Effect of vitamin D supplementation on type 2 diabetes biomarkers: an umbrella of interventional meta-analyses.

BACKGROUND: Vitamin D supplementation exerts several supporting effects on improving glycemic status, however, results are inconclusive. Thus, in the present study, we aimed to conduct an umbrella of meta-analysis regarding the impact of vitamin D on type 2 diabetes (T2DM) biomarkers. METHODS: The Scopus, PubMed, Web of Science, Embase, and Google Scholar online databases were searched up to March 2022. All meta-analyses evaluating the impact of vitamin D supplementation on T2DM biomarkers were considered eligible. Overall, 37 meta-analyses were included in this umbrella meta-analysis. RESULTS: Our findings indicated that vitamin D supplementation significantly decreased fasting blood sugar (FBS) (WMD = - 3.08; 95% CI: - 3.97, - 2.19, p < 0.001, and SMD = - 0.26; 95% CI: - 0.38, - 0.14, p < 0.001), hemoglobin A1c (HbA1c) (WMD = - 0.05; 95% CI: - 0.10, - 0.01, p = 0.016, and SMD = - 0.16; 95% CI: - 0.27, - 0.05, p = 0.004), insulin concentrations (WMD = - 2.62; 95% CI: - 4.11, - 1.13; p < 0.001, and SMD = - 0.33; 95% CI: - 0.56, - 0.11, p = 0.004), and homeostatic model assessment for insulin resistance (HOMA-IR) (WMD = - 0.67; 95% CI: - 1.01, - 0.32, p < 0.001, and SMD = - 0.31; 95% CI: - 0.46, - 0.16, p < 0.001). CONCLUSION: This umbrella meta-analysis proposed that vitamin D supplementation may improve T2DM biomarkers.

Vitamin D and Multiple Myeloma: A Scoping Review.

As the global incidence of multiple myeloma (MM) increases, the identification of modifiable risk factors for disease prevention becomes paramount. Maintaining optimal vitamin D status is a candidate for prevention efforts, based on pre-clinical evidence of a possible role in disease activity and progression. A structured scoping review was performed to identify and describe human-level research regarding the association between vitamin D and MM risk and/or prognosis. Searches of three databases (OVID-Medline, OVID-Embase, and OVID-Cochrane Library) yielded 15 included publications. Vitamin D deficiency is fairly common among patients with MM, with 42.3% of participants in the studies identified as having a vitamin D deficiency. No included publication reported on vitamin D status and the risk of developing or being newly diagnosed with MM. Possible associations with vitamin D that warrant future exploration include the incident staging of MM disease, the occurrence of peripheral neuropathy, and survival/prognosis. Vitamin D receptor (VDR) polymorphisms associated with MM also warrant further investigation. Overall, this scoping review was effective in mapping the research regarding vitamin D and MM and may help support new hypotheses to better describe this association and to better address identified knowledge gaps in the literature.

Exploring the Effects of Vitamin D Supplementation on Cognitive Functions and Mental Health Status in Subjects Under Methadone Maintenance Treatment.

OBJECTIVES: Vitamin D deficiency may be linked to several mental complications including cognitive deficits, depression, and anxiety in patients under methadone maintenance treatment (MMT). This study was designed to explore the effect of vitamin D supplementation on cognitive functions and mental health parameters in subjects under MMT. METHODS: This randomized, double-blinded, placebo-controlled clinical trial was carried out among 64 patients under MMT. Participants were randomly allocated to receive either 50,000 IU vitamin D supplements (n = 32) or placebo (n = 32) every 2 weeks for 24 weeks. Cognitive functions and mental health parameters were taken at baseline and posttreatment to evaluate relevant variables. RESULTS: After the 24-week intervention, compared with the placebo, serum 25(OH) vitamin D levels significantly increased in participants who received vitamin D supplements (ß 14.50; 95% confidence interval [CI], 13.17-15.83; P < 0.001). In addition, compared with the placebo, subjects who received vitamin D had a significant reduction in Iowa Gambling Task (ß -6.25; 95% CI, -8.60 to -3.90; P < 0.001), and significant increases in Verbal Fluency Test (ß 2.82; 95% CI, 0.78-4.86; P = 0.007), Immediate Logic Memory (ß 1. 32; 95% CI, 0.27-2.37; P = 0.01), Reverse Digit Span (ß 2.06; 95% CI, 1.18-2.94; P < 0.001) and visual working memory (ß 0.75; 95% CI, 0.33-1.16; P = 0.001). Also, vitamin D supplementation significantly improved BDI (ß -2.76; 95% CI, -3.97 to -1.55; P < 0.001) compared with the placebo. When we applied Bonferroni correction, LM-Immediate (P = 0.07) became nonsignificant, and other mental health parameters did not alter. CONCLUSIONS: Overall, taking 50,000 IU vitamin D supplements every 2 weeks for 24 weeks by patients under MMT had beneficial effects on cognitive functions and some mental health parameters. Further studies are needed to confirm our findings.

The effects of quercetin supplementation on lipid profiles and inflammatory markers among patients with metabolic syndrome and related disorders: A systematic review and meta-analysis of randomized controlled trials.

Aims: This systematic review and meta-analysis of randomized controlled trials (RCTs) was performed to determine the effect of quercetin administration on lipid profiles and inflammatory markers among patients with metabolic syndrome (MetS) and related disorders.Methods: We searched systematically online databases including Cochrane Library, EMBASE, MEDLINE, and Web of Science to identify the relevant RCTs until November 2018. Q-test and I2 statistics were applied to assess heterogeneity among included studies. Data were combined using fixed- or random-effects model and presented as standardized mean difference (SMD) with 95% confidence interval (CI).Results: Out of 591 citations, 16 RCTs were included in the meta-analysis. The pooled findings showed that quercetin consumption significantly decreased total-cholesterol (SMD = -0.98; 95% CI, -1.48, -0.49; p < 0.001; I2: 94.0), LDL-cholesterol (SMD = -0.88; 95% CI, -1.35, -0.41; p < 0.001; I2: 92.7) and C-reactive protein (CRP) levels (-0.64; 95% CI, -1.03, -0.25; p = 0.001; I2: 90.2). While, quercetin supplementation did not significantly affect triglycerides (TG) (SMD = -0.32; 95% CI, -0.68, 0.04; p = 0.08; I2: 84.8), HDL-cholesterol (SMD = 0.20; 95% CI, -0.20, 0.24; p = 0.84; I2: 70.6), interleukin 6 (IL-6) (SMD = -0.69; 95% CI, -1.69, 0.31; p = 0.17; I2: 94.5) and tumor necrosis factor-alpha (TNF-α) levels (SMD = -0.06; 95% CI, -0.25, 0.14; p = 0.58; I2: 35.6)Conclusions: In summary, the current meta-analysis demonstrated that quercetin supplementation significantly reduced total-cholesterol, LDL-cholesterol, and CRP levels, yet did not affect triglycerides, HDL-cholesterol, IL-6 and TNF-α among patients with MetS and related disorders.

Correction: The effects of melatonin supplementation on blood pressure in patients with metabolic disorders: a systematic review and meta-analysis of randomized controlled trials.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

The effects of vitamin D supplementation on muscle function among postmenopausal women: a systematic review and meta-analysis of randomized controlled trials.

The loss of muscle mass and its strength is one of the most critical changes in aging which is associated with an increased risk of falls, osteoporotic fractures and mobility disability. Vitamin D, with its extra-skeletal benefits, might improve muscle function in elderly. The current systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to summarize available relevant data and determine the effect of vitamin D supplementation on muscle function among postmenopausal women. We reached databases including; Cochrane library, Embase, PubMed, and Web of Science database until the end of May 2018 to identify relevant published RCTs. Heterogeneity among included studies was assessed using Q-test and I2 statistics. Random-effect model was applied to pool data and weighted mean difference (WMD) was calculated representing summary effect size. Outcomes of interest included the effects of vitamin D supplementation on hand grip strength (HGS), back muscle strength (BMS), and Timed Up and Go (TUG). Twelve RCTs out of 1739 potential reports were included in our meta-analysis. The pooled findings showed that vitamin D supplementation had no significant effect on HGS (WMD -0.03 kilogram (Kg); 95 % CI, -0.26, 0.20; P=0.78), BMS (WMD 7.21 newton (N); 95 % CI, -5.98, 20.40; P=0.28), and TUG (WMD 0.01 second (S); 95 % CI, -0.17, 0.18; P=0.93) in postmenopausal women. Overall, the current meta-analysis showed that taking vitamin D supplementation by postmenopausal women did not affect markers of muscle function. Further studies are required to confirm the effect of vitamin D supplementation on markers of muscle function.

Could circRNA be a new biomarker for pre-eclampsia?

Pre-eclampsia is a devastating complication of pregnancy which is characterized by hypertension and proteinuria in pregnant women. Pre-eclampsia is important as it is the leading cause of death. Moreover, untreated pre-eclampsia might lead to other lethal complications, for both fetus and mother. Pre-eclampsia can also affect the quality of life in affected women. Despite a large number of risk factors for pre-eclampsia, these risk factors are able to detect just 30% of women who are susceptible to pre-eclampsia. Heterogeneous manifestations of pre-eclampsia necessitate the discovery of potential biomarkers required for its early detection. Circular RNAs (circRNAs) are a type of RNA which are more abundant, specific, and highly organized compared with other types of RNA. Accordingly, circRNAs have been suggested as one of the potential biomarkers for different diseases. Recently, researchers have shown interest in the effects of circRNAs in pre-eclampsia, although the current evidence is limited. The majority of obstetricians are probably not aware of circRNAs as a useful biomarker. Here, we aimed to summarize recent supporting evidence and assess the mechanisms by which circRNAs are involved in pre-eclampsia.

Vitamin D Status in Women with Pelvic Floor Disorders: A Meta-Analysis of Observational Studies.

The current evidence regarding the association between vitamin D status and pelvic floor disorder (PFD) are inconclusive. This meta-analysis was aimed to summarize existing data demonstrating the association between Vitamin D status and PFD using published observational studies. All national and international databases including Web of Science, PubMed, Google Scholar, and Scopus were searched up until January 30, 2018, and related published studies retrieved for meta-analysis. The effect sizes of Vitamin D status were presented as standardized mean difference (SMD) with 95% confidence interval (CI), using random-effect models and inverse variance method. The Cochran Q statistic and I 2 tests were used to evaluate the heterogeneity across included studies. Seven studies with 3219 women were included our meta-analysis. There was heterogeneity existing among included studies (I 2 = 96.4%, P < 0.001), so a random-effect model was used. The findings of this meta-analysis revealed that the mean serum Vitamin D levels in women with PFD were significantly lower than healthy women (SMD -0.60; 95% CI, -1.06, -0.13; P = 0.01). This meta-analysis demonstrates lower levels of serum Vitamin D in women with PFD rather than healthy women. Additional prospective studies regarding the association between Vitamin D status and PFD are required to confirm our findings.

Long-term vitamin D and high-dose n-3 fatty acids' supplementation improve markers of cardiometabolic risk in type 2 diabetic patients with CHD.

This study was performed to evaluate the effects of vitamin D and n-3 fatty acids' co-supplementation on markers of cardiometabolic risk in diabetic patients with CHD. This randomised, double-blinded, placebo-controlled trial was conducted among sixty-one vitamin D-deficient diabetic patients with CHD. At baseline, the range of serum 25-hydroxyvitamin D levels in study participants was 6·3-19·9 ng/ml. Subjects were randomly assigned into two groups either taking 50 000 IU vitamin D supplements every 2 weeks plus 2× 1000 mg/d n-3 fatty acids from flaxseed oil (n 30) or placebo (n 31) for 6 months. Vitamin D and n-3 fatty acids' co-supplementation significantly reduced mean (P = 0·01) and maximum levels of left carotid intima-media thickness (CIMT) (P = 0·004), and mean (P = 0·02) and maximum levels of right CIMT (P = 0·003) compared with the placebo. In addition, co-supplementation led to a significant reduction in fasting plasma glucose (ß -0·40 mmol/l; 95 % CI -0·77, -0·03; P = 0·03), insulin (ß -1·66 µIU/ml; 95 % CI -2·43, -0·89; P < 0·001), insulin resistance (ß -0·49; 95 % CI -0·72, -0·25; P < 0·001) and LDL-cholesterol (ß -0·21 mmol/l; 95 % CI -0·41, -0·01; P = 0·04), and a significant increase in insulin sensitivity (ß +0·008; 95 % CI 0·004, 0·01; P = 0·001) and HDL-cholesterol (ß +0·09 mmol/l; 95 % CI 0·01, 0·17; P = 0·02) compared with the placebo. Additionally, high-sensitivity C-reactive protein (ß -1·56 mg/l; 95 % CI -2·65, -0·48; P = 0·005) was reduced in the supplemented group compared with the placebo group. Overall, vitamin D and n-3 fatty acids' co-supplementation had beneficial effects on markers of cardiometabolic risk.

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.

Effects of Melatonin Supplementation on Hormonal, Inflammatory, Genetic, and Oxidative Stress Parameters in Women With Polycystic Ovary Syndrome.

Purpose: The aim of the current study was to evaluate the effect of melatonin administration on clinical, hormonal, inflammatory, and genetic parameters in women with polycystic ovarian syndrome (PCOS). Methods: The present randomized, double-blinded, placebo-controlled clinical trial was conducted among 56 patients with PCOS, aged 18-40 years old. Subjects were randomly allocated to take either 5 mg melatonin supplements (n = 28) or placebo (n = 28) twice a day for 12 weeks. Results: Melatonin administration significantly reduced hirsutism (ß -0.47; 95% CI, -0.86, -0.09; P = 0.01), serum total testosterone (ß -0.11 ng/mL; 95% CI, -0.21, -0.02; P = 0.01), high-sensitivity C-reactive protein (hs-CRP) (ß -0.61 mg/L; 95% CI, -0.95, -0.26; P = 0.001), and plasma malondialdehyde (MDA) levels (ß -0.25 µmol/L; 95% CI, -0.38, -0.11; P < 0.001), and significantly increased plasma total antioxidant capacity (TAC) levels (ß 106.07 mmol/L; 95% CI, 62.87, 149.28; P < 0.001) and total glutathione (GSH) (ß 81.05 µmol/L; 95% CI, 36.08, 126.03; P = 0.001) compared with the placebo. Moreover, melatonin supplementation downregulated gene expression of interleukin-1 (IL-1) (P = 0.03) and tumor necrosis factor alpha (TNF-α) (P = 0.01) compared with the placebo. Conclusions: Overall, melatonin administration for 12 weeks to women with PCOS significantly reduced hirsutism, total testosterone, hs-CRP, and MDA, while increasing TAC and GSH levels. In addition, melatonin administration reduced gene expression of IL-1 and TNF-α. Clinical Trial Registration: www.irct.ir, identifier IRCT2017082733941N9, Available online at: https://www.irct.ir/trial/26051.

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).

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 crocin on psychological parameters in patients under methadone maintenance treatment: a randomized clinical trial.

BACKGROUND: Methadone maintenance treatment (MMT) might be associated with the symptoms of depression and anxiety, sleep disturbances and sexual dysfunctions. This study was designed to determine the effects of crocin on psychological parameters in patients under MMT. METHODS: Patients under MMT were randomly allocated into two groups to receive either 30 mg/day crocin (2 plus crocin tablet, 15 mg BID) (n = 25) or placebo (2 tablets per day, 15 mg BID) (n = 25), one hour after taking food, for 8 weeks. Psychological parameters were evaluated at baseline and end of the trial to determine related associations between crocin and patients' mental health status. RESULTS: After 8-week intervention, crocin significantly decreased Beck Depression Inventory (b - 6.66; 95% CI, - 9.88, - 3.45; P < 0.0001), Beck Anxiety Inventory (b - 4.35; 95% CI, - 5.94, - 2.75; P < 0.0001), general health questionnaire (b - 4.45; 95% CI, - 7.68, - 1.22; P = 0.008) and Pittsburgh Sleep Quality Index (b - 2.73; 95% CI, - 3.74, - 1.73; P < 0.0001) in patients under MMT, compared with the placebo. Crocin also significantly improved International Index of Erectile Functions (b 4.98; 95% CI, 2.08, 7.88; P = 0.001) rather than placebo. CONCLUSION: Our findings indicated that taking crocin for 8 weeks by patients under MMT had beneficial effects on their mental health status. Crocin can be recommended as an adjunct to methadone in opioid withdrawal protocols because of the ability to improve the quality of life and decrease opioids side effects in these patients. This trial was registered in the Iranian website for clinical trials registry as http://www.irct.ir : IRCT2017110537243N1. CLINICAL TRIAL REGISTRATION NUMBER: www.irct.ir: http://www.irct.ir: IRCT2017110537243N1 .

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.