Magnetic solid-phase extraction of warfarin and gemfibrozil in biological samples using polydopamine-coated magnetic nanoparticles via core-shell nanostructure.

Herein, polydopamine-coated Fe3 O4 spheres were synthesized using a very simple, easy, cost-effective, efficient, and fast method. First, magnetic nanoparticles (Fe3 O4 ) were synthesized and were followed by accommodating polydopamine on the surface of the prepared Fe3 O4 . The prepared polydopamine-coated Fe3 O4 spheres were utilized as a sorbent in magnetic solid phase extraction of gemfibrozil and warfarin (as the model analytes). The extracted model analytes were desorbed by a suitable organic solvent and were analyzed by high-performance liquid chromatography. Under optimized condition, the linearity of the method was in the range of 0.1-200.0 µg/L for the selected analytes in water. The limits of detection were calculated to be in the range of 0.026-0.055 µg/L for warfarin and gemfibrozil, respectively. The limits of quantification were calculated to be in the range of 0.089-0.185 µg/L. The inter-day and intra-day relative standard deviations were determined to be in the range of 1.4%-3.3% in three concentrations in order to calculate the method precision. Furthermore, the enrichment factors were found to be 78 and 81 for warfarin and gemfibrozil, respectively. Moreover, the calculated absolute recoveries were between 78% and 81%. The obtained recoveries indicated that the method was useful and applicable in complicated real samples.

The effects of zinc supplementation on clinical response and metabolic profiles in pregnant women at risk for intrauterine growth restriction: a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: This investigation was conducted to assess the effects of zinc supplementation on clinical response and metabolic status among pregnant women at risk for intrauterine growth restriction (IUGR). METHODS: This randomized, double-blind, placebo-controlled, clinical trial was conducted among 52 women at risk for IUGR according to abnormal uterine artery Doppler waveform. Participants were randomly assigned to take either 233 mg zinc gluconate (containing 30 mg zinc) supplements (n = 26) or placebo (n = 26) for 10 weeks from 17 to 27 weeks of gestation. Fasting blood samples were taken at baseline and after the 10-week treatment to quantify related variables. RESULTS: After the 10-week intervention, taking zinc led to a significant reduction in serum high-sensitivity C-reactive protein (hs-CRP) (ß â€’1.17 mg/L; 95% CI, -1.77, -0.57; p < .001) and plasma malondialdehyde (MDA) levels (ß -0.23 µmol/L; 95% CI, -0.45, -0.02; p = .03); also a significant rise in total antioxidant capacity (TAC) (ß 59.22 mmol/L; 95% CI, 25.07, 93.36; p = .001) was observed in comparison to placebo. In addition, zinc supplementation significantly reduced serum insulin (ß -1.33 µIU/mL; 95% CI, -2.00, -0.67; p < .001) and insulin resistance (ß -0.30; 95% CI, -0.44, -0.15; p < .001), and significantly increased insulin sensitivity (ß 0.008; 95% CI, 0.003, 0.01; p < .001) compared with the placebo. Zinc supplementation did not influence pulsatility index (PI) and other metabolic parameters. CONCLUSIONS: Overall, zinc supplementation in pregnant women at risk for IUGR had beneficial effects on TAC, MDA, hs-CRP, and insulin metabolism, but did not affect PI and other metabolic profiles.

Evaluation of the efficacy of two doses of vitamin D supplementation on glycemic, lipidemic and oxidative stress biomarkers during pregnancy: a randomized clinical trial.

BACKGROUND: Vitamin D deficiency during pregnancy is common and is likely to be associated with metabolic complications in the mother. The aim of this study was to assess the efficacy of two doses of vitamin D supplementation during pregnancy on maternal and cord blood vitamin D status and metabolic and oxidative stress biomarkers. METHODS: The eligible pregnant women (n = 84) invited to participate in the study and randomly allocated to one of the two supplementation groups (1000 IU/d vitamin D and 2000 IU/d). Biochemical assessments of mothers including serum concentrations of 25(OH)D, calcium, phosphate, iPTH, fasting serum sugar (FBS), insulin, triglyceride, total cholesterol, LDL-C, HDL-C, malondialdehyde (MDA) and total antioxidant capacity (TAC) were done at the beginning and 34 weeks of gestation. Cord blood serum concentrations of 25(OH)D, iPTH, MDA and TAC were assessed at delivery as well. To determine the effects of vitamin D supplementation on metabolic markers 1-factor repeated-measures analysis of variance (ANOVA) was used. Between groups comparisons was done by using Independent-samples Student's t-test or Mann-Whitney test. P < 0.05 was considered as significant. RESULTS: Supplementation with 1000 IU/d and 2000 IU/d vitamin D resulted in significant changes in vitamin D status over pregnancy (24.01 ± 21.7, P < 0.001 in 1000 IU/d group and 46.7 ± 30.6 nmol/L, P < 0.001 in 2000 IU/d group). Daily intake of 2000 compared with 1000 IU/d tended to increase the serum concentration of HDL-C (10 ± 8.37, P < 0.001 in 1000 IU/d group and 9.52 ± 11.39 mg/dL, P < 0.001 in 2000 IU/d group). A significant decrement in serum concentration of iPTH observed in both groups (- 4.18 ± 7.5, P = 0.002 in 1000 IU/d group and - 8.36 ± 14.17, P = 0.002 in 2000 IU/d group). CONCLUSIONS: Supplementation with 2000 IU/d vitamin D as compared with 1000 IU/d, is more effective in promoting vitamin D status and HDL-C serum concentration and in decreasing iPTH over pregnancy. TRIAL REGISTRATION: This trial is registered at clinicaltrials.gov ( NCT03308487 ). Registered 12 October 2017 'retrospectively registered'.

Molecular and Biological Functions of Melatonin in Endometrial Cancer.

Endometrial cancer is the fifth leading cancer among women. This rate is higher in developed countries and its incidence is increasing worldwide. Diabetes mellitus, obesity, hypertension and arteriosclerosis are major risk factors for endometrial cancer. Melatonin is a hormone synthesized in the pineal and extra-pineal organs such as the digestive tract, bone marrow, retina and more. Evidence shows the potential effects of melatonin in endometrial cancer inhibition. Therefore, the focus of this paper is to review this outstanding evidence and to summarize the molecular and biological mechanisms of melatonin for the inhibition of endometrial cancer.

The effects of grape seed extract on glycemic control, serum lipoproteins, inflammation, and body weight: A systematic review and meta-analysis of randomized controlled trials.

The aim of this systematic review and meta-analysis was to analyze the effects of grape seed extract (GSE) on glycemic control and serum lipoproteins, inflammation and body weight. Two independent authors systematically searched online databases including EMBASE, Scopus, PubMed, Cochrane Library, and Web of Science from inception until May 30, 2019. Cochrane Collaboration risk of bias tool was applied to assess the methodological quality of included trials. The heterogeneity among the included studies was assessed using Cochrane's Q test and I-square (I2 ) statistic. Data were pooled using a random-effects model and weighted mean difference (WMD) was considered as the overall effect size. Fifty trials were included in this meta-analysis. Pooling effect sizes from studies demonstrated a significant decrease in fasting plasma glucose (FPG) (WMD): -2.01; 95% confidence interval (CI): -3.14, -0.86), total cholesterol (TC; WMD: -6.03; 95% CI: -9.71, -2.35), low-density lipoprotein (LDL) cholesterol (WMD: -4.97; 95% CI: -8.37, -1.57), triglycerides (WMD: -6.55; 95% CI: -9.28, -3.83), and C-reactive protein (CRP) concentrations (WMD: -0.81; 95% CI: -1.25, -0.38) following GSE therapy. Grape seed did not influence HbA1c, HDL cholesterol levels, and anthropometric measurements. This meta-analysis demonstrated that GSE intake significantly reduced FPG, TC, LDL cholesterol, triglycerides, and CRP levels.

Chitosan is a potential inhibitor of ovarian cancer: Molecular aspects.

Although ovarian cancer has a lower prevalence than breast cancer, its mortality rate is three times higher, which is reported to increase in the coming years. As the early stages of ovarian cancer do not have any obvious symptoms, in most of the cases, this cancer is diagnosed at advanced stages with a poor prognosis. Moreover, in many patients who are diagnosed with advanced stage, relapse of the disease and drug resistance are observed. Over the past years, these women have been treated with chemotherapy and cytoreductive surgeries. However, the chemotherapy could affect the healthy tissues in addition to the malignancies. Therefore, discovering new diagnostic and therapeutic options seems to be a crucial need. Unlike the common invasive and/or nonspecific treatments, nanomedicine is trying to find a new way for cancer imaging, diagnosis, and drug delivery method. Nanoparticles (NPs), which has recently drawn attention, can be used in order to reduce the toxicity and frequent dosing of drugs, tumor-specific delivery, and early diagnosis for malignancies. Chitosan as an NP and product of chitin deacetylation has multiple characteristics, including biocompatibility, biodegradability, and safety. In this review, we cover the studies concerned with the role of chitosan in finding solutions to overcome the problems faced in ovarian cancer treatments. Furthermore, we highlight how chitosan is being used in delivering chemotherapy drugs, gene therapy, and imaging methods for both detection and image-guided therapies.

The Effects of L-Carnitine Supplementation on Serum Lipids: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: The findings of trials investigating the effects of L-carnitine administration on serum lipids are inconsistent. This meta-analysis of randomized controlled trials (RCTs) was performed to summarize the effects of L-carnitine intake on serum lipids in patients and healthy individuals. METHODS: Two authors independently searched electronic databases including MEDLINE, EMBASE, Cochrane Library, Web of Science, PubMed and Google Scholar from 1990 until August 1, 2019, in order to find relevant RCTs. The quality of selected RCTs was evaluated using the Cochrane Collaboration risk of bias tool. Cochrane's Q test and I-square (I2) statistic were used to determine the heterogeneity across included trials. Weight mean difference (SMD) and 95% CI between the two intervention groups were used to determine pooled effect sizes. Subgroup analyses were performed to evaluate the source of heterogeneity based on suspected variables such as, participant's health conditions, age, dosage of L-carnitine, duration of study, sample size, and study location between primary RCTs. RESULTS: Out of 3460 potential papers selected based on keywords search, 67 studies met the inclusion criteria and were eligible for the meta-analysis. The pooled results indicated that L-carnitine administration led to a significant decrease in triglycerides (WMD: -10.35; 95% CI: -16.43, -4.27), total cholesterol (WMD: -9.47; 95% CI: - 13.23, -5.70) and LDL-cholesterol (LDL-C) concentrations (WMD: -6.25; 95% CI: -9.30, -3.21), and a significant increase in HDL-cholesterol (HDL-C) levels (WMD: 1.39; 95% CI: 0.21, 2.57). L-carnitine supplementation did not influence VLDL-cholesterol concentrations. When we stratified studies for the predefined factors such as dosage, and age, no significant effects of the intervention on triglycerides, LDL-C, and HDL-C levels were found. CONCLUSION: This meta-analysis demonstrated that L-carnitine administration significantly reduced triglycerides, total cholesterol and LDL-cholesterol levels, and significantly increased HDL-cholesterol levels in the pooled analyses, but did not affect VLDL-cholesterol levels; however, these findings were not confirmed in our subgroup analyses by participant's health conditions, age, dosage of L-carnitine, duration of study, sample size, and study location.

The Effects of Quercetin Supplementation on Blood Pressures and Endothelial Function Among Patients with Metabolic Syndrome and Related Disorders: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

BACKGROUND: This systematic review and meta-analysis of randomized controlled trials (RCTs) were performed to determine the effect of quercetin administration on blood pressures and endothelial function among patients with metabolic syndrome (MetS) and related disorders. METHODS: We searched systematically online databases including Cochrane Library, EMBASE, MEDLINE, and Web of Science to identify the relevant RCTs until December 2018. Q-test and I2 statistics were applied to assess heterogeneity among the included studies. Data were pooled using a random-effects model and weighted mean difference (WMD) was considered as the overall effect size. RESULTS: Out of 284 citations, 8 RCTs were included in the meta-analysis. We found a significant reduction in systolic blood pressure (SBP) (WMD: -1.69; 95% CI: -3.22, -0.17) following the intake of quercetin supplements. However, quercetin supplementation did not significantly affect diastolic blood pressure (DBP) (WMD: -3.14; 95% CI: -8.24, 1.95), vascular cell adhesion molecule 1 (VCAM-1) (WMD: -24.49; 95% CI: -53.74, 4.77) and intercellular adhesion molecule 1 (ICAM-1) (WMD: -5.78; 95% CI: -12.93, 1.38). CONCLUSION: In summary, the current meta-analysis demonstrated that quercetin supplementation significantly reduced SBP, yet did not affect DBP, VCAM-1 and ICAM-1 among patients with MetS and related disorders.

The effects of magnesium-zinc-calcium-vitamin D co-supplementation on biomarkers of inflammation, oxidative stress and pregnancy outcomes in gestational diabetes.

BACKGROUND: Diabetes is the most common medical condition in pregnant women and its complications affect both mother and fetus. The beneficial effects of vitamin D on gestational diabetes have been shown, though data on the effects of co-administration of vitamin D with other nutrients on pregnancy outcomes in gestational diabetes (GDM) are scarce. This study was aimed to determine the effects of magnesium-zinc-calcium-vitamin D co-supplementation on parameters of inflammation and oxidative stress, and pregnancy outcomes among women with GDM. METHODS: This randomized, double-blinded, placebo-controlled trial was conducted on 60 women with GDM not taking oral hypoglycemic agents. Patients were randomly assigned to take magnesium-zinc-calcium-vitamin D supplements (n = 30) or placebo (n = 30) for 6 weeks. Fasting blood samples were collected from participants at baseline and after the 6-week intervention to measure related biomarkers. RESULTS: Magnesium-zinc-calcium-vitamin D co-supplementation resulted in a significant reduction in serum high-sensitivity C-reactive protein (- 1.2 ± 3.5 vs. + 0.8 ± 2.0 mg/L, P = 0.01) and plasma malondialdehyde concentrations (- 0.3 ± 0.3 vs. + 0.3 ± 1.1 µmol/L, P = 0.003), as well as a significant increase in total antioxidant capacity levels (+ 38.2 ± 76.5 vs. -16.3 ± 93.5 mmol/L, P = 0.01), compared to placebo. We found a decreasing trend in newborns' weight (3089.8 ± 519.9 vs. 3346.3 ± 411.1 g, P = 0.05) and the rate of macrosomia (3.3% vs. 16.7%, P = 0.08) in the magnesium-zinc-calcium-vitamin D supplemented women. CONCLUSIONS: Overall, the findings of this study have demonstrated that magnesium-zinc-calcium-vitamin D co-supplementation for 6 weeks to women with GDM may reduce biomarkers of inflammation and oxidative stress. This study was retrospectively registered on 25 April 2017 in the Iranian website ( www.irct.ir ) for clinical trials registration ( http://www.irct.ir : IRCT201704225623N109).

The effect of zinc and vitamin E cosupplementation on metabolic status and its related gene expression in patients with gestational diabetes.

Objective: The aim of this study was to determine the effects of zinc and vitamin E cosupplementation on metabolic status and gene expression related to insulin and lipid metabolism in women with gestational diabetes mellitus (GDM).Methods: Fifty-four women, in the age range of 18-40 years, diagnosed with GDM were recruited for this randomized, double-blinded, placebo-controlled trial. Subjects were randomly allocated into two intervention groups to either taking 233 mg/day Zinc Gluconate plus 400-IU/day vitamin E supplements or placebo (n = 27 each group) for 6 weeks. Gene expression related to insulin and lipid metabolism was evaluated in peripheral blood mononuclear cells (PBMCs) of women with GDM using RT-PCR method.Results: Participants who received zinc plus vitamin E supplements had significantly lower serum insulin levels (ß = -3.81; 95% CI, -5.90, -1.72; p = .001), homeostasis model of assessment-insulin resistance (ß = -0.96; 95% CI, -1.54, -0.38; p = .002), serum total-cholesterol (ß = -8.56; 95% CI, -16.69, -0.43; p = .03) and low density lipoprotein-cholesterol (LDL)-cholesterol (ß = -8.72; 95% CI, -15.27, -2.16; p = .01), and higher quantitative insulin sensitivity check index (ß = 0.01; 95% CI, 0.005, 0.02; p = .007) compared with the placebo. Moreover, zinc and vitamin E cosupplementation upregulated gene expression of peroxisome proliferator-activated receptor gamma (PPAR-γ; p = .03) and low-density lipoprotein receptor (LDLR; p = .04) compared with the placebo. Though, zinc and vitamin E combination did not affect other metabolic parameters.Conclusions: Overall, zinc and vitamin E cosupplementation for 6 weeks in women with GDM significantly improved insulin metabolism, lipid profile, and the gene expression levels of PPAR-γ and LDLR.

The effects of magnesium and vitamin E co-supplementation on parameters of glucose homeostasis and lipid profiles in patients with gestational diabetes.

BACKGROUND: Magnesium and vitamin E are known to exert multiple beneficial effects, such as anti-glycemic and anti-lipidemic properties. The aim of this study was to determine the effects of magnesium and vitamin E co-supplementation on metabolic status of women with gestational diabetes (GDM). METHODS: This randomized, double-blinded, placebo-controlled trial was conducted among 60 subjects diagnosed with GDM, aged 18-40 years. Subjects were randomly allocated into two groups to receive 250 mg/day magnesium oxide plus 400 IU/day vitamin E supplements or placebo (n = 30 each group) for 6 weeks. Participants' blood samples were taken to determine their metabolic profiles. RESULTS: Subjects who received magnesium plus vitamin E supplements had significantly lower fasting plasma glucose (ß - 5.20 mg/dL; 95% CI, - 7.88, - 2.52; P = 0.002), serum insulin levels (ß - 2.93 µIU/mL; 95% CI, - 5.68, - 0.18; P = 0.02) and homeostasis model of assessment-insulin resistance (ß - 0.78; 95% CI, - 1.42, - 0.14; P = 0.01), and higher quantitative insulin sensitivity check index (ß 0.01; 95% CI, 0.005, 0.02; P = 0.002) compared with placebo. In addition, magnesium plus vitamin E supplementation resulted in a significant reduction in serum triglycerides (ß - 50.31 mg/dL; 95% CI, - 67.58, - 33.04; P < 0.001), VLDL- (ß - 10.06 mg/dL; 95% CI, - 13.51, - 6.60; P < 0.001), total- (ß - 26.10 mg/dL; 95% CI, - 41.88, - 10.33; P = 0.004), LDL- (ß - 15.20 mg/dL; 95% CI, - 29.50, - 0.91; P = 0.03) and total-/HDL-cholesterol ratio (ß - 0.46; 95% CI, - 0.72, - 0.19; P < 0.001) compared with placebo. Magnesium and vitamin E co-supplementation did not affect HDL-cholesterol levels. CONCLUSIONS: Overall, magnesium and vitamin E co-supplementation for 6 weeks in women with GDM significantly improved glycemic control and lipid profiles, except for HDL-cholesterol levels. CLINICAL TRIAL REGISTRATION NUMBER: http://www.irct.ir : IRCT20170513033941N24.

The effects of alpha-lipoic acid supplementation on inflammatory markers among patients with metabolic syndrome and related disorders: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: This systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to determine the effect of alpha-lipoic acid (ALA) supplementation on the inflammatory markers among patients with metabolic syndrome (MetS) and related disorders. METHODS: We searched the following databases until November 2017: PubMed, MEDLINE, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials. Three reviewers independently assessed study eligibility, extracted data, and evaluated risk of bias of included primary studies. Statistical heterogeneity was assessed using Cochran's Q test and I-square (I2) statistic. Data were pooled by using the random-effect model and standardized mean difference (SMD) was considered as the summary effect size. RESULTS: Eighteen trials out of 912 potential citations were found to be eligible for our meta-analysis. The findings indicated that ALA supplementation significantly decreased C-reactive protein (CRP) (SMD = - 1.52; 95% CI, - 2.25, - 0.80; P < 0.001), interlokin-6 (IL-6) (SMD = - 1.96; 95% CI, - 2.60, - 1.32; P < 0.001), and tumor necrosis factor alpha levels (TNF-α) (SMD = - 2.62; 95% CI, - 3.70, - 1.55; P < 0.001) in patients diagnosed with metabolic diseases. CONCLUSION: In summary, the current meta-analysis demonstrated the promising impact of ALA administration on decreasing inflammatory markers such as CRP, IL-6 and TNF-α among patients with MetS and related disorders.

Effects of Probiotic Supplementation on Hormonal Profiles, Biomarkers of Inflammation and Oxidative Stress in Women With Polycystic Ovary Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial.

BACKGROUND: To the best of our knowledge, data on effects of probiotic administration on hormonal profiles, biomarkers of inflammation and oxidative stress in women with polycystic ovary syndrome (PCOS) are scarce. This investigation was conducted to assess the effects of probiotic supplementation on hormonal profiles, biomarkers of inflammation and oxidative stress in women with PCOS. METHODS: This randomized, double-blind, placebo-controlled trial was conducted on 60 women with PCOS, aged 18-40 years old. Subjects were randomly assigned into 2 groups to receive either probiotics or placebo (n = 30 each group) for 12 weeks. Metabolic profiles were quantified at baseline and after a 12-week intervention. RESULTS: After the 12-week intervention, compared with placebo, probiotic supplementation significantly increased serum sex hormone-binding globulin (SHBG) (+25.9 ± 32.5 vs. +0.5 ± 15.6 nmol/L, P < 0.001) and plasma total antioxidant capacity (TAC) (+8.8 ± 120.5 vs. -98.3 ± 246.4 mmol/L, P = 0.04), and significantly decreased serum total testosterone (-0.2 ± 0.7 vs. +0.2 ± 0.6 ng/mL, P = 0.03), modified Ferriman-Gallwey (mF-G) scores (-1.7 ± 1.5 vs. -0.2 ± 1.0, P < 0.001), serum high-sensitivity C-reactive protein (hs-CRP) (-1150.0 ± 1295.2 vs. +202.5 ± 1426.3 ng/mL, P < 0.001) and plasma malondialdehyde (MDA) concentrations (-0.2 ± 0.6 vs. +0.9 ± 1.3 µmol/L, P < 0.001). We did not observe any detrimental effect of probiotic supplementation on other metabolic profiles. CONCLUSION: Overall, probiotic supplementation of PCOS women for 12 weeks had beneficial effects on total testosterone, SHBG, mFG scores, hs-CRP, TAC and MDA levels but did not affect other metabolic profiles.

The Effects of Coenzyme Q10 Supplementation on Lipid Profiles Among Patients with Metabolic Diseases: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

BACKGROUND AND OBJECTIVE: Oxidative stress and inflammation are key parameters in developing metabolic disorders. Hence, antioxidant intake might be an appropriate approach. Several studies have evaluated the effect of coenzyme Q10 (CoQ10) supplementation on lipid profile among patients with metabolic diseases, though findings are controversial. The aim of this systematic review and meta-analysis was to determine the effects of CoQ10 supplementation on lipid profile in patients with metabolic disorders. METHODS: We searched PubMed, EMBASE, Web of Science and Cochrane Library databases until July 2017. Prospective clinical trials were selected assessing the effect of CoQ10 supplementation on different biomarkers. Two reviewers independently assessed the eligibility of studies, extracted data, and evaluated the risk of bias of included studies. A fixed- or random-effects model was used to pool the data, which expressed as a standardized mean difference with 95% confidence interval. Heterogeneity was measured using a Q-test and with I2 statistics. RESULTS: A total of twenty-one controlled trials (514 patients and 525 controls) were included. The meta-analysis indicated a significant reduction in serum triglycerides levels (SMD -0.28; 95% CI, -0.56, -0.005). CoQ10 supplementation also decreased total-cholesterol (SMD -0.07; 95% CI, -0.45, 0.31), increased LDL- (SMD 0.04; 95% CI, -0.27, 0.36), and HDL-cholesterol levels (SMD 0.10; 95% CI, -0.32, 0.51), not statistically significant. CONCLUSION: CoQ10 supplementation may significantly reduce serum triglycerides levels, and help to improve lipid profiles in patients with metabolic disorders. Additional prospective studies are recommended using higher supplementation doses and longer intervention period.

Magnesium supplementation affects gene expression related to insulin and lipid in patients with gestational diabetes.

Magnesium is known to exert several beneficial effects, including antiglycemic and antilipidemic properties. The aim of this study was to evaluate the effects of magnesium supplementation on gene expression related to insulin and lipid metabolism in women with gestational diabetes (GDM) who were not on oral hypoglycemic agents. This randomized double-blind, placebo-controlled trial was conducted among 40 patients diagnosed with GDM, aged 18-40 years. Participants were randomly allocated into two groups to take either 250 mg/day of magnesium supplements in the form of magnesium oxide (n = 20) or placebo (n = 20) for 6 weeks. Gene expression related to insulin and lipid metabolism was assessed in peripheral blood mononuclear cells (PBMCs) of women with GDM using RT-PCR method. Compared with the placebo, magnesium supplementation to women with GDM resulted in a significant decrease in levels of fasting plasma glucose (FPG) (-9.7 ± 5.6 vs. -0.1 ± 8.5 mg/dL, P<0.001). Quantitative results of RT-PCR demonstrated that compared with the placebo, magnesium supplementation upregulated gene expression of peroxisome proliferator-activated receptor gamma (PPAR-γ) (P = 0.003) and glucose transporter 1 (GLUT-1) (P = 0.004) and downregulated gene expression of oxidized low-density lipoprotein receptor (LDLR) (P = 0.001) in PBMCs of women with GDM. In addition, a trend toward a greater decrease in gene expression of lipoprotein (a) [LP(a)] was observed in the patients belonging to magnesium group compared to placebo group (P = 0.08). Overall, magnesium supplementation for 6 weeks in women with GDM significantly improved FPG levels, and gene expression of PPAR-γ, GLUT-1, and LDLR.

The Effects of Vitamin D Supplementation on Metabolic Status of Patients with Polycystic Ovary Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial.

Data on the effects of vitamin D supplementation on metabolic status of patients with polycystic ovary syndrome (PCOS) are scarce. The current study was conducted to evaluate the effects of vitamin D supplementation on metabolic status of patients with PCOS. This randomized double-blind, placebo-controlled trial was performed on 70 vitamin D-deficient (serum concentrations<20 ng/ml) women with phenotype B-PCOS according to the Rotterdam criteria aged 18-40 years old. Participants were randomly allocated into 2 groups to take either 50 000 IU vitamin D (n=35) or placebo (n=35) every 2 weeks for 12 weeks. Metabolic, endocrine, inflammation, and oxidative stress biomarkers were quantified at the beginning of the study and after 12-week intervention. After the 12-week intervention, compared to the placebo, vitamin D supplementation significantly decreased fasting plasma glucose (FPG) (-3.1±7.3 vs. +0.5±6.3 mg/dl, p=0.02), insulin (-1.4±3.6 vs. +2.6±7.0 µIU/ml, p=0.004), homeostasis model of assessment-estimated insulin resistance (-0.3±0.8 vs. +0.6±1.6, p=0.003), homeostasis model of assessment-estimated B cell function (-4.9±13.4 vs. +9.9±26.9, p=0.005), and increased quantitative insulin sensitivity check index (+0.01±0.01 vs. -0.02±0.05, p=0.007). Supplementation with vitamin D also led to significant reductions in serum high-sensitivity C-reactive protein (hs-CRP) (-0.7±1.4 vs. +0.5±2.1 µg/mL, p=0.009) and plasma malondialdehyde (MDA) levels (-0.1±0.5 vs. +0.9±2.1 µmol/l, p=0.01) compared to the placebo. Overall, vitamin D supplementation for 12 weeks in vitamin D-deficient women with phenotype B-PCOS had beneficial effects on glucose homeostasis parameters, hs-CRP, and MDA.

Clinical and Metabolic Response to Vitamin D Supplementation in Endometrial Hyperplasia: a Randomized, Double-Blind, Placebo-Controlled Trial.

There was inconsistent evidence showing that vitamin D intake may be associated with reduced cancer risk due to optimized metabolic profile and reduced oxidative stress. However, we are not aware of any study evaluating the effects of vitamin D supplementation on clinical response and metabolic status of patients with endometrial hyperplasia (EH). This research was done to evaluate the effects of vitamin D supplementation on clinical response and metabolic status of patients with EH. This randomized, double-blind, placebo-controlled trial was conducted among 60 women diagnosed with EH. EH diagnosis was made based on specific diagnostic procedures of biopsy. Participants were randomly assigned into two groups to intake either 50,000 IU vitamin D3 supplements (n = 30) or placebo (n = 30) every 2 weeks for 12 weeks. After the 12-week intervention, compared with the placebo, vitamin D supplementation increased serum-25(OH) vitamin D levels (+12.0 ± 10.4 vs. +1.9 ± 7.1 ng/mL, P < 0.001). In addition, vitamin D administration was associated with significant decreases in fasting plasma glucose (FPG) (-1.6 ± 7.0 vs. +2.1 ± 6.1 mg/dL, P = 0.03), serum insulin levels (-0.8 ± 1.9 vs. +1.1 ± 3.5 µIU/mL, P = 0.01), homeostasis model of assessment-insulin resistance (HOMA-IR) (-0.2 ± 0.6 vs. +0.3 ± 0.8, P = 0.01), and a significant increase in the quantitative insulin sensitivity check index (QUICKI) (+0.003 ± 0.01 vs. -0.01 ± 0.02, P = 0.02) compared with the placebo. Additionally, a significant decrease in serum high-sensitivity C-reactive protein (hs-CRP) (-1.9 ± 2.8 vs. -0.003 ± 2.0 µg/mL, P = 0.003) and a significant rise in plasma total antioxidant capacity (TAC) values (+62.5 ± 53.5 vs. +7.5 ± 34.1 mmol/L, P < 0.001) were observed following supplementation with vitamin D compared with the placebo. In conclusion, vitamin D3 supplementation for 12 weeks among women with EH had beneficial effects on glucose metabolism, serum hs-CRP, and plasma TAC concentrations. In addition, vitamin D may have played an indirect role in reducing complications of EH due to its effect on improved glycemic control, hs-CRP, and TAC concentrations.

Artificial Endometrial Preparation for Frozen-Thawed Embryo Transfer with or without Pretreatment with Depot Gonadotropin Releasing Hormone Agonist in Women with Regular Menses.

OBJECTIVE: To investigate the reproductive outcome of artificial endometrial preparation with exogenous steroids for frozen-thawed embryo transfer with and without pre-treatment with depot gonadotropin releasing hormone agonist (GnRH-a) in women with regular menses. MATERIALS AND METHODS: This is a prospective randomized clinical trial conducted in two ART centers on 176 women undergoing frozen-thawed embryo transfer. All patients received oral estradiol valerate 4 mg daily from day 2 to day 5 and 6 mg per day from day 6 to the day of the pregnancy test. In day 13 of cycle, an ultrasound examination was performed. After ultrasound confirmation of endometrial thickness (≥8 mm) and no ovarian activity, progesterone in cyclogest supp (800 mg daily) was added. The dose of estradiol would be increased to 8 mg per day if the endometrial thickness was less than 8mm. Two or 3 embryos were transferred via transcervical route 48 hours after the beginning of progesterone administration. In group A (93 patients), Difereline (3.75 mg Im), as a depot GnRH agonist was administered in the midluteal phase (day 21) of previous cycle. In the other group B (n = 83) steroid supplementation was commenced without prior pituitary suppression. Chemical and clinical pregnancy rates were compared in two groups. RESULTS: No significant differences were seen between two groups in terms of chemical pregnancy and clinical pregnancy rates. CONCLUSION: The findings support the artificial protocol without any pretreatment suppressive drugs to reduce the adverse side effects of GnRH agonists also to minimize the costs.