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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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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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Features of the 1st trimester of pregnancy course with severe deficiency of 25(OH)D.
Bakleicheva, M, Bespalova, O, Kovaleva, I
Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology. 2021;(sup1):49-53
Abstract
INTRODUCTION The course of physiological pregnancy is provided by many complementary factors. Thus, a deficiency in one of the links of the metabolic network contributes to the development of an imbalance in the work of the whole organism, which ensures the growth and development of the embryo from the first days of gestation. It has been demonstrated that vitamin D can act as an immune regulator during implantation, providing a protective effect in the entire period of pregnancy. OBJECTIVE The aim of this study is to assess the features of the course of pregnancy in patients with different levels of vitamin D in the blood in the first trimester. MATERIALS AND METHODS A prospective multicenter randomized study was conducted in the North-West region of the Russian Federation among 88 pregnant women in the first trimester of gestation (up to 13 weeks). All patients were divided into 3 groups depending on the initial level of vitamin D (group 1-14 women with a 25(OH)D < 10 ng/ml, group 2-62 pregnant women from 10 to 30 ng/ml, group 3-12 pregnant women with a vitamin D content >30 ng/ml). INTERVENTIONS Criteria of inclusion: pregnant women from 20 to 44 years of the first trimester of gestation (up to 13 weeks) with the studied level of vitamin D in the blood serum; singleton pregnancy; BMI ≤30 kg/m2; signing by the patient of informed consent for inclusion in the study group. MAIN OUTCOME MEASURES AND RESULTS In group 1, 86% of patients with severe vitamin D deficiency were diagnosed with threatened miscarriage, which is significantly higher than in group 3 (85.7% and 33.3%, χ2 = 7.490, p = .007). At the same time, retrochorial hematoma in group 1 occurred 3.5 times more often than in group 3 (57.1% and 16.67%, respectively, χ2 = 4.473, p = .035). Subsequently, every 4th woman from the group with vitamin D deficiency gave birth earlier than expected, which was not observed among patients from group 3 (25%, 0%, χ2 = 1.231, p = .268). CONCLUSION Prescribing cholecalciferol vitamin replacement therapy as part of complex preserving therapy for threatening miscarriage, followed by monitoring its blood level and deviating from normal parameters, contributing to a favorable course of pregnancy and improving perinatal outcomes.
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Vitamin D and Allergy Susceptibility during Gestation and Early Life.
Briceno Noriega, D, Savelkoul, HFJ
Nutrients. 2021;(3)
Abstract
Worldwide, the prevalence of allergies in young children, but also vitamin D deficiency during pregnancy and in newborns is rising. Vitamin D modulates the development and activity of the immune system and a low vitamin D status during pregnancy and in early life might be associated with an increased risk to develop an allergy during early childhood. This review studies the effects of vitamin D during gestation and early life, on allergy susceptibility in infants. The bioactive form of vitamin D, 1,25(OH)2D, inhibits maturation and results in immature dendritic cells that cause a decreased differentiation of naive T cells into effector T cells. Nevertheless, the development of regulatory T cells and the production of interleukin-10 was increased. Consequently, a more tolerogenic immune response developed against antigens. Secondly, binding of 1,25(OH)2D to epithelial cells induces the expression of tight junction proteins resulting in enhanced epithelial barrier function. Thirdly, 1,25(OH)2D increased the expression of anti-microbial peptides by epithelial cells that also promoted the defense mechanism against pathogens, by preventing an invasive penetration of pathogens. Immune intervention by vitamin D supplementation can mitigate the disease burden from asthma and allergy. In conclusion, our review indicates that a sufficient vitamin D status during gestation and early life can lower the susceptibility to develop an allergy in infants although there remains a need for more causal evidence.
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Potential immunomodulatory effects of vitamin D in the prevention of severe coronavirus disease 2019: An ally for Latin America (Review).
Turrubiates-Hernández, FJ, Sánchez-Zuno, GA, González-Estevez, G, Hernández-Bello, J, Macedo-Ojeda, G, Muñoz-Valle, JF
International journal of molecular medicine. 2021;(4)
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Abstract
Currently, the world is under a pandemic of severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2), responsible for coronavirus disease 2019 (COVID‑19). This disease is characterized by a respiratory syndrome that can progress to an acute respiratory distress syndrome. To date, limited effective therapies are available for the prevention or treatment of COVID‑19; therefore, it is necessary to propose novel treatment options with immunomodulatory effects. Vitamin D serves functions in bone health and has been recently reported to exert protective effects against respiratory infections. Observational studies have demonstrated an association between vitamin D deficiency and a poor prognosis of COVID‑19; this is alarming as vitamin D deficiency is a global health problem. In Latin America, the prevalence of vitamin D deficiency is unknown, and currently, this region is in the top 10 according to the number of confirmed COVID‑19 cases. Supplementation with vitamin D may be a useful adjunctive treatment for the prevention of COVID‑19 complications. The present review provides an overview of the current knowledge of the potential immunomodulatory effects of vitamin D in the prevention of COVID‑19 and sets out vitamin D recommendations for the Latin American population.
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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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Unraveling the roles of vitamin D status and melanin during Covid‑19 (Review).
Sidiropoulou, P, Docea, AO, Nikolaou, V, Katsarou, MS, Spandidos, DA, Tsatsakis, A, Calina, D, Drakoulis, N
International journal of molecular medicine. 2021;(1):92-100
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Abstract
As the coronavirus disease 2019 (COVID‑19) continues to spread worldwide, it has become evident that the morbidity and mortality rates clearly vary across nations. Although several factors may account for this disparity, striking differences within and between populations indicate that ethnicity might impact COVID‑19 clinical outcomes, reflecting the 'color of disease'. Therefore, the role of key biological variables that could interplay with viral spreading and severity indices has attracted increasing attention, particularly among non‑Caucasian populations. Although the links between vitamin D status and the incidence and severity of COVID-19 remain elusive, several lines of emerging evidence suggest that vitamin D signaling, targeting several immune‑mediated pathways, may offer potential benefits at different stages of SARS-CoV-2 infection. Given that the vitamin D status is modulated by several intrinsic and extrinsic factors, including skin type (pigmentation), melanin polymers may also play a role in variable COVID‑19 outcomes among diverse population settings. Moreover, apart from the well‑known limiting effects of melanin on the endogenous production of vitamin D, the potential crosstalk between the pigmentary and immune system may also require special attention concerning the current pandemic. The present review article aimed to shed light on a range of mostly overlooked host factors, such as vitamin D status and melanin pigments, that may influence the course and outcome of COVID‑19.
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Vitamin D: Vitamin or Hormone?
Ellison, DL, Moran, HR
The Nursing clinics of North America. 2021;(1):47-57
Abstract
Vitamin D can be obtained from diet, direct sunlight, or supplementation. The most common form is synthesized in the skin after exposure to ultraviolet B radiation. Nevertheless, the thought is that vitamin D is more of a multifunctional hormone or prohormone. This is because vitamin D plays contributes to many processes in the body. Calcitriol has been shown to have enhancing effects on the immune system, the cardiovascular system, the endocrine system, and other metabolic pathways. There is evidence that vitamin D has also a role in depression, pain, and cancer.