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Vitamin D supplementation improves the metabolic syndrome risk profile in postmenopausal women.
Ferreira, PP, Cangussu, L, Bueloni-Dias, FN, Orsatti, CL, Schmitt, EB, Nahas-Neto, J, Nahas, EAP
Climacteric : the journal of the International Menopause Society. 2020;(1):24-31
Abstract
Objective: This study aimed to evaluate the effect of isolated vitamin D (VD) supplementation on the metabolic syndrome (MetS) risk profile in postmenopausal women.Methods: In this double-blind, placebo-controlled trial, 160 postmenopausal women aged 50-65 years were randomized into two groups: VD group, supplementation with 1000 IU vitamin D3/day (n = 80); or placebo group (n = 80). The intervention time was 9 months, and the women were assessed at baseline and endpoint. Clinical and anthropometric data were collected. Biochemical parameters, including total cholesterol, high-density lipoprotein, low-density lipoprotein, triglycerides, glucose, and insulin, were measured. The plasma concentration of 25-hydroxyvitamin D (25(OH)D) was measured by high-performance liquid chromatography.Results: After 9 months, there was a significant increase in the 25(OH)D levels for VD group (+45.4%, p < 0.001), and a decrease (-18.5%, p = 0.049) in the placebo group. In the VD group, a significant reduction was observed in triglycerides (-12.2%, p = 0.001), insulin (-13.7%, p = 0.008), and the homeostasis model assessment of insulin resistance (-17.9%, p = 0.007). In the placebo group, there was an increase in glucose (+6.2%, p = 0.009). Analysis of the risk adjusted for age, time since menopause, and body mass index showed that women supplemented with VD had a lower risk of MetS (odds ratio [OR] 0.42; 95% confidence interval [CI] 0.21-0.83), hypertriglyceridemia (OR 0.43; 95% CI 0.22-0.85), and hyperglycemia (OR 0.23; 95% CI 0.10-0.52) compared to the placebo group (p < 0.05).Conclusions: In postmenopausal women with VD deficiency, isolated supplementation with 1000 IU vitamin D3 for 9 months was associated with a reduction in the MetS risk profile. Women undergoing VD supplementation had a lower risk of MetS, hypertriglyceridemia, and hyperglycemia.
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Effects of different vitamin D supplementation strategies in reversing metabolic syndrome and its component risk factors in adolescents.
Al-Daghri, NM, Amer, OE, Khattak, MNK, Sabico, S, Ghouse Ahmed Ansari, M, Al-Saleh, Y, Aljohani, N, Alfawaz, H, Alokail, MS
The Journal of steroid biochemistry and molecular biology. 2019;:105378
Abstract
There is little evidence on the efficacy of various vitamin D supplementation strategies in reversing metabolic syndrome (MetS) in adolescents. The present study aims to fill this gap. A total of 535 (243/292) out of 650 apparently healthy Saudi adolescents were randomly selected from the Vitamin D School Project database which has baseline and post-intervention information of more than 1000 Saudi adolescents 12-18 years old attending 34 schools in Riyadh, Saudi Arabia from Nov 2014-May 2015. Allocation of intervention was done in 3 groups using cluster randomization: vitamin D tablet, 1000IU/day (N = 180; 69 boys, 111 girls); vitamin D fortified milk consumption, 200 ml/day, 40IU/100 ml (N = 189; 93 boys, 96 girls) and control (educational awareness) (N = 166; 81 boys, 85 girls). All groups were given educational awareness on how to increase vitamin D levels. All groups were matched for BMI and analysis adjusted for age. Post-intervention and using intent-to-treat approach, within-group analysis revealed a statistically significant increase in 25(OH)D levels in all groups, and a clinically significant increase in favor of the tablet group (between-group) [10.7 nmol/l (34.7%) versus 6.3 nmol/l (19.8%) in milk and 2.1 nmol/l (7.0%) in control; p < 0.001], adjusted for age and BMI-matched. Between group analysis also revealed a clinically significant decrease in triglycerides (p = 0.05), glucose (p < 0.001) and systolic blood pressure (p = 0.005) as well as a clinically significant increase in HDL-cholesterol (p = 0.004) over time, all in favor of the tablet group. Within-group comparison showed a significant decrease in the incidence of MetS in the tablet group (9.4% versus 4.4%; p < 0.05) only. In conclusion, oral vitamin D supplementation is superior to vitamin D fortified milk in improving vitamin D status. Reduction in the incidence of MetS in the Arab adolescent population secondary to vitamin D correction may be dose-dependent.
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Effects of vitamin D supplementation on depressive symptoms in type 2 diabetes mellitus patients: Randomized placebo-controlled double-blind clinical trial.
Omidian, M, Mahmoudi, M, Abshirini, M, Eshraghian, MR, Javanbakht, MH, Zarei, M, Hasani, H, Djalali, M
Diabetes & metabolic syndrome. 2019;(4):2375-2380
Abstract
AIM: Diabetes increases the odds of depression and depression is often associated with poor glycemic control and complications of diabetes. Vitamin D is also believed to improve glycemic control and ameliorate depressive symptoms. Therefore, we examined effects of vitamin D monotherapy (without antidepressant drugs) on depressive symptoms in Type 2 diabetic patients with mild to moderate depressive symptoms. METHODS We conducted 12 weeks, placebo-controlled, double-blind, randomized trial on 68 subjects with T2DM and mild to moderate depressive symptoms. Subjects received 100 μg (4000 IU) vitamin D (n = 32) or placebo (n = 34) daily. Beck Depression Inventory-II (BDI-II-PERSIAN) was applied for assessment of the severity of depression. Depression scores and metabolic profiles were measured at the beginning and end of trail. RESULTS after 3 months of vitamin D supplementation, mean values of 25(OH) D increased from 15.5 ± 8.8 to 32.2 ± 8.9 ng/ml (p-value <0.001) in the vitamin D group. Moreover, BDI-II scores decreased from 15.2 ± 9.6 to 9.8 ± 7.2 (p-value <0.001) in the vitamin D group and 15.5 ± 11.2 to 13.7 ± 11.5 (p-value = 0.03) in placebo group. This decrease in BDI-II scores were significant (27.6% vs 10.8%) compared with placebo (p-value = 0.02). In term of metabolic profiles, mean change in level of Hemoglobin A1c (HbA1c), insulin and triglycerides (TG) were significantly higher in response to the treatment with vitamin D compared to placebo (p-value <0.02). CONCLUSIONS In conclusion, supplementation of vitamin D in T2DM patients may protect these patients against the onset of major depressive disorder (MDD), with noticeable favorable effects on measures of metabolic profiles. TRIAL REGISTRATION NCT03008057.
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The effect of vitamin C and/or E supplementations on type 2 diabetic adult males under metformin treatment: A single-blinded randomized controlled clinical trial.
El-Aal, AA, El-Ghffar, EAA, Ghali, AA, Zughbur, MR, Sirdah, MM
Diabetes & metabolic syndrome. 2018;(4):483-489
Abstract
BACKGROUND AND AIM Recently, there has been an increasing interest in the influence of antioxidant vitamins on the efficacy of oral hypoglycemic therapy in type 2 diabetic patients (T2DM). This single-blinded randomized controlled clinical trial aimed to investigate the effect of vitamin C and/or E supplementation on the efficacy of oral hypoglycemic therapy in T2DM Palestinian male patients from the Gaza Strip. METHODS Forty T2DM male patients aged 40-60 years on metformin treatment were randomly divided into four groups, each group received an additional one of the following daily oral supplements for 90 days: placebo; vitamin C; vitamin E and vitamin C plus vitamin E. After overnight fasting, venous blood specimens were collected from all individuals into K3-EDTA tubes and serum tubes for measuring the biochemical and hematological parameters of the study at baseline and after 90 days of vitamins supplementation. RESULTS The results revealed that vitamin C and/or E improve fasting blood sugar (FBS), HbA1c, lipid profile, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), reduced glutathione (GSH); and Quantitative Insulin Sensitivity Check Index (QISCI) compared with diabetic patients group that received placebo. CONCLUSION This study provided additional evidence on the beneficial effects of supplementing antioxidant vitamins in T2DM which could improve the clinical condition and attenuate or prevent diabetic pathogenesis and complications that, secondly to poor glycemic control, could attribute to the imbalance between the decline in the endogenous antioxidants and increasing production of the reactive oxygen species leading to the oxidant-mediated damage present in the diabetic context.
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Vitamin D supplementation for the treatment of non-alcoholic fatty liver disease: A randomized double blind placebo controlled trial.
Dabbaghmanesh, MH, Danafar, F, Eshraghian, A, Omrani, GR
Diabetes & metabolic syndrome. 2018;(4):513-517
Abstract
BACKGROUND Low serum vitamin D has been associated with metabolic syndrome and Non-alcoholic fatty liver disease (NAFLD). This study aimed to investigate the impact of vitamin D supplementation in treatment of patients with NAFLD. METHODS In a double blind, randomized, placebo controlled trial patients with NAFLD were randomized to receive one weekly pearl of placebo, 50,000 U vitamin D3 (cholecalciferol) pearl per week and 0.25 mg calcitriol (1,25 dihydroxycholecalciferol) pearl per day for 3 months. RESULTS 106 NAFLD patients were randomized to receive calcitriol, vitamin D3 and placebo pearls for 12 weeks and data for 91 patients were analyzed. After 12 weeks of treatment, serum alkaline phosphatase levels was significantly decreased from baseline levels in vitamin D and calcitriol treated groups (P < 0.05). Serum and gamma glutamyl transferase (GGT) level was also significantly decreased compared to the baseline levels after 12 weeks of treatment with vitamin D. There was no statistically significant difference between placebo, calcitriol, vitamin D groups in terms of serum aminotransferase, alkaline phosphatase, serum GGT and lipid profile (P > 0.05). CONCLUSION While significant reduction of serum alkaline phosphatase and GGT were seen with vitamin D and calcitriol supplementation from baseline levels, no beneficial effects was seen when comparing vitamin D, calcitriol and placebo groups at the end of trial.
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The relationship between 25-hydroxyvitamin D concentration and liver enzymes in overweight or obese adults: Cross-sectional and interventional outcomes.
Naderpoor, N, Mousa, A, de Courten, M, Scragg, R, de Courten, B
The Journal of steroid biochemistry and molecular biology. 2018;:193-199
Abstract
Vitamin D deficiency is prevalent in individuals with non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis. However, there is limited and inconsistent data on the effect of vitamin D supplementation on liver function. Hepatic enzymes have been used as surrogate markers for NAFLD and have been associated with metabolic syndrome. We examined the relationships between 25-hydroxyvitamin D (25(OH)D) and γ-glutamyl transferase (GGT), alanine aminotransferase (ALT), alkaline phosphatase (ALP) in 120 drug-naïve individuals with no history of liver disease. In addition, the effect of vitamin D supplementation (100,000 loading dose of cholecalciferol followed by 4000IU daily for 16 weeks) on hepatic enzymes was investigated in a subgroup of 54 vitamin D-deficient overweight or obese individuals (28 randomised to cholecalciferol and 26 to placebo). Hepatic enzymes, anthropometric parameters, lipid profile, insulin sensitivity (hyperinsulinaemic-euglycaemic clamp, M value) and high sensitivity C-reactive protein (hs-CRP) were measured before and after the intervention. In the cross-sectional study, levels of GGT and ALT were higher in men compared to women (both p=0.001). There were no significant differences in GGT, ALT and ALP between vitamin D categories (25(OH)D<25nmol/L, 25-50nmol/L, and >50nmol/L) and no relationships were found between the three enzymes and 25(OH)D before and after adjustment for age, sex, BMI, WHR, and insulin sensitivity (all p>0.5). In the randomised trial, 25(OH)D concentrations increased in the vitamin D group (mean change 57.0±21.3nmol/L) compared to the placebo group (mean change 1.9±15.1nmol/L). Mean changes in GGT, ALT and ALP were not significantly different between vitamin D and placebo groups (all p>0.2). Change in 25(OH)D concentration was not correlated with changes in GGT, ALT and ALP before and after adjustments for age and sex (all p>0.1). In summary, 25(OH)D concentrations were not related to hepatic enzymes in drug-naive adults with no history of liver disease, and vitamin D supplementation had no effect on the serum levels of hepatic enzymes in vitamin D-deficient and overweight or obese, otherwise healthy individuals. Hence, vitamin D supplementation is unlikely to prevent incident NAFLD.
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Acute effects of a single dose of tocotrienols on insulinemic and inflammatory responses in metabolic syndrome subjects after a high-fat challenge.
Che, HL, Kanthimathi, MS, Loganathan, R, Yuen, KH, Tan, AT, Selvaduray, KR, Nesaretnam, K, Teng, KT
European journal of clinical nutrition. 2017;(1):107-114
Abstract
BACKGROUND/OBJECTIVES Evidence shows that tocotrienols potentially reverse various chronic disease progressions caused by the metabolic syndrome. We aimed to investigate the acute effects of a single-dose supplementation of gamma and delta tocotrienols (γδ-T3, 1:4 ratio) compared with those in placebo on the insulinemic, anti-inflammatory and anti-thrombogenic responses in metabolic syndrome subjects. SUBJECTS/METHODS Thirty metabolic syndrome subjects (15 men and 15 women) were recruited to a randomized, double-blinded and crossover study. The subjects were administered a single dose of 200 mg or 400 mg γδ-T3 emulsions or placebo incorporated into a glass of strawberry-flavored milkshake, consumed together with a high-fat muffin. Blood samples were collected at 0, 5, 15, 30, 60, 90, 120, 180, 240, 300 and 360 min after meal intake. RESULTS Plasma vitamin E levels reflected the absorption of γδ-T3 after treatments. Postprandial changes in serum C-peptide, serum insulin, plasma glucose, triacylglycerol, non-esterified fatty acid and adiponectin did not differ between treatments, with women displaying delayed increase in the aforementioned markers. No significant difference between treatments was observed for plasma cytokines (interleukin-1 beta, interleukin-6 and tumor necrosis factor alpha) and thrombogenic markers (plasminogen activator inhibitor type 1 and D-dimer). CONCLUSIONS Supplementation of a single dose of γδ-T3 did not change the insulinemic, anti-inflammatory and anti-thrombogenic responses in metabolic syndrome subjects.
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Vitamin D, parathyroid hormone and metabolic syndrome - the PORMETS study.
Raposo, L, Martins, S, Ferreira, D, Guimarães, JT, Santos, AC
BMC endocrine disorders. 2017;(1):71
Abstract
BACKGROUND Vitamin D (VitD) and parathyroid hormone (PTH) play important roles in calcium metabolism and skeletal homeostasis. Estimates of the VitD status in several European countries show large variations between them. In addition, no national population-based estimate has been published. VitD and PTH may also play important roles in cardiovascular risk, which has been suggested to be associated with metabolic syndrome (MetS) and is very prevalent in Portugal. The goal of our study was to evaluate the prevalence of hypovitaminosis D and its determinants as well as PTH serum level determinants and associations of the 25-hydroxyvitamin D and PTH serum levels with MetS and its individual components in a sample of the Portuguese mainland population. METHODS PORMETS is a national cross-sectional study that includes a total sample of 4095 adults. A subsample, including 500 participants, was randomly selected for the present study. A structured questionnaire was administered to collect information on personal medical histories and socio-demographic and behavioral characteristics. Blood pressure and anthropometrics measurements were performed. Fasting venous samples were collected and PTH and 25-hydroxyvitamin D were measured. VitD adequacy was classified according to the Institute of Medicine, and MetS was classified according to the Joint Interim Statement recommendations. Multiple linear regression and unconditional logistic regression models were used to estimate the associations between the levels of PTH and 25-hydroxyvitamin D and with MetS and its individual components. RESULTS The prevalence of VitD deficiency was 37.7%, and MetS was present in 191 participants (38.4%). The serum PTH levels showed a positive association (OR: 1.014; 95%CI: 1.002, 1.026) with the waist circumference component of MetS. The serum 25-hydroxyvitamin D levels were negatively associated with MetS (OR: 0.957; 95%CI: 0.922, 0.993) as well as with its blood pressure (OR: 0.949; 95%CI: 0.912, 0.987) and triglycerides (OR: 0.930; 95%CI: 0.892, 0.969) components. CONCLUSION This study showed a high national prevalence of hypovitaminosis D. The PTH levels showed a significant positive association with the WC component of MetS, and the VitD levels were negatively associated with the BP and triglycerides components as well as with the MetS.
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Ubiquinol Effects on Antiphospholipid Syndrome Prothrombotic Profile: A Randomized, Placebo-Controlled Trial.
Pérez-Sánchez, C, Aguirre, MÁ, Ruiz-Limón, P, Ábalos-Aguilera, MC, Jiménez-Gómez, Y, Arias-de la Rosa, I, Rodriguez-Ariza, A, Fernández-Del Río, L, González-Reyes, JA, Segui, P, et al
Arteriosclerosis, thrombosis, and vascular biology. 2017;(10):1923-1932
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Abstract
OBJECTIVE Antiphospholipid syndrome (APS) leukocytes exhibit an oxidative perturbation, directly linked to alterations in mitochondrial dynamics and metabolism. This disturbance is related to the patients' prothrombotic status and can be prevented by in vitro treatment with coenzyme Q10. Our aim was to investigate short-term effects of in vivo ubiquinol (reduced coenzyme Q10 [Qred]) supplementation on markers related to inflammation and thrombosis in APS through a prospective, randomized, crossover, placebo-controlled trial. APPROACH AND RESULTS Thirty-six patients with APS were randomized to receive Qred (200 mg/d) or placebo for 1 month. Thirty-three patients with APS completed the intervention, which increased plasma coenzyme Q10. Qred improved endothelial function and decreased monocyte expression of prothrombotic and proinflammatory mediators, inhibited phosphorylation of thrombosis-related protein kinases, and decreased peroxides and percentage of monocytes with depolarized mitochondria; mitochondrial size was increased, and mitochondrial biogenesis-related genes were upregulated. Qred ameliorated extruded neutrophil extracellular traps in neutrophils and downregulated peroxides, intracellular elastase, and myeloperoxidase. Nanostring microRNA profiling revealed 20 microRNAs reduced in APS monocytes, and 16 of them, with a preponderance of cardiovascular disease-related target mRNAs, were upregulated. Monocytes gene profiling showed differential expression of 29 atherosclerosis-related genes, 23 of them changed by Qred. Interaction networks of genes and microRNAs were identified. Correlation studies demonstrated co-ordinated effects of Qred on thrombosis and endothelial function-associated molecules. CONCLUSIONS Our results highlight the potential of Qred to modulate the overexpression of inflammatory and thrombotic risk markers in APS. Because of the absence of clinically significant side effects and its potential therapeutic benefits, Qred might act as safe adjunct to standard therapies in APS. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT02218476.
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Effect of high-dose vitamin D supplementation on cardiometabolic risk factors in subjects with metabolic syndrome: a randomized controlled double-blind clinical trial.
Salekzamani, S, Mehralizadeh, H, Ghezel, A, Salekzamani, Y, Jafarabadi, MA, Bavil, AS, Gargari, BP
Journal of endocrinological investigation. 2016;(11):1303-1313
Abstract
PURPOSE The evidence in support of the effect of vitamin D deficiency on cardiovascular diseases is inconsistent. The objective of this randomized, controlled, double-blind study was to assess the effect of high-dose vitamin D supplementation on cardiometabolic risk factors in subjects with metabolic syndrome. METHODS Eighty subjects were randomized to receive 50,000 IU vitamin D or matching placebo weekly for 16 weeks. Fasting blood sugar, homeostasis model assessment of insulin resistance, insulin sensitivity (Quicki), serum lipid profiles (low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglyceride (TG) and total cholesterol), anthropometric factors and blood pressure were assessed before and after intervention. Dietary intake and sun exposure were also determined. The trial was registered at http://www.irct.ir (code: IRCT201409033140N14). RESULTS Participants were 40.49 ± 5.04 years and 49 % male. All of the intervention group and 97 % of placebo group were vitamin D deficient or insufficient (25-hydroxyvitamin D <75 nmol/L). After intervention, serum 25(OH)D concentration was increased by 61.93 nmol/L in intervention group, while it was decreased in placebo group (p < 0.001). There was a significant change in TG concentration after 4 months (p < 0.001). Other metabolic or anthropometric factors did not change significantly (p = 0.05). CONCLUSION Supplementation with high-dose vitamin D for 4 months improved vitamin D status and decreased TG levels in subjects with metabolic syndrome. However, it did not have any beneficial effects on other cardiometabolic risk factors; this might be due to the inadequate vitamin D status attained in this study which was conducted in a severely deficient region.