Low Levels Of 25-hydroxyvitamin Research Articles

Vitamin D Receptor Deficiency and Low Vitamin D Diet Stimulate Aortic Calcification and Osteogenic Key Factor Expression in Mice

Low levels of 25-hydroxy vitamin D (25(OH)D) are associated with cardiovascular diseases. Herein, we tested the hypothesis that vitamin D deficiency could be a causal factor in atherosclerotic vascular changes and vascular calcification. Aortic root sections of vitamin D receptor knockout (VDR−/−) mice that were stained for vascular calcification and immunostained for osteoblastic differentiation factors showed more calcified areas and a higher expression of the osteogenic key factors Msx2, Bmp2, and Runx2 than the wild-type mice (P<0.01). Data from LDL receptor knockout (LDLR−/−) mice that were fed western diet with either low (50 IU/kg), recommended (1,000 IU/kg), or high (10,000 IU/kg) amounts of vitamin D3 over 16 weeks revealed increasing plasma concentrations of 25(OH)D (P<0.001) with increasing intake of vitamin D, whereas levels of calcium and phosphorus in plasma and femur were not influenced by the dietary treatment. Mice treated with the low vitamin D diet had more calcified lesions and a higher expression of Msx2, Bmp2, and Runx2 in aortic roots than mice fed recommended or high amounts of vitamin D (P<0.001). Taken together, these findings indicate vitamin D deficiency as a risk factor for aortic valve and aortic vessel calcification and a stimulator of osteogenic key factor expression in these vascular areas.

1 COMBINATION OF LOW FREE TESTOSTERONE AND LOW VITAMIN D PREDICTS MORTALITY IN OLDER MEN REFERRED FOR CORONARY ANGIOGRAPHY

CONTEXT: Low levels of 25-hydroxyvitamin D (25(OH)D) and free testosterone (FT) are both associated with increased mortality. Experimental studies show a complex interplay of vitamin D and androgen metabolism suggesting that a deficiency of both hormones may be associated with a particularly adverse clinical outcome. OBJECTIVE: To evaluate the impact of parallel FT and 25(OH)D deficiency in a large cohort of older men. DESIGN: We measured total testosterone (TT), SHBG, and 25(OH)D levels in 2069 men who were routinely referred for coronary angiography (1997-2000). MAIN OUTCOME MEASURES: Cox proportional hazard ratios (HRs) (with 95% confidence intervals) for mortality from all causes, cardiovascular, and non-cardiovascular causes according to combined deficiency of FT and 25(OH)D. RESULTS: In multivariate adjusted analyses, we found an increased risk for all-cause mortality, cardiovascular and non-cardiovascular mortality for men in the lowest FT (HR 1.26 [1.03-1.54], 1.24 [0.96-1.60], and 1.39 [1.00-1.93], respectively) and 25(OH)D quartile (HR 1.77 [1.47-2.13], 1.65 [1.29-2.10], and 1.89 [1.38-2.60] respectively) compared to men in higher FT and 25(OH)D quartiles. There was no independent association of TT levels with mortality. Multivariate adjusted HRs progressively increased with the number of hormones (FT and 25(OH)D) in the lowest quartile (0 vs 2 hormone deficiencies: 2.11 [1.60-2.79] for all cause, 1.77 [1.23-2.55] for cardiovascular, and 2.33 [1.45-3.47] for non-cardiovascular mortality respectively). CONCLUSION: A combined deficiency of FT and 25(OH)D is significantly associated with fatal events in a large cohort of men referred for coronary angiography.

Vitamin D Deficiency in Women with Fibromyalgia in Saudi Arabia

The relation between low levels of 25-hydroxyvitamin D and nonspecific musculoskeletal pain, including fibromyalgia syndrome, is debatable. Many studies have reported "a positive relation" and others "found no relation." To determine the prevalence of vitamin D deficiency among patients with fibromyalgia in a neurology clinic in the Kingdom of Saudi Arabia (KSA). This study was done at a neurology clinic of Bugshan Hospital, Jeddah, KSA, from January to April 2011. Thirty female patients were diagnosed with fibromyalgia according to new clinical fibromyalgia diagnostic criteria; their serum vitamin D levels were screened. Vitamin D deficiency is defined as <20 ng/mL, vitamin D insufficiency is defined as 21-29 ng/mL, and vitamin D sufficiency is equal to or >30 ng/mL. Thirty female patients were included in the study. The mean age was 34.56 ± 8.1 years. Mean vitamin D level was 4.76 ± 1.46 ng/mL. A significant negative correlation between vitamin D level and widespread pain index was found. Thirty percent of the patients were Saudi Arabian of whom 100% were veiled; 70% were non-Saudi Arabian of whom 47.6% were veiled and 52.4% wore long pants and/or full sleeved clothes. Vitamin D deficiency was equally prevalent among veiled (4.77 ± 1.37 ng/mL) and nonveiled (4.75 ± 1.68 ng/mL). Treatment with high-dose vitamin D resulted in clinical improvement in all patients. Vitamin D deficiency is often seen in patients diagnosed with fibromyalgia in our population. This was equally true in veiled and nonveiled, but conservatively dressed populations. Effective treatment with high-dose vitamin D could lead to resolution of almost all symptoms. Further study of these populations and fortification of foods with vitamin D may be essential.

Low Levels of 25-Hydroxyvitamin D Prior to Allogeneic Transplantation Correlate with the Development of Chronic Graft-Versus-Host Disease

Abstract 4063 Graft-versus-host disease (GVHD) remains a significant cause of morbidity and mortality following allogeneic hematopoietic stem cell transplantation. GVHD is mediated by the activation and expansion of donor derived alloreactive lymphocytes stimulated in part by residual host dendritic cells (DCs) and donor DCs with cross presentation of alloantigens. Vitamin D is a hormone essential for calcium homeostasis and exhibits potent immunomodulatory characteristics. We have demonstrated that vitamin D exposure inhibits DC maturation and DC mediated stimulation of allogeneic T cells. As such, we hypothesized that vitamin D deficiency may result in the enhanced capacity of DCs to induce GVHD. In this study, we performed a retrospective case-control study to evaluate whether monohydroxyvitamin D levels measured in serum samples obtained from patients prior to allogeneic transplantation were predictive of the risk for GVHD. Fifty-three patients aged 18–60 who underwent a myeloablative matched related or matched unrelated donor transplant between December 2000 and December 2009 at Dana Farber Cancer Institute (DFCI) were included in the analysis. 25-OH vitamin D concentrations were measured by an ELISA assay on serum samples that had been cryopreserved between one and three months prior to transplantation. All patients were alive and evaluable at day 100. The median 25-OH vitamin D level was 21.9 ng/mL (range 7.8–45.7). Patients were divided into two cohorts based on a vitamin D level: < 25 ng/mL (32 patients) or ≥25 ng/mL (21 patients). There was no difference between the groups with respect to patient or donor age, donor type (matched related versus unrelated donor), cell source (peripheral blood versus bone marrow), patient-donor sex matching, myeloid versus lymphoid malignancy, risk status, patient/donor CMV status, conditioning regimen, or GVHD prophylaxis regimen. The cumulative incidence of grades II-IV acute GVHD at 100 days was 53.1% in the group with vitamin D level <25 versus 33.3% in the group with vitamin D≥25 (p=0.13). Remarkably, the cumulative incidence (CI) of chronic GVHD (cGVHD) at 2 years in patients with 25-OH vitamin D <25 was 63.8%, compared to 23.8% in patients with vitamin D levels ≥ 25 (p=0.009). Similarly the 2 year CI of extensive cGVHD was significantly greater in patients with vitamin D levels <25 compared to those with ≥25 (54.5% versus 14.3%, p=0.005). This result is consistent in multivariable competing risks model for which patient and transplant related factors mentioned above were adjusted (HR 5.26, p=0.02). [Figure 1][1] represents the CI of cGVHD with death and relapse as a competing risk. Three-year progression-free survival and overall survival were similar between the two groups (51% vs. 47%, p=0.61; and 53% vs. 50%, p=0.57 respectively). In summary, vitamin D deficiency prior to allogeneic transplantation is associated with a significantly increased risk of chronic GVHD. A prospective clinical trial evaluating the use of vitamin D for the prevention of chronic GVHD is planned. ![Figure 1:][2] Figure 1: Cumulative Incidence of cGVHD with Death/Relapse as a Competing Risk Disclosures: No relevant conflicts of interest to declare. [1]: #F1 [2]: pending:yes

A Cross-Sectional Study of the Association between Circulating 25-Hydroxyvitamin D Levels and Predicted Operative Mortality of Patients with Cardiovascular Disease

Recent studies have suggested that low levels of 25-hydroxyvitamin D (25OHD) are associated with cardiovascular risks in medical patients. However, these associations have not been well documented in high risk surgical patients. We hypothesized that serum 25OHD, 1,25-dihydroxyvitamin D (1,25OHD) would be associated with the cardiac operative risk stratification score. The study was conducted with a cross-sectional design at a single academic medical center in Japan. Two hundred five adult patients scheduled for major cardiovascular surgery were included consecutively. Cardiac operative risk was evaluated with the European System for Cardiac Operative Risk Evaluation (EuroSCORE) scoring system. Correlations between 25OHD and 1,25OHD, and EuroSCORE were assessed using simple and multiple linear regression models. Mean 25OHD and 1,25OHD were 20.1 ± 7.1 ng/mL and 51.2 ± 19.2 pg/mL, respectively. Half and 88% of the study population showed deficient (<20 ng/mL) and insufficient (<30 ng/mL) 25OHD levels, respectively. In contrast, only 3% showed 1,25OHD levels lower than normal (<20 pg/mL). Circulating 25OHD levels, but not 1,25OHD levels, were negatively correlated with EuroSCORE (p=0.005) even after adjusted for body mass index, albumin, hypertension, dyslipidemia, diabetes mellitus, creatinine, use of statin, high sensitive C-reactive protein, and intact parathyroid hormone. These results suggest that serum 25OHD levels are inversely associated with operative risk severity of patients undergoing major cardiovascular surgery.

Low Levels of 25-Hydroxyvitamin D Prior to Allogeneic Transplantation Correlate with the Development of Chronic Graft-Versus-Host Disease,

Abstract 4063Graft-versus-host disease (GVHD) remains a significant cause of morbidity and mortality following allogeneic hematopoietic stem cell transplantation. GVHD is mediated by the activation and expansion of donor derived alloreactive lymphocytes stimulated in part by residual host dendritic cells (DCs) and donor DCs with cross presentation of alloantigens. Vitamin D is a hormone essential for calcium homeostasis and exhibits potent immunomodulatory characteristics. We have demonstrated that vitamin D exposure inhibits DC maturation and DC mediated stimulation of allogeneic T cells. As such, we hypothesized that vitamin D deficiency may result in the enhanced capacity of DCs to induce GVHD. In this study, we performed a retrospective case-control study to evaluate whether monohydroxyvitamin D levels measured in serum samples obtained from patients prior to allogeneic transplantation were predictive of the risk for GVHD. Fifty-three patients aged 18–60 who underwent a myeloablative matched related or matched unrelated donor transplant between December 2000 and December 2009 at Dana Farber Cancer Institute (DFCI) were included in the analysis. 25-OH vitamin D concentrations were measured by an ELISA assay on serum samples that had been cryopreserved between one and three months prior to transplantation. All patients were alive and evaluable at day 100. The median 25-OH vitamin D level was 21.9 ng/mL (range 7.8–45.7). Patients were divided into two cohorts based on a vitamin D level: < 25 ng/mL (32 patients) or ≥25 ng/mL (21 patients). There was no difference between the groups with respect to patient or donor age, donor type (matched related versus unrelated donor), cell source (peripheral blood versus bone marrow), patient-donor sex matching, myeloid versus lymphoid malignancy, risk status, patient/donor CMV status, conditioning regimen, or GVHD prophylaxis regimen. The cumulative incidence of grades II-IV acute GVHD at 100 days was 53.1% in the group with vitamin D level <25 versus 33.3% in the group with vitamin D≥25 (p=0.13). Remarkably, the cumulative incidence (CI) of chronic GVHD (cGVHD) at 2 years in patients with 25-OH vitamin D <25 was 63.8%, compared to 23.8% in patients with vitamin D levels ≥ 25 (p=0.009). Similarly the 2 year CI of extensive cGVHD was significantly greater in patients with vitamin D levels <25 compared to those with ≥25 (54.5% versus 14.3%, p=0.005). This result is consistent in multivariable competing risks model for which patient and transplant related factors mentioned above were adjusted (HR 5.26, p=0.02). Figure 1 represents the CI of cGVHD with death and relapse as a competing risk. Three-year progression-free survival and overall survival were similar between the two groups (51% vs. 47%, p=0.61; and 53% vs. 50%, p=0.57 respectively). In summary, vitamin D deficiency prior to allogeneic transplantation is associated with a significantly increased risk of chronic GVHD. A prospective clinical trial evaluating the use of vitamin D for the prevention of chronic GVHD is planned. [Display omitted] Disclosures:No relevant conflicts of interest to declare.

Letter by Tsuda Regarding Article, “Vitamin D Deficiency Is Associated With Subclinical Carotid Atherosclerosis: The Northern Manhattan Study”

HomeStrokeVol. 42, No. 12Letter by Tsuda Regarding Article, “Vitamin D Deficiency Is Associated With Subclinical Carotid Atherosclerosis: The Northern Manhattan Study” Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBLetter by Tsuda Regarding Article, “Vitamin D Deficiency Is Associated With Subclinical Carotid Atherosclerosis: The Northern Manhattan Study” Kazushi Tsuda, MD, FAHA Kazushi TsudaKazushi Tsuda Cardiovascular and Metabolic Research Center Kansai University of Health Sciences Osaka, Japan (Tsuda) Search for more papers by this author Originally published27 Oct 2011https://doi.org/10.1161/STROKEAHA.111.634154Stroke. 2011;42:e639Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: January 1, 2011: Previous Version 1 To the Editor:We read with great interest the article by Carrelli et al1 dealing with the relationship between serum vitamin D levels and carotid atherosclerosis in a free-living, stroke-free, multiethnic, urban cohort. The results of their study demonstrated that serum phosphorus and calcium–phosphorus product were associated with a greater burden of subclinical carotid atherosclerosis. Among those with carotid plaque, the authors found that lower 25-hydroxyvitamin D levels were associated with thicker plaque and higher intima-media thickness of the carotid artery. The authors proposed the strong relationship between vitamin D deficiency and carotid vascular abnormalities that predicts the development of myocardial infarction and stroke.Evidence indicates that there were significant associations between low bone mineral density (BMD) and stroke. Jörgensen et al2 proposed that low BMD might predict first stroke in women. In a study we presented previously, a relationship between BMD and hypertension was investigated in women. Using the dual-energy X-ray absorptiometric method, we demonstrated that BMD in lumbar spine was significantly decreased in elderly hypertensive women compared with elderly normotensive women.3 In addition, BMD was inversely correlated with systolic blood pressure, suggesting that high blood pressure might be associated with the decrease in BMD in elderly women. Several studies have shown that hypertension is related to abnormalities of the calcium metabolism, such as increased calcium losses from the kidney, secondary activation of parathyroid glands, and vitamin D deficiency. It was demonstrated that the greater the 24-hour calcium excretion was, the lower the BMD was in women.3 It was also shown that BMD correlated negatively with serum vitamin D levels in elderly poststroke patients.4 Recently, Pilz et al5 demonstrated that low levels of 25-hydroxyvitamin D and 1, 25-hydroxyvitamin D were independent determinants of fatal stroke and were reduced in patients with a history of previous cerebrovascular diseases. Furthermore, they proposed that vitamin D supplementation might be a promising approach in the prevention of stroke.In this context, it can be speculated that in subjects with hypertension and lowered BMD, the disturbances in the calcium metabolism might be more pronounced. Therefore, we would like to know whether serum vitamin D levels might be related to the magnitudes of blood pressure or BMD in the populations in the study of Carrelli et al. It would be important to assess more precisely the relationships among vitamin D deficiency, BMD losses, and hypertension, and their contribution to stroke incidence.Kazushi Tsuda, MD, FAHA Cardiovascular and Metabolic Research Center Kansai University of Health Sciences Osaka, JapanDisclosuresNone.FootnotesStroke welcomes Letters to the Editor and will publish them, if suitable, as space permits. Letters must reference a Stroke published-ahead-of-print article or an article printed within the past 3 weeks. The maximum length is 750 words including no more than 5 references and 3 authors. Please submit letters typed double-spaced. Letters may be shortened or edited. Include a completed copyright transfer agreement form (available online at http://stroke.ahajournals.org and http://submit-stroke.ahajournals.org).

Depression is associated with low levels of 25-hydroxyvitamin D among Jordanian adults: results from a national population survey

Although low serum 25-hydroxyvitamin D (25(OH)D) and elevated serum parathyroid hormone (PTH) have been associated with depression in clinical settings, this link in community-dwelling individuals is inconclusive. The present study aimed at examining the association between serum 25(OH)D and PTH levels and the presence of depression in a national population-based household sample of 4,002 Jordanian participants aged ≥25 years. The DASS21 depression scale was used to screen for depression, and serum concentrations of 25(OH)D and PTH were measured by radioimmunoassay. Multiple logistic regression models were used to explore the association between serum 25(OH)D and PTH levels and depression. The unadjusted odds ratio (OR) decreased linearly with increasing quartiles of serum 25(OH)D (P(trend) = 0.00). The OR for having depression was significantly higher among individuals in the first and second quartiles (OR = 1.4, 1.23, respectively) than among those in the fourth quartile (P values = 0.00 and 0.03, respectively). This relationship remained significant after adjusting for age, sex, marital status, education, BMI, serum creatinine, number of chronic diseases (OR = 1.39 and 1.21 and P values = 0.00 and 0.05, respectively) and after further adjustment for exercise, altitude, and smoking (OR = 1.48 and 1.24, respectively, and P values = 0.00 and 0.03, respectively). No significant association was found between serum PTH levels and depression. The decrease in risk of depression among participants started to be significant with serum 25(OH) D levels higher than 42.3 ng/ml (lower limit of the range of the third quartile). This value may help pinpoint the desirable level of serum 25(OH)D to be attained to help aid the prevention and treatment of depression.

Low serum 25-hydroxyvitamin D levels are associated with depression in an adult Norwegian population

Observational and intervention studies have suggested an association between low levels of 25-hydroxyvitamin D (25(OH)D) and depressive symptoms in several subgroups of disease and age. This study tests the hypothesis in a general population. Our data are based on 10,086 persons who participated in the sixth Tromsø study carried out in 2007–2008. Depressive symptoms were evaluated using the Hopkins Symptoms Check List 10 (SCL-10) based on answers from a questionnaire. Results were adjusted for known confounders such as age, gender, body-mass index, physical exercise, alcohol, education, marital status, kidney function and chronic disease. Results are presented for smokers (N=1966) and non-smokers (N=8120) separately as our immunoassay seems to overestimate 25(OH)D levels for smokers. Low serum 25(OH)D levels were found to be a significant predictor of depressive symptoms in both smokers and non-smokers. The association seemed to be stronger in women. The odds ratios for depression in the highest 25(OH)D quartile were 0.59 (0.39–0.89) in smokers and 0.74 (0.58–0.95) in non-smokers compared with the lowest quartile. However, no conclusions with regard to causality can be drawn due to the cross-sectional design of the study.

Vitamin D Supplementation: A Promising Approach for the Prevention and Treatment of Strokes

Vitamin D deficiency is highly prevalent due to lifestyle and environmental factors which limit sunlight induced vitamin D production in the skin. This "pandemic" of vitamin D deficiency is of concern because low levels of 25-hydroxyvitamin D (25[OH]D) have been associated with cardiovascular, musculoskeletal, infectious, autoimmune and malignant diseases. Epidemiological studies have largely but not consistently shown that vitamin D deficiency is a risk factor for strokes. This is supported by associations of low 25(OH)D levels with cerebrovascular risk factors, in particular with arterial hypertension. Vitamin D has also been shown to exert neuroprotective, neuromuscular and osteoprotective effects which may reduce cognitive and functional impairments in poststroke patients. Hence, the current literature favours the notion that vitamin D supplementation is a promising approach for the prevention and treatment of strokes but accurate data from interventional studies are missing. Randomized controlled trials are therefore urgently needed to evaluate whether vitamin D supplementation reduces the incidence of strokes and improves the outcome of poststroke patients. We do, however, believe that currently published data on the multiple health benefits of vitamin D and the easy safe and inexpensive way by which it can be supplemented already argue for the prevention and treatment of vitamin D deficiency in order to reduce stroke associated morbidity and mortality.

Vitamin D, Pregnancy, Breastfeeding, and Postpartum Multiple Sclerosis Relapses

To determine whether low levels of 25-hydroxyvitamin D (25[OH]D) contribute to the increased risk of postpartum multiple sclerosis (MS) relapses. Prospective cohort study. Outpatients identified through membership records of Kaiser Permanente Northern California or Stanford University outpatient neurology clinics. Twenty-eight pregnant women with MS. We prospectively followed up patients through the postpartum year and assessed exposures and symptoms through structured interviews. Total serum 25(OH)D levels were measured using the DiaSorin Liaison Assay during the third trimester and 2, 4, and 6 months after giving birth. The data were analyzed using longitudinal multivariable methods. Levels of 25(OH)D and relapse rate. Fourteen (50%) women breastfed exclusively, and 12 women (43%) relapsed within 6 months after giving birth. During pregnancy, the average 25(OH)D levels were 25.4 ng/mL (range, 13.7-42.6) and were affected only by season (P=.009). In contrast, in the postpartum period, 25(OH)D levels were significantly affected by breastfeeding and relapse status. Levels of 25(OH)D remained low in the exclusive breastfeeding group, yet rose significantly in the nonexclusive breastfeeding group regardless of season (P=.007, unadjusted; P=.02, adjusted for season). By 4 and 6 months after childbirth, 25(OH)D levels were, on average, 5 ng/mL lower in the women who breastfed exclusively compared with the nonbreastfeeding group (P=.001). Pregnancy and exclusive breastfeeding are strongly associated with low 25(OH)D levels in women with MS. However, these lower vitamin D levels were not associated with an increased risk of postpartum MS relapses. These data suggest that low vitamin D in isolation is not an important risk factor for postpartum MS relapses.

Low Levels of 25-Hydroxyvitamin D in the Pediatric Populations: Prevalence and Clinical Outcomes

Vitamin D deficiency is becoming increasingly common in the USA. In this review we provide estimates of the prevalence of deficiency, and review the risk factors and the evidence of clinical consequences of vitamin D deficiency. Vitamin D deficiency causes the pediatric disease rickets. In addition, there is some evidence that vitamin D deficiency may lead to other diseases including diabetes mellitus, hypertension, infections, asthma and dyslipidemia.

Vitamin D Metabolites as Clinical Markers in Autoimmune and Chronic Disease

Recent research has implicated vitamin D deficiency (serum levels of 25-hydroxyvitamin D <50 nmol/L) with a number of chronic conditions, including autoimmune conditions such as multiple sclerosis, lupus, and psoriasis, and chronic conditions such as osteoporosis, osteoarthritis, metabolic syndrome, fibromyalgia and chronic fatigue syndrome. It has been assumed that low levels of 25-hydroxyvitamin D (25-D) accurately indicate vitamin D storage and vitamin D receptor (VDR)-mediated control of calcium metabolism and innate immunity. To evaluate this assumption, 25-D and 1,25-dihydroxyvitamin D3 (1,25-D) levels were measured in 100 Canadian patients with these conditions. Additionally, other inflammatory markers (CK, CRP) were measured. Results showed a strong positive association between these autoimmune conditions and levels of 1,25-D >110 pmol/L. However, there was little association with vitamin D deficiency or the other inflammatory markers, meaning that the results challenge the assumption that serum levels of 25-D are a sensitive measure of the autoimmune disease state. Rather, these findings support the use of 1,25-D as a clinical marker in autoimmune conditions. High levels of 1,25-D may result when dysregulation of the VDR by bacterial ligands prevents the receptor from expressing enzymes necessary to keep 1,25-D in a normal range.

Increased Levels of 25 Hydroxyvitamin D and 1,25-Dihydroxyvitamin D After Rosuvastatin Treatment: A Novel Pleiotropic Effect of Statins?

Low levels of 25-hydroxyvitamin D are associated with higher risk of cardiovascular morbidity and mortality. Large trials demonstrated that statins significantly decrease cardiovascular morbidity and mortality. 7-dehydrocholesterol is the precursor of both cholesterol and vitamin D. The aim of this study was to investigate the possible effect of rosuvastatin on vitamin D metabolism. The study was performed in a prospective cohort design. The study group consisted of 91 hyperlipidemic patients who had not been treated with lipid lowering medications. Lipid parameters, 25 hydroxyvitamin-D, 1,25-dihydroxyvitamin D, and bone alkaline phosphatase were obtained at baseline and after 8 weeks of rosuvastatin treatment. None of the subjects withdrew from the study because of the adverse effects. The mean age was 59.9 +/- 12.5 years. The majority of the patients were male (55, 60%). Seventeen patients were diabetic, and 43 patients had systemic hypertension. There was a significant increase in 25-hydroxyvitamin D, from mean 14.0 (range 3.7- 67) to mean 36.3 (range 3.8 -117) ng/ml (p < 0.001), and also an increase of 1,25-dihydroxyvitamin D from mean 22.9 +/- 11.2 to 26.6 +/- 9.3 pg/dl (p = 0.023). Bone alkaline phosphatase decreased after 8 weeks of rosuvastatin treatment, mean 17.7 (range 2.6-214) to mean 9.5 (range 2.3-19.1) u/l (p < 0.001) rosuvastatin treatment. This study has shown an effect of rosuvastatin on vitamin D metabolism, with an increase in both 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D. This may be an important pleiotropic effect whereby rosuvastatin reduces mortality in patients with coronary artery disease. Further studies are needed to clarify the relationship between statins and vitamin D metabolism.

Fok-I vitamin D receptor gene polymorphism (rs10735810) and vitamin D metabolism in multiple sclerosis

Multiple sclerosis (MS) has been associated with low levels of 25-hydroxyvitamin D (25(OH)D). Several genetic polymorphisms of the vitamin D receptor gene (VDRG), of whom Fok-I (rs10735810) has functional consequences for receptor protein structure and the immune system, have been studied in relation to MS with variable results. The purpose of our study was to assess an association of the Fok-I VDRG polymorphism with MS, and to further unravel the interaction of this polymorphism with vitamin D metabolism. Therefore, we genotyped 212 MS patients and 289 healthy controls for the Fok-I polymorphism and determined levels of the vitamin D metabolites 25(OH)D and 1,25(OH) 2D. No association of the Fok-I VDRG polymorphism with MS was found. The F-allele was associated with lower winter and summer serum 25(OH)D levels in our MS patients, and with lower 25(OH)D levels in healthy controls. Remarkably, the F-allele corresponded with higher 1,25(OH) 2D levels in MS patients. In all groups, carriers of the F-allele had higher 1,25(OH) 2D/ 25(OH)D-ratios compared to their f-allele counterparts. In conclusion, we demonstrated the importance of the Fok-I VDRG polymorphism for vitamin D metabolism. This should be taken into account in association and ultimately intervention studies on vitamin D and MS.

25-Hydroxyvitamin D and Risk of Stroke: Possible Mediation by Statin Therapy?

To the Editor: We read with interest a recent study by Pilz et al, which reported an association between low levels of 25-hydroxyvitamin D (25-OH D) and an increased risk of fatal stroke.1 In their study, low circulating 25-OH D levels predicted fatal stroke, independent of traditional cerebrovascular risk factors, including age, sex, body mass index, lipid levels, smoking, hypertension and diabetes mellitus. Despite adjustment for low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol levels, the …

Low Vitamin D Levels and Bone Mineral Density in Stroke

To the Editor: We read with great interest the article by Dr Pilz and colleagues1 dealing with the relationship between vitamin D levels and fatal stroke in patients who were referred to coronary angiography. The results of their study demonstrated that low levels of 25-hydroxyvitamin D [25(OH)D] and 1,25-hydroxyvitamin D [1,25(OH)2D] were independent predictors for fatal stroke and were reduced in patients with a …

Effects of age and renal function on vitamin D status in men.

In general, no study has examined the relationship between vitamin D status and key parameters of bone mineral homeostasis in healthy men in Iran. The effects of age and renal function on vitamin D status were determined in a cross-sectional study on a healthy population of Iranian men. From January through February 2001, 520 men, aged 20 - 74 years were selected through a cluster randomized sampling from Shiraz. Serum 25-hydroxyvitamin D, intact parathyroid hormone, calcium, phosphorus, alkaline phosphatase, creatinine, and albumin were measured. Pearson and partial correlation coefficients were used to determine the association between variables. Five hundred twenty men with a mean+/-SD age of 45+/-15 years and a mean+/-SD 25-hydroxyvitamin D level of 35+/-17 nmol/L were enrolled into the study. Over 33.9% of men in Shiraz had a low level of 25-hydroxyvitamin D (<or=25 nmol/L). Serum 25-hydroxyvitamin D did not decline with age in men. Serum parathyroid hormone increased significantly by age in men, but it did not correlate with the decline in creatinine clearance. Men had a decline in serum phosphorus (r=0.23, P<0.0001) and calcium (r=0.14, P=0.001) concentrations by age. Creatinine clearance declined with age. In healthy men, the serum level of 25-hydroxyvitamin D did not decline with age. Nonetheless, the prevalence of vitamin D deficiency is high which warrants consideration of dietary vitamin D supplement in men.

Low Levels of 25-hydroxyvitamin D3and 1,25-dihydroxyvitamin D3in Patients with Newly Diagnosed Type 1 Diabetes

An epidemiological retrospective study and a recent prospective study from Finland have both concluded that vitamin D3 supplementation at birth protects individuals from type 1 diabetes later in life. Moreover, it is thought that vitamin D3 supplementation, in particular its activated form, 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3], may act as an immunomodulator, facilitating the shift from a Th1 to a Th2 immune response. The aim of this surveillance study was to measure levels of both 25-hydroxyvitamin D3 (25OHD3) and 1,25-dihydroxyvitamin D3 in patients with newly diagnosed type 1 diabetes as compared to normal subjects. We measured plasma levels of 25-hydroxyvitamin D3 [25OHD3] and 1,25-dihydroxyvitamin D3 by radioimmunoassay in 88 consecutive patients with newly diagnosed type 1 diabetes (mean age 14.6 years; diagnosis within the last week), and in 57 healthy age and sex-matched subjects (mean age 16.5 years) born and residing in the Lazio region of continental Italy. Mean levels of both 25OHD3 and 1,25-(OH)2D3 were significantly lower in patients compared to controls (p < 0.01 and p < 0.03, respectively). There was no correlation between 1,25-(OH)2D3 plasma level and metabolic control status at disease diagnosis, age, gender, or most importantly, seasonality of disease diagnosis. This new observation endorses the findings of the Finnish study, even though Italy is a geographic area with more hours of sunlight than Finland. These findings suggest that vitamin D3 may be an important pathogenic factor in type 1 diabetes independent of geographical latitude, and that its supplementation should be considered not only at birth, but also at diagnosis of type 1 diabetes with the aim of favouring a Th2 immune response and protecting residual beta cells from further destruction.

Plasma 25-hydroxy vitamin D concentrations, vitamin D receptor genotype and breast cancer risk in a UK Caucasian population

Low levels of 25-hydroxy vitamin D (25(OH)D) and polymorphisms in the vitamin D receptor gene ( VDR) have been found separately to increase risk of breast cancer. The aim of this study was to determine whether low 25(OH)D levels, alone and in combination with BsmI VDR genotype, increased breast cancer risk in a United Kingdom (UK) Caucasian population. Breast cancer patients ( n = 179) and control women ( n = 179) were recruited and 25(OH)D levels measured by enzyme-linked immunosorbent assay (ELISA). VDR genotype was determined by polymerase chain reaction (PCR) and restriction enzyme digest. Analysis showed that subjects with 25(OH)D levels <50 nM and the bb BsmI VDR genotype are 6.82 times more likely to have breast cancer than subjects with levels of 25(OH)D > 50 nM and either the BB or Bb genotype (95% confidence interval (CI) 2.31–14.7, P < 0.001). This study indicates that low levels of circulating 25(OH)D, both alone and in combination with BsmI VDR genotype, may increase risk of breast cancer in a UK Caucasian population.