first 30 days, those who died had significantly lower levels of 1,25(OH)2D at hospital admission (20.4 versus 31.5 pg/mL, P=0.04). There was no difference at any time during the study in levels of 25(OH)D, however. Parathyroid hormone levels did not differ at admission between survivors and those who died, but they were significantly higher among the patients who died at 24, 48, and 72 hours. In a multivariate analysis, 30-day mortality was significantly predicted by older age (OR 1.08, 95% CI 1.03 to 1.12). The odds of dying within 30 days were lower with higher levels of calcium (OR 0.55, 95% CI 0.38 to 0.80) and 1,25(OH)2D (OR 0.84, 95% CI 0.76 to 0.92). The discriminatory power of all three of those predictors of 30-day mortality -- as measured using the area under the receiving operating characteristics curve -- was 0.98. Nguyen acknowledged that the study was limited by the small sample size and the lack of statistical power. But he said, the study "does suggest that 1,25(OH)2D may be a viable therapeutic target in the design of future sepsis clinical trials while we're trying to tease out the various mechanisms of vitamin D deficiency in these patients." Source : Science Daily via Society of Critical Care Medicine Moromizato T, et al "Pre-hospital vitamin D deficiency and sepsis in the critically ill" SCCM 2013; Abstract 24. Additional source: Society of Critical Care Medicine Sai A, et al "Discovery of a novel outcome prognosticator for sepsis with therapeutic implications: decreased serum 1,25-dihydroxyvitamin D" SCCM 2013; Abstract 23. Link to Source Vitamin D could combat the effects of ageing in eyes Researchers funded by the Biotechnology and Biological Sciences Research Council (BBSRC) have found that vitamin D reduces the effects of ageing in mouse eyes and improves the vision of older mice significantly. The researchers hope that this might mean that vitamin D supplements could provide a simple and effective way to combat age-related eye diseases, such as macular degeneration (AMD), in people. The research was carried out by a team from the Institute of Ophthalmology at University College London and is published in the current issue of the journal Neurobiology of Ageing. Professor Glen Jeffery, who led the work, explains "In the back of the eyes of mammals, like mice and humans, is a layer of tissue called the retina. Cells in the retina detect light as it comes into the eyes and then send messages to the brain, which is how we see. This is a demanding job, and the retina actually requires proportionally more energy than any other tissue in the body, so it has to have a good supply of blood. However, with ageing the high energy demand produces debris and there is progressive inflammation even in normal animals. In humans this can result in a decline of up to 30% in the numbers of light receptive cells in the eye by the time we are 70 and so lead to poorer vision." The researchers found that when old mice were given vitamin D for just six weeks, inflammation was reduced, the debris partially removed, and tests showed that their vision was improved. The researchers identified two changes taking place in the eyes of the mice that they think accounted for this improvement. Firstly, the number of potentially damaging cells, called macrophages, were reduced considerably in the eyes of the mice given vitamin D. Macrophages are an important component of our immune systems where they work to fight off infections. However in combating threats to the aged body they can sometimes bring about damage and inflammation. Giving mice vitamin D not only led to reduced numbers of macrophages in the eye, but also triggered the remaining macrophages to change to a different configuration. Rather than damaging the eye the researchers think that in their new configuration macrophages actively worked to reduce inflammation and clear up debris. The second change the researchers saw in the eyes of mice given vitamin D was a reduction in deposits of a toxic molecule called amyloid beta that accumulates with age. Inflammation and the accumulation of amyloid beta are known to contribute, in humans, to an increased risk of age-related macular degeneration (AMD), the largest cause of blindness in people over 50 in the developed world. The researchers think that, based on their findings in mice, giving vitamin D supplements to people who are at risk of AMD might be a simple way of helping to prevent the disease. Professor Jeffery said "When we gave older mice the vitamin D we found that deposits of amyloid beta were reduced in their eyes and the mice showed an associated improvement of vision. People might have heard of amyloid beta as being linked to Alzheimer's disease and new evidence suggests that vitamin D could have a role in reducing its build up in the brain. So, when we saw this effect in the eyes as well, we immediately wondered where else these deposits might be being reduced." Professor Jeffery and his team then went on to study some of the blood vessels of their mice. They found that the mice that had been given the vitamin D supplement also had significantly less amyloid beta built up in their blood vessels, including in the aorta. Professor Jeffery continues "Finding that amyloid deposits were reduced in the blood vessels of mice that had been given vitamin D supplements suggests that vitamin D could be useful in helping to prevent a range of age-related health problems, from deteriorating vision to heart disease." Professor Jeffery thinks that this link between vitamin D and a range of age-related diseases might be linked to our evolutionary history. For much of human history our ancestors lived in Africa, probably without clothes, and so were exposed to strong sunlight all year round. This would have triggered vitamin D production in the skin. Humans have only moved to less sunny parts of the world and adopted clothing relatively recently and so might not be well adapted to reduced exposure to the sun. Secondly, life expectancy in the developed world has increased greatly over the past few centuries, so reduced exposure to vitamin D is now coupled with exceptionally long lifespan. Professor Jeffery said "Researchers need to run full clinical trials in humans before we can say confidently that older people should start taking vitamin D supplements, but there is growing evidence that many of us in the Western world are deficient in vitamin D and this could be having significant health implications." Professor Douglas Kell, BBSRC Chief Executive said "Many people are living to an unprecedented old age in the developed world. All too often though, a long life does not mean a healthy one and the lives of many older people are blighted by ill health as parts of their bodies start to malfunction. "If we are to have any hope of ensuring that more people can enjoy a healthy, productive retirement then we must learn more about the changes that take place as animals age. This research shows how close study of one part of the body can lead scientists to discover new knowledge that is more widely applicable. By studying the fundamental biology of one organ scientists can begin to draw links between a number of diseases in the hope of developing preventive strategies." Source : BBSRC via Vitamin D rejuvenates aging eyes by reducing inflammation, clearing amyloid beta and improving visual function. By Lee V, Rekhi E, Kam JH, Jeffery G. is available online at: www.ncbi.nlm.nih.gov/pubmed/22217419 Link to Source High Vitamin D Levels in Pregnancy May Protect Mother More Than Baby Against Multiple Sclerosis Pregnant women who have higher levels of vitamin D in their blood may have a lower risk of developing multiple sclerosis (MS) than women with lower levels, while their babies may not see the same protective effect, according to a study published in the November 20, 2012, online issue of Neurology®, the medical journal of the American Academy of Neurology. “In our study, pregnant women and women in general had a lower risk for MS with higher levels of the vitamin, as expected. However, a mother’s levels of vitamin D during early pregnancy did not have an effect on MS risk for her baby,” said study author Jonatan Salzer, MD, with Umeå University Hospital in Sweden. For the study, scientists reviewed information about 291,500 blood samples from 164,000 people collected since 1975 in the northern half of Sweden. Of those, 192 people developed MS an average of nine years after their blood sample was drawn, and there were 37 blood samples drawn during pregnancy from mothers whose children went on to develop MS later in life. The research found that women who had high levels of vitamin D in their blood had a 61 percent lower risk of developing MS, compared to those who had low levels of vitamin D in their blood. Overall, few people had high levels of vitamin D. Only seven of the 192 people who developed MS, or four percent, had high vitamin D levels, compared to 30 of 384 controls without the disease, or eight percent. No association was found between the mother’s vitamin D level and whether her child would later develop MS. “Since we found no protective effect on the baby for women with higher levels of vitamin D in early pregnancy, our study suggests the protective effect may start in later pregnancy and beyond,” said Salzer. “Another interesting finding in our study was that the vitamin D levels became gradually lower with time from 1975 and onward. It is possible that this decline in vitamin D status is linked to the increasing numbers of MS cases seen worldwide.” Sources of vitamin D are diet, supplements and the sun. Source : Newswise Link to Source Vitamin D May Speed TB Recovery Vitamin D supplementation may bolster the performance of antibiotics in patients with pulmonary tuberculosis and accelerate the resolution of inflammatory responses, researchers found. In a randomized, controlled trial, patients who took high-dose vitamin D in addition to anti-tuberculous therapy cleared the bacterium significantly faster than those who took antimicrobials alone (HR 1.69, 95% CI 1.02 to 2.79, P=0.04), reported Adrian Martineau, PhD, of Queen Mary University of London, and colleagues in the Proceedings of the National Academy of Sciences online. "Adding vitamin D to antibiotic therapy accelerated sputum smear conversion, augmented treatment-induced increases in lymphocyte count, and enhanced the suppressive effect of treatment on monocyte count, inflammatory markers, and circulating concentrations of chemokines," they explained. Calcitriol, the active metabolite of vitamin D, has been shown to induce innate antimicrobial responses in vitro, and the vitamin itself was used to treat TB before antibiotics were available. Yet the effects of vitamin D supplementation on immune response in humans hasn't been well-studied. Martineau and colleagues conducted a longitudinal study of immune response in 95 patients on antimicrobial therapy for smear-positive pulmonary TB. Patients were randomized to adjunctive high-dose vitamin D (four doses of 2.5 mg vitamin D3 every 2 weeks) or placebo. They were assessed for a period of 8 weeks. The group noted that many patients had markedly low vitamin D levels at baseline. The researchers found that patients who had the additional vitamin D cleared Mycobacterium tuberculosis from their sputum faster than those who only had antibiotics. The median time to sputum smear conversion was significantly shorter with vitamin D than among controls (23 days versus 36 days, HR 1.69, 95% CI 1.02 to 2.79, P=0.04). Monocyte counts fell more rapidly (P=0.0003) and lymphocyte counts rose faster (P=0.0364) in patients taking vitamin D, they reported. The vitamin also accelerated the effect of anti-tuberculous therapy on 17 circulating parameters, especially affecting the chemokine CXCL9, with serum concentrations falling significantly faster in patients taking vitamin D. Serum concentrations of three other chemokines -- CXCL10, CCL3, and CCL5 -- as well as IFN-γ also fell more rapidly in supplemented patients (P≤0.0164 and P=0.0112, respectively). In further analyses, vitamin D also appeared to suppress antigen-stimulated proinflammatory cytokine responses, in particular for IL-1 receptor agonist (IL-1RA), IL-6, IL-12, and TNF (P≤0.0437). On the other hand, it attenuated the suppressive effect of antimicrobial therapy on antigen-stimulated secretion of IL-4, CC chemokine ligand 5, and IFN-α (P≤0.0323), they reported. Martineau and colleagues also observed that vitamin D appeared to have immunomodulatory effects even in patients who had the TT and Tt genotypes of the TaqI VDR polymorphism, suggesting that benefits are not limited to those with the tt genotype, as had been previously reported. They concluded that the findings suggest "a potential role for adjunctive vitamin D supplementation in the treatment of pulmonary infections to accelerate resolution of inflammatory responses associated with increased risk of mortality." They added that vitamin D may also boost the response to antimicrobial therapy in patients with pneumonia and sepsis. Source reference: Coussens AK, et al "Vitamin D accelerates resolution of inflammatory responses during tuberculosis treatment" PNAS 2012; DOI: 10.1073/pnas.1200072109/-/DCSupplemental. Source : MedPage Today Link to Source Vitamin D May Protect Lung Function in Smokers Vitamin D deficiency is associated with worse lung function and more rapid decline in lung function over time in smokers, suggesting that vitamin D may have a protective effect against the effects of smoking on lung function, according to a new study from researchers in Boston. “We examined the relationship between vitamin D deficiency, smoking, lung function, and the rate of lung function decline over a 20 year period in a cohort of 626 adult white men from the Normative Aging Study,” said lead author Nancy E. Lange, MD, MPH, of the Channing Laboratory, Brigham and Women’s Hospital. “We found that vitamin D sufficiency (defined as serum vitamin D levels of >20 ng/ml) had a protective effect on lung function and the rate of lung function decline in smokers.” The findings were published online ahead of print publication in the American Thoracic Society’s American Journal of Respiratory and Critical Care Medicine. In the study, vitamin D levels were assessed at three different time points between 1984 and 2003, and lung function was assessed concurrently with spirometry. In vitamin D deficient subjects, for each one unit increase in pack-years of smoking, mean forced expiratory volume in one second (FEV1) was 12 ml lower, compared with a mean reduction of 6.5 ml among subjects who were not vitamin D deficient. In longitudinal models, vitamin D deficiency exacerbated the effect of pack years of smoking on the decline in FEV1 over time. No significant effect of vitamin D levels on lung function or lung function decline were observed in the overall study cohort, which included both smokers and non-smokers. “Our results suggest that vitamin D might modify the damaging effects of smoking on lung function,” said Dr. Lange. “These effects might be due to vitamin D’s anti-inflammatory and anti-oxidant properties.” The study has some limitations, including that the data is observational only and not a trial, that vitamin D levels fluctuate over time, and that the study has limited generalizability due to the cohort being all elderly men. “If these results can be replicated in other studies, they could be of great public health importance,” said Dr. Lange. “Future research should also examine whether vitamin D protects against lung damage from other sources, such as air pollution.” “While these results are intriguing, the health hazards associated with smoking far outweigh any protective effect that vitamin D may have on lung function ,” said Alexander C. White MS, MD, chair of the American Thoracic Society’s Tobacco Action Committee. “First and foremost, patients who smoke should be fully informed about the health consequences of smoking and in addition be given all possible assistance to help them quit smoking.” Source : Newswise Link to Source Vitamin D Deficiency and Lung Function in Asthmatic Children Vitamin D deficiency is associated with poorer lung function in asthmatic children treated with inhaled corticosteroids, according to a new study from researchers in Boston.“In our study of 1,024 children with mild to moderate persistent asthma, those who were deficient in vitamin D levels showed less improvement in pre-bronchodilator forced expiratory volume in 1 second (FEV1) after one year of treatment with inhaled corticosteroids than children with sufficient levels of vitamin D,” said Ann Chen Wu, MD, MPH, assistant professor in the Department of Population Medicine at Harvard Medical School and Harvard Pilgrim Health Care Institute. “These results indicate that vitamin D supplementation may enhance the anti-inflammatory properties of corticosteroids in patients with asthma.” The findings were published online ahead of print publication in the American Thoracic Society’s American Journal of Respiratory and Critical Care Medicine. The study was conducted using data from the Childhood Asthma Management Program, a multi-center trial of asthmatic children between the ages of five and 12 years who were randomly assigned to treatment with budesonide (inhaled corticosteroid), nedocromil, or placebo. Vitamin D levels were categorized as deficient (≤ 20 ng/ml), insufficient (20-30 ng/ml), or sufficient (> 30 ng/ml). Among children treated with inhaled corticosteroids, pre-bronchodilator FEV1 increased during 12 months of treatment by 330 ml in the vitamin D insufficiency group and 290 ml in the vitamin D sufficiency group, but only 140 ml in the vitamin D deficient group. Compared with children who were vitamin D sufficient or insufficient, children who were vitamin D deficient were more likely to be older, be African American, and have higher BMI. Compared with being vitamin D deficient, being vitamin D sufficient or insufficient was associated with a greater change in pre-bronchodilator FEV1 over 12 months of treatment after adjustment for age, gender, race, BMI, history of emergency department visits, and season that the vitamin D specimen was drawn. The study had some limitations, including a small sample size of 101 vitamin D deficient children, and the investigators only studied vitamin D levels at one time point. “Our study is the first to suggest that vitamin D sufficiency in asthmatic children treated with inhaled corticosteroids is associated with improved lung function,” said Dr. Wu. “Accordingly, vitamin D levels should be monitored in patients with persistent asthma being treated with inhaled corticosteroids. If vitamin D levels are low, supplementation with vitamin D should be considered.” To read the article in full, please visit: www.thoracic.org//media/press-releases/resources/Wu.docx. Source : Newswise Link to Source High Dose Vitamin D Prevents Fractures High doses of vitamin D prevent fractures in older people – as long as they take the substance regularly, researchers reported. In a meta-analysis, oral doses of at least 800 IU were associated with reductions in the risk of both hip and nonvertebral fractures, according to Heike Bischoff-Ferrari, MD, DrPH, of University Hospital in Zurich, and colleagues. The analysis differs from previous studies and other meta-analyses in that it looked at how much vitamin D participants actually took, rather than what dose they were assigned to take, Bischoff-Ferrari and colleagues reported in the July 5 issue of the New England Journal of Medicine. Fractures are common in older people and one strategy to prevent them might be vitamin D supplements, the researchers noted, but studies of the issue have been inconsistent. To try to clarify the matter, they looked for all controlled studies of oral vitamin D, with or without calcium, among people 65 and older. They included 12 studies and had participant-level data on 30,011 volunteers. The primary end points were the risks of hip fracture and any nonvertebral fracture, and the primary analyses compared the actual intake of vitamin D supplementation, in quartiles, to the controls, with actual intake calculated as the assigned dose plus any additional supplemental dose, adjusted for adherence. The study design is important, because it takes into account the biology of vitamin supplementation, according to Robert Heaney, MD, of the Creighton University Medical Center in Omaha, Neb. In an accompanying editorial in the journal, Heaney argued that the inconsistent outcomes of earlier work might be the result of an overfocus in meta-analyses on the methods used in individual trials. "The question of how much vitamin D is enough is likely to remain muddled as long as meta-analyses focus on trial methodology rather than on biology," he argued. But Heaney noted that the results of the current meta-analysis are in accordance with recommendations of the Endocrine Society. "It would appear to be prudent, and probably helpful as well, to ensure an intake at the upper end of the range" that the researchers found effective. Bischoff-Ferrari and colleagues found that, in an intention-to-treat analysis, there was a nonsignificant 10% reduction in the risk of hip fracture and a significant (at P=0.03) 7% reduction in the risk of nonvertebral fracture. On the other hand, when they took into account actual vitamin D intake, they found a 30% reduction in the risk of hip fracture but only for those in the highest quartile of intake – 792 to 2,000 IU a day. The relative risk in that group, compared with controls, was 0.70, with a 95% confidence interval from 0.58 to 0.86, and was significant at P<0.001. They also found a 14% reduction in the risk of any nonvertebral fracture, but again only in the highest quartile. The relative risk was 0.86, with a 95% confidence interval from 0.66 to 0.96, and was significant at P=0.007. A sensitivity analysis, not including any outside supplements, had similar results, they reported. Heaney commented that the benefits of supplements might be affected by baseline levels of vitamin D but noted that such information has not been routinely collected in trials of the substance. Indeed, baseline levels of hydroxyvitamin D were only available for 4,383 participants, Bischoff-Ferrari and colleagues reported. Despite that, the results among those participants were similar to those in the whole group, they found. In addition to the absence of baseline hydroxyvitamin D levels, other study limitations included inability to separate calcium and vitamin D intake as those receiving high doses of vitamin D were all taking calcium and lack of trial level data for two of the 14 included trials. The study was supported by the Swiss National Foundations, the European Commission, and DSM Nutritional Products. Bischoff-Ferrari reported financial links with DSM, Amgen, Novartis, MSD, WILD, Roche, and Nestle. Heaney reported financial links with the International Dairy Foods Association, the National Dairy Council, the Council for Responsible Nutrition, and the Coca-Cola Co. Primary source: New England Journal of Medicine Source reference: Bischoff-Ferrari HA, et al "A pooled analysis of vitamin D dose requirements for fracture prevention" N Engl J Med 2012; DOI: 10.1056/NEJMoa1109617. Additional source: New England Journal of Medicine Source reference: Heaney RP "Vitamin D -- baseline status and effective dose" N Engl J Med 2012; DOI: 10.1056/NEJMe1206858. Source : Medpage Today Link to Source Mainstream Medicine Takes Another Big Step Backward on Vitamin D A national task force on “preventive” medicine is making dangerous new pronouncements based on profoundly flawed research and thinking. The US Preventive Services Task Force (UPSTF) has issued a draft recommendation to take no vitamin D supplements. In their view, the scientific evidence is “insufficient” to assess the benefits of vitamin D supplementation (with or without calcium) to prevent cancer in adults, nor the benefits of vitamin D and calcium (in combination) to prevent fractures in men or in postmenopausal women. The report recommends against daily supplementation with 400 IU of vitamin D3 and 1,000 mg of calcium carbonate for the prevention of fractures in postmenopausal women, even though the group had previously concluded that vitamin D supplementation is effective in preventing falls in community-dwelling adults aged 65 years or older who are at increased risk for falls. This group’s official recommendation is even more conservative than the Institute of Medicine’s disastrous report from last year. It appears to be driven by a seriously flawed review (a meta-analysis) of vitamin D research, which has skewed the results. The UPSTF was created in 1984 as a federally sponsored national task force in “preventive” medicine to improve the health of Americans. Under the recent healthcare reform legislation, the Agency on Healthcare Research and Quality (AHRQ) was directed to provide further support to the task force. But note how they define preventive medicine: “Evidence-based recommendations about clinical preventive services such as screenings, counseling services, or preventive medications.” This definition does not include diet, supplement, and lifestyle choices to maintain health—in other words, the things that research has shown to be truly preventive. The task force’s research priorities, as listed in their latest newsletter, further emphasize the exclusive focus on screenings, medication and surgery—more of the standard “sick-care” model. With such a strong focus on conventional medicine, it’s not surprising that the task force’s recommendations on vitamin D and calcium supplementation are mostly nonsense. At least the task force got one thing right, even though inadvertently, when they counseled against taking combined D and calcium supplements. Good research tells us to take calcium supplements not only with D, but with other co-factors, especially Vitamin K2, lest the calcium migrate to the wrong part of the body. But how did the task force get it so wrong, telling everyone to take no supplemental D? As the Council for Responsible Nutrition notes, the task force’s original meta-analysis last December ignored many, many important scientific studies, focusing only on nineteen random-controlled trials (RCTs) and twenty-eight observational studies, concluding that vitamin D was effective in reducing cancer risk and fractures among older adults. However, these new draft recommendations look at an even narrower swath of studies. They don’t look at any observational studies, only RCTs. The RCT they focus on the most is the Women’s Health Initiative (WHI). Unfortunately, the control group in the WHI study was compromised. That group was not supposed to receive any calcium supplementation at all, yet some in the group took calcium supplements or had more calcium in their diet than the study allowed. So much for random-controlled studies being the “gold standard” of scientific research! Anyway, RCTs are not the best way to study the therapeutic effects of vitamins and minerals. Often, to be effective, vitamins and minerals need to be taken with important co-factors, as noted above, though these are rarely included in the RCTs. It is also true that each individual is unique and therefore might require different levels of supplementation to be effective. But minimal doses cannot be expected to produce results in anyone. The task force acknowledged that the administered dosage of vitamin D in the WHI and other similar clinical studies “may have been too low to cause an effect”—but they still used them as the basis for their conclusions! Last year’s extraordinarily conservative IOM report recommended 600 IU of vitamin D for people between the ages of 1 and 70, while many integrative physicians recommend much higher doses of D3 supplementation. Both Harvard and the Vitamin D Council recommend 1,000 to 5,000 IU a day. Note that the IOM recommended exactly the same amount of D for infants, pregnant mothers, adults in the prime of life, and older people under 70, no matter what age or weight. This makes no sense at all. And how are people going to be sure of getting even 600 IU of D3 per day without supplements? There is very little D in food and many people live in zones where sunlight is too weak or indirect to produce D on our skin, especially in the winter. Someone living in New York can sunbathe in freezing temperatures all winter but they won’t produce any D. Besides, everyone has been told by conventional doctors not to go out in the sun without sunscreen, and applying sunscreen means that you won’t produce vitamin D either. Studies show that 87% of patients are mildly to severely deficient in vitamin D, and a least one-third of Americans are wholly deficient in it—to the great detriment of their overall health and immunity. Vitamin D’s benefits are many. At the right level, it appears to prevent flu and colds by boosting the innate immune response and turning on an antimicrobial protein, among other actions. Vitamin D also balances the immune response, preventing inflammation that can lead to flu-related complications such as bacterial pneumonia or lung infection. On top of that, a few drug companies (Receptor Therapeutics and Chytochroma, to name two) are spending huge sums of money on clinical trials on vitamin D as a cancer cure—which completely undermines the UPSTF’s statement that there is no reason to believe that vitamin D has anti-cancer benefits! So once again, mainstream medicine pooh-poohs the benefit of nutritional supplements to fight diseases, only to use those same supplements to develop drugs to fight the same diseases—albeit at a much higher cost, and at greater danger to the patient. Source : Alliance for Natural Health Link to Source Treating Vitamin D Deficiency May Improve Depression Women with moderate to severe depression had substantial improvement in their symptoms of depression after they received treatment for their vitamin D deficiency, a new study finds. The case report series will be presented Saturday at The Endocrine Society’s 94th Annual Meeting in Houston.Because the women did not change their antidepressant medications or other environmental factors that relate to depression, the authors concluded that correction of the patients’ underlying shortage of vitamin D might be responsible for the beneficial effect on depression. “Vitamin D may have an as-yet-unproven effect on mood, and its deficiency may exacerbate depression,” said Sonal Pathak, MD, an endocrinologist at Bayhealth Medical Center in Dover, Del. “If this association is confirmed, it may improve how we treat depression.” Pathak presented the research findings in three women, who ranged in age from 42 to 66. All had previously diagnosed major depressive disorder, also called clinical depression, and were receiving antidepressant therapy. The patients also were being treated for either Type 2 diabetes or an underactive thyroid (hypothyroidism). Because the women had risk factors for vitamin D deficiency, such as low vitamin D intake and poor sun exposure, they each underwent a 25-hydroxyvitamin D blood test. For all three women, the test found low levels of vitamin D, ranging from 8.9 to 14.5 nanograms per milliliter (ng/mL), Pathak reported. Levels below 21 ng/mL are considered vitamin D deficiency, and normal vitamin D levels are above 30 ng/mL, according to The Endocrine Society. Over eight to 12 weeks, oral vitamin D replacement therapy restored the women’s vitamin D status to normal. Their levels after treatment ranged from 32 to 38 ng/mL according to the study abstract. After treatment, all three women reported significant improvement in their depression, as found using the Beck Depression Inventory. This 21-item questionnaire scores the severity of sadness and other symptoms of depression. A score of 0 to 9 indicates minimal depression; 10 to 18, mild depression; 19 to 29, moderate depression; and 30 to 63, severe depression. One woman’s depression score improved from 32 before vitamin D therapy to 12, a change from severe to mild depression. Another woman’s score fell from 26 to 8, indicating she now had minimal symptoms of depression. The third patient’s score of 21 improved after vitamin D treatment to 16, also in the mild range. Other studies have suggested that vitamin D has an effect on mood and depression, but there is a need for large, good-quality, randomized controlled clinical trials to prove whether there is a real causal relationship, Dr Pathak said. “Screening at-risk depressed patients for vitamin D deficiency and treating it appropriately may be an easy and cost-effective adjunct to mainstream therapies for depression,” she said. Source : Newswise Link to Source Low Vitamin D Level Is Linked to Greater Chance of Risk Factors For Type 2 Diabetes A new study presents more evidence of a possible link between low vitamin D levels and a higher risk of Type 2 diabetes and heart disease. The results will be presented Saturday at The Endocrine Society’s 94th Annual Meeting in Houston.The study found an inverse relationship between the level of vitamin D in the blood and the presence of the metabolic syndrome, which is a group of risk factors that increases the risk of heart disease and Type 2 diabetes. People with the highest blood levels of vitamin D had a 48 percent lower risk of having the metabolic syndrome than did those with the lowest vitamin D levels, the authors reported. “This association has been documented before, but our study expands the association to people of diverse racial and ethnic backgrounds,” said the lead author, Joanna Mitri, MD, a research fellow at Tufts Medical Center in Boston. “These include minority groups that are already at higher risk of diabetes.” Furthermore, all study participants were at risk of developing diabetes because they had prediabetes, abnormally high blood sugar levels that are not yet high enough to be classified as diabetes. Prediabetes affects an estimated 79 million Americans ages 20 or older, according to 2010 statistics from the Centers for Disease Control and Prevention. Mitri and her co-investigators conducted the study using data from participants of the Diabetes Prevention Program, a large, now-completed study funded by the National Institutes of Health. They divided study subjects into three groups based on plasma 25-hydroxyvitamin D level, which is the most common way used to measure vitamin D status in the body, according to Mitri. The Institute of Medicine recommends a 25-hydroxyvitamin D level of 20 to 30 ng/mL as adequate for healthy people. In the new study, the group with the highest levels of vitamin D had a median vitamin D concentration of 30.6 nanograms per milliliter, or ng/mL, and those in the lowest group had a median vitamin D concentration of 12.1 ng/mL. The risk of having the metabolic syndrome with a high vitamin D level was about one half the risk with a low vitamin D level, Mitri said. The researchers also found an association between vitamin D status and some of the individual components of the metabolic syndrome, which includes a large waist size, low HDL (“good”) cholesterol, high triglycerides (fats in the blood), high blood pressure and high blood glucose (sugar). Study participants with the best vitamin D status had a smaller waist circumference, higher HDL cholesterol and lower blood sugar. Mitri cautioned that their research does not prove that vitamin D deficiency causes Type 2 diabetes, or even that there is a link between the two conditions. “However, the metabolic syndrome is common, and progression to Type 2 diabetes is high,” she said. “If a causal relationship can be established in ongoing and planned studies of vitamin D, this link will be of public health importance, because vitamin D supplementation is easy and inexpensive.” Source : Newswise Link to Source Childrens body fat linked to low vitamin D in moms Low vitamin D status has been linked to obesity in adults and children, but little is known about how variation in a mother’s status affects the body composition of her child. Low vitamin D status is common among young women in the UK, and although women are recommended to take an additional 10μg/day of vitamin D in pregnancy, supplementation is currently not routine. In new research, published in the American Journal of Clinical Nutrition, scientists at the University of Southampton have compared the vitamin D status of 977 pregnant women with the body composition of their children. The differences in the children’s body fat could not be explained by other factors such as mother’s weight gain in pregnancy, or how physically active the children were. The 977 women are part of the Southampton Women’s Survey, one of the largest women’s surveys in the UK. Siân Robinson, principal research fellow at the University of Southampton, who led the study, says: “In the context of current concerns about low vitamin D status in young women, and increasing rates of childhood obesity in the UK, we need to understand more about the long-term health consequences for children who are born to mothers who have low vitamin D status. “Although there is growing evidence that vitamin D status is linked to body fatness in children and adults, this research now suggests that the mother’s status in pregnancy could be important, too. “An interpretation of our data is that there could be programmed effects on the fetus arising from a lack of maternal vitamin D that remain with the baby and predispose him or her to gain excess body fat in later childhood. Although further studies are needed, our findings add weight to current concerns about the prevalence of low vitamin D status among women of reproductive age.” Source : Futurity.org Link to Source Vitamin D Eases Menstrual Cramps By John Gever, Reviewed by Zalman S. Agus, MD; Emeritus Professor, Perelman School of Medicine at the University of Pennsylvania Women with a history of severe menstrual cramps reported significantly less pain when they took an ultra-high dose of vitamin D five days before their next expected period, according to results of a small randomized trial. Of 20 women taking the 300,000-IU dose of vitamin D, 15 reported pain scores at least two points lower than their average over a four-cycle baseline period, on a standard 10-point visual analog scale, reported Antonino Lasco, MD, of the University of Messina in Italy, and colleagues. Only four of 20 participants assigned to placebo in the trial showed any improvement relative to baseline, the researchers indicated in a research letter appearing in the Feb. 27 issue of Archives of Internal Medicine. Additionally, no patients in the vitamin D group reported using NSAID painkillers during the trial's treatment phase, whereas eight women in the placebo group took the medications at least once (P=0.003). But in an accompanying commentary, two U.S. researchers pointed out that the vitamin D dose used in the study, even when averaged over two months, was still higher than the "tolerable upper limit" established last year by the Institute of Medicine. Elizabeth R. Bertone-Johnson, ScD, of the University of Massachusetts in Amherst, and JoAnn E. Manson, MD, DrPH, of Brigham and Women's Hospital in Boston, recommended larger and longer trials not only to confirm the benefit of high-dose vitamin D, but also to determine how long it may last -- and, thus, how frequently the doses would have to be given. Menstrual cramps and other symptoms of dysmenorrhea are caused by an excessive uterine production of prostaglandins, the authors noted in their letter. Cramps are usually managed with the use of nonsteroidal anti-inflammatory drugs (NSAIDs). Lasco and colleagues sought to test vitamin D for menstrual cramps because vitamin D appears to affect pathways that also are involved in pain and in uterine physiology. In particular, it inhibits prostaglandin synthesis, and previous studies have shown that the enzyme that converts vitamin D into its active metabolites is expressed in the uterus. Women complaining of at least four consecutive painful menstrual periods during the previous six months and who had serum levels of 25-hydroxyvitamin-D (25-OH-D) below 45 ng/mL (the lowest quartile of the normal range in the researchers' laboratory) were recruited for the trial. Those with previous or current use of an intrauterine device for contraception were excluded, but birth control by some other means was required during the baseline observation period. Those assigned to the vitamin D group in the double-blinded trial received a single oral dose of 300,000 IU of cholecalciferol five days before they were expected to begin the next menstrual cycle. Participants recorded menstrual pain on the 10-point scale for four cycles during the observation phase and for two cycles during the treatment phase. The primary outcome measure was the difference between the baseline average and the score during the second menstrual cycle post treatment. Most patients in the placebo group had no change in scores relative to baseline. Four had a one-point decrease in pain; four others reported worsening by one or two points after treatment. In the vitamin D group, every participant reported at least some improvement: five by one point, eight by two points, four by three points, two by four points, and one with a six-point improvement. Averages for the whole group were 5.85 at baseline and 3.50 at the second post-treatment cycle (P<0.001). Lasco and colleagues indicated that there were no baseline differences between groups in age, body mass index, menstrual pain, or serum 25-OH-D. In the accompanying commentary, Bertone-Johnson and Manson said the findings were plausible on the basis of known anti-inflammatory effects of vitamin D. These are not confined to the vitamin's suppression of prostaglandin production, but may also involve nuclear factor kappa-B and MAPK phosphatase-5 activity. But the enormous dose used in the study was a concern. "Follow-up of participants in clinical trials of vitamin D must be extended to better evaluate adverse effects and compare risks and benefits," they wrote. Bertone-Johnson and Manson pointed particularly to a 2010 study that found increased fractures and falls in older women given annual 500,000-IU doses. They argued that the 300,000-IU dose could be problematic if, in fact, the benefit only lasts two months and therefore must be repeated that often. Such a dose equates to about 5,000 IU/day -- well above the 4,000 IU/day that the IOM indicated was the maximum tolerable dose. Future studies should also establish a cutoff for baseline serum level of 25-OH-D below which supplementation would most likely be beneficial, Bertone-Johnson and Manson suggested. Source : MedPage Today Link to Source Vitamin D and incidence of diabetes: A prospective cohort study Vitamin D and diabetes incidence. González-Molero I, Rojo-Martínez G, Morcillo S, Gutiérrez-Repiso C, Rubio-Martín E, Almaraz MC, Olveira G, Soriguer F.Source Servicio de Endocrinología y Nutrición, Hospital Universitario Carlos Haya, Málaga, Spain; Ciber de Diabetes y Metabolismo (CIBERDEM), Spain. Abstract BACKGROUND & AIMS: To investigate the relationship between levels of 25-hydroxyvitamin D and the incidence of type 2 diabetes in a Spanish population. METHODS: We undertook a population-based prospective study in a population from southern Spain. The first phase of the study (1996-1998) included 1226 individuals. Of this original cohort, 988 persons were reassessed in 2002-2004 and 961 in 2005-2007. Measurements were made of 25-hydroxyvitamin D and intact parathyroid hormone in 2002-2004 and an oral glucose tolerance test was done in three time points. RESULTS: The incidence of diabetes in subjects with 25-hydroxyvitamin D levels ≤18.5 ng/mL (percentile 25) was 12.4% vs 4.7% in subjects with levels >18.5 ng/mL. The likelihood of having diabetes during the four years of follow-up was significantly lower in the subjects with higher levels of 25-hydroxyvitamin D [OR = 0.17 (0.05-0.61)]. None of the subjects with levels higher than 30 ng/mL developed diabetes. CONCLUSION: In this prospective study, we found a significant inverse association between serum 25-hydroxyvitamin D levels and the risk for type 2 diabetes in a population from the south of Spain. Source : Clinical Nutrition Link to Abstract Randomized trial of vitamin D supplementation to prevent seasonal influenza A in school children Mitsuyoshi Urashima,Takaaki Segawa, Minoru Okazaki, Mana Kurihara,Yasuyuki Wada, and Hiroyuki Ida Abstract Background: To our knowledge, no rigorously designed clinical trials have evaluated the relation between vitamin D and physician-diagnosed seasonal influenza. Objective: We investigated the effect of vitamin D supplements on the incidence of seasonal influenza A in schoolchildren. Design: From December 2008 through March 2009, we conducted a randomized, double-blind, placebo-controlled trial comparing vitamin D3 supplements (1200 IU/d) with placebo in schoolchildren. The primary outcome was the incidence of influenza A, diagnosed with influenza antigen testing with a nasopharyngeal swab specimen. Results: Influenza A occurred in 18 of 167 (10.8%) children in the vitamin D3 group compared with 31 of 167 (18.6%) children in the placebo group [relative risk (RR), 0.58; 95% CI: 0.34, 0.99; P = 0.04]. The reduction in influenza A was more prominent in children who had not been taking other vitamin D supplements (RR: 0.36; 95% CI: 0.17, 0.79; P = 0.006) and who started nursery school after age 3 y (RR: 0.36; 95% CI: 0.17, 0.78; P = 0.005). In children with a previous diagnosis of asthma, asthma attacks as a secondary outcome occurred in 2 children receiving vitamin D3 compared with 12 children receiving placebo (RR: 0.17; 95% CI: 0.04, 0.73; P = 0.006). Conclusion: This study suggests that vitamin D3 supplementation during the winter may reduce the incidence of influenza A, especially in specific subgroups of schoolchildren. Source : The American Journal of Clinical Nutrition Link to Full Article “Vitamin D Warning!” says MSNBC. “High Vitamin D Levels Linked to Serious Heart Condition” says Fox. What could be behind these terrifying headlines? A new study says that taking excessive amounts of vitamin D may cause atrial fibrillation (AF). The research, presented at the annual meeting of American Heart Association, says that people who take too much vitamin D were 2½ times more likely to develop AF. Well, not quite. That’s what the media have been saying the study says. But it didn’t. It says that in their study of 132,000 patients, AF was found in 1.4% of the study participants whose levels of vitamin D were normal, and in 3.8% of those whose levels were excessive. But the journalists couldn’t even get the basic facts straight. All the articles contained the same blunder that rendered the data meaningless. Everyone rushed ahead, relying only on the press release or the abstract, where the error originated, without waiting for the study itself to be published in the future. The amount of vitamin D in the blood is measured in ng/ml—that is, nanograms of the vitamin per milliliter of blood serum. The press release and the study abstract both say, erroneously, that problems arise when vitamin D levels go over 100 ng/dl—that is, nanograms per deciliter. That’s the equivalent of 1 ng/ml. To say that 100 ng/dl is “excessive” is beyond absurd; anything under 30 ng/ml is considered deficient, and 1 ng/ml is next to impossible to achieve! A quick check with the study authors would have corrected that error—which means the journalists knew nothing whatsoever about the subject, and didn’t bother to do any research. Besides, after correcting for this gross error, there is no real story here--the study merely confirms what scientists already thought:
The optimum level of D is more often debated. The scientists who seem to us most expert on the subject think that 60 to 80 is optimal. The authors of this study say the optimum range is 40–80. The trouble with 40 as an optimum is that it probably won’t protect you from getting a virus, although you should be able to handle it better than if your level is lower. Why is a level over 100 ng/ml ill-advised? The best known risk relates to calcium. Vitamin D promotes calcium absorption in the gut; too much vitamin D results in too much calcium in the blood, or hypercalcemia, which can cause nausea, constipation—and sometimes, yes, even atrial fib. The study authors clearly state, however, that “the extent to which 25[OH] Vit D excess may be associated with AF is unknown.” Moreover, while AF was found 2½ times more often in people with levels of D above 100 than with levels of 80 and below, it’s still not a large percentage—only 3.8% of patients. Please note that there’s no magical cut-off where you have to race to the hospital if you take too much D. The higher your blood serum level goes over 100, and the longer you’re there, the greater your risk. According to the Vitamin D Council, what exactly constitutes a toxic dose of vitamin D has yet to be determined, though published cases of toxicity, for which serum levels and dose are known, all involve a consistent intake of at least 40,000 IU per day. It’s really a case of “too much of a good thing,” as Shakespeare put it. There are very few substances under the sun which, when consumed to excess, won’t harm you in the end. Medicines, whether of the natural and herbal variety or the patented and pharmaceutical variety, are dose-sensitive. A few aspirins once in a while (or better yet, white willow bark) can relieve headaches and reduce inflammation; taking a whole bottle will kill you. Heck, even drinking too much water will kill you. But the media emphasis on too much vitamin D in your system is wrong-headed. The real problem, as indicated by the study, is too much calcium. As we have discussed before, taking calcium without the co-factors has been shown to be bad for the heart—you need vitamin K2 and omega-3 fatty acids (and, for other reasons, magnesium too). Did the news stories mention that? So if the vitamin D toxicity doesn’t occur until one has clearly overdosed on the stuff for quite a while, why all the scary headlines? “High dose vitamin D pills ‘can double heart condition risk’ ” says one headline. “High vitamin D levels linked to heart condition” says another. Or worst of all, The Atlantic Monthly’s story on the subject, “Are Supplements Killing You? The Problem With Vitamins, Minerals,” started off with this teaser: “In two recently published studies, researchers suggest that supplements can do more harm than good if taken in addition to a healthy diet.” Outrageous horse-pucky. Another study presented at the same AHA annual meeting, analyzing sixteen years of data gathered from more than 2,000 healthy, postmenopausal women, found a direct correlation between low vitamin D levels and heart problems. About 15 percent of the women with low vitamin D levels either died or suffered heart failure, a heart attack, or stroke during the study period. Which study do you think got more press attention? You guessed it—the one that was thought to imply that vitamins were dangerous. Which of course was not what the study said at all. For more on what this study really said, you can read the Vitamin D Council’s analysis on their website. Besides the scramble for ratings and web page “hits,” is anything else behind this anti-vitamin bias? The pharmaceutical industry is investigating a number of different synthetic versions of vitamin D, all of which are being investigated as treatments for various kinds of cancer. Two of them were complete failures. Two others—one specifically for prostate cancer, the other to be used in conjunction with standard chemotherapy—are showing promise. Interestingly, one of the researchers on the panel that produced the IOM’s anti-scientific vitamin D report sits on the Board of Directors for one of the companies working on the vitamin D drug—a high-potency formulation of intravenous vitamin D. That’s the one–two punch preferred by the pharmaceutical industry and its media partners: first, pretend the vitamin either doesn’t work at all, or will kill you if you take too much of it, and scare off the public; then, reformulate the same vitamin into a drug that can make you millions of dollars. Let’s not forget that much of the major media is currently on financial life support and the support that keeps them alive is coming from Big Pharma. The worst part of what may be a drug company campaign against supplemental vitamin D—and the media headlines warning about the dangers of “excess D”—is that at least one-third of all Americans are actually deficient in vitamin D. Besides causing heart problems in older women, vitamin D deficiency can cause chronic pain, weak bones, frequent infections and illnesses, diabetes, depression, and even cancer. In proper amounts, vitamin D is a potent immune system booster, maintains your calcium balance, helps regulate insulin and blood pressure, and may protect against osteoporosis, cancer, and Alzheimer’s. And of course we have long advocated vitamin D as being the healthy alternative to the dangerous mercury-infused flu shot. It also short-circuits inflammation that can lead to flu-related complications such as bacterial pneumonia or lung infection. Want to be protected from colds and flu this season? Take proper amounts of vitamin D. So what’s the proper amount? How do you get enough, but not too much? Vitamin D supplementation depends on the region where you live, your exposure to sunlight, and your body’s particular ability to synthesize vitamin D3. The only sure-fire way to know if you’re getting enough vitamin D is to have a blood test. Your doctor can do it, or you can go to an independent lab, or you can purchase an easy-to-use in-home test kit and test the levels yourself. The Vitamin D Council has an in-depth discussion of adequate doses of supplemental vitamin D3, but notes that children and adults with chronic health conditions such as autism, MS, cancer, heart disease, or obesity may need twice as much for proper health support. They emphasize that the doses they suggest are just to get you started. There is no substitute for a blood test to help you determine your body’s unique needs. Source : Alliance for Natural Health 22/11/2011 Link to Source Vitamin D controls T cell antigen receptor signaling and activation of human T cells Phospholipase C (PLC) isozymes are key signaling proteins downstream of many extracellular stimuli. Here we show that naive human T cells had very low expression of PLC-1 and that this correlated with low T cell antigen receptor (TCR) responsiveness in naive T cells. However, TCR triggering led to an upregulation of ~75-fold in PLC-1 expression, which correlated with greater TCR responsiveness. Induction of PLC-1 was dependent on vitamin D and expression of the vitamin D receptor (VDR). Naive T cells did not express VDR, but VDR expression was induced by TCR signaling via the alternative mitogen-activated protein kinase p38 pathway. Thus, initial TCR signaling via p38 leads to successive induction of VDR and PLC-1, which are required for subsequent classical TCR signaling and T cell activation Source : Nature Immunology Link to Source Adequate Vitamin D may stop cancer at outset UC San Diego study – In studying the preventive effects of vitamin D, researchers at the Moores Cancer Centre at the University of California, San Diego, have proposed a new model of cancer development that hinges on a loss of cancer cells’ ability to stick together. The model, dubbed DINOMIT, differs substantially from the current model of cancer development, which suggests genetic mutations as the earliest driving forces behind cancer. “The first event in cancer is loss of communication among cells due to, among other things, low vitamin D and calcium levels,” said epidemiologist Cedric Garland, DrPH, professor of family and preventive medicine at the UC San Diego School of Medicine, who led the work. “In this new model, we propose that this loss may play a key role in cancer by disrupting the communication between cells that is essential to healthy cell turnover, allowing more aggressive cancer cells to take over.” Reporting online May 22, 2009 in the Annals of Epidemiology, Garland suggests that such cellular disruption could account for the earliest stages of many cancers. He said that previous theories linking vitamin D to certain cancers have been tested and confirmed in more than 200 epidemiological studies, and understanding of its physiological basis stems from more than 2,500 laboratory studies. “Competition and natural selection among disjoined cells within a tissue compartment, such as might occur in the breast’s terminal ductal lobular unit, for example, are the engine of cancer,” Garland said. “The DINOMIT model provides new avenues for preventing and improving the success of cancer treatment.” Garland went on to explain that each letter in DINOMIT stands for a different phase of cancer development. “D” stands for disjunction, or loss of intercellular communication; “I,” for initiation, where genetic mutations begin to play a role; “N” for natural selection of the fastest-reproducing cancer cells; “O” for overgrowth of cells; “M” for metastasis, when cancer cells migrate to other tissues, where cancer can kill; “I” refers to involution, and “T” for transition, both dormant states that may occur in cancer and potentially be driven by replacing vitamin D. While there is not yet definitive scientific proof, Garland suggests that much of the evolutionary process in cancer could be arrested at the outset by maintaining vitamin D adequacy. “Vitamin D may halt the first stage of the cancer process by re-establishing intercellular junctions in malignancies having an intact vitamin D receptor,” he said. According to Garland, other scientists have found that the cells adhere to one another in tissue with adequate vitamin D, acting as mature epithelial cells. Without enough vitamin D, they may lose this stickiness along with their identity as differentiated cells, and revert to a stem cell-like state. Garland said that diet and supplements can restore appropriate vitamin D levels, and perhaps help in preventing cancer development. “Vitamin D levels can be increased by modest supplementation with vitamin D3 in the range of 2000 IU/day,” he noted. The researchers noted that many studies show an apparent beneficial effect of vitamin D and calcium on cancer risk and survival of patients with breast, colorectal and prostate cancer. However, there are some studies that have not found such benefit, especially when taking smoking, alcohol and viruses into account. While more research needs to be done, Garland recommends that individuals should have their vitamin D level tested during an annual check up. Garland and his colleagues have published epidemiological studies about the potential preventive effects of vitamin D for some two decades. Last year, his team showed an association between deficiency in sunlight exposure, low vitamin D and breast cancer. In previous work, they showed associations between increased levels of vitamin D3 or markers of vitamin D and a lower risk for breast, colon, ovarian and kidney cancers. Source : Chinese Medicine News Link to Source Industry dismisses recent calcium study as ‘flawed’ Following publication of a recent BMJ study slamming calcium supplements over their potential heart risks, industry has been keen to give its response to NutraIngredients. The study, published in the British Medial Journal and reported by NutraIngredients here , warned that the risks of heart problems outweigh the potential benefits of calcium supplementation, with the lead researcher Professor Ian Reid saying that the results suggest that the indiscriminate use of calcium supplements ‘should be abandoned’. However, leading industry figures have come out to counter-slam the results of the study, questioning the “flawed” methodology and statistical interpretation of the meta-analysis. John Hathcock, senior vice president of scientific and international affairs at the Council for Responsible Nutrition (CRN) told NutraIngredients that he “wouldn’t put a lot of weight” on the conclusions, adding that he believed the methodology of the study “raises more questions than it provides answers.” Read more..... “Vitamin D Status and Early Age-Related Macular Degeneration in Postmenopausal Women” Authors: A.E. Millen, R. Voland, S.A. Sondel, N. Parekh, et al. for the CAREDS Study Group Higher blood levels of vitamin D may be associated with a decreased risk of developing age-related macular degeneration (AMD) in women, says new research. According to findings published in the Archives of Ophthalmology, the highest average intakes of vitamin D from food and supplements (15.1 micrograms per day) were associated with a 59 percent decrease in the risk of developing early AMD, compared with the lowest average intakes (7.9 micrograms per day). “This is the second study to present an association between AMD status and 25(OH)D, and our data support the previous observation that vitamin D status may potentially protect against development of AMD,” wrote the authors, led by Amy Millen, PhD, from the University at Buffalo, New York. “More studies are needed to verify this association prospectively as well as to better understand the potential interaction between vitamin D status and genetic and lifestyle factors with respect to risk of early AMD,” they added. AMD As the name suggests, age-related macular degeneration (AMD) is a degenerative retinal disease that causes central vision loss and leaves only peripheral vision. Despite the fact that approximately 25 to 30 million people worldwide are affected by AMD, awareness of the condition is low, says AMD Alliance International. And as Baby Boomers age, the Alliance expects incidence to be on the rise and triple by 2025. The macula is a yellow spot of about five millimeters diameter on the retina. As we age, levels of the pigments in the macula decrease naturally, thereby increasing the risk of AMD. The yellow color is due to the content of the carotenoids lutein and zeaxanthin, which we derive from the diet. Study details Millen and her co-workers analyzed blood levels of vitamin D – measured as 25- hydroxyvitamin D (25(OH)D), the non-active 'storage' form of the vitamin – in 1,313 women aged between 50 and 79. “Serum 25(OH)D is the preferred biomarker for vitamin D status, as it reflects vitamin D exposure from both oral sources and sunlight,” explained the researchers. Vitamin D refers to two biologically inactive precursors - D3, also known as cholecalciferol, and D2, also known as ergocalciferol. Both D3 and D2 precursors are transformed in the liver and kidneys into 25(OH)D, and 1,25-dihydroxyvitamin D (1,25(OH)2D), the biologically active form that is tightly controlled by the body. According to the study’s findings, the top food sources of vitamin D for the women were milk, fish, fortified margarine and fortified cereal. Results showed that no overall relationship was found between vitamin D and any form of AMD, but when the researchers limited their analysis to women younger than 75, they found that higher 25(OH)D levels were associated with a significant decreased risk of early AMD. “The inverse association between early AMD and 25(OH)D in women younger than 75 years was not explained by dietary intake of lutein plus zeaxanthin or polyunsaturated fat,” they added. On the other hand, higher vitamin D levels were associated with a borderline statistically significant increased risk in women over 75. Is it biologically plausible? Commenting on the potential mechanism, Dr Millen and her co-workers note that inflammation is reported to be involved in the development of AMD, and that vitamin D has anti-inflammatory activity. As such the sunshine vitamin “may suppress the cascade of destructive inflammation that occurs at the level of the retinal pigment epithelium–choroid interface in early stages of AMD”, they added. The study was supported by the National Institutes of Health and by Research to Prevent Blindness. It was part of the Carotenoids and Age-Related Eye Disease Study, an ancillary study of the Women’s Health Initiative. Source: Nutraingredients via Archives of Ophthalmology 2011, Volume 129, Number 4, Pages 481-489 Link to NutraIngredients Supplements and sunlight give optimal protection from breast cancer: Study Numerous studies have linked vitamin D levels to a reduction in the risk of certain cancers, including breast cancer, but much debate has focused on the means to boost vitamin D levels – supplements or sunlight. According to new findings published in Cancer Epidemiology, Biomarkers & Prevention, a combination may be the best approach. Data collected over a decade of study from 67,721 women indicated that postmenopausal women living in sunny climes combined with high dietary or supplemental intakes of vitamin D were at a significantly reduced risk of breast cancer compared to women with high sun exposure and low intakes of the vitamin. On the other hand, no associations were observed for dietary and supplemental intakes of vitamin D alone, report researchers led by Pierre Engel from Inserm (Institut National de la Santé et de la Recherche Médicale). “Although, our results do not support a linear dose-response relationship of both UVR dose and dietary vitamin D on BC risk, our findings suggest that a threshold of vitamin D exposure is required to prevent BC; this minimal amount is likely to vary with individual ability to metabolize or synthesize vitamin D from both sources,” they said. D and the big C The link between vitamin D intake and protection from cancer dates from the 1940s when Frank Apperly demonstrated a link between latitude and deaths from cancer, and suggested that sunlight gave "a relative cancer immunity". Since then there have been numerous studies suggesting associations between vitamin D and lower risks of certain cancers. Vitamin D refers to two biologically inactive precursors – cholecalciferol (D3) and ergocalciferol (D2). Both D3 and D2 precursors are hydroxylated in the liver and kidneys to form 25- hydroxyvitamin D (25(OH)D), the non-active 'storage' form, and 1,25-dihydroxyvitamin D (1,25(OH)2D), the biologically active form that is tightly controlled by the body. There is growing evidence that 1,25(OH)2D has anticancer effects, but the discovery that non-kidney cells can also hydroxylate 25(OH)D had profound implications, implying that higher 25(OH)D levels could protect against cancer in the local sites. The association between vitamin D and breast cancer is still ambiguous, however, according to results of a recent meta-analysis published in the European Journal of Cancer (doi: 10.1016/j.ejca.2010.03.037). New data According to findings of Dr Engel and his team, such ambiguity may be related to a combination of dietary, supplemental and sunlight exposure as the source of raising vitamin D levels. The French researchers documented 2,871 cases of breast cancer over the 10 years of their study. While no relationship was observed between dietary and supplemental intakes of the sunshine vitamin, the risk of breast cancer for women residing in regions with the highest average daily UV exposure (living below a latitude of 46°N) combined with high dietary vitamin D intakes was 32 percent lower, while the risk for high UV exposure and high supplemental intakes was reduced by 45 percent. “Considering that, in France, mean vitamin D dietary intake is low, and 25(OH) vitamin D serum concentrations are mostly below the 30 ng/mL recommended threshold, our results suggest that an increase in overall vitamin D intake should be encouraged by food and health agencies, possibly through fortification of foods,” concluded Dr Engel and his co-workers. Jury–in or out? The recent meta-analysis, which reviewed and summarised ten trials investigating the association between serum vitamin D (measured as 25(OH)D levels) and the risk of breast cancer, concluded that the data to date “show ambiguous evidence”. “Data is still sparse and in depth analyses … especially measuring repeatedly 25(OH)D at different time points before diagnosis, are highly desirable to enable more precise estimates and a better understanding of the role of vitamin D in breast cancer development and prevention,” concluded the authors of the meta-analysis. Source : Nutraingredients Link to Source Vitamin D linked to colon cancer protection: Meta-analysis High blood levels of vitamin D are associated with a reduced risk of colorectal cancer, according to a new meta-analysis of observational studies from an international team of researchers. Analysis of data from nine studies revealed that, for every 10 nanograms per milliliter increase in levels of vitamin D (25-hydroxyvitamin D) the associated risk of colorectal cancer decreased by 15 percent. On the other hand, no association was observed between vitamin D levels and the risk of breast or prostate cancer, say results published in the International Journal of Cancer. Shining light on the sunshine vitamin Vitamin D refers to two biologically inactive precursors - D3, also known as cholecalciferol, and D2, also known as ergocalciferol. Both D3 and D2 precursors are transformed in the liver and kidneys into 25- hydroxyvitamin D (25(OH)D), the non-active 'storage' form, and 1,25-dihydroxyvitamin D (1,25(OH)2D), the biologically active form that is tightly controlled by the body. D and the big C The link between vitamin D intake and protection from cancer dates from the 1940s when Frank Apperly demonstrated a link between latitude and deaths from cancer, and suggested that sunlight gave "a relative cancer immunity". Since then there have been numerous studies suggesting associations between vitamin D and lower risks of certain cancers. There is growing evidence that 1,25(OH)2D has anticancer effects, but the discovery that non-kidney cells can also hydroxylate 25(OH)D had profound implications, implying that higher 25(OH)D levels could protect against cancer in the local sites. The new meta-analysis, led by Philippe Autier from the International Prevention Research Institute (IPRI) in Lyon, France, adds to the subject, while also showing the relationship between vitamin D and cancer is ambiguous, depending on the type of cancer. Indeed, a recent meta-analysis published in the European Journal of Cancer (doi: 10.1016/j.ejca.2010.03.037) concluded that the association between vitamin D and breast cancer is still ambiguous. New analysis Dr Autier and his co-workers analyzed data from 35 epidemiological studies of 25(OH)D levels and colorectal, breast and prostate cancer. The analysis showed that for every 10 nanograms per milliliter increase in 25(OH)D levels the associated risk of colorectal cancer decreased by 15 percent, while the risk of breast cancer was associated with an 11 percent decrease. However, when the researchers restricted their analysis to prospective studies only, the breast cancer risk was decreased by only 3 percent, whereas data from case-control studies indicated a risk reduction of 17 percent. “A non-significant decreased risk of breast cancer risk was associated with higher serum 25-hydroxyvitamin D, but results from prospective studies only did not support an association between vitamin D status and breast cancer,” said the researchers. No association between vitamin D levels and prostate cancer were observed at all. “If additional observational studies of vitamin D and cancer are proposed, they should adopt different designs, such as assessment of serum 25-hydroxyvitamin D colorectal at different points in time, or longer follow-up of subjects,” wrote the researcher. “To assess whether vitamin D status is a risk factor or a risk marker for colorectal cancer, it is likely that new randomized trials will need to be organized to test whether increasing the 25-hydroxyvitamin D level changes the risk of colorectal cancer, and to determine how much of an increase is required to change the risk of cancer sufficiently to be useful as a public health measure,” they concluded. Source : Nutraingredients Link to Source Vitamin D may boost urinary tract health: Study supplementation was found to promote production of an anti-microbial peptide called cathelicidin in the urinary tract, thereby offering local and site-specific protection, according to findings published in Public Library of Science One (PLoS ONE ). “This could make [25-hydroxyvitamin D3 (25D3)] an effective and safe way of activating the endogenous antimicrobial response locally at the site of infection,” wrote researchers from the Karolinska Institutet and Karolinska University Hospital in Stockholm. “Determining the vitamin D status of individuals with a history of UTI may be of importance to evaluate their ability to fend off intruding bacteria. “Supplementation to restore proper vitamin D levels may therefore help preparing the bladder epithelium to mount a stronger and faster immune response once bacteria enter the bladder.” Vit D Vitamin D refers to two biologically inactive precursors - D3, also known as cholecalciferol, and D2, also known as ergocalciferol. The former, produced in the skin on exposure to UVB radiation (290 to 320 nm), is said to be more bioactive. Both D3 and D2 precursors are hydroxylated in the liver and kidneys to form 25- hydroxyvitamin D (25(OH)D), the non-active 'storage' form, and 1,25-dihydroxyvitamin D (1,25(OH)2D), the biologically active form that is tightly controlled by the body. While our bodies do manufacture vitamin D on exposure to sunshine, the levels in some northern countries are so weak during the winter months that our body makes no vitamin D at all, meaning that dietary supplements and fortified foods are seen by many as the best way to boost intakes of vitamin D. And the science supports maintaining adequate levels, with vitamin D deficiency in adults reported to precipitate or exacerbate osteopenia, osteoporosis, muscle weakness, fractures, common cancers, autoimmune diseases, infectious diseases and cardiovascular diseases. There is also some evidence that the vitamin may reduce the incidence of several types of cancer and type-1 diabetes. The new study indicates that the benefits of the sunshine vitamin may also extend to urinary tract health – a health category traditionally dominated by cranberry juice and extracts. Study details The Stockholm-based scientists analyzed vitamin D blood levels in 22 postmenopausal and six premenopausal Swedish women. An additional eight women with a median age of 62 were recruited to participate in a supplementation trial (2000 units per day of 25D3 for 12 weeks, Recip, Meda Pharmaceuticals). Five women completed the trial. The Swedish researchers note that 1,25(OH)2D was measured in bladder cell cultures, which indicated that the cells of the bladder are capable of producing the active form of the vitamin. Results from the supplementation trial showed that 25-hydroxyvitamin D3 was associated with an induction in the expression of cathelicidin when bladder biopsies were exposed to E. coli. No general induction of the antimicrobial peptide was observed during vitamin D supplementation, added the researchers. “Here we show that oral 25D3 supplementation of healthy postmenopausal women prepares the bladder tissue to fight E. coli infection by increased production of cathelicidin upon bacterial contact,” report the researchers. “25D3 is locally converted to 1,25D3 in bladder epithelial cells, binds to vitamin D receptor, which leads to […] synthesis of cathelicidin. “The increased production in turn enhances the direct antibacterial effect on uropathogenic E. coli,” they added. An alternative to antibiotics “In light of the emerging resistance to antibiotics used against UTI, new treatment strategies are needed,” report the researchers. “Our data suggest that vitamin D can stimulate an increased production of the antimicrobial peptide cathelicidin. By inducing and activating cathelicidin with vitamin D, a local rather than a systemic effect can be achieved. “This could offer selective and site-specific treatment of pathogens without perturbing commensal microbes elsewhere in the body.” Source : Nutraingredients Link to source Vitamin D3 ’87 percent more potent’ than D2: Study Vitamin D3 is 87 percent more potent at raising blood levels of the vitamin than vitamin D2, according to a new study from the US. In addition to the increase in potency, results published in Journal of Clinical Endocrinology & Metabolism indicate that vitamin D3 also produced a 2- to 3-fold increase in the storage of the vitamin, compared with vitamin D2. Scientists led by Robert Heaney, MD, from Creighton University in Nebraska supplemented 33 health adults with 50,000 International Units (IU) of either vitamin D2 or D3 per week for 12 weeks. Results showed that about 17 percent of the D3 ingested was stored by the subjects, and the rest was consumed or metabolized or both. “This is a daily utilization rate of about 6500 IU at a [blood vitamin D] concentration of 50 ng/ml at the end of treatment,” write the researchers. Optimal levels of vitamin D are considered to be between 50–80 ng/mL. “At the doses used in this study, most vitamin D is metabolically consumed. This is the first study, to our knowledge, to have quantified this issue,” added Dr Heaney and his co-workers. Shining light on the sunshine vitamin Vitamin D refers to two biologically inactive precursors - D3, also known as cholecalciferol, and D2, also known as ergocalciferol. Both D3 and D2 precursors are transformed in the liver and kidneys into 25- hydroxyvitamin D (25(OH)D), the non-active 'storage' form, and 1,25-dihydroxyvitamin D (1,25(OH)2D), the biologically active form that is tightly controlled by the body. The relative bioavailability of the two forms of vitamin D is an area of intense interest and debate. Several studies have reported that vitamin D2 is between 30 and 50 per cent less effective as the D3 form in maintaining blood levels in humans. On the other hand, a 2008 study by Boston University researchers reported that both forms are equally effective at maintaining 25-hydroxyvitamin D status (Journal of Clinical Endocrinology & Metabolism, Vol. 93, pp. 677-681). New data Dr Heaney and his co-workers acknowledge the inconsistencies in the literature, and attempt to “clarify this issue”. Thirty-three healthy adults with an average age of 49.5 were recruited and assigned to receive weekly doses of vitamin D2 (Banner Pharmacaps, Inc.) or vitamin D3 (BTR Group, Inc.). After 12 weeks of supplementation with 50,000 IU of vitamin D, the researchers report that levels increased significantly more in the D3 group than in the D2 group. “By the various measures employed, D3 was from 56 to 87 percent more potent than D2 in raising serum 25(OH)D, and more than three times as potent in increasing fat calciferol content,” stated the researchers. “[T]hese results can, we believe, not only safely be generalized to routine clinical practice, but also are pertinent to what clinicians are actually prescribing.” Dr Heaney and his co-workers noted that their results are limited by the relatively short duration of the intervention, and by their methods, which approximated vitamin D content in total body fat by extrapolating from a measure of percentage fat. “Hence, a longer study with multiple fat biopsies would be in order,” they added. “Given its greater potency and lower cost, D3 should be the preferred treatment option when correcting vitamin D deficiency,” concluded the researchers. Source : Nutraingredients Link to Source Calcium plus vitamin D shows bone boosting benefits for teenage girls Supplements of calcium and vitamin D may boost the bone health of girls undergoing puberty, and potentially reduce the risk of osteoporosis later in life, suggests a new study from Down Under. Australian researchers report that a supplement containing 800 mg of calcium and 400 IU of vitamin D3 produced significant increases in the bone density and strength of peripubertal female identical twins, compared with placebo. The study is published in the journal Osteoporosis International. Osteoporosis is characterized by low bone mass, which leads to an increase risk of fractures, especially the hips, spine and wrists. An estimated 75 million people suffer from osteoporosis in Europe, the USA and Japan. Women are four times more likely to develop osteoporosis than men. Potential reduction of osteoporosis has traditionally been a two-pronged approach by either attempting to boost bone density in high-risk post-menopausal women by improved diet or supplements, or by maximising the build up of bone during the highly important pubescent years. About 35 per cent of a mature adult's peak bone mass is built-up during puberty. Study details Researchers from the Australian Catholic University recruited 20 pairs of identical twins and randomly assigned one from each set of twins to receive the vitamin D, calcium combination, and the other to receive a placebo for six months. The study, reportedly the first to use peripheral quantitative computed tomography (pQCT) to measure bone responses to the combined supplement in peripubertal children, found that the vitamin D and calcium combination was associated with increased bone density and bone strength in the shinbone (tibia) and in the arm (radius). Indeed, shin and arm bone strength was improved by between 4 and 66 percent, depending on the specific site of the bone tested. Strong supporting science The study supports previous findings, including results from an 18-month randomised trial from scientists at the University of Sheffield in the UK (American Journal of Clinical Nutrition, February 2008, Vol 87, Pages 455-462). In the Sheffield study, a daily 792 mg calcium supplement was associated with increases in bone mineral content and density. However, the effects were then reversed once supplementation was discontinued. Commenting on the mechanism, the Sheffield scientists proposed that the mineral most likely worked by suppressing bone turnover. Calcium is reported to be the biggest seller in the US supplements industry. Annual sales were about $993m (€836m) in 2004, according to the Nutrition Business Journal. Source: NutraIngredients.com via Osteoporosis International (February 2011, Volume 22, Issue 2, Pages 489-98 “Calcium and vitamin-D supplementation on bone structural properties in peripubertal female identical twins: a randomised controlled trial” Authors: D.A. Greene, G.A. Naughton Link to NutraIngredients.com Vitamin D deficiency linked to Parkinson's disease, cognitive decline Studies of vitamin D have been on the rise in recent years, and with good reason--a 2009 estimate suggests that nearly three quarters of teens and adults in the U.S. are deficient in this vital nutrient. Vitamin D deficiency not only causes rickets, a skeletal disorder in which the bones are soft and weak, but has also been associated with a rapidly increasing range of chronic conditions like cancer, heart disease, and type 2 diabetes. Now, two new studies suggest a link between vitamin D and neurological disorder: Older people with insufficient vitamin D levels may be more likely to develop Parkinson's disease and experience cognitive decline. The first, led by Paul Knekt and colleagues at the National Institute for Health and Welfare, Finland, examined levels of vitamin D in the blood of 3,173 Finnish men and women aged 50 to 79 determined to be free of Parkinson's disease at the start of the study. The researchers then examined the incidence of Parkinson's disease in these participants over a 29-year follow-up period. They found that participants with the highest levels of vitamin D (more than 50 nmol/L) had a 65 percent lower risk of developing Parkinson's disease than those with the lowest vitamin D levels (less than 25 nmol/L). The researchers accounted for potentially confounding variables such as age, sex, marital status, education, alcohol consumption, smoking, physical activity and month of blood draw. Parkinson's disease is a progressive neurodegenerative disorder that leads to impaired movement and speech, and is thought to result from insufficient dopamine levels in the brain. How vitamin D may protect against Parkinson's is not understood, although there is limited evidence from cell-based and animal models that vitamin D may prevent the loss of dopaminergic neurons (cells that produce dopamine). One important limitation to the study is that the average vitamin D concentration of all the study participants (approximately 40 nmol/L) falls well below what is considered to be optimal (more than 75 nmol/L). Therefore, whether supplementation with vitamin D would further lower the risk for Parkinson's remains unknown. Nevertheless, the study suggests that not having enough vitamin D may predispose individuals to Parkinson's, and provides a starting point for further investigation. The results were published online July 12 in the Archives of Neurology. In the second study, David Llewellyn of the University of Exeter and colleagues examined vitamin D levels among 858 Italian men and women age 65 and older. They found that more than half of the participants with dementia were vitamin D deficient (less than 50 nmol/L). What's more, cognitive tests revealed that severely deficient individuals (less than 25 nmol/L) were 60 percent more likely to undergo cognitive decline over the six-year follow-up period. This study appears online July 12 in the Archives of Internal Medicine. Humans can obtain vitamin D by eating oily fish or fortified foods, and it is also photosynthesized in the skin upon exposure to adequate amounts of ultraviolet B (UVB) rays in sunlight. Major factors that influence vitamin D status in humans include season, latitude, age, skin tone, diet and supplement use. The U.S. Institute of Medicine currently recommends that adult men and women aim for a daily intake of 200 to 600 International Units (IU) of vitamin D. New guidelines for vitamin D intake were published online July 12 in the Canadian Medical Association Journal by scientists from Osteoporosis Canada, a nonprofit organization. Because vitamin D influences calcium absorption and may protect against osteoporosis, the authors advise an increased daily intake of 400 to 1000 IU for healthy Canadians under age 50, and up to 2000 IU for those older than 50. The researchers state the changes are necessary because winter sunlight north of the 35th parallel (which coincides with the southern border of Tennessee) provides insufficient UVB for people living in that region to adequately make vitamin D. The studies by Knekt and Llewellyn are not the first to link vitamin D deficiency with neurological problems, however. A role for vitamin D has previously been suggested in multiple sclerosis, autism and schizophrenia. Some experts advise interpreting the results of these and other observational studies of vitamin D with caution. The above studies relied on participants from specific geographic areas, so more study is needed to determine whether the findings apply to other regions. Furthermore, "low vitamin D levels may simply be a marker for lower health status rather than a cause of it," Andrew Grey, professor of medicine at the University of Auckland, wrote in an editorial in the Archives of Internal Medicine. This is because vitamin D levels are directly related to sunlight exposure and physical activity; less healthy individuals are therefore likely to be less active and more sunlight-deprived, and have lower levels of vitamin D. "It is now time to test the various hypotheses generated by observational studies of vitamin D…in adequately designed and conducted randomized controlled trials," Grey concluded. "We should invest in trials that provide the best possible evidence on the benefits and risks of vitamin D before we invest in costly, difficult, and potentially unrewarding interventional strategies." |