Effects of Selenium Supplementation on the Indices of Disease Activity, Inflammation and Oxidative Stress in Patients with Rheumatoid Arthritis: a Randomized Clinical Trial.

The aim of study was to evaluate the effect of selenium supplementation on disease activity, inflammation, and oxidative stress in patients with rheumatoid arthritis (RA). This study was a randomized double-blind placebo-controlled trial on 59 patients with RA. Participants were randomly divided to receive 200 µg/day of selenium or a placebo for 12 weeks. The disease activity score (DAS.CRP and DAS.ESR), erythrocyte sedimentation rate (ESR), serum levels of C-reactive protein (CRP), fasting blood glucose, lipids, antibodies to cyclic citrullinated protein (anti-CCP), nitric oxide, glutathione, and total antioxidant capacity were assessed. The mean of DAS.CRP and DAS.ESR decreased significantly within both study groups after the intervention. However, the between-group comparisons revealed no significant differences. The CRP levels decreased significantly in the selenium group, and this decrease was near the significance level compared to the placebo (P = 0.05). However, after adjusting for baseline values, the observed difference between groups did not remain significant. In addition, the values of ESR and anti-CCP decreased significantly within the selenium group. Although, between-group comparison did not statistically significant, the change in ESR and anti-CCP in the selenium group was small clinically relevant compared to the placebo [the effect size (95% CI) for ESR: 0.38 (- 0.14, 0.89), and for anti-CCP: 0.32 (- 0.2, 0.83)]. Our study showed that selenium caused a small clinically relevant improvement in some RA biomarkers such as ESR and anti-CCP. Future studies that evaluate the effects of novel forms of supplements such as selenium nanoparticles on the clinical symptoms and biomarkers of RA are suggested. Trial Registration: At www.irct.ir as IRCT20190924044869N1 on 2020-06-14.

The effect of yoga therapy directed by virtual training on depression of adolescent girls with type 1 diabetes: a randomized controlled trial.

Background: Recently, the depression-alleviating impact of yoga therapy was documented among patients with type 2 diabetes; nonetheless, whether this consequence is similar in individuals with type 1 diabetes (T1D) is still unclear. Therefore, this trial sought to investigate the potential impact of yoga therapy on the depression of adolescents with T1D. Methods: This randomized controlled trial recruited 62 girls with T1D, aged 12-17 years, from January to June 2020. The participants were randomly allocated to equal experimental and control arms (31 per group) through a block randomization approach. The routine care was implemented in two study arms, while the experimental arm additionally received yoga therapy directed by virtual training for eight consecutive weeks (one session per week). Maria Kovacs Children's Depression Inventory was completed at baseline and the end of the 8-week intervention. Results: The mean of the depression total score was significantly lower in the experimental arm in comparison with the control arm at the trial end (9.38 ± 8.44 vs. 12.77 ± 6.96, p = 0.014). Also, the reduction in mean change from the baseline to the trial end was significantly more in the experimental arm (- 5.25 ± 1.13 vs. - 0.80 ± 1.00, p = 0.013). Conclusions: The administration of yoga therapy directed by virtual training seems to be potentially effective in reducing depression among adolescent girls with T1D. However, further long-term trials with a larger sample size are needed to shed light on the obtained findings and address the intervention's efficacy on glycemic outcomes. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-023-01245-x.

Effects of Folic Acid Supplementation on Liver Enzymes, Lipid Profile, and Insulin Resistance in Patients with Non-Alcoholic Fatty Liver Disease: A Randomized Controlled Trial.

Background: Previous evidence revealed an association between folate deficiency and non-alcoholic fatty liver disease (NAFLD). This study is the first one investigating the effects of folic acid on hepatic steatosis grade, liver enzymes, insulin resistance, and lipid profile in NAFLD cases. Materials and Methods: Sixty-six participants with NAFLD were allocated randomly to take either a placebo or one oral tablet of folic acid (1 mg) on a daily basis within eight weeks. Serum folate, homocysteine, glucose, aminotransferases, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), and lipids were assessed. Ultrasonography was used for assessing the liver steatosis grade. Results: The serum alanine transaminase, grade of hepatic steatosis, and aspartate transaminase significantly were decreased within both study groups; however, the between-group comparison was not statistically significant. Of note, the decrease in ALT was more pronounced in folic acid compared with the placebo group (-5.45 ± 7.45 vs. -2.19 ± 8.6 IU/L). The serum homocysteine was decreased after receiving folic acid compared to the placebo (-0.58 ± 3.41 vs. +0.4 ± 3.56 µmol/L; adjusted P = 0.054). Other outcomes did not significantly change. Conclusion: Supplementation with folic acid (1 mg/d) for eight weeks among cases with NAFLD did not change significantly the serum levels of liver enzymes, the hepatic steatosis grade, insulin resistance and lipid profile. However, it was able to prevent the increase in homocysteine in comparison with the placebo. Conducting further research is suggested with the longer duration and different doses of folic acid, adjusted to the genotypes of methylenetetrahydrofolate reductase polymorphism, among NAFLD patients.

The effects of vitamin B12 supplementation on metabolic profile of patients with non-alcoholic fatty liver disease: a randomized controlled trial.

The present study is the first effort to evaluate the effects of vitamin B12 supplementation on the serum level of liver enzymes, homocysteine, grade of hepatic steatosis, and metabolic profiles in patients with non-alcoholic fatty liver disease (NAFLD). Forty patients with NAFLD were enrolled in a double-blind placebo-controlled trial to receive either one oral tablet of vitamin B12 (1000 µg cyanocobalamin) or a placebo per day for 12 weeks. We investigated serum levels of homocysteine, aminotransferases, fasting blood glucose (FBG), lipids, malondialdehyde (MDA), and homeostasis model assessment of insulin resistance (HOMA-IR). The grade of liver steatosis and fibrosis was measured by real-time 2-dimensional shear wave elastography. Vitamin B12 supplementation significantly decreased serum levels of homocysteine compared to placebo (medians: - 2.1 vs. - 0.003 µmol/l; P = 0.038). Although serum alanine transaminase (ALT) in the vitamin B12 group decreased significantly, this change did not reach a significant level compared to the placebo group (medians: - 7.0 vs. 0.0 IU/l; P > 0.05). Despite the significant within-group decrease in FBG, MDA, and liver steatosis in the vitamin B12 group, between-group comparisons did not reveal any significant difference. Vitamin B12 supplementation might decrease serum levels of homocysteine in patients with NAFLD. The fasting blood glucose and serum levels of MDA were significantly improved in the trial group who received vitamin B12. However, these changes did not reach a significant level compared to the placebo group. In this respect, further studies with larger sample sizes, different doses, and types of vitamin B12 will reveal additional evidence.Trial Registration: At  http://irct.ir/  as IRCT20120718010333N5 on December 25, 2019.

The Effect of Dietary Phosphorus Restriction on Urine Protein Excretion in Patients With Proteinuria: A Randomized Controlled Trial.

OBJECTIVES: The present study was designed to determine the effect of dietary phosphorus restriction, independent of protein intake, on the urinary protein excretion in patients with proteinuria. METHODS: Seventy-one patients with proteinuria were enrolled in a parallel randomized controlled trial study. The patients were randomly allocated to receive either a recommended phosphorus-restricted diet (n = 36) or a recommended control diet (n = 35), for 8 weeks. A diet was designed and recommended to participants in a way that both trial groups would receive the same amount of energy and protein and the only significant difference between them was the amount of phosphorus intake. The study outcomes included the changes in spot urine protein-to-creatinine ratio, the changes in serum and urine levels of phosphorus, as well as the changes in estimated glomerular filtration rate (eGFR). RESULTS: The mean ± standard deviation of age, body mass index, and eGFR of the participants were 59 ± 14 years, 29 ± 5.5 kg/m2, and 56.1 ± 21.7 mL/min/1.73 m2, respectively. The amount of phosphorus intake decreased significantly in the phosphorus-restricted group compared to the control one (-709 vs. -369 mg/day; P < .001). This decrease is accompanied by a significant reduction in urine protein-to-creatinine ratio in the phosphorus-restricted group; however, this change did not reach a significant level when compared to the control one (the mean change: -75.78 vs. -55.25 mg/g; P = .539). Limiting the phosphorus intake did not change its serum and urine values as well as eGFR at the end of the trial. CONCLUSIONS: Although adherence to a phosphorus-restricted diet by patients with proteinuria led to a significant decrease in urinary protein excretion, this change was not significantly different from that of the control diet. Further studies with larger sample sizes and different designs will reveal more evidence for a link between phosphorus intake and proteinuria.

Anti-cancer effects of cinnamon: Insights into its apoptosis effects.

Cancer is known as a leading cause of death worldwide. In the last two decades, the incidence of cancer has been dramatically increased mostly due to lifestyle changes. The importance of this issue has attracted further attention to discover novel therapies to prevent and treat cancers. According to previous studies, drugs used to treat cancer have shown significant limitations. Therefore, the role of herbal medicines alone or in combination with chemotherapy drugs has been extensively studied in cancer treatment. Cinnamon is a natural component showing a wide range of pharmacological functions including anti-oxidant, anti-microbial and anti-cancer activities. Impaired apoptosis plays critical roles in the initiation and progression of cancer. Increasing evidence indicates that cinnamon, as a therapeutic agent, has anti-cancer effects via affecting numerous apoptosis-related pathways in cancer cells. Here, we highlighted anticancer properties of cinnamon, particularly through targeting apoptosis-related mechanisms.

A comparison between the effects of flaxseed oil and fish oil supplementation on cardiovascular health in type 2 diabetic patients with coronary heart disease: A randomized, double-blinded, placebo-controlled trial.

This study compared the effects of flaxseed and fish oil supplementation on cardiovascular risk parameters in diabetic patients with coronary heart disease. Participants were randomly allocated into three intervention groups to receive either 1,000 mg of omega-3 fatty acids from fish oil or 1,000 mg of omega-3 fatty acids from flaxseed oil or placebo (n = 30 each group) twice a day for 12 weeks. A significant reduction in insulin levels (.04) was observed following flaxseed oil and fish oil supplementation compared with the placebo. In addition, a significant reduction in high-sensitivity C-reactive protein (.02) was seen after flaxseed oil supplementation compared with the placebo and a significant increase in total nitrite (.001) was seen after flaxseed oil and fish oil intake compared with placebo. Additionally, a significant increase in total antioxidant capacity (p < .001) after consuming flaxseed oil and fish oil compared with placebo and glutathione levels (.001) after consuming fish oil compared with flaxseed oil and placebo was observed. Overall, our study revealed the beneficial effects of flaxseed oil and fish oil supplementation on few metabolic profiles. This study suggests that the effect of flaxseed oil in reducing insulin and increasing total nitrite and total antioxidant capacity is similar to fish oil.

Vitamin D supplementation and non-alcoholic fatty liver disease: A critical and systematic review of clinical trials.

Previous observational studies have found a relationship between vitamin D deficiency and non-alcoholic fatty liver disease (NAFLD). However, this type of study could not show the causal relationship between these two conditions. Therefore, we systematically and critically reviewed the available clinical trials to elucidate such relationship. We searched databases such as Medline, Scopus and Cochrane to identify the clinical trials that assessed the effects of vitamin D supplementation in adults with NAFLD. The outcome variables of interest were indicators of hepatic steatosis, liver enzymes, insulin resistance, inflammation and oxidative stress. A total of 6 studies were included in the qualitative analysis. Only in two studies the grade of hepatic steatosis decreased significantly after vitamin D supplementation. The changes in insulin resistance parameters were reported significant only in one. Of the 3 included studies that measured biomarkers of inflammation and oxidative stress, one revealed a significant decrease in these biomarkers after vitamin D supplementation. Findings from current review study provided new insight into the factors that could affect the therapeutic role of vitamin D in NAFLD. Factors such as gender differences, baseline serum status of vitamin D, co-supplementation with calcium and gene polymorphism should be considered when designing future clinical trials.

The effects of vitamin E supplementation on endometrial thickness, and gene expression of vascular endothelial growth factor and inflammatory cytokines among women with implantation failure.

OBJECTIVE: Data on the effects of vitamin E supplementation on endometrial thickness, and gene expression of vascular endothelial growth factor (VEGF) and inflammatory cytokines among women with implantation failure are limited. This research was performed to determine the effects of vitamin E supplementation on endometrial thickness, and gene expression of VEGF and inflammatory cytokines among women with implantation failure. METHODS: A randomized clinical trial was done among 40 women with implantation failure aged 18-37 years old. Participants were randomly divided into two groups: group A (n = 20) received 400-IU vitamin E supplements and group B (n = 20) received placebo for 12 weeks. Fasting blood samples were taken at baseline and after the 12-week treatment to determine biomarkers of oxidative stress, and gene expression of VEGF and inflammatory cytokines. RESULTS: After the 12-week intervention, compared with the placebo, women with implantation failure who consumed vitamin E supplements had significantly increased serum vitamin E levels (+18.6 ± 15.0 versus -1.5 ± 1.0 nmol/mL, p < .001) and endometrial thickness (+1.1 ± 0.9 versus -0.5 ± 0.3 mm, p = .01), and significantly decreased plasma malondialdehyde (MDA) concentrations (-0.4 ± 0.3 versus +0.4 ± 0.3 µmol/L, p < .004). In addition, results of RT-PCR demonstrated that compared with the placebo, vitamin E intake downregulated gene expression of low-density lipoprotein receptor (LDLR) (p = .008), interleukin-1 (IL-1) (p = .02), and tumor necrosis factor alpha (TNF-α) (p = .007) in peripheral blood mononuclear cells of women with implantation failure. CONCLUSIONS: Overall, vitamin E supplementation for 12 weeks among women with implantation failure had beneficial effects on endometrial thickness, MDA values, and gene expression of LDLR, IL-1, and TNF-α.

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.

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

INTRODUCTION: Although several trials have assessed the effect of coenzyme Q10 (CoQ10) supplementation on blood pressures among patients with metabolic diseases, findings are controversial. AIM: This review of randomized controlled trials (RCTs) was performed to summarize the evidence on the effects of CoQ10 supplementation on blood pressures among patients with metabolic diseases. METHODS: Randomized-controlled trials (RCTs) published in PubMed, EMBASE, Web of Science and Cochrane Library databases up to 10 August 2017 were searched. Two review authors independently assessed study eligibility, extracted data, and evaluated risk of bias of included studies. Heterogeneity was measured with a Q-test and with I2 statistics. Data were pooled by using the fix or random-effect model based on the heterogeneity test results and expressed as standardized mean difference (SMD) with 95% confidence interval (CI). RESULTS: A total of seventeen randomized controlled trials (684 participants) were included. Results showed that CoQ10 supplementation significantly decreased systolic blood pressure (SBP) (SMD - 0.30; 95% CI - 0.52, - 0.08). However, CoQ10 supplementation decreased diastolic blood pressure (DBP), but this was not statistically significant (SMD - 0.08; 95% CI - 0.46, 0.29). CONCLUSIONS: CoQ10 supplementation may result in reduction in SBP levels, but did not affect DBP levels among patients with metabolic diseases. Additional prospective studies regarding the effect of CoQ10 supplementation on blood pressure in patients with metabolic diseases are necessary.

The effects of folate supplementation on lipid profiles among patients with metabolic diseases: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND OBJECTIVE: Although several studies have assessed the effect of folate supplementation on lipid profiles among patients with metabolic diseases, findings are inconsistent. This review of randomized controlled trials (RCTs) was conducted to summarize the evidence on the effects of folate supplementation on lipid profiles among patients with metabolic diseases. METHODS: Randomized-controlled trials (RCTs) published in PubMed, EMBASE, Web of Science and Cochrane Library databases up to until 20 August 2017 were searched. Two review authors independently assessed study eligibility, extracted data, and evaluated risk of bias of included studies. Heterogeneity was measured with a Q-test and with I2 statistics. Data were pooled by using the fix or random-effect model based on the heterogeneity test results and expressed as standardized mean difference (SMD) with 95% confidence interval (CI). RESULTS: A total of thirteen randomized controlled trials were included. Folate supplementation did not affect systolic blood pressure (SMD -0.87; 95% CI, -1.83, 0.09) and diastolic blood pressure (SMD -0.59; 95% CI, -1.55, 0.37), and lipid profiles including triglycerides (SMD 0.10; 95% CI, -0.42, 0.63), total- (SMD 0.06; 95% CI, -0.31, 0.43), HDL- (SMD 0.04; 95% CI, -0.36, 0.44), VLDL- (SMD 0.08; 95% CI, -0.24, 0.41), and LDL-cholesterol (SMD -0.14; 95% CI, -0.55, 0.28). CONCLUSIONS: Folate supplementation did not affect blood pressures and lipid profiles among patients with metabolic diseases. Additional prospective studies regarding the impact of folate supplementation on blood pressures and lipid profiles in patients with metabolic diseases are necessary.

The Effects of Coenzyme Q10 Supplementation on Glucose Metabolism, Lipid Profiles, Inflammation, and Oxidative Stress in Patients With Diabetic Nephropathy: A Randomized, Double-Blind, Placebo-Controlled Trial.

OBJECTIVE: Data on the effects of coenzyme Q10 (CoQ10) supplementation on glucose metabolism, lipid profiles, inflammation, and oxidative stress in subjects with diabetic nephropathy (DN) are scarce. This research was done to determine the effects of CoQ10 supplementation on metabolic status in subjects with DN. METHODS: This randomized double-blind placebo-controlled clinical trial was done in 50 subjects with DN. Participants were randomly assigned into two groups to intake either 100 mg/day CoQ10 supplements (n = 25) or placebo (n = 25) for 12 weeks. Fasting blood samples were obtained at first and after 12-week intervention to quantify metabolic profiles. RESULTS: After 12 weeks of treatment, compared with the placebo, CoQ10 supplementation resulted in significant decreases in serum insulin levels (-3.4 ± 6.8 vs +0.8 ± 6.4 µIU/mL, p = 0.02), homeostasis model of assessment-estimated insulin resistance (-1.0 ± 2.0 vs +0.2 ± 1.8, p = 0.03), homeostasis model of assessment-estimated B cell function (-12.3 ± 26.3 vs +3.5 ± 23.1, p = 0.02) and HbA1c (-1.1 ± 1.0 vs -0.1 ± 0.2%, p < 0.001), and a significant improvement in quantitative insulin sensitivity check index (+0.009 ± 0.01 vs -0.006 ± 0.01, p = 0.01). In addition, CoQ10 supplementation significantly decreased plasma malondialdehyde (MDA) (-0.6 ± 0.5 vs +0.5 ± 1.0 µmol/L, p < 0.001) and advanced glycation end products levels (AGEs) (-316.4 ± 380.9 vs +318.6 ± 732.0 AU, p < 0.001) compared with the placebo. Supplementation with CoQ10had no significant impacts on fasting plasma glucose (FPG), lipid profiles, and matrix metalloproteinase-2 (MMP-2) compared with the placebo. CONCLUSIONS: Taken together, our study demonstrated that CoQ10 supplementation for 12 weeks among DN patients had favorable effects on glucose metabolism, MDA, and AGEs levels, but unchanged FPG, lipid profiles, and MMP-2 concentrations.

Metabolic Response to Mulberry Extract Supplementation in Patients With Diabetic Nephropathy: a Randomized Controlled Trial.

INTRODUCTION: This study aimed to evaluate the effects of mulberry extract administration on markers of insulin metabolism, lipid concentrations, and biomarkers of inflammation and oxidative stress in patients with diabetic nephropathy (DN). MATERIALS AND METHODS: Sixty patients were randomly allocated into 2 groups to receive either 300 mg/d of mulberry extract (n = 30) or placebo (n = 30), twice per day for 12 weeks. Fasting blood samples were taken at the onset of the study and 12 weeks after supplementation to examine markers of insulin metabolism, lipid concentrations, and biomarkers of inflammation and oxidative stress. RESULTS: Mulberry extract, compared to placebo, resulted in significant reductions in serum triglycerides (-37.3 ± 64.7 mg/dL versus 3.0 ± 78.8 mg/dL, P = .03) and very low-density lipoprotein cholesterol (-7.4 ± 12.9 mg/dL versus 0.6 ± 15.8 mg/dL, P = .03), and a significant increase in high-density lipoprotein cholesterol concentration (0.5 ± 4.0 mg/dL versus -2.0 ± 5.0 mg/dL, P = .03). Other significant changes were in serum high-sensitivity C-reaction protein (-2.3 ± 4.5 µg/mL versus -0.1 ± 2.2 µg/mL, P = .02), plasma glutathione (87.8 ± 159.7 µmol/L versus -24.2 ± 138.8 µmol/L, P = .005) and malondialdehyde (-0.03 ± 0.5 µmol/L versus 0.7 ± 1.0 µmol/L, P < .001).   Conclusions. These findings showed that mulberry extract administration had favorable effects on serum lipids, HSCRP, glutathione, and malondialdehyde levels in DN patients; however, it did not affect markers of insulin metabolism or biomarkers of inflammation and oxidative stress.

Sub-chronic oral toxicity of Cuminum cyminum L.'s essential oil in female Wistar rats.

The current study was performed to evaluate the toxicity of Cuminum cyminum L. (C. cyminum)'s essential oil after 23 days and 45 days of repeated oral administration in female Wistar rats. A total of 80 healthy female Wistar rats were randomly selected and divided into 4 groups. The rats were gavaged with C. cyminum's essential oil at dose levels of 0, 250, 500 and 1000 mg/kg/day. Clinical signs, body weight, hematology, serum biochemistry and organ histopathology were assessed once after 23 days and again after 45 days passed from the start of the intervention. Oral administration of C. cyminum's essential oil had no observed adverse effects on clinical signs, mortality, body weight, hematology, biochemistry and organ histology (liver, kidneys, spleen and lungs) in a sample of healthy female Wistar rats after 23 days and 45 days from the start of the study. However, an increase in serum levels of alanine transaminase (ALT) was found only at dose level of 1000 mg/kg/d C. cyminum's essential oil, after the 23-days interval. We conservatively defined the non-observed adverse effect level (NOAEL) for C. cyminum's essential oil as 500 mg/kg/d in female Wistar rats. The present study results should be treated with cautious in terms of the other organs' toxicity.

Clinical and Metabolic Response to Selenium Supplementation in Pregnant Women at Risk for Intrauterine Growth Restriction: Randomized, Double-Blind, Placebo-Controlled Trial.

Data on the effects of selenium supplementation on clinical signs and metabolic profiles in women at risk for intrauterine growth restriction (IUGR) are scarce. This study was designed to assess the effects of selenium supplementation on clinical signs and metabolic status in pregnant women at risk for IUGR. This randomized double-blind placebo-controlled clinical trial was performed among 60 women at risk for IUGR according to abnormal uterine artery Doppler waveform. Participants were randomly assigned to intake either 100 µg selenium supplements as tablet (n = 30) or placebo (n = 30) for 10 weeks between 17 and 27 weeks of gestation. After 10 weeks of selenium administration, a higher percentage of women in the selenium group had pulsatility index (PI) of <1.45) (P = 0.002) than of those in the placebo group. In addition, changes in plasma levels of total antioxidant capacity (TAC) (P < 0.001), glutathione (GSH) (P = 0.008), and high-sensitivity C-reactive protein (hs-CRP) (P = 0.004) in the selenium group were significant compared with the placebo group. Additionally, selenium supplementation significantly decreased serum insulin (P = 0.02), homeostasis model of assessment-estimated insulin resistance (HOMA-IR) (P = 0.02), and homeostatic model assessment for B-cell function (HOMA-B) (P = 0.02) and significantly increased quantitative insulin sensitivity check index (QUICKI) (P = 0.04) and HDL-C levels (P = 0.02) compared with the placebo. We did not find any significant effect of selenium administration on malondialdehyde (MDA), nitric oxide (NO), fasting plasma glucose (FPG), and other lipid profiles. Overall, selenium supplementation in pregnant women at risk for IUGR resulted in improved PI, TAC, GSH, hs-CRP, and markers of insulin metabolism and HDL-C levels, but it did not affect MDA, NO, FPG, and other lipid profiles.Clinical trial registration number http://www.irct.ir : IRCT201601045623N64.

The effects of high-dose vitamin E supplementation on biomarkers of kidney injury, inflammation, and oxidative stress in patients with diabetic nephropathy: A randomized, double-blind, placebo-controlled trial.

BACKGROUND: Limited data are available that evaluated the effects of high-dose vitamin E supplementation on biomarkers of kidney injury, inflammation, and oxidative stress in patients with diabetic nephropathy (DN). OBJECTIVE: This study was conducted to evaluate the effects of high-dose vitamin E supplementation on biomarkers of kidney injury, inflammation, and oxidative stress in patients with DN. METHODS: This randomized double-blind placebo-controlled clinical trial was carried out among 60 patients with DN. Patients were randomly allocated into two groups to take either 1200 IU/d of vitamin E supplements (n = 30) or placebo (n = 30) for 12 weeks. Fasting blood samples were obtained at the onset of the study and after 12-week intervention to assess biomarkers of kidney injury, inflammation, and oxidative stress. RESULTS: After 12 weeks of intervention, compared with the placebo, vitamin E supplementation resulted in a significant increase in serum vitamin E levels (+42.3 ± 13.4 vs -0.8 ± 0.8 nmol/mL, P < .001) and a significant decrease in urine protein (-6.8 ± 4.3 vs -1.0 ± 8.0 mg/dL, P = .001) and protein-to-creatinine ratio (-0.2 ± 0.1 vs 0.0 ± 0.1, P < .001). In addition, a significant reduction in serum tumor necrosis factor-α (-35.4 ± 34.9 vs +5.6 ± 6.2 ng/L, P < .001), matrix metalloproteinase-2 (-556.7 ± 485.9 vs +60.4 ± 53.7 ng/mL, P < .001), matrix metalloproteinase-9 (-1461.5 ± 1456.0 vs +225.7 ± 488.2 ng/L, P < .001), malondialdehyde (-0.9 ± 0.5 vs +0.3 ± 0.4 µmol/L, P < .001), advanced glycation end products (-1832.2 ± 1941.6 vs +177.3 ± 324.1 arbitrary unit, P < .001), and insulin concentrations (-0.5 ± 2.7 vs +0.7 ± 1.0 µIU/mL, P = .03) was seen after the administration of vitamin E supplements compared with the placebo. Supplementation with vitamin E had no significant effects on other biomarkers of kidney injury, fasting plasma glucose, and insulin resistance compared with the placebo. CONCLUSION: Overall, our study demonstrated that oral high-dose vitamin E supplementation for 12 weeks among DN patients had favorable effects on biomarkers of kidney injury, inflammation, and oxidative stress.

Vitamin D and Evening Primrose Oil Administration Improve Glycemia and Lipid Profiles in Women with Gestational Diabetes.

UNLABELLED: Limited data are available assessing the effects of vitamin D and evening primrose oil (EPO) administration on markers of insulin resistance and lipid concentrations in gestational diabetes mellitus (GDM). This study was designed to evaluate the effects of vitamin D and EPO administration on insulin resistance and lipid concentrations among women with GDM. In this prospective randomized, double-blind, placebo-controlled clinical trial, 60 participants with GDM were divided into 2 groups of either 1000 IU vitamin D3 and 1000 mg EPO or placebo for 6 weeks. At the beginning and end of the study, fasting blood samples were obtained from the participants to measure related variables. After 6 weeks of intervention, changes in fasting plasma glucose (-3.6 ± 7.5 vs. +1.5 ± 11.4 mg/dL, P = 0.04), serum insulin concentrations (-2.0 ± 5.3 vs. +4.6 ± 10.7 µIU/mL, P = 0.004), homeostasis model of assessment (HOMA) insulin resistance (-0.5 ± 1.1 vs. +1.1 ± 2.5, P = 0.003), HOMA-B cell function (-7.7 ± 23.3 vs. +17.4 ± 42.9, P = 0.007) and the quantitative insulin sensitivity check index (+0.01 ± 0.02 vs. -0.01 ± 0.02, P = 0.007) in the vitamin D plus EPO group were significantly different from the placebo group. In addition, compared with the placebo, vitamin D and EPO supplementation resulted in significant reductions in serum TAG (-20.0 ± 54.3 vs. +34.3 ± 38.2 mg/dL, P < 0.001), VLDL (-4.0 ± 10.9 vs. +6.9 ± 7.6 mg/dL, P < 0.001), TC (-22.1 ± 32.6 vs. +5.3 ± 20.1 mg/dL, P < 0.001), LDL concentrations (-18.0 ± 25.5 vs. +1.8 ± 15.7 mg/dL, P = 0.001) and TC/HDL (-0.3 ± 0.4 vs. +0.3 ± 0.5 mg/dL, P < 0.001). We did not observe any significant effect of vitamin D and EPO supplementation on serum HDL concentrations. CLINICAL TRIAL REGISTRATION NUMBER: http://www.irct.ir : IRCT201509115623N52.

Women may respond different from men to vitamin D supplementation regarding cardiometabolic biomarkers.

Evidence has revealed that vitamin D status is associated with the cardiometabolic risk factors. Moreover, few gender-specific analyses have been performed in the clinical trials regarding vitamin D supplementation. As a result, assessing gender differences regarding the effects of vitamin D supplementation on some cardiometabolic biomarkers in patients with non-alcoholic fatty liver disease (NAFLD) was the aim of present study. We conducted a post hoc subgroup analysis of a double blind placebo controlled study. Patients with NAFLD randomly allocated to receive one oral pearl consisting of 50,000 IU vitamin D3 (n = 27, 13 men and 14 women) or a placebo (n = 26, 13 men and 13 women) every 14 days for four months. Serum lipid profiles, aminotransferases, high-sensitive C-reactive protein (hs-CRP), adiponectin as well as insulin resistance and dietary intakes were assessed pre- and post-study. In both genders, serum 25(OH) D3 increased significantly (P < 0.001). This increase was accompanied by significant decrease in serum total cholesterol (TC) (% of change: -7% in vitamin D vs. + 0.4% in placebo, P = 0.04) and LDL-C (%of change: -9.6% in vitamin D vs. -4% in placebo, P = 0.006) in women. However, in men, vitamin D supplementation increased the levels of serum TC (% of change: +9.2% in vitamin D vs. -10% in placebo, P = 0.02) with no significant effects on LDL-C. Moreover, vitamin D significantly reduced serum hs-CRP in women. The median daily calcium intake in both genders was well below the dietary reference intake for adults. In conclusion, improved vitamin D status might decrease serum TC and LDL-C levels as well as hs-CRP in women with NAFLD. However, it might increase serum TC in men who have low daily calcium intake. Further studies with larger sample sizes are needed to confirm these results.

Does vitamin D improve liver enzymes, oxidative stress, and inflammatory biomarkers in adults with non-alcoholic fatty liver disease? A randomized clinical trial.

The aim of this study was to investigate the effects of vitamin D supplementation on serum aminotransferases, insulin resistance, oxidative stress, and inflammatory biomarkers in adult patients with non-alcoholic fatty liver disease (NAFLD). Fifty-three patients with NAFLD were enrolled in a parallel, double-blind, placebo-controlled study. The patients were randomly allocated to receive either one oral pearl consisting of 50,000 IU vitamin D3 (n = 27) or a placebo (n = 26), every 14 days for 4 months. Serum aminotransferases, high-sensitive C-reactive protein (hs-CRP), tumor necrosis factor α, malondialdehyde (MDA), total antioxidant capacity, transforming growth factor ß1, as well as grade of hepatic steatosis and homeostasis model assessment of insulin resistance were assessed pre- and post-intervention. In patients who received vitamin D supplement compared to the controls, the median of serum 25(OH)D3 significantly increased (16.2 vs. 1.6 ng/ml, P < 0.001). This increase accompanied by significant decrease in serum MDA (-2.09 vs. -1.23 ng/ml, P = 0.03) and near significant changes in serum hs-CRP (-0.25 vs. 0.22 mg/l, P = 0.06). These between-group differences remained significant even after controlling for baseline covariates. Other variables showed no significant changes. Improved vitamin D status led to amelioration in serum hs-CRP and MDA in patients with NAFLD. This might be considered as an adjunctive therapy to attenuate systemic inflammation and lipid peroxidation alongside other treatments for NAFLD patients.