Neuroprotective effect of ebselen against intracerebroventricular streptozotocin-induced neuronal apoptosis and oxidative stress in rats.

The goal of this study was to examine the neuroprotective effect of ebselen against intracerebroventricular streptozotocin (ICV-STZ)-induced oxidative stress and neuronal apoptosis in rat brain. A total of 30 adult male Sprague-Dawley rats were randomly divided into 3 groups of 10 animals each: control, ICV-STZ, and ICV-STZ treated with ebselen. The ICV-STZ group rats were injected bilaterally with ICV-STZ (3 mg/kg) on days 1 and 3, and ebselen (10 mg/kg/day) was administered for 14 days starting from 1st day of ICV-STZ injection to day 14. Rats were killed at the end of the study and brain tissues were removed for biochemical and histopathological investigation. Our results demonstrated, for the first time, the neuroprotective effect of ebselen on Alzheimer's disease (AD) model in rats. Our present study, in ICV-STZ group, showed significant increase in tissue malondialdehyde levels and significant decrease in enzymatic antioxidants superoxide dismutase and glutathione peroxidase in the frontal cortex tissue. The histopathological studies in the brain of rats also supported that ebselen markedly reduced the ICV-STZ-induced histopathological changes and well preserved the normal histological architecture of the frontal cortex tissue. The number of apoptotic neurons was increased in frontal cortex tissue after ICV-STZ administration. Treatment of ebselen markedly reduced the number of degenerating apoptotic neurons. The study demonstrates the effectiveness of ebselen, as a powerful antioxidant, in preventing the oxidative damage and morphological changes caused by ICV-STZ in rats. Thus, ebselen may have a therapeutic value for the treatment of AD.

Low serum Insulin Like Growth Factor - 1 in patients with Stress Urinary Incontinence.

OBJECTIVE: SUI, involuntary loss of urine, occurs when intra abdominal pressure exceeds urethral pressure in women. Recent animal study has shown that there are therapeutic effects of Insulin-like growth factors (IGF-1) on stress urinary incontinence in rats with simulated childbirth trauma. IGF-1 is an important mediator of cell growth, differentiation and transformation in various tissues and stimulates fibroblast proliferation and enhances collagen synthesis. The purpose of the current study was to determine the association between IGF-1 levels and SUI. MATERIALS AND METHODS: All patients were evaluated for SUI and divided into two groups: 116 women with SUI and 76 women without SUI. Diagnosis of SUI was based on the International Consultation on Incontinence Questionnaire-Short Form (ICIQSF). Levels of IGF-1 were measured in serum by enzyme-linked immunosorbent assay. The relationship between IGF-1 levels and SUI in patients was evaluated statisticaly. RESULTS: The mean age of patients wiyh SUI was 49.9±8.6 and 48.7±7.8 in control group. Plasma IGF-1 levels were significantly lower in SUI than in control group (106.5±26.4 and 133.3±37.1ng/mL, respectively, P <0.001). Body mass indexes were higher in women with SUI than women without SUI. CONCLUSION: In this study lower serum IGF-1 levels were found to be associated with SUI. Serum IGF-1 level appears to be a specific predictor of SUI, and it may be used in early prediction of SUI in female population.

The association of vitamin D with inflammatory cytokines in diabetic peripheral neuropathy.

[Purpose] The effects of vitamin D on the circulating levels of IL-17 and IL-13 were investigated in patients with diabetic peripheral neuropathy, patients with diabetes mellitus type 2 without neuropathy, and healthy controls. [Subjects and Methods] A single-blind controlled clinical study was performed, including70 type 2 diabetic patients with or without diabetic peripheral neuropathy and 33 healthy volunteer controls. The 25(OH)D levels were evaluated using ultra-performance liquid chromatography, and IL-17 and IL-13 levels were assessed using enzyme-linked immunosorbent assays. [Results] The 25(OH) vitamin D concentration was lower in diabetic peripheral neuropathy patients than in diabetes mellitus patients without neuropathy and healthy controls. Similarly, 25(OH)D levels were lower in diabetes mellitus patients than healthy controls. IL-17 and IL-13 levels were higher in diabetes mellitus patients than in controls. Additionally, IL-13 levels were higher in diabetic peripheral neuropathy patients than in diabetes mellitus patients without neuropathy. These differences were statistically significant. There was a significant positive correlation between 25(OH)D and IL-13,and a negative correlation between 25(OH)D andIL-17 in the diabetic and diabetic neuropathy groups. [Conclusion] Vitamin D is a potential modifiable risk factor for diabetic peripheral neuropathy and may regulate inflammatory mediators, e.g., IL-17 and IL-13.

The protective effects of ω-3 fatty acids on doxorubicin-induced hepatotoxicity and nephrotoxicity in rats.

This study aims to evaluate the protective effects of ω-3 fatty acids (FAs) on doxorubicin (DOX)-induced hepatotoxicity and nephrotoxicity in rats. A total of 24 adult male Sprague Dawley rats were divided into three groups. Control group was given only saline by intragastric gavage. DOX group received DOX at the dose of 30 mg/kg intraperitoneally on day 28. DOX-ω-3 FA group was given as ω-3 FAs at the dose of 400 mg/kg daily by intragastric gavage for 30 days and received DOX at the dose of 30 mg/kg intraperitoneally on day 28. At the end of the 30-day experimental period, the serum, liver and kidney tissue specimens were taken from the animals by giving a general anesthesia. Glutathione (GSH) and malondialdehyde (MDA) levels in serum and GSH and MDA levels and superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in liver and kidney tissues were measured spectrophotometrically. In our study, a significant increase in MDA levels was observed in rats when given a dose of DOX and a significant decrease in the levels of GSH, SOD and GSH-Px activities in serum, liver and kidney tissues was determined when compared with control group. In addition, a significant decrease in MDA levels was observed in rats when a dose of ω-3 FAs was given with DOX and a significant increase was determined in the levels of GSH, SOD and GSH-Px activities in serum, liver and kidney tissues, when compared with DOX group. We concluded that ω-3 FA had favorable effects in rat liver and kidney tissues by preventing oxidative damage.

Evaluation of paraoxonase and arylesterase activities in patients with irritable bowel syndrome.

The aims of the present study were to evaluate oxidative status, by investigating the serum Paraoxonase/Arylesterase (PON/ARE) activities along with conjugated dienes in patients with IBS and controls and to confirm the link between oxidative stress and IBS. Thirty IBS patient and 30 healthy subjects were recruited. Total serum cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides (TG), PON and ARE activities and conjugated dienes levels were measured. Mean serum PON1 activity was lower in IBS group compared to that of the control group whereas there was no significant difference in ARE activity between IBS and control groups (p < 0.000, p < 0.716, respectively). Serum conjugated diene levels of the IBS group was significantly higher than that of the control group (p < 0.01). The drop in PON activity accompanied with an increase in conjugated diene levels indicate the presence of oxidative stress, a disturbance in prooxidant - antioxidant balance and increased inflammation in IBS patients.

The role of oxidants and reactive nitrogen species in irritable bowel syndrome: a potential etiological explanation.

BACKGROUND: The aim of this study was to evaluate the plasma concentrations of malondialdehyde (MDA) and nitric oxide (NO) and the plasma activities of oxidant and antioxidant enzymes in patients with IBS. MATERIAL/METHODS: A total of 36 patients with IBS were included in the study. Thirty-five healthy subjects were selected to form the control group. Superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), xanthine oxidase (XO), adenosine deaminase (AD) activities, and malondialdehyde (MDA) and nitric oxide (NO) concentrations were studied in the serum samples of all patients and controls. RESULTS: Plasma XO and AD activities, and MDA and NO concentrations were significantly higher in IBS patients than in controls. The SOD, CAT, and GSH-Px activities in the serum of patients with IBS were significantly lower than that of controls. CONCLUSIONS: These results suggest that lipid peroxidation and alterations in the oxidant-antioxidant enzymatic system may play a role in the pathogenesis of IBS. Increased lipid peroxidation in IBS may be related to an increase in NO level and XO activity and a decrease in antioxidant enzymes activities. In addition, increased AD activity may have a role in immunological changes of IBS patients.

Effect of overweight on P-wave and QT dispersions in childhood.

OBJECTIVES: The effects of obesity on atrial conduction and ventricular repolarization have been studied in detail, but these parameters have not been well documented in overweight children. The aim of our study was to investigate the effects of overweight on atrial conduction and ventricular repolarization in children by using P-wave dispersion (Pw-d) and QT dispersion (QT-d) analyses. STUDY DESIGN: Sixty-seven overweight children and 70 children within normal limits were included in this cross-sectional prospective controlled study. All subjects underwent electrocardiographic and anthropometric evaluation, and blood samples were obtained. Pw-d and QT-d were investigated between two groups. RESULTS: Homeostatic model assessment of insulin resistance levels were higher in the overweight group (2.9±1.2 vs. 1.1±0.8, p=0.001). No statistically significant differences were found in Pw-d and QT-d when the groups were compared. The following findings were recorded for the overweight and control groups, respectively: mean RR interval (635±42 msec vs. 645±45 msec, p=0.867), Pw-d [30 (10-55) msec vs. 27.5 (15-50) msec, p=0.441] and QT-d (30 (15-55) msec vs. 22.5 (10-60) msec, p=0.476). In addition, Pw-d and QT-d were not correlated with the levels of insulin or body mass index. CONCLUSION: There was no significant difference in atrial conduction or ventricular repolarization features between overweight children and normal-weight children.

Delayed cutaneous wound healing in aged rats compared to younger ones.

Delayed wound healing in elderly males is a complex process in which the factors responsible are not fully understood. This study investigated the hormonal, oxidative and angiogenic factors affecting wound healing in aged rats. Two groups consisting of eight healthy male Wistar Albino rats [young (30 ± 7 days) and aged (360 ± 30 days)], and a cutaneous incision wound healing model were used. Scar tissue samples from wounds on the 7th, 14th and 21st days of healing were evaluated for hydroxyproline and vascular endothelial growth factor content. Macrophage, lymphocyte, fibroblast and polymorphonuclear cell infiltration; collagen formation and vascularization were assessed by light and electron microscopy. The free oxygen radical content of the wounds was measured by a chemiluminescence method. Blood sample analysis showed that the hydroxyproline and total testosterone levels were significantly higher, and the oxygen radical content was significantly lower in young rats. Histopathological, immunohistochemical and ultrastructural evaluations revealed higher amounts of fibroblasts and collagen fibers, and more vascularization in young rats. These results are indicative of the delayed wound healing in aged rats. A combination of multiple factors including hormonal regulation, free oxygen radicals and impaired angiogenesis appears to be the cause of delayed cutaneous healing.

Influences of genetic variants in interleukin-15 gene and serum interleukin-15 levels on coronary heart disease.

Interleukin-15 (IL-15) is a potent proinflammatory cytokine that is now considered a key component of atherosclerosis. Proinflammatory gene polymorphisms lead to variations in the production and level of the proteins. In light of these findings, we hypothesized that variations in the gene coding for IL-15 influence the risk of coronary heart disease (CHD) by modulating the IL-15 levels. To test this hypothesis, we examined 5 single nucleotide polymorphisms (SNPs) in IL-15 gene and IL-15 levels in 102 patients with acute coronary syndrome (ACS), 102 patients with chronic ischemic stable CHD and 162 healthy control subjects. This study is the first report showing the influences of IL-15 gene variants and IL-15 levels on CHD. The five single nucleotide polymorphisms (SNPs) within the IL-15 gene, G367A, C267T, A14035T, C13687A, and A10504G were carried out by polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP). Serum IL-15 levels were significantly higher in both acute and chronic patients than in controls. Genetic variants of IL-15 gene and IL-15 levels were associated with CHD. In conclusion, our study supports the hypothesis that genetic variation in IL-15 gene and IL-15 levels influence the risk of CHD. Further studies are needed to confirm our hypothesis.

Homocysteine and pro-inflammatory cytokine concentrations in acute heart disease.

Inflammation is involved in development and progression of atherosclerosis. Interleukin-2 (IL-2) and interleukin-6 (IL-6) have been correlated with various cardiovascular diseases. Hyperhomocysteinemia is an important risk factor for atherosclerosis and thrombotic disease. Recent studies have demonstrated that homocysteine (Hcy) enhances productions of several pro-inflammatory cytokines. In the light of these findings, we decided to determine if any relationship exists between IL-2 and IL-6, the pro-inflammatory cytokines, and total homocysteine (tHcy) in acute coronary syndrome (ACS). A total of 102 patients with ACS and 90 healthy subjects were included in the study. The levels of tHcy, IL-2 and IL-6 were higher and folic acid was lower in patients as compared with those of controls. Furthermore, data of the area under ROC plot for IL-2 demonstrated that IL-2 had higher sensitivity. These data suggest that enhanced inflammation may be associated with tHcy-related cardiovascular disease.

Is Overweight a Risk of Early Atherosclerosis in Childhood?

We measured brachial artery flow-mediated dilatation (FMD) and common carotid intima-media thickness (cIMT) in overweight (n = 67) and normal weight children (n = 115, controls). Age at examination ranged from 72 to 182 months (mean 123 ± 27). Compared to controls, the overweight children had increased weight, waist and hip circumference, systolic and diastolic blood pressures (all P < .001), right and left mean cIMT (mm; 0.58 [0.42-0.68] vs 0.44 [0.3-0.64], P < .001 and 0.56 [0.32-0.70] vs 0.44 [0.3-0.60], P < .001), respectively, and decreased FMD (%; 6.25 [3.33-19.05] vs 7.69 [3.45-16], P < .001). The cIMT and FMD were closely related to the serum insulin concentrations. Age, waist circumferences, and serum triglycerides were independent predictive risk factors for increased cIMT, and fasting glucose and BMI were independent predictive variables for decreased FMD. Overweight children are also potentially at risk of early atherosclerosis as much as obese children.

Association of genetic variants in Methylenetetrahydrofolate Reductase and Paraoxonase-1 genes with homocysteine, folate and vitamin B12 in coronary artery disease.

BACKGROUND: The aim of the present study was to investigate the association between genetic variants in metylenetetrahydrofolate reductase (MTHFR) and Paraoxonase-1 (PON1) 55/192 genes and total homocysteine (tHcy), folate, B12 vitamin, and PON1 levels in patients with coronary artery disease (CAD). METHODS: The study included 235 patients with CAD and 268 healthy control subjects. RESULTS: LL and LM genotypes and L allele of PON1 55 were over-represented in patients. In contrast, MM genotype and M allele were more frequent in controls. QQ genotype and Q allele of PON1 192 and CT genotype of MTHFR were significantly diminished and QR genotype and R allele were significantly elevated in CAD patients compared with controls. The plasma tHcy were elevated but B12 levels were diminished in patients. PON1 55 and 192 genetic variants were significantly associated with PON1 activity, triglyceride, total cholesterol, tHcy and, high-density lipoprotein-cholesterol and low-density lipoprotein-cholesterol in patients, respectively. CONCLUSION: Genetic variants of PON1 55/192 and MTHFR were associated with CAD.

Asymmetric dimethylarginine contributes to airway nitric oxide deficiency in patients with COPD.

INTRODUCTION: Asymmetric dimethylarginine (ADMA) and nitric oxide (NO) show their mechanism of action reciprocally, the balance between these molecules contributes to the tight regulation of airways tone and function. OBJECTIVES: The aim of this study to determine the serum levels of ADMA and NO in patients with chronic obstructive pulmonary disease (COPD) and establish whether their level vary in relation to forced expiratory volume in 1s (FEV1 ), to assess their role in pathophysiology of COPD. MATERIALS AND METHODS: This study consisted of 58 patients with COPD and 30 healthy subjects. Serum ADMA and NO levels were measured using enzyme-linked immunosorbent assay and the colorimetric method, respectively. RESULTS: Serum ADMA levels were significantly higher, however, NO levels were lower in patients with COPD compared with controls. ADMA levels were inversely correlated with NO levels. Serum ADMA and NO were significantly correlated with FEV1 . Multivariable logistic regression analysis revealed that serum ADMA and NO were independently and significantly associated with the presence of COPD. Multiple linear regression analysis showed that COPD was positively associated with ADMA, additionally COPD and ADMA were independently and inversely associated with NO. NO levels were decreased, ADMA levels were increased compliant with progression of COPD stages. CONCLUSION: While circulating ADMA is higher, NO is lower in COPD and both show a strong correlation to the degree of airflow limitation. ADMA seems to be a possible new marker of prognosis of COPD and can be a novel therapeutic target for the treatment of COPD.

Vitamin D levels in white coat and sustained hypertension.

OBJECTIVE: The plasma levels of vitamin D in patients with white coat hypertension (WCHT) have not been studied previously. The aim of this study was to evaluate vitamin D levels in WCHT and compare with sustained hypertension (SHT) and with normotension (NT). PATIENTS AND METHODS: Fifty-three normotensive, 42 WCHT, and 59 SHT patients were recruited in this study. The participants were matched for age, sex, and BMI. The vitamin D levels were determined using the electrochemiluminescence immunoassay method. RESULTS: Plasma vitamin D levels were significantly lower in SHT than in the WCHT and NT groups (26.4±4.9, 34.3±3.6, and 36±5 ng/ml, respectively), and were similar in the WCHT and NT groups. There was a negative correlation between vitamin D levels and blood pressure parameters such as clinic systolic blood pressure (SBP), clinic diastolic blood pressure (DBP), 24-h SBP, 24-h DBP, daytime SBP, daytime DBP, night-time SBP, and night-time DBP (r=-0.554, -0.419, -0.629, -0.427, -0.559, -0.534, -0.607, -0.462, respectively, and all P<0.001) in the entire study group. Clinic SBP (B±SE=-0.97±0.037, P=0.009) and 24-h SBP (B±SE=-0.138±0.055, P=0.013) were identified as predictors for vitamin D levels in the entire study group. CONCLUSION: Our data show that sustained hypertensive patients have lower vitamin D levels than white coat hypertensive and normotensive individuals. White coat hypertensive patients without other cardiovascular risk factors have higher vitamin D levels than sustained hypertensive patients, suggesting that they have a lower cardiovascular risk.

Peroxynitrite induced decrease in Na+, K+-ATPase activity is restored by taurine.

AIM: Peroxynitrite (ONOO-) is a powerful oxidant shown to damage membranes. In the present study, the effect of taurine on changes of liver plasma membrane Na+, K+-ATPase induced by ONOO- was investigated. METHODS: Liver plasma membrane was exposed to ONOO- with or without taurine. Na+, K+-ATPase activity and lipid peroxidation as thiobarbituric acid reactive substances (TBARS) levels were measured. RESULTS: Different concentrations of ONOO- (100, 200, 500, and 1000 micromol/L) were found to decrease liver plasma membrane Na+, K+-ATPase activity significantly. The depletion of enzyme activity was not concentration dependent. Effects of different concentrations of taurine on liver plasma membrane Na+, K+-ATPase activity were also measured. Taurine did not cause any increase in enzyme activity. When plasma membranes were treated with 200 micromol/L ONOO- with different concentrations of taurine, a restoring effect of taurine on enzyme activity was observed. TBARS levels were also measured and taurine was found to decrease the elevated values. CONCLUSION: Taurine is observed to act as an antioxidant of ONOO- to decrease lipid peroxidation and thus affect liver plasma membrane Na+, K+-ATPase by restoring its activity.

Neutrophil/lymphocyte ratio in obese adolescents.

OBJECTIVE: Obesity is a growing health problem in most of the developed countries. It is associated with many chronic diseases, affecting particularly endocrine and cardiovascular systems. Inflammation plays a key role in pathophysiology of obesity. In this study, we aimed to investigate the inflammation status in obese children using neutrophil/lymphocyte ratio. METHODS: In this study 130 obese and 57 healthy children were assessed retrospectively. According to Centers for Disease Control 2000 (CDC) BMI percentiles for childhood and adulthood, 85-95 percentile was considered as overweight and >95 percentile as obese. RESULTS: Lymphocyte/neutrophil ratios in the obese group were significantly higher compared to those in healthy controls (p=0.03 and p=0.045, respectively). Neutrophil/lymphocyte ratio and CRP level in the obese group were significantly higher compared to those in healthy controls (p=0.02 and p=0.00, respectively). Thrombocyte/lymphocyte ratios were not significantly different between two groups (p=0.156). CONCLUSION: It is possible that childhood obesity which has been increasingly prevalent recently triggers the pathogenesis of atherosclerosis during the early years of life. Increased neutrophil/lymphocyte ratio might be associated with the severity of inflammation which plays a role in the early stages of atherosclerosis. Therefore, taking childhood obesity under control using diet and other treatment methods will prevent mortality and morbidity in the elderly.

Growth Differentiation Factor-15 Is a Novel Biomarker Predicting Acute Exacerbation of Chronic Obstructive Pulmonary Disease.

Exacerbations in chronic obstructive pulmonary disease (COPD) reduce quality of life and are associated with a more rapid deterioration of the disease. Growth differentiation factor-15 (GDF-15) is a novel candidate exacerbation biomarker. In this study, we aimed to assess GDF-15 as a biomarker of acute exacerbation of COPD (AE-COPD). Lung function parameters, arterial blood gas analysis, and circulating levels of GDF-15, C-reactive protein (CRP), and fibrinogen were assessed in 29 patients on admission to the hospital for AE-COPD, in 29 age-, gender-, and body mass index (BMI)-matched patients with stable COPD, and 29 matched controls with normal lung function. Patients with AE-COPD had higher circulating concentrations of GDF-15 (p < 0.001), CRP (p < 0.001), and fibrinogen (p < 0.002) compared with patients with stable COPD and healthy controls. GDF-15 levels correlated with systemic inflammatory marker CRP in patients with AE-COPD (r = 0.677, p < 0.001) and with stable COPD (r = 0.417, p = 0.024). Multivariate logistic regression analysis revealed GDF-15 (odds ratio 18.16, 95% confidence interval (CI) 2.51-134.32; p = 0.005) as an independent predictor of AE-COPD. In receiver operating characteristic analysis, GDF-15 achieved an area under the curve of 0.78 for the identification of AE-COPD. In conclusion, GDF-15 is a novel blood biomarker of AE-COPD that is more sensitive than that of CRP. GDF-15 may offer new insights into the pathogenesis of AE-COPD.

Protective effect of IGF-1 on experimental liver cirrhosis-induced common bile duct ligation.

BACKGROUND/AIMS: The causes of malnutrition in liver cirrhosis are multifactorial. Levels of IGF-1 (insulin like growth factor-1) that is a crucial regulator of intermediary metabolism decreases. The aim of this study was to analyze the effect of IGF-1 supplementation during liver cirrhosis induced by common bile duct ligation. METHODOLOGY: Rats were divided into five different groups: One sham and four experimental groups. Rats in three of four groups were treated with 2 micrograms/day IGF-1 with a different time of experiment in each group. Blood biochemical parameters, tissue malondialdehyde, glutathione levels and the activity of tissue antioxidant enzymes and conventional and immunohistochemical analysis of liver samples were studied for each group. RESULTS: Serum albumin, total protein, fibrinogen levels decreased and prothrombin time was prolonged in the bile duct ligated and transected experimental group but not in the IGF-I treated rats compared with the rats in sham group. Liver malondialdehyde levels significantly increased in control group but not in IGF-1 treated groups. The activities of antioxidant enzymes were decreased compared with the other groups. Histopathology findings of liver biopsy demonstrated intense degree fibrosis and overexpression of fibroblast growth factor and desmin in the control group but a lesser degree of those in the IGF-1 treated groups. CONCLUSIONS: IGF-1 treatment improves liver function and decreases oxidative liver damage and histopathological findings. Further studies are required to delineate the mechanisms of protective effects of IGF-1.

Investigation of serum macrophage migration inhibitor factor and monocyte chemotactic protein-1 levels in irritable bowel syndrome.

AIM: Irritable bowel syndrome (IBS), a functional disorder of the bowel, has been thought to result from immune activation. The aim of this study was to evaluate macrophage migration inhibitory factor (MMIF) and monocyte chemotactic protein-1 (MCP-1) levels in IBS patients. MATERIALS AND METHODS: We enrolled 30 IBS patients and 30 healthy controls. The MMIF and MCP-1 levels of all patients and controls were detected using commercial enzyme-linked immunosorbent assay kits. RESULTS: Serum MMIF and MCP-1 levels were markedly higher in IBS patients than in controls. White blood cell, neutrophil, lymphocyte, monocyte, eosinophil, and basophil counts did not differ significantly between groups. CONCLUSION: These results show that alterations in MMIF and MCP-1 affect the proinflammatory process. They also suggest that MMIF and MCP-1 may play a substantial role in IBS.

Possible association between vitamin D deficiency and restless legs syndrome.

BACKGROUND AND AIM: Restless legs syndrome (RLS) is a distressing sleep disorder that occurs worldwide. Although there have been recent developments in understanding the pathophysiology of RLS, the exact mechanism of the disease has not been well elucidated. An increased prevalence of neurologic and psychiatric diseases involving dopaminergic dysfunction in vitamin D-deficient patients led us to hypothesize that vitamin D deficiency might result in dopaminergic dysfunction and consequently, the development of RLS (in which dopaminergic dysfunction plays a pivotal role). Thus, the aim of this study was to evaluate the relationship between vitamin D deficiency and RLS. METHODS: One hundred and fifty-five consecutive patients, 18-65 years of age, who were admitted to the Department of Internal Medicine with musculoskeletal symptoms and who subsequently underwent neurological and electromyography (EMG) examination by the same senior neurologist, were included in this study. The patients were divided into two groups according to serum 25-hydroxyvitamin D (25(OH)D) (a vitamin D metabolite used as a measure of vitamin D status) level: 36 patients with serum 25(OH)D levels ≥20 ng/mL comprised the normal vitamin D group, and 119 patients with serum 25(OH)D levels <20 ng/mL comprised the vitamin D deficiency group. The two groups were compared for the presence of RLS and associated factors. RESULTS: The two groups were similar in terms of mean age, sex, mean body mass index (BMI), and serum levels of calcium, phosphate, alkaline phosphatase (ALP), and ferritin. The presence of RLS was significantly higher in the vitamin D deficiency group (χ (2)=12.87, P<0.001). Regression analysis showed vitamin D deficiency and serum 25(OH)D level to be significantly associated with the presence of RLS (odds ratio [OR] 5.085, P<0.001 and OR 1.047, P=0.006, respectively). CONCLUSION: The present study demonstrated a possible association between vitamin D deficiency and RLS. Given the dopaminergic effects of vitamin D, 25(OH)D depletion may lead to dopaminergic dysfunction and may have a place in the etiology of RLS. Prospective vitamin D treatment studies are needed to confirm this relationship and to evaluate the efficacy of vitamin D as a treatment for RLS patients.