A systematic review on the mechanisms of vitamin K effects on the complications of diabetes and pre-diabetes.

Diabetes mellitus and pre-diabetes are prevalent endocrine disorders associated with substantial morbidity and premature mortality. Vitamin K is known to have several beneficial effects on complications of diabetes and pre-diabetes. However, systematic consolidation of evidence is required to quantify these effects in order to inform clinical practice and research. A systematic search in PubMed, Scopus, Embase, ProQuest, and Google Scholar databases was undertaken from database inception up to October 2018 to evaluate functional roles of different forms of vitamin K on diabetes and pre-diabetes. From 3,734 identified records, nine articles met the inclusion criteria and were evaluated. Vitamin K supplementation was found to be associated with significant reductions in blood glucose (six studies), increased fasting serum insulin (four studies), reduced hemoglobin A1c (three studies), reduced homeostatic model assessment-insulin resistance index (HOMA-IR) (two studies), and increased ß-cell function (two studies) in diabetic animal studies. Following 2-hour oral glucose tolerance test, vitamin K supplementation was observed to be effective in reducing blood glucose and insulin levels in the pre-diabetic population. However, no evidence of effect was observed for fasting blood sugar, insulin, HOMA-IR, and homeostatic model assessment-ß-cell function index (two studies). A statistically significant effect was also noted with vitamin K in improving dyslipidemia (three studies) as well as oxidative stress and inflammatory markers (five studies) in diabetic animals. In conclusion, clinical trials and animal studies confirm that vitamin K supplementation may improve both clinical features and complications of diabetes and pre-diabetes. However, quantification of clinical efficacy in the pre-diabetic population and among individuals with comorbidities requires further investigation.

Independent and Additive Effects of Coenzyme Q10 and Vitamin E on Cardiometabolic Outcomes and Visceral Adiposity in Women With Polycystic Ovary Syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in reproductive age women. OBJECTIVE: This study was conducted to investigate the effects of CoQ10 and/or vitamin E on cardiometabolic outcomes in patients with PCOS. METHODS: This randomized clinical trial was carried out among 86 women with PCOS. Patients were assigned to take CoQ10, vitamin E, CoQ10 plus vitamin E or placebo for 8 weeks. Fasting blood samples were obtained at the beginning and end of the study. RESULTS: A significant decrease in serum triglycerides (TG) (p <0.001) was found following the administration of CoQ10 and/or vitamin E supplements compared with the placebo group. Supplementation with CoQ10 and vitamin E failed to affect total cholesterol levels. However, co-administration of CoQ10 and vitamin E resulted in a significant decrease in serum total cholesterol levels (9.92 [15.11, 4.74]). Additionally, only the combination of supplements was able to significantly reduce low-density lipoprotein-cholesterol (LDL-C) (‒9.63 [‒15.34, ‒3.92]), increase high-density lipoprotein-cholesterol (HDL-C) (2.33 [0.51, 4.16), reduce atherogenic coefficient (AC) (‒0.29 [‒0.43, ‒0.16], p = 0.03) and decrease visceral adiposity index (VAI) values. Co-Q10 and vitamin E (alone or in combination) had significant effects on non-HDL-C (p = 0.004), atherogenic Index of Plasma (AIP) (p = <0.001) and lipid accumulation product (LAP) (p <0.001) and SBP (p = 0.005). However, the reduction in DBP was statistically significant only for patients who received combined supplementations (p = 0.04). CONCLUSIONS: In conclusion, CoQ10, vitamin E (alone or in combination) had beneficial effects on cardiometabolic outcomes among women with PCOS.

Vitamin D supplementation has no effect on matrix metalloproteinases-2, -9, and tissue inhibitor matrix metalloproteinase-1 in subjects with metabolic syndrome: A pilot study.

The present randomized, double-blind, placebo controlled study aimed to evaluate the effect of vitamin D supplementation on matrix metalloproteinases-2, -9 (MMP-2 and MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in subjects with metabolic syndrome. Forty-six eligible subjects were randomly assigned to either vitamin D or placebo groups for 16 weeks. The participants were asked to take 50,000 IU vitamin D or matching placebo every week. Metabolic and anthropometric indices, serum MMP-2, MMP-9, TIMP-1 and high-sensitivity C-reactive protein (hsCRP) were assessed before and after intervention. Moreover, dietary intake, sun exposure and physical activity were also determined. The trial was registered at http://www.irct.ir (No. IRCT201409033140N14). Participants were 40.20 ± 4.60 y and 45.50% males. Compared to the baseline values, MMP-9 and TIMP-1 concentrations were decreased after 16 weeks in the intervention group (p = 0.03 and p = 0.04, respectively). However, the changes of MMP-2, MMP-9, TIMP-1 and hsCRP in the intervention group were not significant compared to the placebo group (p > 0.05). Furthermore, the metabolic or anthropometric indices between two study groups remained unchanged (p > 0.05). The findings of the present study demonstrated no effect of vitamin D supplementation on MMP-2, MMP-9 and TIMP-1 concentrations in subjects with metabolic syndrome. However, there is a need for more longitudinal trials to investigate the role of vitamin D on atherosclerosis and cardiovascular diseases in subjects with metabolic syndrome.

The effects of vitamin D supplementation on lipid profiles and oxidative indices among diabetic nephropathy patients with marginal vitamin D status.

AIMS: Diabetic nephropathy is one of the major microvascular complications of type 2 diabetes which insufficient vitamin D might -have a role in it's incidence. This study evaluated the effects of vitamin D supplementation on lipid profiles and oxidative/anti-oxidative indices in marginal vitamin D status patients with diabetic nephropathy. METHODS: For the current paralleled, randomized, double-blinded, placebo-controlled clinical trial, 50 diabetic nephropathy patients with marginal serum vitamin D were selected. Intervention group received 1,25-dihydroxycholecalciferol (50000 IU/week, n = 25), and placebo group (n = 25) received an identical placebo, for 8 weeks. Lipid profiles (LDL, HDL, TG and TC) and oxidative/anti-oxidative markers (TAC, SOD, CAT, GPX and MDA) were measured. RESULTS: Vitamin D supplementation significantly increased vitamin D status in the intervention group, compared to the control group (P = 0.001). The reductions in the serum levels of TG, LDL and TC were significant (P = 0.04, P = 0.006 and P = 0.02, respectively) in the intervention group. The changes in oxidative/anti-oxidative markers and HDL levels were not significant after intervention. CONCLUSION: In conclusion, vitamin D supplementation for 8 weeks among diabetic nephropathy patients has beneficial effects on serum vitamin D status and dyslipidemia.

Hormonal and Metabolic Effects of Coenzyme Q10 and/or Vitamin E in Patients With Polycystic Ovary Syndrome.

Context: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in reproductive-age women. The hormonal and metabolic effects of coenzyme Q10 (CoQ10) and/or vitamin E in patients with PCOS have not been studied, to our knowledge. Objective: To evaluate the effects of CoQ10 and/or vitamin E on glucose homeostasis parameters and reproductive hormones in women with PCOS. Design, Setting, Participants: Randomized, double-blind, placebo-controlled clinical trial among 86 women with PCOS. Intervention: CoQ10 or vitamin E or combination for 8 weeks. Main Outcome Measures: Glucose homeostasis parameters and sex hormone concentrations. Results: After adjustment for potential confounders, supplementation with CoQ10 alone or in combination with vitamin E, compared with placebo, had significant effects on fasting blood sugar (FBS); vitamin E's effect on FBS was not significant. A significant reduction in homeostasis model assessment of insulin resistance (HOMA-IR) was observed in the CoQ10 and combined groups. CoQ10, vitamin E, and cosupplementation led to decreased serum total testosterone levels (P < 0.001) compared with those of the placebo group. CoQ10 supplementation in combination with vitamin E significantly improved in sex hormone-binding globulin (SHBG) levels compared with other groups (P = 0.008). Linear regression analysis revealed that changes in FBS, insulin, and HOMA-IR were predictors of change in free androgen index (P < 0.05). Conclusion: CoQ10 with or without vitamin E supplementation among women with PCOS had beneficial effects on serum FBS and insulin levels, as well as HOMA-IR and total testosterone levels. However, only cosupplementation affected SHBG concentrations.

Lower glycemic indices and lipid profile among type 2 diabetes mellitus patients who received novel dose of Silybum marianum (L.) Gaertn. (silymarin) extract supplement: A Triple-blinded randomized controlled clinical trial.

OBJECTIVE: This randomized clinical trial was conducted to evaluate the effects of silymarin supplementation on glycemic indices and serum lipid profile in type 2 diabetes mellitus (T2DM) patients. METHODS: 40 T2DM patients (twenty male and twenty female), 25-50 years of age and on stable medication, were recruited for the present paralleled, randomized, triple-blinded, placebo-controlled clinical trial. The participants were randomly assigned to the silymarin or placebo groups, in which the patients either received 140 mg of silymarin, thrice daily (n = 20) or placebo (n = 20) for 45 days. Anthropometric and dietary intake data were collected at the baseline and end of the trial. Fasting blood samples were collected, and glycemic indices and lipid profile were determined at baseline, as well as the end of the study. RESULTS: Silymarin supplementation led to significant reduction in fasting blood sugar, serum insulin, homeostatic model assessment for insulin resistance, serum triglyceride and triglyceride to high-density lipoprotein cholesterol ratio as compared to the placebo, by 11.01, 14.35, 25.92, 23.7 and 27.67% respectively. There was significant increase in high-density lipoprotein cholesterol levels and quantitative insulin sensitivity check index in the silymarin group as compared to the placebo group, by 6.88 and 5.64% respectively, (p < 0.05). Total cholesterol and low-density lipoprotein cholesterol concentrations significantly decreased in the silymarin group as compared to the baseline, by 7.93 (p = 0.001) and 7.15% (p = 0.02), respectively. CONCLUSION: Silymarin supplementation may improve the glycemic indices and lipid profiles of T2DM patients. More studies are needed to validate the adjunct use of silymarin for metabolic control of T2DM patients.

Vitamin K1 Supplementation Did Not Alter Inflammatory Markers and Clinical Status in Patients with Rheumatoid Arthritis.

Background: Rheumatoid arthritis (RA) is an inflammatory disorder in which the disease severity might be decreased by anti-inflammatory agents. There are several lines of evidence which support anti-inflammatory effects of vitamin K. The aim of this study was to examine whether vitamin K is a useful strategy for reducing inflammation in RA subjects. Materials and methods: In this double-blind placebo controlled trial, 58 patients with definitive RA were randomly allocated into two groups to receive vitamin K1 as phylloquinone [10 mg/day] or placebo pills for 8 weeks. Clinical status using disease activity score-28 (DAS-28) and serum concentrations of some inflammatory markers (IL-6, hs-CRP, TNFα) were assessed at baseline and at the end of intervention. Results: There were no significant differences between the two groups regarding any of the baseline characteristics. In the vitamin K1 group, a 27 % decrease in serum levels of IL-6 (P = 0.006) and a 13 % decrease in DAS-28 (P = 0.041) were observed. However, after adjusting for relevant confounders, i. e.; duration of RA, intake of folic acid supplements, energy intake, weight and baseline values of each variable, by comparing the two groups, we found no significant reduction in these markers. Conclusion: Vitamin K1 supplementation at 10 mg/day for 8 weeks had no significant effects on blood biomarkers of inflammation and disease severity of patients with rheumatoid arthritis compared with the placebo group.

The effects of vitamin D supplementation on proatherogenic inflammatory markers and carotid intima media thickness in subjects with metabolic syndrome: a randomized double-blind placebo-controlled clinical trial.

PURPOSE: Metabolic syndrome may predispose to cardiovascular diseases. Since, in recent studies, vitamin D is advocated for cardioprotective roles, this study was designed to investigate the effects of vitamin D supplementation on proatherogenic inflammatory markers and common carotid intima media thickness in subjects with metabolic syndrome. METHODS: This randomized double blind clinical trial was conducted in Tabriz, Iran. Eligible subjects (n = 80) with metabolic syndrome were recruited thorough advertisement and randomized to receive either vitamin D (50,000 IU/week) or matching placebo for 16 weeks. Interlukin-6, high sensitivity C-reactive protein, vascular cell adhesion molecule-1, E-selectin, and common carotid intima media thickness were measured at the beginning and end of the study. The study was registered at http://www.irct.ir (code: IRCT201409033140N14). RESULTS: Sixteen weeks supplementation with vitamin D increased median of serum 25-hydroxy vitamin D [25(OH)D] and mean calcium levels (p < 0.001) in the intervention group. There was also a significant difference in parathyroid hormone level at the end of the study (p < 0.001). Vitamin D treatment reduced IL-6 level after 16 weeks (p = 0.027). Compared to baseline, vascular cell adhesion molecule-1 and E-selectin levels decreased significantly in vitamin D treated subjects; however, there were no significant differences between two groups. No effect of vitamin D supplementation was observed in either common carotid intima media thickness or high sensitivity C-reactive protein concentrations at the end of the study (p > 0.05). CONCLUSIONS: Vitamin D supplementation improved some proatherogenic inflammatory markers in subjects with metabolic syndrome. No changes of high sensitivity C-reactive protein and carotid intima media thickness were shown after 16 weeks.

Effects of vitamin D supplementation on metabolic indices and hs-CRP levels in gestational diabetes mellitus patients: a randomized, double-blinded, placebo-controlled clinical trial.

BACKGROUND/OBJECTIVES: Vitamin D plays an important role in the etiology of gestational diabetes mellitus (GDM). This study evaluated the effect of vitamin D supplementation on metabolic indices and hs-C-reactive protein (CRP) levels in GDM patients. SUBJECTS/METHODS: The study was a randomized, placebo-controlled, double-blinded clinical trial. Seventy-six pregnant women with GDM and gestational age between 24-28 weeks were assigned to receive four oral treatments consisting of 50,000 IU of vitamin D3 (n = 38) or placebo (n = 38) once every 2 weeks for 2 months. Fasting blood glucose (FG), insulin, HbA1c, 25-hydroxyvitamin D, lipid profile, hs-CRP, and homeostasis model assessment-insulin resistance (HOMA-IR) were measured before and after treatment. Independent and paired t-tests were used to determine intra- and intergroup differences, respectively. ANCOVA was used to assess the effects of vitamin D supplementation on biochemical parameters. RESULTS: Compared with the placebo group, in the vitamin D group, the serum level of 25-hydroxyvitamin D increased (19.15 vs. -0.40 ng/ml; P < 0.01) and that of FG (-4.72 vs. 5.27 mg/dl; P = 0.01) as well as HbA1c (-0.18% vs. 0.17%; P = 0.02) decreased. Improvements in the lipid profiles were observed in the vitamin D group, but without statistical significance. Significant increases in concentrations of hs-CRP, FG, HbA1c, total cholesterol, and LDL cholesterol were observed in the placebo group. No significant change in fasting insulin and HOMA-IR was observed in either group. CONCLUSIONS: In GDM patients, vitamin D supplementation improved FG and HbA1c but had no significant effects on lipid profile or hs-CRP.

Vitamin E Improves Serum Paraoxonase-1 Activity and Some Metabolic Factors in Patients with Type 2 Diabetes: No Effects on Nitrite/Nitrate Levels.

OBJECTIVE: It is known that markers of oxidative stress and nitrite/nitrate anion (NOx) increase and activity of antioxidative enzyme paraoxonase-1 decline in type 2 diabetes mellitus (DM). The effects of vitamin E on paraoxonase-1 activity and NOx in patients with type 2 diabetes are not known. The purpose of this study was to examine the hypothesis that vitamin E supplementation would affect paraoxonase-1 activity, metabolic factors, and NOx in patients with DM. METHODS: This double-blind, randomized, controlled clinical trial was conducted on 83 patients with DM aged 30-60 years. Forty-two of the subjects had taken 400 IU/day vitamin E and 41 were given placebo over 8 weeks. Fasting blood samples, anthropometric measurements, and dietary intake data were collected at the baseline and at the end of the trial. RESULTS: Vitamin E significantly increased serum vitamin E level, paraoxonase-1 activity, and total antioxidant status (TAS) and decreased fasting blood sugar (FBS) compared to the control group (p < 0.05). Hemoglobin A1c, serum insulin, and insulin resistance significantly decreased in the vitamin E group compared to baseline values (p < 0.05). Alterations in serum levels of malondialdehyde and NOx were not significant in any of groups (p > 0.05). CONCLUSIONS: Vitamin E improved serum vitamin E level, paraoxonase-1 activity, TAS, and FBS in patients with type 2 diabetes. Longitudinal studies are warranted to assess the outcome of these results in reducing complications of diabetes in patients with type 2 diabetes.

Effects of Vitamin K on Matrix Metalloproteinase-3 and Rheumatoid Factor in Women with Rheumatoid Arthritis: A Randomized, Double-Blind, Placebo-Controlled Trial.

OBJECTIVES: Rheumatoid arthritis (RA) is an autoimmune disease characterized by an increase in some autoantibodies and proteolytic enzymes, leading to joint destruction. Although recent investigations have considered vitamin K as an anti-inflammatory nutrient with an important role in bone metabolism, there is currently limited information on its efficacy in RA. We aimed to examine the effects of vitamin K1 (phylloquinone) on the biomarker of joint destruction and autoantibody in patients with RA. MATERIALS AND METHODS: This was a randomized clinical trial in which 64 women with RA who fulfilled the eligibility criteria were randomly allocated to an intervention or a control group. Vitamin K1 or placebo was administered to the participants for 8 weeks. Baseline characteristics and anthropometric measures were obtained. Clinical status using disease activity score in 28 joints (DAS-28), serum levels of matrix metalloproteinase-3 (MMP-3), and rheumatoid factor (RF) were assessed before and after the intervention. RESULTS: The serum level of MMP-3 compared with the baseline values did not change significantly in the groups. However, the serum concentration of RF decreased significantly in the vitamin K1 group (p = 0.041). Intergroup comparison showed no significant change in RF serum level after adjusting for relevant confounders (p > 0.05). CONCLUSIONS: Vitamin K1 supplementation at 10 mg/day for 8 weeks did not alter joint destruction and immune status in the patients with RA compared with the controls.

Is there any place for resistant starch, as alimentary prebiotic, for patients with type 2 diabetes?

OBJECTIVE: The aim of the present study was to determine effects of Resistant Starch (RS2) on metabolic parameters and inflammation in women with type 2 diabetes (T2DM). METHODS: In this randomized controlled clinical trial, 60 females with T2DM were divided into intervention (n = 28) and placebo groups (n = 32). They received 10 g/d RS2 or placebo for 8 weeks, respectively. Fasting blood sugar (FBS), glycated hemoglobin (HbA1c), lipid profile, high-sensitive C-reactive protein (hs-CRP), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) were measured at baseline and at the end of the trial. Paired t test, unpaired t-test and ANCOVA were used to compare the quantitative variables. The data were analyzed using SPSS software version 13.0. RESULTS: RS2 decreased HbA1c (-0.3%, -3.6%), TNF-α (-3.4 pg/mL, -18.9%), triglyceride (-33.4 mg/dL, -15.4%), and it increased HDL-c (+9.4 mg/dL, +24.6%) significantly compared with the placebo group (p < 0.05). Changes in FBS, total cholesterol, low-density lipoprotein, hs-CRP and IL-6 were not significant in the RS2 group compared with the control group. RS2 can improve glycemic status, inflammatory markers and lipid profile in women with T2DM. CONCLUSIONS: Although findings of the present study indicated positive effects of RS2 on inflammation and metabolic parameters, more studies are needed to confirm efficacy of RS2 as an adjunct therapy in diabetes.

Effects of Alpha-Lipoic Acid Supplementation on Inflammatory Biomarkers and Matrix Metalloproteinase-3 in Rheumatoid Arthritis Patients.

OBJECTIVE: Although many studies have considered alpha-lipoic acid (ALA) as a potent antioxidant with anti-inflammatory functions in oxidative stress-associated inflammatory diseases, few studies have evaluated its efficacy in rheumatoid arthritis (RA). Therefore, we aimed to examine the effects of ALA on serum biomarkers of joint damage and inflammation in women with RA. METHODS: We performed a randomized, double-blind, placebo-controlled clinical trial in which RA patients (n = 70) aged 20-50 years were randomly assigned 1:1 to receive either ALA (1200 mg/day) or placebo for 8 weeks. Fasting blood samples were taken before and after the study to analyze inflammatory biomarkers including serum high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and serum matrix metalloproteinase-3 (MMP-3) as a marker of joint erosion. Moreover, 3-day dietary records, the International Physical Activity Questionnaire (IPAQ), and the Spielberger State-Trait anxiety inventory form Y (STAI-Y) were assessed before and after the intervention. RESULTS: Sixty-five RA patients completed the trial. No statistically significant differences were observed in serum levels of hs-CRP, TNF-α, IL-6, and MMP-3 within and between the ALA and placebo groups (p > 0.05). There were no statistically significant differences in dietary intakes, physical activity, and anxiety levels between groups at baseline and they remained statistically unchanged during the study period (p > 0.05). CONCLUSION: Although in theory ALA supplementation could serve as a beneficial nutraceutical in RA patients, in the present study serum inflammatory biomarkers and MMP-3 were not significantly affected by 8 weeks of ALA supplementation.

Effects of Silybum marianum (L.) Gaertn. (silymarin) extract supplementation on antioxidant status and hs-CRP in patients with type 2 diabetes mellitus: a randomized, triple-blind, placebo-controlled clinical trial.

AIM: Diabetes is a serious metabolic disorder and oxidative stress and inflammation contribute to its pathogenesis and complications. Since Silybum marianum (L.) Gaertn. (silymarin) extract is an antioxidant with anti-inflammatory properties, this randomized clinical trial was conducted to evaluate the effects of silymarin supplementation on oxidative stress indices and hs-CRP in type 2 diabetes mellitus patients. METHODS: For the present paralleled, randomized, triple-blinded, placebo-controlled clinical trial, 40 type 2 diabetes patients aged 25-50 yr old and on stable medication were recruited from the Iranian Diabetes Society and endocrinology clinics in East Azarbayjan (Tabriz, Iran) and randomly assigned into two groups. Patients in the silymarin treatment group received 140 mg, thrice daily of dried extracts of Silybum marianum (n = 20) and those in the placebo group (n = 20) received identical placebos for 45 days. Data pertaining to height, weight, waist circumference and BMI, as well as food consumption, were collected at base line and at the conclusion of the study. Fasting blood samples were obtained and antioxidant indices and hs-CRP were assessed at baseline, as well as at the end of the trial. RESULTS: All 40 patients completed the study and did not report any adverse effects or symptoms with the silymarin supplementation. Silymarin supplementation significantly increased superoxide dismutase (SOD), glutathione peroxidase (GPX) activity and total antioxidant capacity (TAC) compared to patients taking the placebo, by 12.85%, 30.32% and 8.43%, respectively (p < 0.05). There was a significant reduction in hs-CRP levels by 26.83% (p < 0.05) in the silymarin group compared to the placebo group. Malondialdehyde (MDA) concentration significantly decreased by 12.01% (p < 0.05) in the silymarin group compared to the baseline. CONCLUSIONS: Silymarin supplementation improves some antioxidant indices (SOD, GPX and TAC) and decrease hs-CRP levels in T2DM patients.

Effect of L-arginine and selenium added to a hypocaloric diet enriched with legumes on cardiovascular disease risk factors in women with central obesity: a randomized, double-blind, placebo-controlled trial.

BACKGROUND/AIMS: We aimed to discover if L-arginine and selenium alone or together can increase the effect of a hypocaloric diet enriched in legumes (HDEL) on central obesity and cardiovascular risk factors in women with central obesity. METHODS: This randomized, double-blind, placebo-controlled trial was undertaken in 84 premenopausal women with central obesity. After a 2-week run-in period on an isocaloric diet, participants were randomly assigned to a control diet (HDEL), L-arginine (5 g/day) and HDEL, selenium (200 µg/day) and HDEL or L-arginine, selenium and HDEL for 6 weeks. Cardiovascular risk factors were assessed before intervention and 3 and 6 weeks afterwards. RESULTS: After 6 weeks, L-arginine had significantly reduced waist circumference (WC); selenium had significantly lowered fasting concentrations of serum insulin and the homeostasis model assessment of insulin resistance index; the interaction between L-arginine and selenium significantly reduced the fasting concentration of nitric oxides (NO(x)), and HDEL lowered triglycerides (TG) and WC and significantly increased the fasting concentration of NO(x). HDEL reduced high-sensitivity C-reactive protein levels in the first half of the study and returned them to basal levels in the second half. CONCLUSION: These data indicate the beneficial effects of L-arginine on central obesity, selenium on insulin resistance and HDEL on serum concentrations of NO(x) and TG.

Effect of folic acid supplementation on homocysteine, serum total antioxidant capacity, and malondialdehyde in patients with type 2 diabetes mellitus.

OBJECTIVE: Metformin is widely used in patients with type 2 diabetes, but it may decrease vitamin B12 and folate levels and increase levels of homocysteine (Hcy). Hyperhomocysteinemia (HHC) and hyperglycemia induce oxidative stress in type 2 diabetes. Thus, this study was performed to determine the effects of folate supplementation on the concentration of homocysteine, total antioxidant capacity (TAC), and malondialdehyde (MDA). METHODS: This was a double-blind randomized controlled clinical trial. Sixty-eight men with type 2 diabetes participated in the study with written consent. Patients were divided randomly into 2 groups: folic acid 5 mg/d and placebo. All patients received the tablets for 8 weeks. Anthropometric and nutrient intake data were obtained from each patient. Baseline and eighth-week homocysteine, total antioxidant capacity, malondialdehyde, folate, and B12 levels were measured. RESULTS: After folate supplementation in the folic acid group, homocysteine was significantly decreased (15.1 ± 3.2 to 12.1 ± 3.1 µmol/L, p < 0.001) and folate and B12 levels were significantly increased (p < 0.001). A significant increase in total antioxidant capacity (0.96 ± 0.2 to 1.14 ± 0.3 mmol Fe2+/L, p < 0.001) and a significant decrease in malondialdehyde (2.6 ± 0.7 to 1.7 ± 0.2 µmol/L, p < 0.001) were observed in the folic acid group, whereas no significant changes occurred in the placebo group (p > 0.05). CONCLUSION: Pharmacological doses of folate supplementation lowered plasma homocysteine and serum malondialdehyde levels and improved serum total antioxidant capacity and folate and B12 levels in patients with type 2 diabetes.

Effect of folic acid supplementation on biochemical indices in overweight and obese men with type 2 diabetes.

AIMS: This study performed to determine the effects of folate supplementation on indices of glycemic control, insulin resistance and lipid profile in overweight and obese men with type 2 diabetes under metformin (at least 1500 mg daily) treatment. METHODS: The study was a double-blind randomized controlled clinical trial. Forty-eight overweight and obese men (aged 58.2±8.9 years; BMI=28.6±2.9 kg/m(2)) with type 2 diabetes participated in the study. Patients were divided randomly into two groups of folic acid (5 mg/d) and placebo. All patients received the tablets for eight weeks. RESULTS: Supplementation with folic acid led to 8% decrease in HbA1C (p=0.048), 7.5% in fasting blood glucose (p=0.051), 16.2% in serum insulin (p=0.021), 20.5% in insulin resistance (p=0.041) and 21.2% in plasma homocysteine (p=0.000). A significant increase in serum folate and B12 levels (19% and 17.3%, p=0.000, respectively) were observed in the folic acid group, whereas no significant changes occurred in the placebo group. Also, in the folic acid and placebo groups, there were no significant changes in body weight. CONCLUSIONS: Folic acid supplementation lowered plasma level of homocysteine, improved glycemic control and insulin resistance in patients with type 2 diabetes.

Effect of retinol on iron bioavailability from Iranian bread in a Caco-2 cell culture model.

OBJECTIVE: Iron and vitamin A deficiencies are among the most prevalent nutritional problems. There are no data on iron bioavailability in Iran. In addition, interaction of vitamin A with iron bioavailability is not well documented, so we determined iron bioavailability from the most widely consumed food in Iran, lavash bread, and the effect of vitamin A on this bioavailability. METHODS: In vivo human studies for determining iron bioavailability are cumbersome, time consuming, and costly to perform, so we used an in vitro model in Caco-2 cells. Bread samples were digested with or without vitamin A (10 microg/1.0 g of dried bread). We used an iron solution containing vitamin C as a positive control. Iron absorption was measured using 59FeCl3. Bioavailability was defined as the percentage of radiolabeled iron taken up and transferred by Caco-2 cells after 1.5 h of incubation. Experiments were carried out two to four times. RESULTS: Mean +/- standard deviations for iron bioavailability in bread samples digested without or with additional vitamin A and in controls were 2.53 +/- 1.55%, 6.62 +/- 3.40%, and 20.80 +/- 2.30%, respectively (P < 0.001). Vitamin A caused a 2.62-fold increase in iron absorption from bread samples. CONCLUSIONS: Iranian lavash bread has low iron bioavailability, but this can be increased by vitamin A supplementation. Increasing vitamin A intake can be considered as a method for increasing iron bioavailability, thus combating iron and vitamin A deficiencies simultaneously.