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Vitamin D Supplementation Improves Cognitive Function Through Reducing Oxidative Stress Regulated by Telomere Length in Older Adults with Mild Cognitive Impairment: A 12-Month Randomized Controlled Trial.
Yang, T, Wang, H, Xiong, Y, Chen, C, Duan, K, Jia, J, Ma, F
Journal of Alzheimer's disease : JAD. 2020;(4):1509-1518
Abstract
BACKGROUND Cognitive decline in older adults is a serious public health problem today. Association between vitamin D supplementation and cognition remains controversial. OBJECTIVE To determine whether a 12-month vitamin D supplementation improves cognitive function in elderly subjects with mild cognitive impairment (MCI), and whether it is mediated through the mechanism in which telomere length (TL) regulate oxidative stress. METHODS This was a double-blind, randomized, placebo-controlled trial in Tianjin, China. Participants were all native Chinese speakers aged 65 years and older with MCI. 183 subjects were randomized to an intervention group (vitamin D 800 IU/day, n = 93) or a placebo group (the matching starch granules, n = 90), and followed up for 12 months. Tests of cognitive function and mechanism-related biomarkers were evaluated at baseline, 6 months, and 12 months. RESULTS Repeated-measures ANOVA showed substantial improvements in the full scale intelligence quotient (FSIQ), information, digit span, vocabulary, block design, and picture arrangement scores in the vitamin D group over the placebo group (p < 0.001). Leukocyte TL was significantly higher, while serum 8-OXO-dG, OGG1mRNA, and P16INK4amRNA revealed greater decreases in the vitamin D group over the placebo group (p < 0.001). According to mixed-model repeated-measures ANOVA analysis, vitamin D group showed a significant enhancement in the FSIQ score for 12 months compared with the control (estimate value = 5.132, p < 0.001). CONCLUSION Vitamin D supplementation for 12 months appears to improve cognitive function through reducing oxidative stress regulated by increased TL in order adults with MCI. Vitamin D may be a promising public health strategy to prevent cognitive decline.
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Randomized Study of the Effect of Vitamin D and Omega-3 Fatty Acids Cosupplementation as Adjuvant Chemotherapy on Inflammation and Nutritional Status in Colorectal Cancer Patients.
Haidari, F, Abiri, B, Iravani, M, Ahmadi-Angali, K, Vafa, M
Journal of dietary supplements. 2020;(4):384-400
Abstract
This study aimed to evaluate the effects of vitamin D3 and omega-3 fatty acids cosupplementation on inflammation and nutritional status in colorectal cancer patients. In this clinical trial, 81 colorectal cancer patients were randomly assigned into four groups: (1) control group: receiving a vitamin D3 placebo weekly + omega-3 fatty acid placebo capsules daily; (2) omega-3 fatty acid group: receiving 2 omega-3 fatty acid capsules (each capsule containing 330 mg of omega-3 fatty acids) daily + a vitamin D3 placebo weekly; (3) vitamin D group: receiving a 50,000 IU vitamin D3 soft gel weekly + 2 omega-3 fatty acid placebo capsules daily; (4) cosupplementation group: receiving a 50,000 IU vitamin D3 soft gel weekly + 2 omega-3 fatty acids capsules daily for 8 weeks. Before and after the intervention, height, weight, fat-free mass (FFM), serum levels of 25(OH)D, tumor necrosis factor alpha (TNF-α), and interleukin 6 (IL-6), C-reactive protein (CRP), and albumin, were measured. After 8 weeks of intervention, patients who received combined vitamin D3 and omega-3 fatty acids supplements compared with omega-3, vitamin D3, and placebo groups had significantly decreased CRP and TNF-α. In addition, serum level of IL-6 was decreased significantly in omega-3, vitamin D3, and cosupplementation groups compared with baseline. Regarding nutritional status, weight, BMI, and FFM% were increased significantly in vitamin D3, omega-3, and cosupplementation groups at the end of the intervention. Vitamin D3 plus omega-3 fatty acids cosupplementation in colorectal cancer patients has beneficial impacts on inflammation and nutritional status.
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Improving the endothelial dysfunction in type 2 diabetes with chromium and vitamin D3 byreducing homocysteine and oxidative stress: A randomized placebo-controlled trial.
Imanparast, F, Mashayekhi, FJ, Kamankesh, F, Rafiei, F, Mohaghegh, P, Alimoradian, A
Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS). 2020;:126639
Abstract
BACKGROUND Chromium picolinate (CrPic) and vitamin D3 are known as two antioxidant micronutrients. Through inducing endothelial dysfunction, oxidants such as homocysteine (Hct) and malondialdehyde (MDA) lead to cardiovascular disease in type 2 diabetes mellitus (T2DM). No published data has directly examined the effects of these two antioxidants on improving the endothelial dysfunction in T2DM throughreducing homocysteine and oxidative stress. METHODS Subjects (n = 92) in this randomized, double blind, placebo-control study were randomly assigned to receive oral placebo (group I), D3 (group II: 50,000 IU/ week), chromium picolinate (CrPic) (group III: 500 μg/day), and both vitamin D3 and CrPic (group IV) for four months. Fasting blood samples were drawn at study baseline and following intervention to determine Hct, MDA, total antioxidant capacity (TAC), total thiol groups (SHs), vascular cell adhesion molecule- 1 (VCAM-1), and plasminogen activator inhibitor-1 (PAI-1). RESULTS After intervention, MDA significantly decreased in groups II and IV; TAC significantly increased in group IV, and SHs significantly augmented in group III; Hct was significantly reduced in groups II, III, and IV; and VCAM-1 significantly decreased in groups III and IV and PAI-1 was significantly reduced in groups II, III, and IV. CONCLUSION Our findings suggest that through reducing homocysteine and oxidative stress and improving endothelial dysfunction, chromium and vitamin D3 co-supplementation might be predictive and preventive of cardiovascular diseasesassociated with T2DM. IRCT, IRCT20190610043852N1, registered 21 October 2019, https://fa.irct.ir/user/trial/42293/view.
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Effect of vitamin D3 supplementation on vascular and metabolic health of vitamin D-deficient overweight and obese children: a randomized clinical trial.
Rajakumar, K, Moore, CG, Khalid, AT, Vallejo, AN, Virji, MA, Holick, MF, Greenspan, SL, Arslanian, S, Reis, SE
The American journal of clinical nutrition. 2020;(4):757-768
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BACKGROUND Obese children are vulnerable to vitamin D deficiency and impaired cardiovascular health; vitamin D replenishment might improve their cardiovascular health. OBJECTIVES The aims were to determine, in vitamin D-deficient overweight and obese children, whether supplementation with vitamin D3 1000 or 2000 IU/d is more effective than 600 IU/d in improving arterial endothelial function, arterial stiffness, central and systemic blood pressure (BP), insulin sensitivity (1/fasting insulin concentration), fasting glucose concentration, and lipid profile and to explore whether downregulation of adipocytokines and markers of systemic inflammation underlies vitamin D effects. METHODS We conducted a randomized, double-masked, controlled clinical trial in 225 10- to 18-y-old eligible children. Change in endothelial function at 6 mo was the primary outcome. RESULTS Dose-response increases in serum 25-hydroxyvitamin D concentrations were significant and tolerated without developing hypercalcemia. Changes at 3 and 6 mo in endothelial function, arterial stiffness, systemic-systolic BP, lipids, and inflammatory markers did not differ between children receiving 1000 or 2000 IU vitamin D and children receiving 600 IU. Some secondary outcomes differed between groups. Compared with the 600-IU group, central-systolic, central-diastolic, and systemic-diastolic BP was lower at 6 mo in the 1000-IU group [-2.66 (95% CI: -5.27, -0.046), -3.57 (-5.97, -1.17), and -3.28 (-5.55, -1.00) mm Hg, respectively]; insulin sensitivity increased at 3 and 6 mo and fasting glucose concentration declined at 6 mo (-2.67; 95% CI: -4.88, -0.46 mg/dL) in the 2000-IU group. CONCLUSIONS Correction of vitamin D deficiency in overweight and obese children by vitamin D3 supplementation with 1000 or 2000 IU/d versus 600 IU/d did not affect measures of arterial endothelial function or stiffness, systemic inflammation, or lipid profile, but resulted in reductions in BP and fasting glucose concentration and in improvements in insulin sensitivity. Optimization of children's vitamin D status may improve their cardiovascular health. This trial was registered at clinicaltrials.gov as NCT01797302.
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Evaluation of the effect of vitamin D3 supplementation on quantitative and qualitative parameters of spermograms and hormones in infertile men: A Randomized controlled trial.
Amini, L, Mohammadbeigi, R, Vafa, M, Haghani, H, Vahedian-Azimi, A, Karimi, L, Jahanfar, S, Jamialahmadi, T, Talebi, A, Sahebkar, A
Complementary therapies in medicine. 2020;:102529
Abstract
BACKGROUND 25-Hydroxy Vitamin D3 is known to have an effect on reproductive system in both genders and may change the semen parameters in men. OBJECTIVE Our study aimed to evaluate the effect of oral vitamin D3 supplementation on spermogram quantitative and qualitative parameters in infertile men. MATERIALS AND METHODS This study was a triple-blind randomized controlled trial involving 62 infertile men with impaired spermatogonial tests. They were randomly divided into placebo and D3-supplemented groups. Spermograms and tests for LH (Luteinizing Hormone), FSH (Follicle Stimulating Hormone), TT (Total Testosterone), FT (Free Testosterone), SHBG (Sex Hormone Bonding Globulin), FAI (Free Androgen Index) and vitamin D3 levels were performed before and after the intervention. RESULTS There were no significant differences between the two groups in parameters of the spermograms or serum levels of LH, FSH, TT, and FAI. In the intervention group, SHBG was significantly decreased after intervention (p = 0.01) and there was a significant increase in FT in the placebo group (p = 0.03). CONCLUSION The intake of vitamin D3 did not change the quality and quantity of spermograms and serum levels of LH, FSH, TT, and FAI but affected FT and SHBG. Further studies are still needed to clarify the biological role of vitamin D3 on fertility particularly on male fertility. This study lays a foundation for more extensive studies on male infertility.
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Supplemental 25-Hydroxycholecalciferol Is More Effective than Cholecalciferol in Raising Serum 25-Hydroxyvitamin D Concentrations in Older Adults.
Graeff-Armas, LA, Bendik, I, Kunz, I, Schoop, R, Hull, S, Beck, M
The Journal of nutrition. 2020;(1):73-81
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BACKGROUND There are few studies directly comparing the pharmacokinetics of 25-hydroxycholecalciferol [25(OH)D3] to cholecalciferol (D3). OBJECTIVES The primary objectives were to compare the effectiveness of D3 and 25(OH)D3 in raising 25-hydroxyvitamin D [25(OH)D] serum concentrations and achieving steady state. METHODS This was a randomized, double-blind, active comparator trial of 91 participants (53 females, 38 males), aged 63.3 ± 7.9 y. 25(OH)D3 (10, 15, and 20 µg) and D3 (20 µg) were dosed daily for 6 mo followed by 6 mo of washout. Frequent measurements of serum 25(OH)D were performed. Pharmacokinetic parameters were fitted for each individual and the treatment average was modeled with linear regression using the individual baseline level, sex, and gender as covariates. RESULTS Mean baseline 25(OH)D was similar in all groups (47.1-49.5 nmol/L). Increases in 25(OH)D to steady state were higher in the 25(OH)D3 groups than in the D3 group [least squares (LS) means (95% CI): 50.1 (43.3-58.0), 72.5 (64.3-81.7), 97.4 (86.6-109.6) nmol/L in 10, 15, and 20 µg/d and 38.7 (33.1-45.2) nmol/L in the D3 group; P = 0.0173, P < 0.0001, P < 0.0001]. The rate to reach steady state was similar in all groups, but the time to reach 25(OH)D concentrations of 75 nmol/L was faster in the higher-dosed 25(OH)D3 groups than in the D3 group (7 and 10 d compared with 40 d, P < 0.0001 and P < 0.0001 for 15 and 20 µg/d). The rate of elimination was 59-109% higher in the 25(OH)D3 groups than in the D3 group. The area under the curve (AUC)/µg dose demonstrated that 25(OH)D3 was 3 times as effective as D3 at raising 25(OH)D concentrations. CONCLUSIONS 25(OH)D3 is ∼3 times as effective as D3 at raising 25(OH)D concentrations. Once supplementation is discontinued, the elimination rate of 25(OH)D3 is faster than D3. This trial was registered at clinicaltrials.gov as NCT02333682.
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Correlation of Vitamin D3 with the Expression of RORγt and Foxp3 mRNAs in the Peripheral Blood of Myasthenia Gravis Patients.
Huang, P, He, XY, Xu, M
Neuroimmunomodulation. 2020;(2):97-103
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OBJECTIVES to investigate the expression levels of 1,25(OH)2D3 in the peripheral blood from patients with myasthenia gravis (MG) and to correlate levels with retinoid-related orphan receptor γt (RORγt) and forkhead or winged-helix transcription factor 3 (Foxp3) mRNA expression. METHODS Sixty-seven patients with MG were enrolled in the experimental group, and 50 normal subjects were selected as the control group. The expression levels of 1,25(OH)2D3 and RORγt and Foxp3 mRNAs were measured in the serum of the 2 patient groups and the relationship between factors were correlated with the severity score of MG. The relationship between the levels of 1,25(OH)2D3 and the relative expressions of RORγt and Foxp3 mRNAs was determined. RESULTS There were no differences between groups regarding patient's baseline data. 1,25(OH)2D3 and RORγt and Foxp3 mRNAs are differentially expressed in the MG group and the control group (p < 0.05). QMG score is negatively correlated with the expression level of peripheral blood 1,25(OH)2D3 and Foxp3 mRNA (r = -0.797, -0.543; p < 0.01) and positively correlated with the relative expression level of RORγt mRNA (r = 0.539; p < 0.01). 1,25(OH)2D3 expression level was negatively correlated with the relative expression of RORγt mRNA (r = -0.559; p < 0.01) and positively correlated with the relative expression of Foxp3 mRNA (r = 0.390; p < 0.01). CONCLUSIONS The levels of 1,25(OH)2D3 were shown to be lower in patients with MG compared to normal controls. The observed low levels of 1,25(OH)2D3 may lead to changes in the expression of RORγt and Foxp3 mRNAs involved in MG.
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Vitamin D3 as Potential Treatment Adjuncts for COVID-19.
Malaguarnera, L
Nutrients. 2020;(11)
Abstract
Severe acute respiratory syndrome coronavirus type (SARS-CoV2, also known as COVID-19), which is the latest pandemic infectious disease, constitutes a serious risk to human health. SARS-CoV2 infection causes immune activation and systemic hyperinflammation which can lead to respiratory distress syndrome (ARDS). ARDS victims are characterized by a significant increase in IL-6 and IL-1. Macrophage activation, associated with the "cytokine storm", promotes the dysregulation of the innate immunity. So far, without vaccines or specific therapy, all efforts to design drugs or clinical trials are worthwhile. Vitamin D and its receptor vitamin D receptor (VDR) exert a critical role in infections due to their remarkable impact on both innate and adaptive immune responses and on the suppression of the inflammatory process. The protective properties of vitamin D supplementation have been supported by numerous observational studies and by meta-analysis of clinical trials for prevention of viral acute respiratory infection. In this review, we compare the mechanisms of the host immune response to SARS-CoV2 infection and the immunomodulatory actions that vitamin D exerts in order to consider the preventive effect of vitamin D supplementation on SARS-CoV2 viral infection.
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Effect of Oral Versus Intramuscular Vitamin D Replacement on Oxidative Stress and Outcomes in Traumatic Mechanical Ventilated Patients Admitted to Intensive Care Unit.
Hasanloei, MAV, Rahimlou, M, Eivazloo, A, Sane, S, Ayremlou, P, Hashemi, R
Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition. 2020;(3):548-558
Abstract
BACKGROUND This study aimed to evaluate the safety and efficacy of 2 forms of vitamin D supplementation on oxidative stress and weaning from the ventilator in patients with traumatic injury and vitamin D deficiency. METHODS Seventy-two patients were randomly divided into 3 groups: receiving 50,000 IU pearl cholecalciferol daily for 6 days, 1 intramuscular injection of 300,000 IU of cholecalciferol, or a control group that did not receive any supplement. Duration of mechanical ventilation, body composition, and biochemical biomarkers were measured before and after the intervention. RESULT At the end of the study, the mean serum 25(OH)D increased in the intervention groups compared with the control group (P < .05). The interleukin 6, erythrocyte sedimentation rate, C-reactive protein levels, Sequential Organ Failure Assessment score, duration of mechanical ventilation, and length of intensive care unit admission significantly decreased; however, total antioxidant capacity concentration did not differ significantly between the 2 intervention groups. Among the body composition variables, extracellular water ratio changes were statically different in oral vitamin D group compared with the control group (P = .001). No side effects were reported with the supplements. CONCLUSIONS Vitamin D administration improved clinical signs and biochemical biomarkers in a small group of patients with traumatic injury. Well-designed multicenter clinical studies with longer intervention duration are necessary for this field.
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The Effects of Vitamin D-Enriched Mushrooms and Vitamin D3 on Cognitive Performance and Mood in Healthy Elderly Adults: A Randomised, Double-Blinded, Placebo-Controlled Trial.
Zajac, IT, Barnes, M, Cavuoto, P, Wittert, G, Noakes, M
Nutrients. 2020;(12)
Abstract
Despite abundant cross-sectional evidence that low vitamin D status is associated with risk of cognitive decline in ageing, interventional evidence for benefits of vitamin D supplementation is lacking. This study was a 6 month randomised, double-blinded placebo-controlled clinical trial of the effects of vitamin D3 (D3), enhanced vitamin D2 in a mushroom matrix (D2M), standard mushroom (SM) and placebo (PL) on cognition and mood in n = 436 healthy older male (49%) and female volunteers aged ≥ 60 years. Primary end points were change in serum vitamin D metabolites (25-OH-D, 25-OH-D2 and 25-OH-D3), cognitive performance, and mood over 24 weeks. Levels of total 25-OH-D and 25-OH-D3 were maintained in the D3 arm but decreased significantly (p < 0.05) in the remaining arms (D2M, SM and PL). Analysis also revealed differential changes in these metabolites depending on total vitamin D status at baseline. There were no significant effects of treatment on any of the measures of cognitive function or mood. Overall, the results show that daily supplementation of ~600 IU of vitamin D3 was sufficient to maintain 25-OH-D throughout winter months, but in contrast to existing cross-sectional studies there was no support for benefit of vitamin D supplementation for mood or cognition in healthy elderly people.