The effects of combined magnesium and zinc supplementation on metabolic status in patients with type 2 diabetes mellitus and coronary heart disease.

BACKGROUND: The present research aimed to analyze the impacts of magnesium and zinc supplements on glycemic control, serum lipids, and biomarkers of oxidative stress and inflammation in patients suffering from coronary heart disease (CHD) and type 2 diabetes mellitus (T2DM). METHODS: According to the research design, a randomized, double-blind, placebo-controlled trial has been implemented on 60 subjects suffering from CHD and T2DM. Therefore, participants have been randomly divided into 2 groups for taking placebo (n = 30) or 250 mg magnesium oxide plus 150 mg zinc sulfate (n = 30) for 12 weeks. RESULTS: Magnesium and zinc significantly decreased fasting plasma glucose (FPG) (ß - 9.44 mg/dL, 95% CI, - 18.30, - 0.57; P = 0.03) and insulin levels (ß - 1.37 µIU/mL, 95% CI, - 2.57, - 0.18; P = 0.02). Moreover, HDL-cholesterol levels significantly enhanced (ß 2.09 mg/dL, 95% CI, 0.05, 4.13; P = 0.04) in comparison to the placebo. There was an association between magnesium and zinc intake, and a significant decrease of C-reactive protein (CRP) (ß - 0.85 mg/L, 95% CI, - 1.26, - 0.45; P < 0.001), a significant increase in total nitrite (ß 5.13 µmol/L, 95% CI, 1.85, 8.41; P = 0.003) and total antioxidant capacity (TAC) (ß 43.44 mmol/L, 95% CI, 3.39, 83.50; P = 0.03) when compared with placebo. Furthermore, magnesium and zinc significantly reduced the Beck Depression Inventory index (BDI) (ß - 1.66; 95% CI, - 3.32, - 0.009; P = 0.04) and Beck Anxiety Inventory (BAI) (ß - 1.30; 95% CI, - 2.43, - 0.16; P = 0.02) when compared with the placebo. CONCLUSIONS: In patients with T2DM and CHD, the 12-week intake of magnesium plus zinc had beneficial effects on FPG, HDL-cholesterol, CRP, insulin, total nitrite, TAC levels, and BDI and BAI score. This suggests that magnesium and zinc co-supplementation may be beneficial for patients with T2DM and CHD. Further studies on more patients and lasting longer are needed to determine the safety of magnesium and zinc co-supplementation. TRIAL REGISTRATION: Current Controlled Trials http://www.irct.ir: IRCT20130211012438N31 at 11 May 2019 of registration. This study retrospectively registered.

The Effects of Melatonin Supplementation on Parameters of Mental Health, Glycemic Control, Markers of Cardiometabolic Risk, and Oxidative Stress in Diabetic Hemodialysis Patients: A Randomized, Double-Blind, Placebo-Controlled Trial.

OBJECTIVE: This study evaluated the effects of melatonin supplementation on parameters of mental health, glycemic control, markers of cardiometabolic risk, and oxidative stress in diabetic hemodialysis (HD) patients. DESIGN: A randomized, double-blind, placebo-controlled clinical trial was conducted in 60 diabetic HD patients, 18-80 years of age. Participants were randomly divided into 2 groups to take either melatonin (2 x 5mg/day) (n = 30) or placebo (n = 30) 1 hour before bedtime for 12 weeks. The effects of melatonin on mental health, metabolic status, and gene expression related to metabolic status were assessed using multiple linear regression adjusting for age and BMI. RESULTS: Melatonin supplementation significantly decreased Pittsburgh Sleep Quality Index (P = .007), Beck Depression Inventory index (P = .001), and Beck Anxiety Inventory index (P = .01) compared with the placebo. Additionally, melatonin administration significantly reduced fasting plasma glucose (ß = -21.77 mg/dL, 95% CI -33.22 to -10.33, P < .001), serum insulin levels (ß = -1.89 µIU/mL, 95% CI -3.34 to -0.45, P = .01), and homeostasis model of assessment-insulin resistance (ß = -1.45, 95% CI -2.10 to -0.80, P < .001), and significantly increased the quantitative insulin sensitivity check index (ß = 0.01, 95% CI 0.007-0.02, P < .001) compared with placebo treated subjects. In addition, melatonin administration resulted in a significant reduction in serum high sensitivity C-reactive protein (ß = -1.92 mg/L, 95% CI -3.02 to -0.83, P = .001) and plasma malondialdehyde (ß = -0.21 µmol/L, 95% CI -0.36 to -0.06, P = .005); also, significant rises in plasma total antioxidant capacity (ß = 253.87 mmol/L, 95% CI 189.18-318.56, P < .001) and nitric oxide levels (ß = 2.99 µmol/L, 95% CI 0.71-5.28, P = .01) were observed compared with the placebo. CONCLUSION: Overall, melatonin supplementation for 12 weeks to diabetic HD patients had beneficial effects on mental health, glycemic control, inflammatory markers, and oxidative stress.

The effects of magnesium and vitamin E co-supplementation on wound healing and metabolic status in patients with diabetic foot ulcer: A randomized, double-blind, placebo-controlled trial.

This study was carried out to determine the effects of magnesium and vitamin E co-supplementation on wound healing and metabolic status in patients with diabetic foot ulcer (DFU). The current randomized, double-blind, placebo-controlled trial was conducted among 57 patients with grade 3 DFU. Participants were randomly divided into two groups to take either 250 mg magnesium oxide plus 400 IU vitamin E (n = 29) or placebo per day (n = 28) for 12 weeks. Compared with the placebo, taking magnesium plus vitamin E supplements reduced ulcer length (ß [difference in the mean of outcomes measures between treatment groups] -0.56 cm; 95% CI, -0.92, -0.20; p = 0.003), width (ß -0.35 cm; 95% CI, -0.64, -0.05; p = 0.02) and depth (ß -0.18 cm; 95% CI, -0.33, -0.02; p = 0.02). In addition, co-supplementation led to a significant reduction in fasting plasma glucose (ß -13.41 mg/dL; 95% CI, -20.96, -5.86; p = 0.001), insulin (ß -1.45 µIU/ml; 95% CI, -2.37, -0.52; p = 0.003), insulin resistance (ß -0.60; 95% CI, -0.99, -0.20; p = 0.003) and HbA1c (ß -0.32%; 95% CI, -0.48, -0.16; p < 0.003), and a significant elevation in insulin sensitivity (ß 0.007; 95% CI, 0.003, 0.01; p < 0.001) compared with the placebo. Additionally, compared with the placebo, taking magnesium plus vitamin E supplements decreased triglycerides (ß -10.08 mg/dL; 95% CI, -19.70, -0.46; p = 0.04), LDL-cholesterol (ß -5.88 mg/dL; 95% CI, -11.42, -0.34; p = 0.03), high sensitivity C-reactive protein (hs-CRP) (ß -3.42 mg/L; 95% CI, -4.44, -2.41; p < 0.001) and malondialdehyde (MDA) (ß -0.30 µmol/L; 95% CI, -0.45, -0.15; p < 0.001), and increased HDL-cholesterol (ß 2.62 mg/dL; 95% CI, 0.60, 4.63; p = 0.01) and total antioxidant capacity (TAC) levels (ß 53.61 mmol/L; 95% CI, 4.65, 102.57; p = 0.03). Overall, magnesium and vitamin E co-supplementation for 12 weeks to patients with DFU had beneficial effects on ulcer size, glycemic control, triglycerides, LDL- and HDL-cholesterol, hs-CRP, TAC, and MDA levels.

Effects of magnesium supplementation on carotid intima-media thickness and metabolic profiles in diabetic haemodialysis patients: a randomised, double-blind, placebo-controlled trial.

This study evaluated the effects of Mg administration on carotid intima-media thickness (CIMT), glycaemic control and markers of cardio-metabolic risk in diabetic haemodialysis (HD) patients. This randomised, double-blind, placebo-controlled clinical trial was conducted in fifty-four diabetic HD patients. Participants were randomly divided into two groups to take either 250 mg/d Mg as magnesium oxide (n 27) or placebo (n 27) for 24 weeks. Mg supplementation resulted in a significant reduction in mean (P<0·001) and maximum levels of left CIMT (P=0·02) and mean levels of right CIMT (P=0·004) compared with the placebo. In addition, taking Mg supplements significantly reduced serum insulin levels (ß=-9·42 pmol/l; 95% CI -14·94, -3·90; P=0·001), homoeostasis model of assessment-insulin resistance (ß=-0·56; 95 % CI -0·89, -0·24; P=0·001) and HbA1c (ß=-0·74 %; 95 % CI -1·10, -0·39; P<0·001) and significantly increased the quantitative insulin sensitivity check index (ß=0·008; 95 % CI 0·002, 0·01; P=0·002) compared with the placebo. In addition, Mg administration led to a significant reduction in serum total cholesterol (ß=-0·30 mmol/l; 95% CI -0·56, -0·04; P=0·02), LDL-cholesterol (ß=-0·29 mmol/l; 95% CI -0·52, -0·05; P=0·01), high-sensitivity C-reactive protein (hs-CRP) (P<0·001) and plasma malondialdehyde (MDA) (P=0·04) and a significant rise in plasma total antioxidant capacity (TAC) levels (P<0·001) compared with the placebo. Overall, we found that taking Mg for 24 weeks by diabetic HD patients significantly improved mean and maximum levels of left and mean levels of right CIMT, insulin metabolism, HbA1c, total cholesterol and LDL-cholesterol, hs-CRP, TAC and MDA levels.

Clinical and metabolic response to vitamin D plus probiotic in schizophrenia patients.

BACKGROUND: This study determined the effects of a novel combination of vitamin D and probiotic on metabolic and clinical symptoms in chronic schizophrenia. METHODS: This trial was conducted among 60 patients with chronic schizophrenia to receive either 50,000 IU vitamin D3 every 2 weeks plus 8 × 109 CFU/day probiotic (n = 30) or placebo (n = 30) for 12 weeks. RESULTS: Vitamin D and probiotic co-supplementation was associated with a significant improvement in the general (- 3.1 ± 4.7 vs. + 0.3 ± 3.9, P = 0.004) and total PANSS scores (- 7.4 ± 8.7 vs. -1.9 ± 7.5, P = 0.01). Vitamin D and probiotic co-supplementation also significantly increased total antioxidant capacity (+ 51.1 ± 129.7 vs. -20.7 ± 53.3 mmol/L, P = 0.007), and significantly decreased malondialdehyde (- 0.3 ± 0.9 vs. + 0.2 ± 0.4 µmol/L, P = 0.01) and high sensitivity C-reactive protein levels (- 2.3 ± 3.0 vs. -0.3 ± 0.8 mg/L, P = 0.001) compared with the placebo. Moreover, taking vitamin D plus probiotic significantly reduced fasting plasma glucose (- 7.0 ± 9.9 vs. -0.2 ± 9.9 mg/dL, P = 0.01), insulin concentrations (- 2.7 ± 2.3 vs. + 0.4 ± 2.0 µIU/mL, P < 0.001), homeostasis model of assessment-estimated insulin resistance (- 0.8 ± 0.7 vs. + 0.1 ± 0.7, P < 0.001), triglycerides (- 7.8 ± 25.2 vs. + 10.1 ± 30.8 mg/dL, P = 0.01) and total cholesterol levels (- 4.9 ± 15.0 vs. + 5.9 ± 19.5 mg/dL, P = 0.04) and total-/HDL-cholesterol ratio (- 0.1 ± 0.6 vs. + 0.3 ± 0.8, P = 0.04). CONCLUSION: Probiotic and vitamin D for 12 weeks to chronic schizophrenia had beneficial effects on the general and total PANSS score, and metabolic profiles. TRIAL REGISTRATION: This study was retrospectively registered in the Iranian website ( www.irct.ir ) for clinical trials registration ( http://www.irct.ir : IRCT2017072333551N2). 07-31-2017 2.

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 effects of melatonin supplementation on mental health, metabolic and genetic profiles in patients under methadone maintenance treatment.

This investigation was designed to determine the effect of melatonin supplementation on mental health parameters, metabolic and genetic profiles in patients under methadone maintenance treatment (MMT). This randomized, double-blind, placebo-controlled, clinical trial was conducted among 54 patients under MMT. Participants were randomly allocated to receive either 10 mg melatonin (2 melatonin capsules, 5 mg each) (n = 26) or placebo (n = 28) once a day, 1 hour before bedtime for 12 weeks. Melatonin supplementation significantly decreased Pittsburgh Sleep Quality Index (ß -4.08; 95 percent CI, -5.51, -2.65; P < 0.001), Beck Depression Inventory index (ß -5.46; 95% CI, -8.92, -2.00; P = 0.003) and Beck Anxiety Inventory index (ß -3.87; 95% CI, -5.96, -1.77; P = 0.001) and significantly increased International Index of Erectile Functions (ß 5.59; 95% CI, 1.76, 9.42; P = 0.005) compared with the placebo. Subjects who received melatonin supplements had significantly lower serum insulin levels (ß -2.53; 95% CI, -4.48, -0.59; P = 0.01), homeostasis model of assessment-insulin resistance (ß -0.56; 95% CI, -1.03, -0.09; P = 0.01) and higher quantitative insulin sensitivity check index (ß 0.01; 95% CI, 0.004, 0.02; P = 0.009) and HDL-cholesterol levels (ß 3.71; 95% CI, 1.77, 5.64; P = 0.002) compared to placebo. Additionally, melatonin intake resulted in a significant reduction in serum high sensitivity C-reactive protein (ß -0.15; 95% CI, -0.27, -0.02; P = 0.02), malondialdehyde (ß -0.31; 95% CI, -0.57, -0.05; P = 0.02) and protein carbonyl (ß -0.06; 95% CI, -0.09, -0.04; P < 0.001). This trial indicated that taking melatonin supplements for 12 weeks by patients under MMT had beneficial effects on their mental health metabolic profiles.

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.

The beneficial effects of probiotic administration on wound healing and metabolic status in patients with diabetic foot ulcer: A randomized, double-blind, placebo-controlled trial.

BACKGROUND: This study was conducted to evaluate the effects of probiotic supplementation on wound healing and metabolic status in subjects with diabetic foot ulcer (DFU). METHODS: This randomized, double-blind, placebo-controlled trial was conducted among 60 subjects (aged 40-85 years old) with grade 3 diabetic foot ulcer. Individuals were randomly divided into 2 groups (30 subjects each group) to receive either probiotic or placebo daily for 12 weeks. RESULTS: After the 12-week intervention, compared with the placebo, probiotic supplementation led to significant reductions in ulcer length (-1.3 ± 0.9 vs. -0.8 ± 0.7 cm, P = .01), width (-1.1 ± 0.7 vs. -0.7 ± 0.7 cm, P = .02), and depth (-0.5 ± 0.3 vs. -0.3 ± 0.3 cm, P = .02). Furthermore, significant reductions in fasting plasma glucose (-29.6 ± 30.3 vs. -5.8 ± 39.8 mg/dL, P = .01), serum insulin concentrations (-4.3 ± 7.9 vs. +0.4 ± 8.5 µIU/mL, P = .03), and haemoglobin A1c (-0.6 ± 0.5 vs. -0.2 ± 0.4%, P = .003) and a significant rise in the quantitative insulin sensitivity check index (+0.01 ± 0.01 vs. -0.01 ± 0.02, P = .003) were seen following supplementation of probiotic compared with the placebo. Additionally, compared with the placebo, probiotic supplementation resulted in significant decreases in serum total cholesterol (-4.8 ± 16.1 vs. +7.0 ± 27.1 mg/dL, P = .04), high-sensitivity C-reactive protein (-9.0 ± 14.7 vs. -1.7 ± 8.6 mg/L, P = .02), plasma malondialdehyde (-0.8 ± 0.8 vs. -0.2 ± 0.8 µmol/L, P = .001), and significant increases in plasma nitric oxide (+6.2 ± 8.2 vs. +0.8 ± 8.0 µmol/L, P = .01) and total antioxidant capacity concentrations (+179.3 ± 97.2 vs. -85.1 ± 203.4 mmol/L, P < .001). CONCLUSIONS: Overall, probiotic supplementation for 12 weeks among subjects with diabetic foot ulcer had beneficial effects on ulcer size, glycaemic control, total cholesterol, high-sensitivity C-reactive protein, plasma nitric oxide, total antioxidant capacity, and malondialdehyde levels.

High-dose ω-3 Fatty Acid Plus Vitamin D3 Supplementation Affects Clinical Symptoms and Metabolic Status of Patients with Multiple Sclerosis: A Randomized Controlled Clinical Trial.

Background: Combined omega-3 fatty acid and vitamin D supplementation may improve multiple sclerosis (MS) by correcting metabolic abnormalities and attenuating oxidative stress and inflammation. Objective: This study aimed to determine the effects of ω-3 fatty acid and vitamin D cosupplementation on the disability score and metabolic status of patients with MS. Methods: This was a randomized, placebo-controlled clinical trial with Expanded Disability Status Scale (EDSS) score and inflammation as primary outcomes and oxidative stress biomarkers and metabolic profile as secondary outcomes. Patients, aged 18-55 y, were matched for disease EDSS scores, gender, medications, BMI, and age (n = 53) and randomly received a combined 2 × 1000 mg/d ω-3 fatty acid and 50,000 IU/biweekly cholecalciferol supplement or placebo for 12 wk. The placebos were matched in colour, shape, size, packaging, smell, and taste with supplements. Fasting blood samples were collected at baseline and end of intervention to measure different outcomes. Multiple linear regression models were used to assess treatment effects on outcomes adjusting for confounding variables. Results: Patients taking ω-3 fatty acid plus vitamin D supplements showed a significant improvement in EDSS (ß -0.18; 95% CI: -0.33, -0.04; P = 0.01), compared with placebo. Serum high-sensitivity C-reactive protein (ß -1.70 mg/L; 95% CI: -2.49, -0.90 mg/L; P < 0.001), plasma total antioxidant capacity (ß +55.4 mmol/L; 95% CI: 9.2, 101.6 mmol/L; P = 0.02), total glutathione (ß +51.14 µmol/L; 95% CI: 14.42, 87.87 µmol/L; P = 0.007), and malondialdehyde concentrations (ß -0.86 µmol/L; 95% CI: -1.10, -0.63 µmol/L; P < 0.001) were significantly improved in the supplemented group compared with the placebo group. In addition, ω-3 fatty acid and vitamin D cosupplementation resulted in a significant reduction in serum insulin, insulin resistance, and total/HDL-cholesterol, and a significant increase in insulin sensitivity and serum HDL-cholesterol concentrations. Conclusion: Overall, taking ω-3 fatty acid and vitamin D supplements for 12 wk by patients with MS had beneficial effects on EDSS and metabolic status. This trial was registered at the Iranian website (www.irct.ir) for registration of clinical trials as IRCT2017090133941N20.

Clinical Trial on the Effects of Vitamin D Supplementation on Metabolic Profiles in Diabetic Hemodialysis.

The current study was conducted to assess the effects of vitamin D supplementation on insulin metabolism, lipid fractions, biomarkers of inflammation, and oxidative stress in diabetic hemodialysis (HD) patients. This randomized double-blind placebo-controlled clinical trial was carried out among 60 diabetic HD patients. Subjects were randomly allocated into two groups to intake either oral vitamin D3 supplements at a dosage of 50 000 IU (n=30) or placebo (n=30) every 2 weeks for 12 weeks. After 12 weeks of intervention, subjects who received vitamin D supplements compared with the placebo had significantly decreased serum insulin concentrations (-3.4±3.7 vs. +2.0±4.2 µIU/ml, p<0.001), homeostasis model of assessment-estimated insulin resistance (HOMA-IR) (-1.2±1.8 vs. +0.9±2.3, p<0.001), and improved quantitative insulin sensitivity check index (QUICKI) (+0.02±0.03 vs. -0.01±0.02, p<0.001). In addition, compared with the placebo, vitamin D supplementation led to significant reductions in serum high-sensitivity C-reactive protein (hs-CRP) (-1.4±2.5 vs. +1.4±4.8 mg/l, p=0.007), plasma malondialdehyde (MDA) (-0.1±0.2 vs. +0.1±0.2 µmol/l, p=0.009) and a significant increase in plasma total antioxidant capacity (TAC) concentrations (+33.8±56.7 vs. -2.0±74.5 mmol/l, p=0.04). We did not see any significant effect of vitamin D supplementation on lipid profiles and other biomarkers of inflammation and oxidative stress compared with the placebo. Overall, we found that vitamin D supplementation had beneficial effects on serum insulin, HOMA-IR, QUICKI, serum hs-CRP, plasma MDA, and TAC levels among diabetic HD patients for 12 weeks. CLINICAL REGISTRATION:: http://www.irct.ir: IRCT201611155623N92.

Selenium supplementation lowers insulin resistance and markers of cardio-metabolic risk in patients with congestive heart failure: a randomised, double-blind, placebo-controlled trial.

This study was carried out to evaluate the effects of Se supplementation on metabolic profiles in patients with congestive heart failure (CHF). This randomised double-blind, placebo-controlled trial was performed among fifty-three subjects with CHF, aged 45-85 years old. Subjects were randomly allocated into two groups to take either 200 µg/d of Se as Se yeast (n 26) or placebo (n 27) for 12 weeks. Metabolic profiles were assessed at baseline and at the end of trial. Compared with the placebo, Se supplementation led to significant reductions in serum insulin (-18·41 (sd 27·53) v. +13·73 (sd 23·63) pmol/l, P<0·001), homoeostatic model of assessment for insulin resistance (-1·01 (sd 1·61) v. +0·55 (sd 1·20), P<0·001) and a significant increase in quantitative insulin sensitivity check index (QUICKI) (+0·007 (sd 0·03) v. -0·01 (sd 0·01), P=0·007). In addition, Se supplementation significantly decreased LDL-cholesterol (-0·23 (sd 0·29) v. -0·04 (sd 0·28) mmol/l, P=0·03) and total-:HDL-cholesterol ratio (-0·47 (sd 0·31) v. -0·06 (sd 0·42), P<0·001), and significantly increased HDL-cholesterol levels (+0·18 (sd 0·19) v. +0·02 (sd 0·13) mmol/l, P=0·001) compared with the placebo. In addition, taking Se supplements was associated with a significant reduction in high-sensitivity C-reactive protein (hs-CRP) (-1880·8 (sd 3437·5) v. +415·3 (sd 2116·5) ng/ml, P=0·01), and a significant elevation in plasma total antioxidant capacity (TAC) (+30·9 (sd 118·0) v. -187·9 (sd 412·7) mmol/l, P=0·004) and total glutathione levels (+33·7 (sd 130·4) v. -39·2 (sd 132·8) µmol/l, P=0·003) compared with the placebo. When we applied Bonferroni correction for multiple outcome testing, QUICKI (P=0·11), LDL-cholesterol (P=0·51), hs-CRP (P=0·17), TAC (P=0·06) and GSH (P=0·05) became non-significant, and other metabolic profiles did not alter. Overall, our study supported that Se supplementation for 12 weeks to patients with CHF had beneficial effects on insulin metabolism and few markers of cardio-metabolic risk.

The effects of synbiotic supplementation on hormonal status, biomarkers of inflammation and oxidative stress in subjects with polycystic ovary syndrome: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: To our knowledge, no reports are available indicating the effects of synbiotic supplementation on hormonal status, biomarkers of inflammation and oxidative stress in subjects with polycystic ovary syndrome (PCOS). This research was done to assess the effects of synbiotic supplementation on hormonal status, biomarkers of inflammation and oxidative stress in subjects with PCOS. METHODS: This randomized double-blind, placebo-controlled trial was conducted on 60 subjects diagnosed with PCOS according to the Rotterdam criteria. Subjects were randomly assigned into two groups to take either synbiotic (n = 30) or placebo (n = 30) for 12 weeks. Endocrine, inflammation and oxidative stress biomarkers were quantified at baseline and after the 12-week intervention. RESULTS: After the 12-week intervention, compared with the placebo, synbiotic supplementation significantly increased serum sex hormone-binding globulin (SHBG) (changes from baseline in synbiotic group: + 19.8 ± 47.3 vs. in placebo group: + 0.5 ± 5.4 nmol/L, p = 0.01), plasma nitric oxide (NO) (changes from baseline in synbiotic group: + 5.5 ± 4.8 vs. in placebo group: + 0.3 ± 9.1 µmol/L, p = 0.006), and decreased modified Ferriman Gallwey (mF-G) scores (changes from baseline in synbiotic group: - 1.3 ± 2.5 vs. in placebo group: - 0.1 ± 0.5, p = 0.01) and serum high-sensitivity C-reactive protein (hs-CRP) (changes from baseline in synbiotic group: - 950.0 ± 2246.6 vs. in placebo group: + 335.3 ± 2466.9 ng/mL, p = 0.02). We did not observe any significant effect of synbiotic supplementation on other hormonal status and biomarkers of oxidative stress. CONCLUSIONS: Overall, synbiotic supplementation for 12 weeks in PCOS women had beneficial effects on SHBG, mFG scores, hs-CRP and NO levels, but did not affect other hormonal status and biomarkers of oxidative stress. TRIAL REGISTRATION: This study was retrospectively registered in the Iranian website ( www.irct.ir ) for registration of clinical trials ( IRCT201509115623N53 ), on 2015-09-27.

Long-Term Vitamin D Supplementation and the Effects on Recurrence and Metabolic Status of Cervical Intraepithelial Neoplasia Grade 2 or 3: A Randomized, Double-Blind, Placebo-Controlled Trial.

OBJECTIVE: This study was conducted to evaluate the effects of vitamin D supplementation on the recurrence and metabolic status of patients with cervical intraepithelial neoplasia grade 2 or 3 (CIN2/3). METHODS: This randomized, double-blind, placebo-controlled trial was carried out among 58 women diagnosed with CIN2/3. Participants were randomly assigned into 2 groups to receive either 50,000 IU vitamin D3 (n = 29) or placebo (n = 29) every 2 weeks for 6 months. RESULTS: The recurrence rate of CIN1/2/3 was 18.5 and 48.1% in the vitamin D and placebo groups respectively (p = 0.02). When we excluded CIN1, the recurrence rate of CIN2/3 became nonsignificant. Vitamin D supplementation significantly decreased fasting plasma glucose (-7.8 ± 9.2 vs. -1.1 ± 8.6 mg/dL, p = 0.006) and insulin levels (-3.2 ± 4.8 vs. -0.9 ± 3.4 µIU/mL, p = 0.03), and significantly increased quantitative insulin sensitivity check index (0.01 ± 0.02 vs. 0.002 ± 0.01, p = 0.02) compared with the placebo. Additionally, there was a significant decrease in high-sensitivity C-reactive protein (-815.3 ± 1,786.2 vs. 717.5 ± 1,827.3 ng/mL, p = 0.002) and a significant increase in total antioxidant capacity (113.4 ± 137.4 vs. -53.7 ± 186.7 mmol/L, p < 0.001) following the supplementation of vitamin D compared with the placebo. CONCLUSIONS: Vitamin D3 supplementation for 6 months among women with CIN2/3 had beneficial effects on CIN1/2/3 recurrence and metabolic status; however, it did not affect CIN2/3 recurrence.

Probiotic supplementation in diabetic hemodialysis patients has beneficial metabolic effects.

This study determined the effects of probiotic supplementation on glycemic control, lipid concentrations, biomarkers of inflammation and oxidative stress in 60 diabetic patients on hemodialysis in a parallel randomized double-blind placebo-controlled clinical trial. Participants were initially matched based on sex, duration of dialysis and diabetes, body mass index and age. Subsequently, they were randomly divided into two groups to take either a capsule containing the probiotics Lactobacillus acidophilus, Lactobacillus casei and Bifidobacterium bifidum or placebo for 12 weeks. Based on three-day dietary records throughout the trial, there was no significant change in dietary macro- and micro-nutrients or total dietary fiber to confound results. After the 12 weeks, analysis of patients who received probiotic supplements compared with the placebo showed they had significantly decreased fasting plasma glucose (-22.0 vs. +6.6 mg/dl), serum insulin (-6.4 vs. +2.3 µIU/ml), homeostasis model of assessment-estimated insulin resistance (-2.9 vs. +2.5), homeostasis model of assessment-estimated beta-cell function (-14.1 vs. +6.1) and HbA1c (-0.4 vs. -0.1%,), and improved quantitative insulin sensitivity check index (+0.03 vs. -0.02). Additionally, compared with the placebo, probiotic supplementation resulted in significant reductions in serum high-sensitivity C-reactive protein (-1933 vs. +252 ng/ml), plasma malondialdehyde (-0.3 vs. +1.0 µmol/l), subjective global assessment scores (-0.7 vs. +0.7) and total iron binding capacity (-230 vs. +33 µg/dl), and a significant increase in plasma total antioxidant capacity (+15 vs. -88 mmol/l). Thus, probiotic supplementation for 12 weeks among diabetic hemodialysis patients had beneficial effects on parameters of glucose homeostasis, and some biomarkers of inflammation and oxidative stress.

Comparison of myo-inositol and metformin on clinical, metabolic and genetic parameters in polycystic ovary syndrome: A randomized controlled clinical trial.

OBJECTIVE: To our knowledge, data on comparison of myo-inositol and metformin on clinical, metabolic and genetic parameters in subjects with polycystic ovary syndrome (PCOS) are limited. This study was carried out to compare myo-inositol and metformin on clinical, metabolic and genetic parameters in subjects with PCOS. DESIGN, PATIENTS AND MEASUREMENTS: This randomized controlled trial was conducted among 60 subjects with PCOS aged 18-40 years. Subjects were randomly allocated into two groups to receive either myo-inositol (N=30) or metformin (N=30) for 12 weeks. Gene expression of inflammatory cytokines was assessed in peripheral blood mononuclear cells (PBMCs) of PCOS women by RT-PCR. RESULTS: After the 12-week intervention, compared with metformin, myo-inositol intake significantly decreased serum total testosterone (-1.4±4.2 vs +0.7±1.4 nmol/L, P=.03), modified Ferriman-Gallwey (mF-G) scores (-1.1±0.7 vs -0.5±0.8, P=.01) and serum high-sensitivity C-reactive protein (hs-CRP) levels (-2.6±3.9 vs +0.2±1.5 mg/L, P<.001). RT-PCR demonstrated that compared with metformin, myo-inositol downregulated gene expression of interleukin-1 (IL-1) (P=.02) in PBMCs of subjects with PCOS. We did not observe any significant effect of myo-inositol intake compared with metformin on other hormonal profiles, plasma nitric oxide (NO) or gene expression of IL-8 and tumour necrosis factor alpha (TNF-α). CONCLUSIONS: Overall, taking myo-inositol, compared with metformin, for 12 weeks in patients with PCOS with hyperinsulinism and normoinsulinism had beneficial effects on total testosterone, mFG scores, serum hs-CRP levels and gene expression of IL-1, but did not affect other hormonal profiles, NO levels or gene expression of IL-8 and TNF-α.

Long-Term Vitamin D Supplementation Affects Metabolic Status in Vitamin D-Deficient Type 2 Diabetic Patients with Coronary Artery Disease.

Background: Vitamin D might be beneficial in diabetic patients with coronary artery disease (CAD) through its favorable effects on metabolic profiles and biomarkers of inflammation and oxidative stress.Objective: This study was performed to examine the effects of 6 mo of vitamin D supplementation on metabolic status in diabetic patients with CAD.Methods: This randomized, double-blind, placebo-controlled clinical trial was conducted in 60 vitamin D-deficient diabetic patients with CAD aged 40-85 y. Subjects were randomly assigned into 2 groups to take either 50,000-IU vitamin D supplements (n = 30) or placebo (n = 30) every 2 wk for 6 mo. Fasting blood samples were obtained at the beginning of the study and after the 6-mo intervention to quantify glycemic indicators, lipid concentrations, and biomarkers of inflammation and oxidative stress.Results: Compared with placebo, vitamin D supplementation resulted in significant reductions in fasting plasma glucose (-14.9 ± 7.1 compared with +19.3 ± 7.1 mg/dL; P = 0.001), serum insulin (-2.7 ± 1.1 compared with +1.8 ± 1.1 µIU/mL; P = 0.006), homeostasis model assessment of insulin resistance (-0.7 ± 0.3 compared with +0.5 ± 0.3; P = 0.01), and ß cell function (-9.1 ± 4.2 compared with +5.7 ± 4.2; P = 0.01) and a significant increase in serum vitamin D (+6.8 ± 0.9 compared with +0.1 ± 0.9 ng/mL; P < 0.001) and the Quantitative Insulin Sensitivity Check Index (+0.008 ± 0.004 compared with -0.007 ± 0.004; P = 0.01). In addition, changes in serum high-sensitivity C-reactive protein (hs-CRP; -1.0 ± 0.5 compared with +0.6 ± 0.5 µg/mL; P = 0.02), plasma nitric oxide (NO; +7.0 ± 2.0 compared with -4.6 ± 2.0 µmol/L; P < 0.001), total reduced glutathione (GSH; +104 ± 16.4 compared with +24.8 ± 16.4 µmol/L; P = 0.001), and malondialdehyde concentrations (-0.2 ± 0.1 compared with +0.2 ± 0.1 µmol/L; P < 0.001) in the supplemented group were significantly different from the changes in these indicators in the placebo group.Conclusions: Overall, 6 mo of vitamin D supplementation among vitamin D-deficient diabetic patients with CAD had beneficial effects on glycemic control and serum hs-CRP, NO, GSH, and malondialdehyde concentrations. This trial was registered on the Iranian website (www.irct.ir) for registration of clinical trials as IRCT201510315623N56.

The effects of zinc supplementation on wound healing and metabolic status in patients with diabetic foot ulcer: A randomized, double-blind, placebo-controlled trial.

This study was performed to determine the effects of zinc supplementation on wound healing and metabolic status in patients with diabetic foot ulcer. The current randomized, double-blind, placebo-controlled trial was conducted among 60 patients (aged 40-85 years old) with grade 3 diabetic foot ulcer. Participants were randomly divided into two groups (30 participants in each group) to take either 220 mg zinc sulfate supplements containing 50 mg elemental zinc or placebo daily for 12 weeks. After the 12-week intervention, compared with the placebo, zinc supplementation was associated with significant reductions in ulcer length (-1.5 ± 0.7 vs. -0.9 ± 1.2 cm, p = 0.02) and width (-1.4 ± 0.8 vs. -0.8 ± 1.0 cm, p = 0.02). In addition, changes in fasting plasma glucose (-40.5 ± 71.0 vs. -3.9 ± 48.5 mg/dl, p = 0.02), serum insulin concentration (-8.0 ± 15.4 vs. +1.1 ± 10.3 µIU/ml, p = 0.009), homeostasis model of assessment-estimated insulin resistance (-3.9 ± 7.1 vs. +0.8 ± 5.9, p = 0.007), the quantitative insulin sensitivity check index (+0.01 ± 0.03 vs. -0.002 ± 0.02, p = 0.04) and HbA1c (-0.5 ± 0.8 vs. -0.1 ± 0.5%, p = 0.01) in the supplemented group were significantly different from the changes in these indicators in the placebo group. Additionally, significant increases in serum HDL-cholesterol (+4.1 ± 4.3 vs. +1.1 ± 5.1 mg/dl, p = 0.01), plasma total antioxidant capacity (+91.7 ± 213.9 vs. -111.9 ± 188.7 mmol/L, p < 0.01) and total glutathione (+68.1 ± 140.8 vs. -35.0 ± 136.1 µmol/L, p = 0.006), and significant decreases in high sensitivity C-reactive protein (-20.4 ± 24.6 vs. -6.8 ± 21.3 µg/ml, p = 0.02) and plasma malondialdehyde concentrations (-0.6 ± 0.9 vs. -0.2 ± 0.7 µmol/L, p = 0.03) were seen following supplementation with zinc compared with the placebo. Zinc supplementation for 12 weeks among diabetic foot ulcer patients had beneficial effects on parameters of ulcer size and metabolic profiles.

Synbiotic supplementation and the effects on clinical and metabolic responses in patients with rheumatoid arthritis: a randomised, double-blind, placebo-controlled trial.

Synbiotic intake may be associated with reduced inflammation in patients with rheumatoid arthritis (RA) due to optimised inflammatory markers, oxidative stress and insulin resistance. This research was conducted to assess the effects of synbiotic supplementation on the clinical and metabolic parameters of patients with RA. A total of fifty-four patients with RA were allocated into two groups to receive either a synbiotic capsule (n 27) or a placebo (n 27) for 8 weeks in this randomised, double-blind, placebo-controlled trial. Fasting blood samples were taken at baseline and week 8 of the study to quantify related markers. After the 8-week intervention, compared with the placebo, synbiotic supplementation resulted in a significant reduction in serum high-sensitivity C-reactive protein (hs-CRP) levels (-1427·8 (sd 3267·2) v. +2833·4 (sd 5639·7) ng/ml, P=0·001). In addition, compared with the placebo, synbiotic supplementation improved disease activity score-28 joints (DAS-28) (-1·6 (sd 0·8) v. -0·3 (sd 0·5), P<0·001) and visual analogue scales (VAS) pain (-30·4 (sd 18·7) v. -11·5 (sd 15·9), P<0·001). In addition, a significant elevation in plasma nitric oxide (NO) (+0·8 (sd 4·4) v. -2·6 (sd 4·5) µmol/l, P=0·008), and significant reductions in insulin values (-13·8 (sd 26·4) v. +4·2 (sd 28·2) pmol/l, P=0·01), homoeostasis model of assessment-estimated insulin resistance (HOMA-IR) (-0·5 (sd 1·0) v.+0·1 (sd 1·1), P=0·03) and homoeostatic model assessment-ß-cell function (HOMA-B) (-9·4 (sd 17·9) v. +3·3 (sd 18·9), P=0·01) following supplementation with the synbiotic compared with the placebo. Compared with the placebo, synbiotic supplementation also resulted in a significant increase in plasma GSH (+36·6 (sd 63·5) v. -58·5 (sd 154·4) µmol/l, P=0·005). Overall, our study demonstrated that synbiotic supplementation for 8 weeks among patients with RA had beneficial effects on hs-CRP, DAS-28, VAS, NO, insulin levels, HOMA-IR, HOMA-B and GSH levels.