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Vitamin D/VDR in the pathogenesis of intervertebral disc degeneration: Does autophagy play a role?
Lan, T, Shen, Z, Hu, Z, Yan, B
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2022;:112739
Abstract
To date, the underlying mechanisms involved intervertebral disc degeneration (IDD) remain unclear, which has hindered the development of molecular biological therapy for IDD. Autophagy is vital for intracellular quality control and metabolic balance in intervertebral disc cells. Hence, autophagy homeostasis is important. Emerging evidence has implicated vitamin D (VD) and the vitamin D receptor (VDR) in IDD progression because of their effects on different autophagy steps. However, the results of clinical trials in which VD supplementation was assessed as a treatment for IDD are controversial. Furthermore, experimental studies on the interplay between VD/VDR and autophagy are still in their infancy. In view of the significance of the crosstalk between VD/VDR and autophagy components, this review focuses on the latest research on VD/VDR modulation in autophagy and investigates the possible regulatory mechanisms. This article will deepen our understanding of the relationship between VD/VDR and autophagy and suggests novel strategies for IDD prevention and treatment.
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Vitamin D supplementation and cardiometabolic risk factors among diverse schoolchildren: a randomized clinical trial.
Sacheck, JM, Huang, Q, Van Rompay, MI, Chomitz, VR, Economos, CD, Eliasziw, M, Gordon, CM, Goodman, E
The American journal of clinical nutrition. 2022;(1):73-82
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Abstract
BACKGROUND There remains a lack of evidence demonstrating a potential relationship between vitamin D and cardiometabolic risk among children. OBJECTIVES We examined the effect of 3 different dosages of vitamin D on cardiometabolic risk factors among children at risk of deficiency. METHODS Racially diverse schoolchildren aged 8-15 y were randomly assigned in a double-blind fashion to supplementation with 600, 1000, or 2000 IU vitamin D3/d for 6 mo. Changes in HDL cholesterol, triglycerides, LDL cholesterol, total cholesterol, and blood glucose over 6 mo and at 12 mo (6 mo post-supplementation) were assessed. Subgroup analyses were also performed by weight status and race. RESULTS Among 604 children, 40.9% were vitamin D-inadequate at baseline (<20 ng/mL; mean ± SD: 22.0 ± 6.8 ng/mL), 46.4% were overweight/obese, and 60.9% had ≥1 suboptimal blood lipids or glucose. Over 6 mo, serum 25-hydroxyvitamin D increased in all 3 dosage groups from baseline (mean ± SE change: 4.4 ± 0.6 ng/mL, 5.7 ± 0.7 ng/mL, and 10.7 ± 0.6 ng/mL for 600, 1000, and 2000 IU/d, respectively; P < 0.001). Whereas HDL cholesterol and triglycerides increased in the 600 IU group (P = 0.002 and P = 0.02, respectively), LDL cholesterol and total cholesterol decreased across dosage groups. At 6 mo post-supplementation, HDL cholesterol remained elevated in the 600 and 1000 IU groups ( P < 0.001 and P = 0.02, respectively) whereas triglycerides remained elevated in the 1000 and 2000 IU groups (P = 0.04 and P = 0.006, respectively). The suppression of LDL cholesterol and total cholesterol persisted in the 2000 IU group only (P = 0.04 and P < 0.001, respectively). There were no significant changes in blood glucose and similar responses were observed overall by weight status and racial groups across dosages. CONCLUSIONS Vitamin D supplementation demonstrated generally positive effects on HDL cholesterol, LDL cholesterol, and total cholesterol, especially at the lower dosage of 600 IU/d, with several significant changes persisting during the post-supplementation period. Increases in triglycerides across dosage groups may be due to natural changes during adolescence warranting further study.This trial was registered at clinicaltrials.gov as NCT01537809.
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Bone Mineral Density Changes in Long-Term Kidney Transplant Recipients: A Real-Life Cohort Study of Native Vitamin D Supplementation.
Battaglia, Y, Bellasi, A, Bortoluzzi, A, Tondolo, F, Esposito, P, Provenzano, M, Russo, D, Andreucci, M, Cianciolo, G, Storari, A
Nutrients. 2022;(2)
Abstract
Vitamin D insufficiency has been associated with reduced bone mineral density (BMD) in kidney transplant patients (KTRs). However, the efficacy of vitamin D supplementation on BMD remains poorly defined, especially for long-term KTRs. We aimed to investigate the effect of native vitamin D supplementation on the BMD of KTRs during a 2-year follow-up. Demographic, clinical, and laboratory data were collected. BMD was evaluated with standard DEXA that was performed at baseline (before vitamin D supplementation) and at the end of study period. BMD was assessed at lumbar vertebral bodies (LV) and right femoral neck (FN) by a single operator. According to WHO criteria, results were expressed as the T-score (standard deviation (SD) relative to young healthy adults) and Z-score (SD relative to age-matched controls). Osteoporosis and osteopenia were defined as a T-score ≤ -2.5 SD and a T-score < -1 and a > -2.5 SD, respectively. Based on plasma levels, 25-OH-vitamin D (25-OH-D) was supplemented as recommended for the general population. Data from 100 KTRs were analyzed. The mean study period was 27.7 ± 3.4 months. At study inception, 25-OH-D insufficiency and deficiency were recorded in 65 and 35 patients. At the basal DEXA, the percentage of osteopenia and osteoporosis was 43.3% and 18.6% at LV and 54.1% and 12.2% at FN, respectively. At the end of the study, no differences in the Z-score and T-score gains were observed. During linear mixed model analysis, native vitamin D supplementation was found to have a negative nitration with Z-score changes at the right femoral neck in KTRs (p < 0.05). The mean dose of administered cholecalciferol was 13.396 ± 7.537 UI per week; increased 25-OH-D levels were found (p < 0.0001). Either low BMD or 25-OH-vitamin D concentration was observed in long-term KTRs. Prolonged supplementation with 25-OH-D did not modify BMD, Z-score, or T-score.
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Does vitamin D deficiency increase the risk of obesity in adults and the elderly? A systematic review of prospective cohort studies.
Pereira, M, Ribas de Farias Costa, P, Miranda Pereira, E, Russoni de Lima Lago, I, Marlucia Oliveira, A
Public health. 2021;:123-131
Abstract
OBJECTIVES Epidemiological studies indicate an association between vitamin D deficiency and obesity. However, there is no consistent evidence of the direction or causal relationship between these conditions. Thus, we analysed the longitudinal relationship between vitamin D deficiency and obesity/adiposity in different age groups. STUDY DESIGN This study was a systematic review with PROSPERO registry (CRD42016047523). METHODS Electronic searches were undertaken in Lilacs, Medline, Science Direct, Scopus and Web of Science databases until April 2020. For each study, we collected the frequency of vitamin D deficiency and obesity. RESULTS In total, 5071 articles were identified and 8 were ultimately included in this systematic review. Five cohort studies involved adults, two of which recorded a positive association between vitamin D deficiency and obesity. The other three studies found a borderline or null association between vitamin D deficiency and obesity. Three studies investigated the elderly population; two of these recorded an association between vitamin D and greater adiposity, and one study recorded that 25-hydroxyvitamin D levels ≥30 ng/ml were associated with less weight gain in the follow-up. CONCLUSIONS This review reports that the majority of studies included show that vitamin D deficiency can contribute to the occurrence of obesity in adults and the elderly. It is recommended that prospective studies are conducted, with varying age groups and weather conditions, designed to test the longitudinal relationship between vitamin D deficiency and obesity outcomes.
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The Role of Vitamin D Supplementation in Children with Autism Spectrum Disorder: A Narrative Review.
Kittana, M, Ahmadani, A, Stojanovska, L, Attlee, A
Nutrients. 2021;(1)
Abstract
Children with autism spectrum disorder (ASD) present with persistent deficits in both social communication and interactions, along with the presence of restricted and repetitive behaviors, resulting in significant impairment in significant areas of functioning. Children with ASD consistently reported significantly lower vitamin D levels than typically developing children. Moreover, vitamin D deficiency was found to be strongly correlated with ASD severity. Theoretically, vitamin D can affect neurodevelopment in children with ASD through its anti-inflammatory properties, stimulating the production of neurotrophins, decreasing the risk of seizures, and regulating glutathione and serotonin levels. A Title/Abstract specific search for publications on Vitamin D supplementation trials up to June 2021 was performed using two databases: PubMed and Cochrane Library. Twelve experimental studies were included in the synthesis of this review. Children with ASD reported a high prevalence of vitamin D deficiency or insufficiency. In general, it was observed that improved vitamin D status significantly reduced the ASD severity, however, this effect was not consistently different between the treatment and control groups. The variations in vitamin D dose protocols and the presence of concurrent interventions might provide an explanation for the variability of results. The age of the child for introducing vitamin D intervention was identified as a possible factor determining the effectiveness of the treatment. Common limitations included a small number of participants and a short duration of follow-ups in the selected studies. Long-term, well-designed randomized controlled trials are warranted to confirm the effect of vitamin D on severity in children with ASD.
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Effect of Vitamin D Deficiency on Liver Cancer Risk: A Systematic Review and Meta-Analysis.
Yi, Z, Wang, L, Tu, X
Asian Pacific journal of cancer prevention : APJCP. 2021;(4):991-997
Abstract
UNLABELLED Epidemiological studies have showed that vitamin D deficiency can increase the risk of liver cancers. Hence, we conducted a meta-analysis to explore the relationship between 25-hydroxyvitamin D [25(OH)D] levels and liver cancer risk. METHODS Cochrane Library, Medline, Web of Science, and Embase were searched up to Mar. 2020, and the references of those studies were also searched by hand. A meta-analysis of 11 studies was performed which met the inclusion criteria. Six case-control studies and five cohort studies were included. RESULTS A total of 11 studies (6 case-control and 5 cohort studies) with 12,895 incident cases were included in the meta-analysis. The meta-analysis showed that liver cancer risk was significantly increased for vitamin D deficiency, and the pooled RR and its 95% CIs was 2.16 (1.2, 3.88; P = 0.01). In comparative analyses between 25(OH)D levels in patients with hepatocellular carcinoma(HCC) and those in the control group individuals, the summary RR of liver cancer was -1.11 (95% CI=-1.96 to -0.25). The subgroup analysis of the different geographical region of the population showed that the risk of liver cancer in Asian subgroup, European subgroup and Egyptian subgroup increased for vitamin D deficiency (RR=1.34,95% CI 0.72 to 2.48, p <0.00001; RR=2.53,95% CI 1.62 to 3.93,p <0.0001;RR=29.5,95% CI 4.14 to 209.93, P=0.88). CONCLUSION The results of this meta-analysis indicate that vitamin D deficiency is associated with increased risk of liver cancer. The 25(OH)D3 levels are lower in HCC patients than those in health controls. Maintenance of sufficient serum vitamin D levels would be beneficial for prevention of liver cancer.
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The relevance of vitamin D in the oral health of HIV infected patients.
Mumena, CH, Mudhihiri, MH, Sasi, R, Mlawa, M, Nyerembe, S, Akimbekov, NS, Razzaque, MS
The Journal of steroid biochemistry and molecular biology. 2021;:105905
Abstract
HIV infection affects 36.9 million people globally, and vitamin D deficiency is a global public health concern for HIV patients. Approximately 70 %-80 % of HIV-infected patients have vitamin D deficiency. The deficiency is associated with many pathologies such as immune disorders, infectious diseases, chronic inflammation, oral diseases, as well as the fast progression of HIV. The causes of vitamin D deficiency in HIV infections include HIV itself, traditional factors such as less sun exposure, mal-absorption, hypercholesterolemia, seasonal variation, poor nutrition as well as some HAART drugs like efavirenz. Vitamin D has an immunomodulatory, anti-inflammatory, and anti-proliferative function. In the oral cavity, it plays a significant role in preventing oral infections such as periodontal and gum diseases, dental caries, and oral candidiasis. The consequences of vitamin D deficiency are bone resorption, increased productions of pro-inflammatory cytokines, T-lymphocytes, increased T-helper-1 functions, and decreased T-helper-2 functions. Consequently, this leads to increased infections, chronic inflammation, and the occurrence of oral diseases such as oral candidiasis, periodontal and gum diseases, and dental caries. The majority of these oral diseases are encountered in HIV patients. Vitamin D deficiency is significantly found in HIV patients. There is a lack of studies that directly link vitamin D to most oral diseases in HIV patients; however, the role of vitamin D in immunoregulation, prevention of oral diseases, and HIV infection is substantiated.
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Vitamin D: Current Challenges between the Laboratory and Clinical Practice.
Máčová, L, Bičíková, M
Nutrients. 2021;(6)
Abstract
Vitamin D is a micronutrient with pleiotropic effects in humans. Due to sedentary lifestyles and increasing time spent indoors, a growing body of research is revealing that vitamin D deficiency is a global problem. Despite the routine measurement of vitamin D in clinical laboratories and many years of efforts, methods of vitamin D analysis have yet to be standardized and are burdened with significant difficulties. This review summarizes several key analytical and clinical challenges that accompany the current methods for measuring vitamin D. According to an external quality assessment, methods and laboratories still produce a high degree of variability. Structurally similar metabolites are a source of significant interference. Furthermore, there is still no consensus on the normal values of vitamin D in a healthy population. These and other problems discussed herein can be a source of inconsistency in the results of research studies.
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Mechanisms Involved in the Relationship between Vitamin D and Insulin Resistance: Impact on Clinical Practice.
Contreras-Bolívar, V, García-Fontana, B, García-Fontana, C, Muñoz-Torres, M
Nutrients. 2021;(10)
Abstract
Recent evidence has revealed anti-inflammatory properties of vitamin D as well as extra-skeletal activity. In this context, vitamin D seems to be involved in infections, autoimmune diseases, cardiometabolic diseases, and cancer development. In recent years, the relationship between vitamin D and insulin resistance has been a topic of growing interest. Low 25-hydroxyvitamin D (25(OH)D) levels appear to be associated with most of the insulin resistance disorders described to date. In fact, vitamin D deficiency may be one of the factors accelerating the development of insulin resistance. Vitamin D deficiency is a common problem in the population and may be associated with the pathogenesis of diseases related to insulin resistance, such as obesity, diabetes, metabolic syndrome (MS) and polycystic ovary syndrome (PCOS). An important question is the identification of 25(OH)D levels capable of generating an effect on insulin resistance, glucose metabolism and to decrease the risk of developing insulin resistance related disorders. The benefits of 25(OH)D supplementation/repletion on bone health are well known, and although there is a biological plausibility linking the status of vitamin D and insulin resistance supported by basic and clinical research findings, well-designed randomized clinical trials as well as basic research are necessary to know the molecular pathways involved in this association.
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The association between vitamin D and acute rejection in human kidney transplantation: A systematic review and meta-analysis study.
Mirzakhani, M, Mohammadkhani, S, Hekmatirad, S, Aghapour, S, Gorjizadeh, N, Shahbazi, M, Mohammadnia-Afrouzi, M
Transplant immunology. 2021;:101410
Abstract
BACKGROUND Vitamin D (VitD) deficiency is associated with several diseases such as multiple sclerosis, rheumatoid arthritis, respiratory infection, and so forth. In the field of transplantation (kidney transplantation), some studies reported that patients with VitD deficiency are of increased chance of acute rejection, but other studies did not show such a chance. On the other hand, since VitD is a modulatory factor and can reduce the inflammatory response, understanding the exact role of it in transplantation may contribute to tolerance condition in these patients. METHODS The electronic databases, including PubMed, Scopus, Embase, ProQuest, Web of Science, and Google Scholar, were searched for eligible studies. In general, 14 studies with a total of 4770 patients were included in this meta-analysis. Regarding the methodological heterogeneity, we selected a random-effects combination model. Moreover, OR was chosen as an effect size for this study. RESULTS After the combination of 14 studies, we showed that patients in the VitD-deficient group had an 82% increased chance of acute rejection compared with patients in the VitD-sufficient group, and this effect was significant (OR 1.82; 95% confidence interval [CI] [1.29, 2.56]; I2 = 52.3%). This result was significant, and, regarding the narrow CI, it can be a conclusive result. Study quality and gender variables were the main sources of inconsistent results in the primary studies. Moreover, using meta-regression, we showed that VitD deficiency (independent from the estimated glomerular filtration rate (eGFR) of patients) increased the chance of acute rejection. CONCLUSION The normal VitD status of patients a few days before and after transplantation can reduce the chance of acute rejection.