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Online Library: Vitamin D

The following pages provide an overview of the most recent research and clinical studies about the health benefits of vitamin D. This collection of scientific facts proves that anyone who privately or publicly questions the health value of micronutrients does not serve YOUR health, or the health of the people, but rather the multi-billion dollar investment 'business with disease' based on patented pharmaceutical drugs.

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Decreased bioavailability of vitamin D in obesity

Source: The American journal of clinical nutrition 2000; 72(3):690-3

Author: Wortsman J, Matsuoka LY, Chen TC, Lu Z, Holick MF

Affiliation: Southern Illinois University School of Medicine, Springfield, USA.

Abstract: Obesity is associated with vitamin D insufficiency and secondary hyperparathyroidism. This study assessed whether obesity alters the cutaneous production of vitamin D(3) (cholecalciferol) or the intestinal absorption of vitamin D(2) (ergocalciferol). Healthy, white, obese [body mass index (BMI; in kg/m(2)) > or = 30] and matched lean control subjects (BMI

Vitamin D Deficiency in Obese Children and Its Relationship to Glucose Homeostasis

Source: Journal of Clinical Endocrinology & Metabolism November 2011 jc.2011-1507

Author: Olson ML, Maalouf NM, Oden JD et al.

Affiliation: Departments of Pediatrics and Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas.

Abstract: The aim of the study was to compare the prevalence of vitamin D deficiency in obese and non-overweight children in North Texas, to examine relationships between dietary habits and 25-hydroxyvitamin D [25(OH)D] level in obese children, and to examine the relationship between 25(OH)D level and markers of abnormal glucose metabolism and blood pressure. Using a cross-sectional design, systolic and diastolic blood pressure, dietary information, serum 25(OH)D, fasting glucose and insulin, 2-h glucose from oral glucose tolerance test, hemoglobin A1c (HbA1c), and homeostasis model assessment of insulin resistance were recorded for 411 obese subjects (616 yr old) at an obesity referral clinic. 25(OH)D was also obtained from 87 control non-overweight subjects (616 yr old). Ninety-two percent of obese subjects had a 25(OH)D level below 75 nmol/liter, and 50% were below 50 nmol/liter. Among non-overweight subjects, these frequencies were 68 and 22%, respectively. 25(OH)D was negatively associated with soda intake, juice intake, and skipping breakfast. 25(OH)D was negatively correlated with homeostasis model assessment of insulin resistance and 2-h glucose after adjustment for body mass index and age but was not correlated with hemoglobin A1c, systolic blood pressure Z score*, or diastolic blood pressure Z score. Conclusions: Vitamin D deficiency is common in children in this southern United States location and is significantly more prevalent in obese children. Lower 25(OH)D level is associated with risk factors for type 2 diabetes in obese children.

* A Z-Score is a statistical measure. A Z-Score tells how a single data point compares to normal data. A Z-Score says not only whether a point was above or below average, but how unusual the measurement is.

An exploratory study of postpartum depression and vitamin D

Source: Journal of the American Psychiatric Nurses Association 2010 May; 16(3):170-7

Author: Murphy PK, Mueller M, Hulsey TC, Ebeling MD, Wagner CL

Affiliation: Medical University of South Carolina, Charleston, USA.

Abstract: Low levels of serum 25-hydroxyvitamin D (25[OH]D), a reliable measurement of vitamin D, have been implicated in several mood disorders. To date, studies exploring the relationship between vitamin D and postpartum depression are absent from the literature. To determine whether a relationship exists between symptoms associated with postpartum depression and vitamin D levels and to determine if serum 25(OH) D levels can predict the incidence of symptoms associated with postpartum depression. An exploratory, descriptive study was conducted, using a convenience sample of 97 postpartum women attending seven monthly visits. Women provided serum 25(OH)D samples and completed the Edinburgh Postpartum Depression Scale (EPDS) at each visit. A significant relationship over time was found between low 25(OH)D levels and high EPDS scores, indicative of postpartum depression. Future rigorous studies investigating vitamin D and postpartum depression are warranted with larger sample sizes using confirmatory methods to diagnose postpartum depression.

Improvement of Primary Dysmenorrhea Caused by a Single Oral Dose of Vitamin D: Results of a Randomized, Double-blind, Placebo-Controlled Study

Source: Archives of internal medicine 2012;172(4):366-367

Author: Lasco A, Catalano A, Benvenga S

Affiliation: Dipartimento di Medicina Interna (Drs Lasco and Catalano), Sezione di Endocrinologia, Dip Clinico Sperimentale di Medicina e Farmacologia (Dr Benvenga), and Master di Endocrinologia dellInfanzia, dell Adolescenza e della Donna (Dr Benvenga), Universit di Messina, Messina, Italy; and Programma Interdisciplinare di Endocrinologia Molecolare Clinica e Salute Endocrina della Donna, Policlinico A.O.U. G. Martino (Dr Benvenga), Messina.

Abstract: Primary dysmenorrhea is a common disorder characterized by painful uterine cramping, just before or during menstruation, in the absence of any pelvic pathologic conditions. It is frequently accompanied by other symptoms such as nausea, vomiting, diarrhea, asthenia, and insomnia. Primary dysmenorrhea affects almost half of menstruating women, often resulting in school and work absenteeism with major educational and economic consequences. An excessive uterine production of prostaglandins (PGs) is the pathogenetic trigger of dysmenorrhea. Nonsteroidal anti-inflammatory drugs (NSAIDs) are the currently accepted drugs for the management of this disorder. Because the vitamin D receptor is widespread and the mitochondrial cytochrome P450 enzyme 25-hydroxyvitamin D3 (25[OH]D)-1α-hydroxylase (1α-OHase), which catalyzes the synthesis of 1α,25-dihydroxyvitamin D3 (1,25[OH]2D) from its precursor 25(OH)D, is expressed in the human uterus and in immune system cells, and because vitamin D reduces the synthesis of PGs, a beneficial effect of vitamin D in the uterus pathophysiology is possible. The aim of this prospective intervention study was to evaluate the effect of a single-loading oral dose of cholecalciferol (300 000 IU) on primary dysmenorrhea.Forty women aged 18 to 40 years, attending the outpatient clinics of the Department of Internal Medicine of the University of Messina, Messina, Italy, for primary dysmenorrhea were enrolled. Patients were included if (1) their menstrual cycles lasted 21 to 35 days, with menstruation lasting 3 to 7 days; (2) they experienced at least 4 consecutive painful periods in the past 6 months with the pain starting one day before or on the day of onset of bleeding; (3) they showed a 25(OH)D serum level below the upper limit of the lowest quartile. Patients had to be in good health and taking no medications including calcium, vitamin D, and oral contraceptives. Use of NSAIDs was permitted and it had to be recorded in a sheet given to each woman.Women were randomized into 2 groups: 20 women received a single oral dose of cholecalciferol (300 000 IU/1 mL) 5 days before the putative beginning of their next menstrual cycle, while another 20 women received placebo.The primary outcome was the intensity of menstrual pain as measured by a visual analog scale. The secondary outcome was use of NSAIDs during the 2-month duration of the study. The 2 groups did not differ significantly in age, body mass index, severity of pain, and 25(OH)D levels at baseline. There was a negative correlation between the pain score at baseline and the levels of 25(OH)D (r = −0.36; P = .02). The authors observed a significant reduction of pain in the vitamin D group compared with the placebo group (P < .001) over the 2-month duration of the study. The greatest reduction of pain score was seen in women with severe pain at baseline in vitamin D group. The authors recorded no NSAID use in vitamin D group at 1 and 2 months, while 40% of women in placebo group took NSAIDs at least once.

Effect of cholecalciferol recommended daily allowances on vitamin D status and fibroblast growth factor-23: An observational study in acute burn patients.


Author: Rousseau AF, et al.

Affiliation: Burn Centre and General Intensive Care Department, University of Lige, University Hospital, Sart-Tilman, Lige, Belgium.

Abstract: Burn patients are at risk of hypovitaminosis D. Optimal vitamin D (VD) intakes are not defined in burn nutrition guidelines and studies mostly focused on ergocalciferol (VD2) supplementation in burn children. Aim of the study was to describe adult burns VD status, to measure effects of our cholecalciferol (VD3) supplementation on VD metabolism during acute burn care, and to assess correlation between FGF23 and C-reactive protein (CRP). From March 2012 to January 2013, patients >18 years, admitted within 24h after injury with burn surface area (BSA) 10% were included. Patients daily received VD3 from oral or enteral nutrition (400-600IU) and from oral or intravenous multivitamin complex (200-220IU). Serum levels of 25(OH)-D, 1-25(OH)2-D, 3rd generation PTH, C-terminal FGF23, total calcium, phosphate, albumin and CRP were measured at admission (D0) and every week during 4 weeks of follow-up. Data are expressed as percentage or median (min-max). Paired data were compared using Wilcoxon test. Correlation between CRP and FGF23 was assessed using nonparametric Spearman test. The researchers initially included 24 patients. Median age and BSA were, respectively, 46 years and 15%. At D0, 75% presented a VD insufficiency (25(OH)-D 21-29ng/ml) and 17% presented a deficiency (25(OH)-D 20ng/ml). The researchers followed 12 patients until day 28: 25(OH)-D was unchanged while 1-25(OH)2-D and FGF23 decreased without reaching significance. They observed a significant positive correlation between FGF23 and CRP. Most of the adult burns presented hypovitaminosis D regardless of age. Nutrition supplemented with low dose of VD3 (intakes reaching recommended daily allowances) was insufficient to correct 25(OH)-D level. Moreover, an interesting correlation between CRP and FGF23 was found.

Higher serum 25-hydroxyvitamin D concentrations associate with a faster recovery of skeletal muscle strength after muscular injury.


Author: Barker T, Henriksen VT, Martins TB, Hill HR, et al.

Affiliation: The Orthopedic Specialty Hospital, Murray, USA

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. The authors 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)-, and interleukin-4 were measured prior to and following intense exercise. Following exercise, serum 25(OH) D concentrations increased immediately, but within minutes, subsequently decreased. Circulating albumin increases predicted serum 25(OH) D increases, while IFN- increases predicted serum 25(OH) D decreases. Muscular weakness persisted within the exercise leg and compared to the control leg after the exercise protocol. Serum 25(OH) D concentrations inversely predicted muscular weakness (i.e., control leg vs. exercise leg peak isometric force) immediately and days after exercise, suggesting the attenuation of exercise-induced muscular weakness with increasing serum 25(OH) D prior to exercise. Based on these data, the authors conclude that pre-exercise serum 25(OH) D concentrations could influence the recovery of skeletal muscle strength after an acute bout of intense exercise.

Higher vitamin D intake in preterm infants fed an isocaloric, protein- and mineral-enriched postdischarge formula is associated with increased bone accretion.


Author: van de Lagemaat M, Rotteveel J, Schaafsma A, van Weissenbruch MM, Lafeber HN.

Affiliation: Department of Pediatrics, VU University Medical Center, Amsterdam, The Netherlands.

Abstract: During the first half of infancy, bone accretion in preterm infants fed an isocaloric, protein- and mineral-enriched postdischarge formula (PDF) is higher compared with those fed term formula (TF) or human milk (HM). This may be related to higher protein, calcium, phosphorus, and vitamin D intakes. This study investigated serum calcium, phosphate, and 25-hydroxyvitamin D [25(OH)D] in relation to bone mineral content (BMC) in PDF-, TF-, and HM-fed preterm infants between term age (40 wk postmenstrual age) and 6 mo corrected age (CA). Between term age and 6 mo CA, 52 preterm infants were fed PDF (per 100 mL: 67 kcal, 1.7 g protein, 65 mg calcium, 38 mg phosphorus, 56 IU vitamin D), 41 were fed TF (per 100 mL: 67 kcal, 1.47 g protein, 50 mg calcium, 30 mg phosphorus, 48 IU vitamin D), and 46 were fed HM. Serum calcium, phosphorus, and 25(OH)D were measured at term age and at 3 and 6 mo CA. BMC (g) was measured by whole-body dual-energy X-ray absorptiometry at term age and at 6 mo CA. Between term age and 6 mo CA, intakes of calcium, phosphorus, and vitamin D were significantly higher in PDF- compared with TF-fed infants, and PDF-fed infants reached significantly higher serum 25(OH)D concentrations at 6 mo CA. Between term age and 6 mo CA, increases in serum 25(OH)D were associated with an increase in BMC. In conclusion, during the first 6 mo postterm, higher vitamin D intake and greater increase in serum 25(OH)D concentration in PDF-fed preterm infants were associated with increased bone accretion.

The effect of acute administration of vitamin D on micro vascular endothelial function in Caucasians and South Asian Indians.


Author: Petrofsky J, Alshammari F, Khowailed IA, Rodrigues S, et al.

Affiliation: Deptartment of Physical Therapy, School of Allied Health Professions, Loma Linda University, USA

Abstract: Vitamin D is a modulator of the immune system. There is some limited evidence that it also increases local blood flow in response to stress. In the present study, the authors examined 20 age matched subjects; 10 whom were from India and 10 Caucasians from the United States. Subjects were administered 4000 IU of Vitamin D3 for 3 weeks at breakfast. The function of the endothelial cells was evaluated in 2 ways; first, the response to 4 minutes of vascular occlusion was measured with a laser Doppler flow meter and second, the blood flow response to local heat at 42C for 6 minutes. The results of the experiments showed that, as reported previously, the endothelial function in people from India was less than their Caucasian counterparts. The blood flow response to heat was reduced after 3 weeks administration of vitamin D in both groups and the response to vascular occlusion in the Caucasian group. But there was only a 20% reduction in the blood flow response to heat in the Caucasian group and a 50% reduction in the group from India. Conclusion: Acute doses of vitamin D may increase vascular tone and reduce blood flow to tissue during stressors. Dosages administered for a longer duration may have beneficial effects on endothelial function but this was not examined here.

Vitamin D Status and Parathyroid Hormone Concentrations Influence the Skeletal Response to Zoledronate and Denosumab.


Author: Mosali P, et al.

Affiliation: Department of Clinical Chemistry, St Thomas' Hospital, London

Abstract: Studies suggest that optimal vitamin D status is required for the maximal effect of antiresorptive agents. The authors investigated the relationship between vitamin D status, serum parathyroid hormone (PTH) concentrations, and change in bone mineral density (BMD) following iv zoledronate and denosumab. They carried out a retrospective analysis of 111 patients, mean age 70 (SD 13) years, 89 women and 22 men, prescribed zoledronate and 43 postmenopausal women treated with denosumab for osteoporosis. Researchers measured BMD at the lumbar spine (LS) and total hip (TH), serum 25 (OH) vitamin D, PTH, and bone turnover markers (plasma CTX, P1NP) at 1 year. In patients on zoledronate, BMD increased at the LS and TH (mean LS change [SEM] = 2.6 % [0.5 %], mean TH change = 1.05 % [0.5 %]). A significant increase in BMD was seen at the LS only in the denosumab group. Significant decreases in CTX and P1NP were observed at 12 months in both treatment groups. At baseline and at 12 months, 34 % and 23 % of the patients on zoledronate had a serum vitamin D of <50 nmol/L, respectively. The mean PTH concentration in patients with 25 (OH) vitamin D <50 nmol/L was 44 ng/L (SEM 16.6). Patients with PTH concentration <44 ng/L had significantly higher increases in TH BMD compared to those with PTH >44 ng/L (zoledronate 1.9 [0.83] vs. -0.43 [0.81]; denosumab 4.1 [0.054] vs. -1.7 [0.04]). Concluding, optimal vitamin D status and PTH concentrations improve the skeletal response to zoledronate and denosumab.

Pharmacokinetics of oral vitamin D(3) and calcifediol.


Author: Jetter A, et al.

Affiliation: Department of Clinical Pharmacology and Toxicology, University Hospital Zurich, Switzerland.

Abstract: The researchers claimed that long-term pharmacokinetics after supplementation with vitamin D3 or calcifediol (the 25-hydroxyvitamin D3 metabolite) was not well studied, and it was unclear whether bolus doses of vitamin D3 or calcifediol lead to 25(OH)D3 plasma concentrations considered desirable for fracture prevention (30 ng/mL). Therefore they investigated plasma pharmacokinetics of 25(OH) D3 during different vitamin D3 and calcifediol supplementation regimens. In this seven-arm, randomized, double-blind, controlled parallel-group study, 35 healthy females aged 5070 years (5 per group) received 20 g calcifediol or vitamin D(3) daily, 140 g calcifediol or vitamin D(3) weekly, for 15 weeks, or a single bolus of either 140 g calcifediol, or vitamin D(3), or both. 25(OH) D3 plasma concentrations were quantified using LCMS/MS in 14 clinical visits among all participants. For daily (weekly) dosing, the area under the concentrationtime curve (AUC024h), which is the measure for exposure, was 28% (67%) higher after the first dose of calcifediol than after the first dose of vitamin D3. After 15 weeks, this difference was 123% (178%). All women in the daily and weekly calcifediol groups achieved 25(OH) D3 concentrations > 30 ng/mL (mean, 16.8 days), but only 70% in the vitamin D3 daily or weekly groups reached this concentration (mean, 68.4 days). A single dose of 140 g calcifediol led to 117% higher 25(OH) D3 AUC096h values than 140 g vitamin D3, while the simultaneous intake of both did not further increase exposure. Calcifediol given daily, weekly, or as a single bolus is about 23 times more potent in increasing plasma 25(OH) D3 concentrations than vitamin D3. Plasma 25(OH) D3 concentrations of 30 ng/mL were reached more rapidly and reliably with calcifediol.

Vitamin D Intake and Cardiometabolic Risk Factors in Adolescents.


Author: Moreira C, Moreira P, et al.

Affiliation: Research Centre in Physical Activity, Health and Leisure, Faculty of Sport, University of Porto , Portugal.

Abstract: The authors introduction: A growing body of research suggests that vitamin D might play an important role in overall health. No data exist on vitamin D intake for the Azorean adolescent population. The purpose of this study was to assess vitamin D intake and investigate a possible association between vitamin D intake and cardiometabolic risk factors in Azorean adolescents. The cross-sectional school-based study was conducted on 496 adolescents (288 girls) aged 15-18 years from the Azorean Islands, Portugal. Anthropometric measurements (waist circumference and height), blood pressure (systolic), and plasma biomarkers [fasting glucose, insulin, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TGs)] were measured to assess metabolic risk. Homeostasis model assessment (HOMA), TC-to-HDL-C ratio, and waist-to-height ratio were calculated. For each of these variables, a Z-score was computed by age and sex. A metabolic risk score was constructed by summing the Z-scores of all individual risk factors. High risk was considered when the individual had 1 standard deviation (SD) of this score. Vitamin D intake was assessed with a semiquantitative food frequency questionnaire. Participants were classified into quartiles of vitamin D intake. Logistic regression was used to determine odds ratios for high cardiometabolic risk scores after adjusting for total energy intake, pubertal stage, fat mass percentage, and cardiorespiratory fitness. Mean (SD) vitamin D intake was 5.8 (6.5) g/day, and 9.1% of Azorean adolescents achieved the estimated average requirement of vitamin D (10 g/day or 400 IU). Logistic regression showed that the odds ratio for a high cardiometabolic risk score was 3.35 [95% confidence interval (CI) 1.28-8.75] for adolescents in the lowest vitamin D intake quartile in comparison with those in the highest vitamin D intake quartile, even after adjustment for confounders. Concluding, a lower level of vitamin D intake was associated with worse metabolic profile among Azorean adolescents.

Vitamin D and caudal primary motor cortex: a magnetic resonance spectroscopy study.


Author: Annweiler C et al.

Affiliation: University of Western Ontario, London, Ontario, Canada; University of Anger, Angers, France.

Abstract: Vitamin D is involved in brain physiology and lower-extremity function. The researchers investigated spectroscopy in a cohort of older adults to explore the hypothesis that lower vitamin D status was associated with impaired neuronal function in caudal primary motor cortex (cPMC) measured by proton magnetic resonance spectroscopic imaging. Twenty Caucasian community-dwellers (meanstandard deviation, 74.66.2 years; 35.0% female) from the 'Gait and Brain Study' were included in this analysis. Ratio of N-acetyl-aspartate to creatine (NAA/Cr), a marker of neuronal function, was calculated in cPMC. Participants were categorized according to mean NAA/Cr. Lower vitamin D status was defined as serum 25-hydroxyvitamin D (25OHD) concentration <75 nmol/L. Age, gender, number of comorbidities, vascular risk, cognition, gait performance, vitamin D supplements, undernourishment, cPMC thickness, white matter hyperintensities grade, serum parathyroid hormone concentration, and season of evaluation were used as potential confounders. Compared to participants with high NAA/Cr (n = 11), those with low NAA/Cr (i.e., reduced neuronal function) had lower serum 25OHD concentration and more frequently lower vitamin D status. Lower vitamin D status was cross-sectionally associated with a decrease in NAA/Cr after adjustment for clinical characteristics, neuroimaging measures and serum measures. The conclusion is that lower vitamin D status was associated with reduced neuronal function in cPMC. These novel findings need to be replicated in larger and preferably longitudinal cohorts. They contribute to explain the pathophysiology of gait disorders in older adults with lower vitamin D status, and provide a scientific base for vitamin D replacement trials.

Prevalence of vitamin D deficiency and its related factors in children and adolescents living in North Khorasan, Iran.


Author: Habibsadat S, Ali K, Shabnam JM, Arash A.

Affiliation: Faculty of Public Health, School of Medicine, North Khorasan University of Medical Sciences, Bojnurd, Iran, Department of Pediatrics, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran, Faculty of Health and Environmental Science, Auckland University of Technology, Auckland, New Zealand

Abstract: Vitamin D deficiency is recognized as an epidemic among children. The present study has analyzed serum 25 hydroxyvitamin D [25(OH)D] levels of children living in the city of Bojnurd, located in the North Khorasan province of Iran. In this cross-sectional study, 361 subjects (175 boys and 186 girls) aged 7-18 years participated; 25(OH)D, parathyroid hormone (PTH), and anthropometric measurements were obtained. Deficiency, insufficiency and sufficiency of vitamin D was assessed based on the relationship between 25(OH)D and PTH. Vitamin D status was reported according to gender and age group of participants. The prevalence of vitamin D deficiency was 16.1% and its insufficiency was 25.2%. Girls had higher levels of vitamin D deficiency (30.6%) and insufficiency (38.7%). The mean level of serum 25(OH)D decreased in older age groups. The age-adjusted odds of serum 25(OH)D <30 was 21.12 higher in girls compared to boys. Conclusion: The prevalence of vitamin D deficiency and insufficiency was high. The ratio in girls was higher than in boys.

Subclinical Vitamin D Insufficiency in Korean School-aged Children


Author: Han SW, et al

Affiliation: Department of Pediatrics, Eulji General Hospital, Seoul, Korea; Department of Medicine, Eulji University, Daejeon, Korea.

Abstract: Recently, vitamin D insufficiency has increased and has been correlated to growth and puberty in children. This study was conducted to find the prevalence of subclinical vitamin D insufficiency and its influence on school-aged children in Korea. The subjects of this study were 397 children aged 7 to 15 years who had been tested for 25-OH vitamin D3 among the outpatients of the Department of Pediatrics in Eulji General Hospital from March 2007 to February 2011. Data for age, sex, comorbidities, serum 25-OH vitamin D3, height, weight, body mass index (BMI), and sunlight exposure time were collected before and after 3 months of vitamin D administration, retrospectively. Vitamin D insufficiency was present in 343 (86%) of the subjects. In the vitamin D insufficient group, chronological age was 8.961.72 years, mean height (z-score [z]) was 0.511.26, mean BMI (z) was 0.812.20, and bone age was 10.261.75 years. In the vitamin D sufficient group, chronological age was 9.611.77 years, mean height (z) was-0.660.98, mean BMI (z) was-0.011.16, and bone age was 9.442.12 years. A paired t-test showed that three months after vitamin D administration, the mean 25-OH vitamin D3 level in the insufficient group increased to 24.38 10.03 ng/mL and mean BMI (z) decreased to 0.671.06. The studys conclusion was that in Korean school-aged children, vitamin D insufficiency were relatively higher and may be closely related with higher BMI. Insufficient rise of the level of vitamin D after supplementation suggest the new supplementation guidelines.

Severe vitamin D deficiency is associated with frequently observed diseases in medical inpatients.


Author: Marra A, Leoncini G, et al.

Affiliation: Department of Internal Medicine, IRCCS-AOU San Martino-IST, University of Genova, Italy.

Abstract: Vitamin D deficiency consequences may go beyond altered calcium homeostasis and musculoskeletal disease. Medical inpatients are often vitamin D-deficient, but little information is available about the relation of vitamin D status with extra-skeletal disorders in this population. Researchers analysed the relationship between the concentrations of 25-hydroxyvitamin D [25(OH)D], the marker of vitamin D status, and the conditions most commonly causing admission in 115 consecutive medical inpatients. Sixty-five subjects (56.5%) had severe vitamin D deficiency [25(OH)D < 8 ng/ml]. Age and hepatic disease were significant correlates of 25(OH)D levels. Compared with patients with 8 ng/ml 25(OH)D, those with < 8 ng/ml 25(OH)D had significantly higher parathyroid hormone (PTH) concentrations [123 (92.7-208.2) ng/l vs. 88 (68.5-129.5) ng/l], were significantly more likely to have arterial hypertension (OR 2.76, 95% CI 1.16-6.58), heart failure (HF) (OR 2.49, 95% CI 1.14-5.47), cerebrovascular disease (OR 3.23, 95% CI 1.41-7.39), and infections (OR 2.44, 95% CI 1.02-5.87), and stayed in hospital significantly longer (10 days vs. 7.5 days). Only the probability of having an infection remained significantly higher in cases with severe vitamin D deficiency after adjustment for age and persisted after further correcting for presence of hepatic disease and PTH values. A significant association between PTH and HF and length of hospitalisation emerged in the fully adjusted regression models. The conclusion is that severe vitamin D deficiency is associated with commonly presenting extra-skeletal diseases in medical inpatients. With the exception of infections, this association is mainly driven by age.

Vitamin D levels in Indian systemic lupus erythematosus patients: association with disease activity index and interferon alpha.


Author: Mandal M, et al.

Affiliation: Indian Institute of Technology, Kharagpur, India

Abstract: Low levels of vitamin D3 have been associated with several autoimmune disorders including multiple sclerosis, rheumatoid arthritis, type 1 diabetes and systemic lupus erythematosus (SLE). The major source of vitamin D3 is sunlight but exposure of SLE patients to UV rays has been shown to exacerbate disease pathology. Studies in various populations have shown an association between low vitamin D levels and higher SLE disease activity. The researchers enrolled 129 patients who fulfilled American College of Rheumatology criteria in the study. There were 79 treatment naive cases and 50 patients who were under treatment for underlying SLE. There were 100 healthy subjects from similar geographical areas included as controls. Plasma 25-OH vitamin D3 and interferon (IFN)-alpha levels were quantified by enzyme linked immunosorbent assay (ELISA). The gene expression level of IFN-alpha was determined by quantitative real-time reverse transcriptase polymerase chain reaction (RT-PCR). Plasma 25-OH vitamin D3 significantly correlated in an inverse manner with systemic lupus erythematosus disease activity index (SLEDAI) scores, anti-dsDNA, plasma IFN-alpha (P <0.0001, r = -0.43) and levels of IFN-alpha gene expression. Further, plasma levels of IFN-alpha positively correlated with gene expression of IFN-alpha. Treatment naive SLE patients displayed significantly higher plasma levels of IFN-alpha compared to patients under treatment and controls. These results suggest an important role of vitamin D in regulating disease activity in SLE patients and the need to supplement vitamin D in their treatment.

Vitamin D and cutaneous lupus erythematosus: effect of vitamin D replacement on disease severity.


Author: Cutillas-Marco E et al.

Affiliation: Department of Dermatology, Hospital de la Vega Lorenzo Guirao, Murcia, Spain.

Abstract: The aims of this study were to identify variables associated with lower serum 25-hydroxyvitamin D [25(OH)D] levels in CLE patients and assess the effect of vitamin D restoration on disease severity. Vitamin D status in 60 CLE patients and 117 apparently healthy subjects was compared. The researchers recommended oral vitamin D3 to 27 CLE patients. After one year of treatment, changes in disease severity were assessed and compared to 25 untreated CLE patients. Disease severity was measured by the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI), number of exacerbations, duration of active lesions and patient assessment.ResultsPresence of CLE raised the odds of having vitamin D deficiency (OR 3.47, 95% CI 1.79-6.69). Increasing age and disease duration were associated with higher odds of having vitamin D deficiency. After a one-year follow-up, disease activity improved in the treatment group (CLASI A 2.7  2.9 vs. 0.9  1.4), as confirmed by the patient assessment. Vitamin D inadequacy is more prevalent in CLE participants than in healthy controls. Treating vitamin D insufficiency is associated with improved disease severity according to physician and patient assessments.

A Homozygous CaSR Mutation Causing a FHH Phenotype Completely Masked by Vitamin D Deficiency Presenting as Rickets.


Author: Szczawinska D, et al.

Affiliation: Division of Endocrinology and Diabetes, Department of Medicine I, Friedrich-Alexander University Erlangen-Nuremberg, Germany

Abstract: Heterozygous inactivating calcium-sensing receptor (CaSR) mutations lead to familial hypocalciuric hypercalcemia (FHH) while homozygous mutations usually cause neonatal severe hyperparathyroidism (NSHPT). To investigate the pathophysiologic mechanisms of a homozygous inactivating CaSR mutation identified in a 16-year old female. Design. Clinical, biochemical and genetic analyses of the index patient and her family were performed. Functional capacity of CaSRQ459R and CaSR mutants causing FHH (Q27R, P39A, S417C) or NSHPT (W718X) was assessed. Activation of the cytosolic calcium pathway and inhibition of PTH-induced cAMP-signaling were measured. A 16-year old girl presented with adolescent rickets, vitamin D deficiency and secondary hyperparathyroidism. Vitamin D treatment unmasked features resembling FHH and genetic testing revealed a homozygous CaSRQ459R mutation. Two apparently healthy siblings were homozygous for CaSRQ459R and had asymptomatic hypercalcemia and hypocalciuria. The CaSRQ459R mutation leads to mild functional inactivation in-vitro which explains the FHH-like phenotype in homozygous family members and the grossly exaggerated PTH response to vitamin D deficiency in the index case. The patient's parents and two other siblings were heterozygous, had normal serum calcium and PTH, but marked hypocalciuria, which appeared to be associated with impaired in-vitro activation of the calcium signaling pathway by CaSRQ459R. The Q459R mutation responded well to calcimimetic treatment in-vitro. CaSR mutations causing mild functional impairment can lead to FHH even in homozygous patients. The skeletal deformities in the index case were mainly due to severe vitamin D deficiency, CaSR mutation did not appear to have played a major independent role in the skeletal phenotype.

Vitamin D deficiency in South Europe: effect of smoking and aging.


Author: Cutillas-Marco E, et al.

Affiliation: Department of Dermatology, Hospital de la Vega Lorenzo Guirao, Cieza, Spain.

Abstract: The main source of vitamin D is synthesis in the skin during exposure to ultraviolet radiation. The existence of photo-aggravated diseases and the increasing incidence of skin cancer have prompted recommendations to avoid the sun. The researchers studied the status of vitamin D in a healthy population and its relation to their habits of sun exposure. To do so, they designed a cross-sectional study that included 177 healthy people. In this study, researchers analysed parameters about demographic data, sun exposure, and protection habits and estimated vitamin D dietary intake. Blood tests were performed to measure serum 25-hydroxyvitamin D [25(OH)D], calcium, phosphorus, and intact parathyroid hormone. Mean levels ( standard deviation) of 25(OH)D were 24.0 ( 8.5) ng/ml. Seventy-six percent of the population did not reach recommended levels of vitamin D (30 ng/ml), including 4.5% who were vitamin D deficient (< 10 ng/ml). Levels were higher in young people and those with more sun exposure. Smoking was associated with an increased risk of hypovitaminosis D. On the basis of the findings, the risk of hypovitaminosis should be considered when sun avoidance is recommended.

Beneficial role for supplemental vitamin D3 treatment in chronic urticaria: a randomized study


Author: Rorie A, Goldner WS, Lyden E, Poole JA.

Affiliation: Department of Medicine, College of Medicine, University of Nebraska Medical Center, The Nebraska Medical Center, Omaha, Nebraska.

Abstract: The objective of this study was to determine whether high-dose vitamin D supplementation would decrease Urticaria Symptom Severity (USS) scores and medication burden in patients with chronic urticaria. In a prospective, double-blinded, single-center study, 42 subjects with chronic urticaria were randomized to high (4,000 IU/d) or low (600 IU/d) vitamin D3 supplementation for 12 weeks. All subjects were provided with a standardized triple-drug therapy (cetirizine, ranitidine, and montelukast) and a written action plan. Data on USS scores, medication use, blood for 25-hydroxyvitamin D, and safety measurements were collected. Triple-drug therapy decreased total USS scores by 33% in the first week. There was a further significant decrease (40%) in total USS scores in the high, but not low, vitamin D3 treatment group by week 12. Compared with low treatment, the high treatment group demonstrated a trend (P = .052) toward lower total USS scores at week 12, which was driven by significant decreases in body distribution and number of days with hives. Beneficial trends for sleep quality and pruritus scores were observed with high vitamin D3. Serum 25-hydroxyvitamin D levels increased with high vitamin D3 supplementation, but there was no correlation between 25-hydroxyvitamin D levels and USS scores. There was no difference in allergy medication use between groups. No adverse events occurred. The conclusion is that add-on therapy with high-dose vitamin D3 (4,000 IU/d) could be considered a safe and potentially beneficial immunomodulator in patients with chronic urticaria.

Vitamin D insufficiency is associated with higher carotid intima-media thickness in psoriatic patients.


Author: Orgaz-Molina J, et al.

Affiliation: University Hospital of San Cecilio, Granada

Abstract: Psoriasis has been associated with vitamin D insufficiency and cardiovascular risk factors. Reports show that serum 25-hydroxyvitamin D (25-OHD) levels are inversely associated with chronic inflammatory systemic diseases, cardiovascular risk factors and cardiovascular outcomes. The aim of the research was to analyze the association between 25-hydroxyvitamin D serum levels and subclinical carotid atherosclerosis (maximal intima-media thickness (MIMT)) in psoriasis patients and controls. MIMT was compared and associated factors were analyzed. This was a case-control study with 44 psoriatic patients without arthritis from a Dermatology outpatient clinic in Granada (Spain) and 44 controls. Confounding factors related to 25-OHD serum levels and cardiovascular risk factors were also analyzed. 25-OHD levels were significantly lower in the psoriatic than in the control group (29.20 vs. 38.00 ng/mL) and a significant negative correlation was found between serum 25-OHD levels and the MIMT in psoriatic patients. No correlation was found in healthy controls. This association remained after adjusting for confounders. Serum 25-OHD levels were significantly lower in psoriatic patients with carotid atheromatous plaque than in those without. Patients with a longer history of psoriasis presented significantly higher MIMT than controls (638.70 76.21 vs 594.67 80.20 m; for 6 yrs with psoriasis). In psoriasis patients, lower serum 25-OHD levels were associated with higher MIMT after adjusting for selected confounding factors. The MIMT risk increases with a longer history of psoriasis, regardless of the patient's age.

A pilot study assessing the effect of prolonged administration of high daily doses of vitamin D on the clinical course of vitiligo and psoriasis.


Author: Finamor DC, Sinigaglia-Colmbra R, et al.

Affiliation: Universidade Federal de Sao Paolo, Brazil; Universidade Paulista, Sao Paulo, Brazil

Abstract: Autoimmunity has been associated with vitamin D deficiency and resistance, with gene polymorphisms related to vitamin D metabolism frequently described in affected patients. High doses of vitamin D3 may conceivably compensate for inherited resistance to its biological effects. This study aimed to assess the efficacy and safety of prolonged high-dose vitamin D3 treatment of patients with psoriasis and vitiligo. Nine patients with psoriasis and 16 patients with vitiligo received vitamin D3 35,000 IU once daily for six months in association with a low-calcium diet (avoiding dairy products and calcium-enriched foods like oat, rice or soya "milk") and hydration (minimum 2.5 L daily). All psoriasis patients were scored according to "Psoriasis Area and Severity Index" (PASI) at baseline and after treatment. Evaluation of clinical response of vitiligo patients required a quartile grading scale. All patients presented low vitamin D status (serum 25(OH)D3 30 ng/mL) at baseline. After treatment 25(OH)D3 levels significantly increased (from 14.9 7.4 to 106.3 31.9 ng/mL and from 18.4 8.9 to 132.5 37.0 ng/mL) and PTH levels significantly decreased (from 57.8 16.7 to 28.9 8.2 pg/mL and from 55.3 25.0 to 25.4 10.7 pg/mL) in patients with psoriasis and vitiligo respectively. PTH and 25(OH)D3 serum concentrations correlated inversely. The PASI score significantly improved in all nine patients with psoriasis. Fourteen of 16 patients with vitiligo had 25-75% repigmentation. Serum urea, creatinine and calcium (total and ionized) did not change and urinary calcium excretion increased within the normal range. High-dose vitamin D3 therapy may be effective and safe for vitiligo and psoriasis patients.

25-Hydroxyvitamin D Levels and Acute Cellular Rejection in Liver Transplant Patients.


Author: Sheikh-Ali M, et al.

Affiliation: Division of Endocrinology, Department of Medicine, University of Florida-Jacksonville, Florida, USA.

Abstract: To investigate the association between 25-hydroxyvitamin D [25(OH)D] levels prior to liver transplantation (LT) and the development of acute cellular rejection (ACR) within the first year post-LT. This retrospective study included 275 consecutive LTs performed in 262 patients at Mayo Clinic, Jacksonville over 13 months. A total of 149 patients met the inclusion criteria. The correlation between 25(OH)D levels and the development, severity, and number of biopsy-proven ACR episodes, was assessed. The prevalence of 25-hydroxyvitamin D levels <30 ng/mL, was 92%. No association was found between pre-LT 25(OH)D levels and the diagnosis of ACR. Mean SD pre-LT 25(OH)D levels were 16.1 6.8 ng/mL for 48 subjects with no rejection, 16.1 8.2 ng/mL for those with a mild first episode of ACR (n = 58), and 18.4 12.4 ng/mL for those who experienced a moderate/severe first ACR (n = 39). However, in a subgroup analysis of patients with 25-hydroxyvitamin D <30 ng/mL, there was a statistically significant negative correlation between the level of 25-hydroxyvitamin D and rate of ACR. Vitamin D insufficiency and deficiency prior to LT was prevalent in our cohort. There was no statistically significant association between low 25(OH)D levels and the diagnosis or severity of ACR, or the number of rejection episodes within the first year post-LT. However, there was a negative correlation between 25-hydroxyvitamin D levels below 30 ng/mL and the rate of ACR within one year post LT.

Vitamin D status among patients visiting a tertiary care center in Riyadh, Saudi Arabia: a retrospective review of 3475 cases.


Author: Alfawaz H, et al.

Affiliation: King Saud University,Riyadh, Saudi Arabia.

Abstract: Vitamin D deficiency has been implicated in several chronic, non-communicable diseases independent of its conventional role in bone and calcium homeostasis. In this retrospective study, the researchers determined the prevalence of vitamin D deficiency and its association to several cardiometabolic indices among patients visiting King Abdulaziz Medical City (KAMC), a tertiary hospital in Riyadh, Saudi Arabia. A total of 3475 charts of out-patient subjects who visited KAMC last September 2009 until December 2010 were reviewed and included. Variables of interest included measurements of vitamin D status, glycemic and renal profile, as well as trace elements (calcium and phosphorous). The over-all prevalence of vitamin D deficiency in the cohort studied was 78.1% in females and 72.4% in males. 25(OH) vitamin D was significantly associated with increasing age and weight. It was also positively associated with albumin, calcium and phosphorous and negatively associated with alkaline phosphatase as well as circulating levels of PTH. In conclusion, vitamin D deficiency is overwhelmingly common among patients seen at KAMC regardless of the medical condition, and it is significantly associated with increasing age, weight and markers of calcium homeostasis. Findings of the present study further stress the spotlight on vitamin D deficiency epidemic in the country and region in general.

Intracranial volume inversely correlates with serum 25(OH)D level in healthy young women.


Author: Plzer E, et al.

Affiliation: Department of Neurology, Medical School, University of Pcs, Pcs, Hungary

Abstract: Vitamin D is important in normal brain development. In animals low vitamin D level is associated with brain morphological alterations including enlargement of the brain. Whether a similar association exists in humans is unknown. The researchers investigated the relationship between vitamin D and total intracranial volume as well as total volume of the cortical grey and cerebral white matter and that of the ventricles in young healthy women. To assess volumes, researchers applied semi-automatic user-independent MR volumetry. For the vitamin D measurements automated electrochemiluminescence immunoassay was used. The results showed a significant negative correlation between vitamin D and total intracranial volume as well as total cortical grey and cerebral white matter volumes. This association may reflect a trait-like relationship between vitamin D and brain size possibly determined in early development.

Sickle Cell Disease and Vitamin D


Author: Shams T, Al Wadani H, et al.

Affiliation: Department of Anaesthesia and ICU, Faculty of Medicine, Mansoura University, Mansoura, Egypt; Department of Surgery, King Faisal University, Kingdom of Saudi Arabia

Abstract: Few previous studies proved that complications related to sickle cell disease (SCD) were common with regional anaesthesia compared with general anaesthesia while others reported no differences. This study was carried out to evaluate the role of prophylactic vitamin D on anaesthetic outcome among male children with SCD undergoing surgery. A comparative study was carried out on 58 children undergoing circumcision with the regional block under light general anaesthesia. The study sample was classified into two groups: one group received daily 400 IU vitamin D for 6 months before surgery while the other group without vitamin D. All patients were followed regarding the post-operative analgesia and the incidence of post-operative SCD related complications (acute chest syndrome, painful crisis and cerebrovascular accident). Data were analyzed with Statistical Package for Social Sciences version 13, produced by IBM SPSS, Inc. in Chicago, Illinois, USA. There was a highly significant difference between the two groups (P < 0.001) regarding first analgesic request and total analgesic consumption per day: there was delayed analgesic request and less total analgesic consumption per day in vitamin D group. Comparison of post-operative sedation scores showed highly significant difference (P < 0.001) between the two groups, Sedation scores was increased significantly in vitamin D group. This study also reported that the administration of vitamin D was associated with less noticeable post-operative SCD complications. The use of prophylactic vitamin D in SCD will result in delayed post-operative analgesic request and less total analgesic requirement. Administration of vitamin D was also associated with less post-operative complications.

Vitamin D supplements with or without calcium to prevent fractures.


Author: Lips P, et al.

Affiliation: Endocrine Section, Department of Internal Medicine, VU University Medical Center, Amsterdam, The Netherlands.

Abstract: Vitamin D deficiency is associated with fractures. This relationship is biologically plausible. The results of 19 randomized clinical trials with vitamin D with or without calcium show varying results: a decreased fracture incidence in 7, neutral in 10 trials, whereas 2 trials with a high dose of vitamin D once per year showed an increased fracture incidence. In three out of four well-powered trials that used recommended doses of vitamin D 700-1000 IU per day, vitamin D supplementation did not significantly influence fracture risk. In one of these trials, a statistically significant fracture reduction was observed in nursing home residents having severe vitamin D deficiency, low calcium intake and good compliance. Thirteen meta-analyses were done, and 11 of these showed a significantly decreased fracture incidence in the supplemented groups. Vitamin D alone was not effective, studies combining vitamin D and calcium showed inconsistent results. Analyses for vertebral fractures were negative in all cases. In conclusion, a vitamin D supplement of 800 IU per day in combination with calcium may decrease the incidence of non-vertebral fractures, especially in persons in the older age groups having low-baseline vitamin D status and low calcium intake and showing good compliance.

Vitamin D Supplementation and the Effects on Glucose Metabolism During Pregnancy: A Randomized Controlled Trial.


Author: Yap C, et al.

Affiliation: Diabetes and Endocrinology, Westmead Hospital, Sydney, New South Wales, Australia.

Abstract: Vitamin D deficiency in pregnancy is associated with an increased risk of gestational diabetes mellitus (GDM) and neonatal vitamin D deficiency. The researchers conducted a double-blind, randomized controlled trial of low-dose (LD) versus high-dose (HD) vitamin D supplementation to investigate the effects of vitamin D supplementation on glucose metabolism during pregnancy. Women with plasma 25-hydroxyvitamin D (25OHD) levels <32 ng/mL before 20 weeks' gestation were randomized to oral vitamin D3 at 5,000 IU daily (HD) (n = 89) or the recommended pregnancy dose of 400 IU daily (LD) (n = 90) until delivery. The primary end point was maternal glucose levels on oral glucose tolerance test (OGTT) at 26-28 weeks' gestation. Secondary end points included neonatal 25OHD, obstetric and other neonatal outcomes, and maternal homeostasis model assessment of insulin resistance. Analysis was by intention to treat. There was no difference in maternal glucose levels on OGTT. Twelve LD women (13%) developed GDM versus seven (8%) HD women. Neonatal cord 25OHD was higher in HD offspring, and deficiency was more common in LD offspring. Post hoc analysis in LD women showed an inverse relationship between pre-treatment 25OHD and both fasting and 2-h blood glucose level on OGTT. Baseline 25OHD remained an independent predictor after multiple regression analysis. Conclusion: vitamin D supplementation commencing at a mean of 14 weeks' gestation does not improve glucose levels in pregnancy. However, in women with baseline levels <32 ng/mL, 5,000 IU per day was well tolerated and highly effective at preventing neonatal vitamin D deficiency.

Effects of six months of vitamin D supplementation in patients with heart failure: A randomized double-blind controlled trial.


Author: Dalbeni A, et al.

Affiliation: Department of Medicine, University of Verona, Verona, Italy

Abstract: Low plasma vitamin D levels have been associated with heart failure (HF). This research attempts to explain the role of vitamin D supplementation on myocardial function in elderly patients with HF. Twenty-three chronic HF patients were randomized in a small parallel group, double-blind, placebo-controlled trial. All patients, with a mean age of 74 years and vitamin D levels <30 ng/mL, received 800,000 IU (4000 IU/daily) of cholecalciferol or placebo for 6 months. The outcomes measured at baseline and after 6 months were ejection fraction (EF) and other echocardiography parameters, carboxyterminal propeptide of procollagen type I (PIP), natriuretic peptides, lipid profile, renin, parathyroid hormone, blood pressure, and body mass index (BMI). In 13 patients under active treatment for 6 months, mean plasma 25-hydroxy vitamin D concentrations and plasma calcium increased significantly. However, other biomarkers of bone metabolism did not differ between the treatment and placebo groups. EF increased significantly in the intervention group, and the serum concentration of PIP increased only in the placebo group after 6 months. Systolic blood pressure was lower after 6 months of cholecalciferol treatment. No significant variations were observed for other parameters. Conclusion: Six months of vitamin D supplementation significantly improves EF in elderly patients with HF and vitamin D deficiency.

Blood 25-hydroxy vitamin D levels and incident type 2 diabetes: a meta-analysis of prospective studies.


Author: Song Y, et al.

Affiliation: Department of Medicine, Harvard Medical School, Boston, MA, USA.

Abstract: The objective of this study was to quantitatively assess the strength and shape of the association between blood 25-hydroxy vitamin D [25(OH)D] levels and incident risk of type 2 diabetes. A systematic search of the MEDLINE and Embase databases and a hand search of references from original reports were conducted up to 31 October 2012. Prospective observational studies that assessed the association between blood levels of 25(OH)D and risk of incident type 2 diabetes were included for meta-analysis. A total of 21 prospective studies involving 76,220 participants and 4,996 incident type 2 diabetes cases were included for meta-analysis. Comparing the highest to the lowest category of 25(OH)D levels, the summary relative risk for type 2 diabetes was 0.62. A spline regression model showed that higher 25(OH)D levels were monotonically associated with a lower diabetes risk. This inverse association did not differ by sex, duration of follow-up, study sample size, diabetes diagnostic criteria, or 25(OH)D assay method. A linear trend analysis showed that each 10 nmol/L increment in 25(OH)D levels was associated with a 4% lower risk of type 2 diabetes. This meta-analysis showed an inverse and significant association between circulating 25(OH)D levels and risk of type 2 diabetes across a broad range of blood 25(OH)D levels in diverse populations.

Circulating 25-hydroxy-vitamin D and risk of cardiovascular disease: a meta-analysis of prospective studies.


Author: Wang L, et al.

Affiliation: Brigham and Womens Hospital, Boston, MA, USA.

Abstract: Vitamin D status has been linked to the risk of cardiovascular disease (CVD). However, the optimal 25-hydroxy-vitamin D (25[OH]-vitamin D) levels for potential cardiovascular health benefits remain unclear. The researchers searched MEDLINE and EMBASE from 1966 through February 2012 for prospective studies that assessed the association of 25(OH)-vitamin D concentrations with CVD risk. A total of 24 articles met the inclusion criteria, from which 19 independent studies with 6123 CVD cases in 65 994 participants were included for a meta-analysis. In a comparison of the lowest with the highest 25(OH)-vitamin D categories, the pooled relative risk was 1.52 for total CVD, 1.42 for CVD mortality, 1.38 for coronary heart disease, and 1.64 for stroke. These associations remained strong and significant when analyses were limited to studies that excluded participants with baseline CVD and were better controlled for season and confounding. The researchers used a fractional polynomial spline regression analysis to assess the linearity of dose-response association between continuous 25(OH)-vitamin D and CVD risk. The CVD risk increased monotonically across decreasing 25(OH)-vitamin D below 60 nmol/L, with a relative risk of 1.03 per 25-nmol/L decrement in 25(OH)-vitamin D. This meta-analysis demonstrated a generally linear, inverse association between circulating 25(OH)-vitamin D ranging from 20 to 60 nmol/L and risk of CVD.

Serum 25-hydroxyvitamin D and incidence of fatal and nonfatal cardiovascular events: a prospective study with repeated measurements.


Author: Perna L, et al.

Affiliation: Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany.

Abstract: Several studies suggested that low serum concentrations of 25-hydroxyvitamin D (25(OH)D) are associated with an increased risk of cardiovascular disease (CVD). The researchers aimed to assess the association of 25(OH)D with fatal and nonfatal CVD in the same study population, using repeated 25(OH)D measurements and competing risks analysis. This was a population-based cohort study (ESTHER study, baseline 2000-2002). Follow-up data, including survival status, were collected after 2, 5, and 8 years. The response rate for survival was 99.9%. Participants were recruited during a health screening examination by their general practitioners. 25(OH)D was measured in blood samples collected at baseline and the 5-year follow-up visit. A total of 9949 men and women, aged 50 to 74 years at baseline, with sufficient knowledge of the German language and resident in the German state of Saarland were included in the study. Outcomes included CVD, coronary heart disease (CHD), and stroke, in total and differentiated into fatal and nonfatal events. Overall, 854 study participants had a nonfatal and 176 a fatal CVD event during 8 years of follow-up. Comparing subjects with 25(OH)D levels below 30 nmol/L and above 50 nmol/L resulted in a hazard ratio of 1.27 for total CVD and 1.62 for fatal CVD in a model adjusted for important potential confounders. No significant association for nonfatal CVD was observed. In dose-response analysis, the researchers observed an increased cardiovascular risk at 25(OH)D levels below 75 nmol/L. Results for CHD and stroke were comparable to the results obtained for the composite outcome CVD. These results support evidence that low 25(OH)D levels are associated with moderately increased risk of CVD and indicate that the observed association is much stronger for fatal than for nonfatal events.

Avoidance of sun exposure is a risk factor for all-cause mortality: results from the Melanoma in Southern Sweden cohort.

Source: Journal of Internal Medicine 2014 Jul;276(1):77-86. doi: 10.1111/joim.12251. Epub 2014 Apr 23

Author: Lindqvist PG, Epstein E, Landin-Olsson M, Ingvar C, Nielsen K, Stenbeck M, Olsson H

Affiliation: Department of Obstetrics and Gynecology, Clintec, Karolinska University Hospital, Stockholm, Sweden

Abstract: Sunlight exposure and fair skin are major determinants of human vitamin D production, but they are also risk factors for cutaneous malignant melanoma (MM). There is epidemiological evidence that all-cause mortality is related to low vitamin D levels. METHODS: We assessed the avoidance of sun exposure as a risk factor for all-cause mortality for 29 518 Swedish women in a prospective 20-year follow-up of the Melanoma in Southern Sweden (MISS) cohort. Women were recruited from 1990 to 1992 and were aged 25 to 64 years at the start of the study. We obtained detailed information at baseline on their sun exposure habits and potential confounders. Multivariable flexible parametric survival analysis was applied to the data. RESULTS: There were 2545 deaths amongst the 29 518 women who responded to the initial questionnaire. We found that all-cause mortality was inversely related to sun exposure habits. The mortality rate amongst avoiders of sun exposure was approximately twofold higher compared with the highest sun exposure group, resulting in excess mortality with a population attributable risk of 3%. CONCLUSION: The results of this study provide observational evidence that avoiding sun exposure is a risk factor for all-cause mortality. Following sun exposure advice that is very restrictive in countries with low solar intensity might in fact be harmful to women's health.