The relationship between Vitamin D deficiency and polycystic ovary syndrome

BackgroundVitamin D deficiency is frequently seen in patients with polycystic ovary syndrome (PCOS) and has been shown to exhibit multiple effects on the disease process. The purpose of this study was to investigate the role of vitamin D deficiency in complex PCOS pathophysiological pathways.MethodsTwo hundred sixty-seven patients with PCOS were divided into two groups Group 1 with 25(OH)D3 deficiency, and Group 2 with normal 25(OH)D3. Biochemical and hormonal parameters (androgen hormones, gonadotropins, and thyroid function tests) were compared between the two groups.ResultsEighty-six percent of the patients (n=231) were in Group 1 and 14% (n=36) in Group 2. Statistically significantly higher concentrations of serum testosterone, dehydroepiandrosterone-sulfate and LH were determined in Group 1 (p<0.05). 25(OH)D3 concentrations were negatively correlated with body mass index (r=−0.459), serum testosterone (r =−0.374) and dehydroepiandrosterone-sulfate levels (r=−0.418); (all; p< 0.05).ConclusionThe study findings show that low 25(OH)D3 levels are associated with high androgen levels in women with PCOS. Vitamin D deficiency should be considered as an additional risk factor in the development of PCOS. We think that providing vitamin D supplementation for women from identified deficiency areas can reduce the risk of PCOS development.     

Vitamin D deficiency in multicultural primary care: a case series of 299 patients.

An increase in diagnoses of vitamin D deficiency prompted a review of cases from four general practices. Of the 299 cases identified, the predominant patient group comprised adult Somali females presenting with symptoms of chronic musculoskeletal pain. Women of childbearing age were particularly at risk. Known at-risk groups were not receiving supplementation. Significant clinical need appears not to be met in this population group and consideration of vitamin D deficiency during consultations is warranted.     

Laryngeal Spasm Mimicking Asthma and Vitamin D Deficiency

We present a woman with heterozygous carnitine palmitoyl transferase 2 (CPT-2) deficiency who in the last 6 months suffered from episodic dyspnea and choking. Symptoms could not be attributed to her muscular energy defect, since heterozygous CPT-2 deficiency is usually asymptomatic or causes only mild muscle fatigability. Myopathy is usually triggered by concurrent factors, either genetic (additional muscle enzymes defects) or acquired (metabolic stress). The patient was referred to our respiratory clinic for suspect bronchial asthma. Spirometry showed mild decrease in inspiratory flows. Methacholine challenge was negative. Dyspnea was triggered by hyperventilation-induced hypocapnia, which produced marked decrease in airflow rates, particularly in inspiratory flows, consistent with laryngospasm. Nutritional assessment of the patient showed low serum level of calcium and vitamin D, attributable to avoidance of milk and dairy products for lactose intolerance and to insufficient sunlight exposure. After calcium and vitamin D supplementation episodic laryngospasm disappeared and hypocapnic hyperventilation test induced very mild change in airflow rates. Calcium and vitamin D deficiency may favour laryngeal spasm mimicking asthma, particularly in subjects with underlying myopathy.     

Proteoglycan Synthesis in Vitamin D-Deficient Cartilage: Recovery from Vitamin D deficiency

Vitamin D appears to be required for mineralization of skeletal elements. There is also evidence that cartilage proteoglycans may be involved in the regulation of mineralization. Previous studies have shown an alteration in the structure of the proteoglycans of the epiphyseal growth cartilage as a result of the decrease in serum calcium related to deficiency of dietary vitamin D. Vitamin D deficiency also induces a thickening of the epiphyseal growth plate presumably because of the inhibition of maturation of the growth plate chondrocytes. In order to compare the effect on proteoglycan structure with that on growth plate morphology, the proteoglycans of healing epiphyseal cartilage were characterized. The results indicate that, consistent with previous data, in vitamin D-deficient hatchling chicks, the proteoglycans of the growth cartilage, but not of the articular cartilage, are smaller in monomer size with slightly smaller chondroitin sulfate chains whose sulfation pattern is unaltered. Sternal cartilage proteoglycans are unaffected. During recovery from vitamin D deficiency, the proteoglycans isolated from the growth cartilage are still not completely normal one day after supplementation with vitamin D, but are indistinguishable from normal by four days. In addition, the results conflict with those of a previous study in which only growth cartilage of hatchling chicks, not sternal or articular cartilage, was reported to synthesize large proteoglycans. Instead, all of these cartilages in the normal chicken have been found in this study to produce large proteoglycans of a size typical for mammalian cartilage and embryonic chick cartilage.     

Vitamin D deficiency associated with number of neurofibromas in neurofibromatosis 1

Neurofibromatosis 1 (NF1) is a tumour suppressor gene syndrome characterized by multiple cutaneous and plexiform neurofibromas. Focal osseous abnormalities, short stature, and decreased bone mineral density are also frequent in people with NF1. We measured serum 25-hydroxyvitamin D concentrations in 55 patients with NF1 and 58 healthy controls, and correlated the findings in the patients with NF1 with their estimated number of dermal neurofibromas. Geometric mean (SD) serum 25-hydroxyvitamin D concentration was 14.0 (1.6) ng/mL among the patients with NF1 compared with 31.4 (1.7) ng/mL among healthy controls (p<0.0001). The serum vitamin D concentration and number of dermal neurofibromas reported by patients with NF1 were inversely correlated (Spearman's rho = -0.572, p<0.00001). The occurrence of low serum vitamin D concentrations in people with NF1, especially those with many dermal neurofibromas, may provide new pathogenic insights and have important therapeutic implications.     

Vitamin D and its role in allergic disease

In Western countries, the incidence of atopy and allergic diseases is high and further rising. While genetic factors certainly play a role, epigenetic or even nutritional factors might also be important in the pathogenesis of allergies. Vitamin D - the 'sunshine hormone' - exerts profound effects on both adaptive and innate immune functions involved in the development and course of allergic diseases. As also the incidence of vitamin D insufficiency is surprisingly high in the general population, clinical and experimental studies have started to investigate if correcting vitamin D levels [measured as serum 25 hydroxy vitamin D -25(OH)D] is beneficial or even protective in patients with allergies or children at risk. This review highlights current data on the effects of vitamin D on the allergy-mediating immune system and the vitamin D status in atopic patients. Furthermore, the benefits and risks of vitamin D supplementation during pregnancy, childhood and in adults with respect to the development and course of allergic disease are discussed.     

Prevalence of Vitamin D Deficiency in Korean Children Presenting with Nonspecific Lower-Extremity Pain

Purpose

Although interest in the role played by vitamin D in bone health is increasing, little is known about the role of this vitamin in musculoskeletal pain in children. This study aimed to assess the prevalence of vitamin D deficiency in children presenting with nonspecific lower extremity pains.

Materials and Methods

From 2011 to 2012, 183 children underwent evaluation for nonspecific lower-extremity pains. Patients with valid causes, such as fractures or transient synovitis, were excluded, as were those with underlying medical conditions, such as cerebral palsy and metabolic disease. Ultimately, 140 patients met the inclusion criteria. Levels of serum 25-hydroxy vitamin D [25-(OH)D], the ideal indicator of vitamin D status, were measured in these children.

Results

Eighty-seven boys (62.1%) and 53 girls (37.9%) were included. The mean age at presentation was 5.2 years (range, 2-15). Serum 25-(OH)D levels were <10 ng/mL in 5.7% of patients, 10 to <20 ng/mL in 51.4%, 20 to <30 ng/mL in 37.9%, and ≥30 ng/mL in only 5.0%. Most patients visited the hospital in the winter (41.4%) (summer, 12.9%), and serum 25-(OH)D levels were also lowest in the winter (17.2±5.5 ng/mL).

Conclusion

This study found a high prevalence of vitamin D deficiency or insufficiency in Korean children with nonspecific lower-extremity pains, indicating a positive association between vitamin D deficiency and growing pains. More attention should be directed toward vitamin D and its role in the optimization of bone health.     

Correlation Between Serum Vitamin D Level and the Severity of Atopic Dermatitis Associated With Food Sensitization

Purpose

A growing body of literature has linked vitamin D deficiency with allergic diseases, particularly atopic dermatitis (AD). In this study, we investigated the association between serum vitamin D status and the clinical manifestation of AD. We also developed an analytical method for the simultaneous determination of 25-hydroxy vitamin D₃ (25(OH)D₃), using liquid chromatography (LC) coupled with tandem mass spectrometry (MS/MS).

Methods

This study included 157 patients (79 males and 78 females) with AD, aged 4 months to 56 years. We evaluated disease severity using the SCORing Atopic Dermatitis (SCORAD) index. Serum levels of 25(OH)D₃ were determined by LC coupled with MS/MS. Total IgE and specific IgE levels were assayed using the immunoCAP system. ANOVA was used for statistical evaluation.

Results

We found mild, moderate, and severe AD in 30 (11.1%), 87 (55.4%), and 40 (25.5%) patients, respectively. There was no significant correlation between serum levels of 25(OH)D₃ and AD severity. However, among the 36 patients with food sensitization, the mean±SD serum levels of 25(OH)D₃ were significantly higher (P<0.05) in patients with mild disease (21.2±5.18 ng/mL) compared with the levels in patients with moderate (17.9±4.02 ng/mL) or severe AD (13.3±5.11 ng/mL) disease.

Conclusions

These results suggest that vitamin D deficiency is related to the severity of AD associated with food sensitization. Thus, these data suggest a role for vitamin D in a select group of AD patients.     

Treatment of Calcium and Vitamin D Deficiency in HIV-Positive Men on Tenofovir-Containing Antiretrovial Therapy

Abstract

Background: Hypophosphatemia and bone disease are common in HIV-positive (HIV+) patients on tenofovir disoproxil fumarate–containing antiretroviral therapy (TDF-containing ART). The underlying etiology is not completely understood. Objective: To examine the effects of treatment of calcium and vitamin D deficiency on phosphate metabolism and bone disease in HIV+ patients on tenofovir. Methods: This was an open-label, pilot study of calcium and phosphate metabolism, bone turnover, and bone density in 24 HIV+ patients on TDF, who were receiving a 1-year treatment for vitamin D and/or calcium deficiency according to a predefined protocol. Eight patients without calcium or vitamin D deficiency served as controls. Results: One-year treatment improved vitamin D levels, decreased serum parathyroid hormone (PTH), and improved calcium balance and bone mineral density. It did not affect the serum levels of PTH-related peptide (PTH-rp) or fibroblast growth factor 23 (FGF-23) nor did it raise serum phosphate levels or decrease renal phosphate loss. Conclusion: Treatment of calcium or vitamin D deficiency in HIV+ patients on ART including TDF has favorable effects on bone density, but it does not improve serum phosphate levels. Renal phosphate wasting in these patients is not caused by excess PTH, PTH-rp, or FGF-23 nor by vitamin D or calcium deficiency.     

High prevalence of maternal vitamin D deficiency in preterm births in northeast China,Shenyang

Introduction: Maternal vitamin D deficiency has been associated with a number of fetal and neonatal health problems. Preterm birth is one of the most detrimental, and the role of maternal vitamin D deficiency in preterm births has not been universally acknowledged. There had been limited epidemiological studies of vitamin D deficiency on the Chinese population. Subjects and methods: 1103 women delivered in Shengjing Hospital, China Medical University from January 1^st, 2012 to January 1^st, 2013. Finally, 821 mother-newborn pairs which contained 143 mother-newborn pairs who were preterm delivery were recruited for analysis. Results: There was significant difference between spring and summer (P<0.0001) as well as spring and autumn (P<0.01). Compared to those in summer and autumn, the 25 (OH) D level was significantly lower in winter (summer vs winter P<0.0001, autumn vs winter P<0.0001). Maternal vitamin D level showed obvious variation with months and seasons, with higher level in summer months and lower level in winter months. There were significant difference between the vitamin D level of the very preterm group and the mildly preterm groups (P<0.01), as well as the very preterm group and the in-term groups (P<0.001). Prevalence of Vitamin D deficiency occurred in 63.04% of pregnant women in very preterm group, compared with 36.61% in in-term group. Conclusion: Vitamin D nutritional status of pregnant women and their newborns in Shenyang were relatively good compared to cities in similar latitudes. Vitamin D deficiency was most severe in late spring and least in summer. Severe preterm births before 31 weeks of gestation was associated with maternal vitamin D deficiency.     

Vitamin D immunoregulation through dendritic cells

Vitamin D (VD3) has been linked to immunological processes, and its supplementation may have a role in treatment or prevention of diseases with underlying autoimmune or pro‐inflammatory states. As initiators of the immune responses, dendritic cells (DC) are a potential target of VD3 to dampen autoimmunity and inflammation, but the role of DC in VD3‐mediated immunomodulation in vivo is not understood. In addition to being targets of VD3, DC can provide a local source of bioactive VD3 for regulation of T‐cell responses. Here we review existing studies that describe the tolerogenic potential of VD3 on DC, and discuss them in the context of current understanding of DC development and function. We speculate on mechanisms that might account for the potent but poorly understood tolerogenic activities of VD3 and the role of DC as both targets and sources of this hormone.     

Vitamin D and respiratory health

Vitamin D is now known to be of physiological importance outside of bone health and calcium homeostasis, and there is mounting evidence that it plays a beneficial role in the prevention and/or treatment of a wide range of diseases. In this brief review the known effects of vitamin D on immune function are described in relation to respiratory health. Vitamin D appears capable of inhibiting pulmonary inflammatory responses while enhancing innate defence mechanisms against respiratory pathogens. Population‐based studies showing an association between circulating vitamin D levels and lung function provide strong justification for randomized controlled clinical trials of vitamin D supplementation in patients with respiratory diseases to assess both efficacy and optimal dosage.     

Vitamin D attenuates proteinuria by inhibition of heparanase expression in the podocyte

The glomerular filtration barrier consists of podocytes, the glomerular basement membrane, and endothelial cells covered with a glycocalyx. Heparan sulphate (HS) in the glomerular filtration barrier is reduced in patients with proteinuria, which is associated with increased expression of the HS‐degrading enzyme heparanase. Previously, we showed that heparanase is essential for the development of proteinuria in experimental diabetic nephropathy. Vitamin D supplementation reduces podocyte loss and proteinuria in vitro and in vivo. Therefore, we hypothesize that vitamin D reduces proteinuria by reducing glomerular heparanase. Adriamycin‐exposed rats developed proteinuria and showed increased heparanase expression, which was reduced by 1,25‐dihydroxyvitamin D₃ (1,25‐D₃) treatment. In vitro, adriamycin increased heparanase mRNA in the podocyte, which could be corrected by 1,25‐D₃ treatment. In addition, 1,25‐D₃ treatment reduced transendothelial albumin passage after adriamycin stimulation. In line with these results, we showed direct binding of the vitamin D receptor to the heparanase promoter, and 1,25‐D₃ dose‐dependently reduced heparanase promoter activity. Finally, 1,25‐D₃‐deficient 25‐hydroxy‐1α‐hydroxylase knockout mice developed proteinuria and showed increased heparanase, which was normalized by 1,25‐D₃ treatment. Our data suggest that the protective effect of vitamin D on the development of proteinuria is mediated by inhibiting heparanase expression in the podocyte. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Vitamin D reserve is higher in women with endometriosis

BACKGROUND: An immune-mediated defect in recognition and elimination of endometrial fragments refluxed in the peritoneal cavity has been hypothesized to play a crucial role in endometriosis development. Since vitamin D is an effective modulator of the immune system, we have hypothesized that the vitamin D status may have a role in the pathogenesis of endometriosis. METHODS: Women of reproductive age selected for surgery for gynecological indications were enrolled in this prospective cohort study. Serum levels of 25-hydroxyvitamin-D(3), 1,25-dihydroxyvitamin-D(3) and Ca(2+) were assessed. RESULTS: Eighty-seven women with endometriosis and 53 controls were recruited. Mean (+/- SD) levels of 25-hydroxyvitamin-D(3) in women with and without endometriosis were 24.9 +/- 14.8 ng/ml and 20.4 +/- 11.8, respectively (P = 0.05). The Odds Ratio (95% Confidence Interval) for endometriosis in patients with levels exceeding the 75th percentile of the serum distribution of the molecule (28.2 ng/ml) was 4.8 (1.7-13.5). A positive gradient according to the severity of the disease was also documented. A trend towards higher levels of 1,25-dihydroxyvitamin-D(3) and Ca(2+) was observed in women with endometriosis, but differences did not reach statistical significance. As expected, serum concentrations of 25-hydroxyvitamin-D(3) and 1,25-dihydroxyvitamin-D(3,) but not Ca(2+), are influenced by the season (P < 0.001, P = 0.004, P = 0.57, respectively), while levels of the three molecules did not vary according to the phase of the menstrual cycle. CONCLUSIONS: Endometriosis is associated with higher serum levels of vitamin D.     

Vitamin D serum levels and allergic rhinitis

In addition to its role in the regulation of calcium metabolism, vitamin D has a number of immunological effects. Several studies in children found an effect of oral supplementation on allergic sensitization but so far there are no population-based studies of vitamin D serum levels. We therefore examined 25(OH)-D(3) status in 18,224 adults of the Third National Health and Nutrition Examination Survey. There was no effect on sensitization to a single allergen while the prevalence of allergic rhinitis increased across quartile groups of current vitamin D serum levels. The association could be due to unrecognized confounding, however, could also point towards an altered metabolism or an increased sensitivity to vitamin D in allergic patients.     

Hypovitaminosis D in a Young Lebanese Population: Effect of GC Gene Polymorphisms on Vitamin D and Vitamin D Binding Protein Levels

Bioactive vitamin D is a steroid hormone transported in blood via the vitamin D binding protein (DBP). Our study aimed to investigate the vitamin D status in a young Lebanese population and study the association of hypovitaminosis with levels of DBP. Polymorphisms in the GC gene that encodes DBP were also screened. Blood samples were collected from 179 university students. Vitamin D status and DBP levels were assayed by enzyme‐linked immunosorbent assay (ELISA). DNA was extracted from 128 participants, and genotyping of the two GC gene SNPs, rs7041, and rs4588, was carried out by restriction fragment length polymorphism. Forty‐seven percent of participants had hypovitaminosis D (<20 ng/ml). A significant positive correlation was observed between vitamin D status and DBP. Genotyping data showed that participants carrying the rs7041 GG and rs4588 AA genotypes had higher concentrations of DBP than those carrying other genotypes. Four allelic versions of the GC gene were observed, one of which, GC*3, was encountered for the first time in this study, and was found to be associated with both normal vitamin D and high DBP levels. Modifying genes such as GC could therefore affect DBP levels, and contribute, along with environmental factors, to the hypovitaminosis D observed in sunny countries.