Association between vitamin D and hepatitis C virus infection: a meta-analysis.

AIM: To evaluate the association between 25-hydroxyvitamin D [25(OH)D] and sustained virological response (SVR) in hepatitis C virus (HCV) infected individuals. METHODS: Relevant studies were identified by systematically searching MEDLINE databases up to March 2012 and abstracts of the European and American Congress of Hepatology conducted in 2011. Studies must provide information on SVR and the levels of 25(OH)D3 and/or 25(OH)D2 [henceforth referred to as 25(OH)D] in sera samples from HCV infected individuals. The inclusion criteria were: clinical studies that included HCV infected patients aged older than 18 years regardless of HCV genotype or ethnic group; provided information on SVR rates; and were reported in the English language as full papers. Due to the heterogeneity of studies in categorizing serum vitamin D levels, a cut-off value of 30 ng/mL of serum 25(OH)D was used. Heterogeneity was assessed using I² statistics. The summary odds ratios with their corresponding 95%CI were calculated based on a random-effects model. RESULTS: Overall, 11 studies (8 observational and 3 interventional) involving 1575 individuals were included and 1117 HCV infected individuals (71%) showed low vitamin D levels. Most of the studies included mono-infected HCV individuals with the mean age ranging from 38 to 56 years. Four studies were conducted in human immunodeficiency virus/HCV infected individuals. Regarding vitamin D measurement, most of the studies employed radioimmunoassays (n = 5) followed by chemiluminescence (n = 4) and just one study employed high performance/pressure liquid chromatography (HPLC). Basal vitamin D levels varied from 17 to 43 ng/mL in the studies selected, and most of the HCV infected individuals had genotype 1 (1068/1575) with mean viral load varying from log 4.5-5.9 UI/mL. With regard to HCV treatment, most of the studies (n = 8) included HCV individuals without previous treatment, where the pooled SVR rate was 46.4%. High rates of SVR were observed in HCV individuals with vitamin D levels above 30 ng/mL (OR = 1.57; 95%CI: 1.12-2.2) and those supplemented with vitamin D (OR = 4.59; 95%CI: 1.67-12.63) regardless of genotype. CONCLUSION: Our results demonstrated high prevalence of vitamin D deficiency and high SVR in individuals with higher serum vitamin D levels or receiving vitamin D supplementation.

25-Hydroxyvitamin D [25(OH)D] levels and diabetic foot ulcer: is there any relationship?

AIMS: In recent years, there has been an effort to understand possible roles of 25(OH)D, including its role in the immune system particularly on T cell medicated immunity, pancreatic insulin secretion and insulin action. 25(OH)D stimulates the cell differentiation and reduces cell proliferation, which is essential for cell growth and wound healing. However, data on the association between low level of plasma 25(OH)D and diabetic foot syndrome are scarce. MATERIALS AND METHODS: Circulating plasma levels of 25(OH)D were measured in diabetic patients with ulcer (n=162) and without ulcer (n=162) in a prospective cohort hospital based study. RESULTS: Of these patients, 85.1% had type 2 diabetes. Subjects with diabetic foot ulcer showed lower median plasma level of 25(OH)D [6.3(4.2-11.1) vs 28.0(21.4-37.0)] ng/ml after adjusting the age and BMI. Regardless of the low levels of 25(OH)D in cases and controls, it was associated with neuropathy, sex (female), duration of ulcer healing, and smoking status and independent of confounding factors, including BMI (kg/m²), A1c (%), hypertension, nephropathy, foot ulcer, retinopathy, CAD, PAD, HDL-C (mg/dl) and LDL-C (mg/dl). The factors which predict the risk of developing ulcer independent of 25(OH)D status were A1c (>6.9%) [OR 4.37; RR 1.77], HDL-C (<40mg/dl) [OR 1.16; RR 1.07], LDL-C (>100mg/dl) [OR 1.07; RR 1.03], triglycerides (>200mg/dl) [OR 1.40; RR 1.19], neuropathy [OR 6.88; RR 3.12], retinopathy [OR 3.34; RR 1.91], hypertension [OR 1.64; RR 1.28], nephropathy [OR 3.12; RR 1.87] and smoking [OR 4.53; RR 2.99] using odds and risk ratios. CONCLUSION: It is not clear whether the suppression of delayed wound healing seen during 25(OH)D deficiency is due to the secondary effect or is a direct action of vitamin D on certain components of the immune system. Long-term randomized trials are needed to see the impact of vitamin D supplementation on the outcome of diabetic foot patients.

A randomized trial of high-dose vitamin D2 in relapsing-remitting multiple sclerosis.

OBJECTIVE: Higher latitude, lower ultraviolet exposure, and lower serum 25-hydroxyvitamin D (25OHD) correlate with higher multiple sclerosis (MS) prevalence, relapse rate, and mortality. We therefore evaluated the effects of high-dose vitamin D2 (D2) in MS. METHODS: Adults with clinically active relapsing-remitting MS (RRMS) were randomized to 6 months' double-blind placebo-controlled high-dose vitamin D2, 6,000 IU capsules, dose adjusted empirically aiming for a serum 25OHD 130-175 nM. All received daily low-dose (1,000 IU) D2 to prevent deficiency. Brain MRIs were performed at baseline, 4, 5, and 6 months. Primary endpoints were the cumulative number of new gadolinium-enhancing lesions and change in the total volume of T2 lesions. Secondary endpoints were Expanded Disability Status Scale (EDSS) score and relapses. RESULTS: Twenty-three people were randomized, of whom 19 were on established interferon or glatiramer acetate (Copaxone) treatment. Median 25OHD rose from 54 to 69 nM (low-dose D2) vs 59 to 120 nM (high-dose D2) (p = 0.002). No significant treatment differences were detected in the primary MRI endpoints. Exit EDSS, after adjustment for entry EDSS, was higher following high-dose D2 than following low-dose D2 (p = 0.05). There were 4 relapses with high-dose D2 vs none with low-dose D2 (p = 0.04). CONCLUSION: We did not find a therapeutic advantage in RRMS for high-dose D2 over low-dose D2 supplementation. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that high-dose vitamin D2 (targeting 25OHD 130-175 nM), compared to low-dose supplementation (1,000 IU/d), was not effective in reducing MRI lesions in patients with RRMS.

Responses of parathyroid hormone to vitamin D supplementation: a systematic review of clinical trials.

The beneficial bone effects of vitamin D supplementation have been attributed to suppression of secondary hyperparathyroidism by 25-hydroxyvitamin D (25-OHD) levels at least 50nmol/l. In this systematic review, we have analyzed the results of 52 clinical trials, including 72 intervention groups and 6290 patients, on vitamin D supplementation in order to evaluate the experimental evidence and the effects of age and chronic immobility on responses of parathyroid hormone (PTH). The papers for this systematic review were selected through a search in PubMed and through a review of the reference lists of articles. Negative logarithmic (R(2)=0.318, p<0.001) and linear (R(2)=0.294, p<0.001) correlations were found between 25-OHD and PTH levels, when all pre- and post-trial values were scattered. Negative linear (R(2)=0.385, p<0.001) and logarithmic (R(2)=0.406, p<0.001) correlations were also found between the changes in 25-OHD and PTH levels. Age correlated negatively with changes in PTH (r=-0.476, p<0.001). The vitamin D supplementation of the chronically immobile patients resulted in a smaller decrease in PTH levels (-8.4 vs. -17.4%, p<0.001) despite a larger increase in 25-OHD levels (187.2% vs. 109.8%, p<0.001). According to the multiple regression analysis the changes in PTH were independently predicted by pre-trial PTH, changes in 25-OHD, age and chronic immobility, explaining 53.2% (R(2)=0.532) of the variation. This meta-analysis shows that responses of PTH to vitamin D supplementation are not only determined by the baseline PTH levels and changes in vitamin D status, but also by age and mobility of the patients. Our results also suggest that PTH decreases quite linearly during vitamin D supplementation at any given 25-OHD level. Longitudinal vitamin D supplementation studies on populations with wide range of mobility and age are needed to further elucidate their confounding effects. In determining the sufficient doses of vitamin D supplementation and adequate 25-OHD levels, these confounding effects and the inter-individual variation in responses of PTH to vitamin D supplementation should be taken into account.

Metabolismo, fuentes endógenas y exógenas de vitamina D / Metabolism, endogenous and exogenous sources of vitamin D

Hoy en día sabemos que la vitamina D se comporta como una hormona con múltiples funciones en el organismo. De todas sus acciones la mejor estudiada y la más importante se relaciona con la salud ósea. Los depósitos adecuados de la vitamina mantienen el metabolismo calcio-fósforo dentro de la normalidad. Las fuentes naturales principales son la síntesis cutánea de la hormona, inducida por la radiación solar y el aceite de pescado. En determinadas situaciones la síntesis cutánea no es del todo eficaz. Esto unido a que los alimentos naturales contienen escasa cantidad de vitamina D, hace que gran parte de la población esté en riesgo de presentar déficit/insuficiencia de este micronutriente. Por ello, diferentes autores recomiendan la ingesta de alimentos funcionales y de suplementos farmacológicos de la vitamina. Sin embargo, la fortificación de los alimentos naturales, tal y como se realiza en la actualidad, presenta varios problemas. De igual forma no existen unas recomendaciones universalmente aceptadas de cuánta cantidad de vitamina D se debe ingerir como suplemento farmacológico y qué población debe ingerirlo. Los datos disponibles señalan que la mayoría de la población se beneficiaría con la ingesta de 800 UI de vitamina D en combinación con calcio

At present, we know that vitamin D behaves as a hormone with multiple functions in the body. The best studied and most important of all its actions is related with bone health. Adequate deposits of the vitamin maintain the calcium-phosphorus metabolism within normality limits. The main natural sources are solar radiation and fish oil induced cutaneous synthesis of the hormone. In certain situation, cutaneous synthesis is not completely effective. This, together with the fact that natural foods contain scarce amounts of vitamin D, causes a large part of the population to be at risk of having a deficit/insufficiency of this micronutrient. Thus, different authors recommend the intake of functional foods and drug supplements of the vitamin. However, fortification of natural foods, as is presently done, has several problems. Furthermore, there are no universally accepted recommendations for the amount of vitamin D that should be taken as a drug supplement and which population should take it. The data available indicate that most of the population would benefit from taking 800 IU of vitamin D combined with calcium