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1.
Vitamin D, respiratory infections, and chronic disease: Review of meta-analyses and randomized clinical trials.
Ganmaa, D, Enkhmaa, D, Nasantogtokh, E, Sukhbaatar, S, Tumur-Ochir, KE, Manson, JE
Journal of internal medicine. 2022;(2):141-164
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Abstract
BACKGROUND Observational studies have suggested associations of vitamin D deficiency (VDD) with respiratory tract infections, impaired bone health, and myriad chronic diseases. OBJECTIVE To assess potential causal relationships between vitamin D supplementation and a reduced risk of these conditions, a review of the evidence across available meta-analyses of randomized control trials (RCTs) and RCTs was performed. METHOD PubMed, Embase, Cochrane Library, and Web of Science were searched from their inception to March 2021. We included only RCTs and meta-analyses of RCTs focusing on the association between vitamin D and respiratory disease, bone health, cardiovascular disease (CVD), diabetes mellitus, and cancer. RESULTS A total of 107 RCTs and 62 meta-analysis of RCTs were included. Although most RCTs did not support benefits of vitamin D supplementation, suggestive evidence for benefit was found in populations at greater risk of VDD and for acute respiratory infections, fractures in institutionalized older adults, type 2 diabetes among patients with prediabetes, and cancer mortality. In contrast, no compelling evidence for benefit was found for other respiratory conditions, fractures in community-dwelling adults, falls, cancer incidence, or CVD. CONCLUSIONS Current evidence from RCTs and meta-analyses of RCTs is inconsistent regarding the effects of vitamin D supplementation on respiratory infections and chronic diseases. Individuals most likely to benefit are those with baseline VDD or with selected high-risk conditions. Public health initiatives are needed to eliminate VDD globally, and future research will be enhanced by a 'precision prevention' approach to identify those most likely to benefit from vitamin D supplementation.
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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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The Action of Vitamin D in Adipose Tissue: Is There the Link between Vitamin D Deficiency and Adipose Tissue-Related Metabolic Disorders?
Szymczak-Pajor, I, Miazek, K, Selmi, A, Balcerczyk, A, Śliwińska, A
International journal of molecular sciences. 2022;(2)
Abstract
Adipose tissue plays an important role in systemic metabolism via the secretion of adipocytokines and storing and releasing energy. In obesity, adipose tissue becomes dysfunctional and characterized by hypertrophied adipocytes, increased inflammation, hypoxia, and decreased angiogenesis. Although adipose tissue is one of the major stores of vitamin D, its deficiency is detective in obese subjects. In the presented review, we show how vitamin D regulates numerous processes in adipose tissue and how their dysregulation leads to metabolic disorders. The molecular response to vitamin D in adipose tissue affects not only energy metabolism and adipokine and anti-inflammatory cytokine production via the regulation of gene expression but also genes participating in antioxidant defense, adipocytes differentiation, and apoptosis. Thus, its deficiency disturbs adipocytokines secretion, metabolism, lipid storage, adipogenesis, thermogenesis, the regulation of inflammation, and oxidative stress balance. Restoring the proper functionality of adipose tissue in overweight or obese subjects is of particular importance in order to reduce the risk of developing obesity-related complications, such as cardiovascular diseases and diabetes. Taking into account the results of experimental studies, it seemed that vitamin D may be a remedy for adipose tissue dysfunction, but the results of the clinical trials are not consistent, as some of them show improvement and others no effect of this vitamin on metabolic and insulin resistance parameters. Therefore, further studies are required to evaluate the beneficial effects of vitamin D, especially in overweight and obese subjects, due to the presence of a volumetric dilution of this vitamin among them.
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Critical Appraisal of Large Vitamin D Randomized Controlled Trials.
Pilz, S, Trummer, C, Theiler-Schwetz, V, Grübler, MR, Verheyen, ND, Odler, B, Karras, SN, Zittermann, A, März, W
Nutrients. 2022;(2)
Abstract
As a consequence of epidemiological studies showing significant associations of vitamin D deficiency with a variety of adverse extra-skeletal clinical outcomes including cardiovascular diseases, cancer, and mortality, large vitamin D randomized controlled trials (RCTs) have been designed and conducted over the last few years. The vast majority of these trials did not restrict their study populations to individuals with vitamin D deficiency, and some even allowed moderate vitamin D supplementation in the placebo groups. In these RCTs, there were no significant effects on the primary outcomes, including cancer, cardiovascular events, and mortality, but explorative outcome analyses and meta-analyses revealed indications for potential benefits such as reductions in cancer mortality or acute respiratory infections. Importantly, data from RCTs with relatively high doses of vitamin D supplementation did, by the vast majority, not show significant safety issues, except for trials in critically or severely ill patients or in those using very high intermittent vitamin D doses. The recent large vitamin D RCTs did not challenge the beneficial effects of vitamin D regarding rickets and osteomalacia, that therefore continue to provide the scientific basis for nutritional vitamin D guidelines and recommendations. There remains a great need to evaluate the effects of vitamin D treatment in populations with vitamin D deficiency or certain characteristics suggesting a high sensitivity to treatment. Outcomes and limitations of recently published large vitamin D RCTs must inform the design of future vitamin D or nutrition trials that should use more personalized approaches.
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Polycystic ovarian syndrome-current pharmacotherapy and clinical implications.
Rashid, R, Mir, SA, Kareem, O, Ali, T, Ara, R, Malik, A, Amin, F, Bader, GN
Taiwanese journal of obstetrics & gynecology. 2022;(1):40-50
Abstract
Polycystic ovary syndrome (PCOS), the most common endocrinopathy in women is characterized by polycystic ovaries, chronic anovulation and hyperandrogenism. The treatment in PCOS is mainly symptomatic and involves lifestyle interventions and medications such as Metformin, Oral contraceptives and Antiandrogens. However, the management of PCOS is challenging and current interventions are not able to deal with outcomes of this syndrome. This review encompasses latest pharmacotherapeutic and non-pharmacotherapeutic interventions currently in use to tackle various symptomatic contentions in PCOS. Our focus has been mainly on novel therapeutic modalities for treatment/management of PCOS, like use of newer insulin sensitizers viz., Inositols, Glucagon-like peptide-1(GLP-1) agonists, Dipeptidyl pepdidase-4 (DPP-4) inhibitors, and sodium-glucose transport protein 2 (SGLT2) inhibitors. Also, evidence suggesting the use of vitamin D, statins, and Letrozole as emerging therapies in PCOS have been summarized in this review. Additionally, novel cosmetic techniques like electrolysis, laser and use of topically applied eflornithine to tackle the most distressing feature of facial hirsutism associated with PCOS, non-pharmacological therapy like acupuncture and the role of herbal medicine in PCOS management have also been discussed.
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Vitamin D, Epstein-Barr virus, and endogenous retroviruses in multiple sclerosis - facts and hypotheses.
Brütting, C, Stangl, GI, Staege, MS
Journal of integrative neuroscience. 2021;(1):233-238
Abstract
The pathogenesis of multiple sclerosis (MS) remains poorly understood. Presumably, MS is caused by multiple environmental, epigenetic, and genetic factors. Among them, human endogenous retroviruses (HERVs), Epstein-Barr virus (EBV) and vitamin D have been suggested to play a role in the pathogenesis and course of MS. Because vitamin D can affect the immune system and infections, it can be hypothesized that there is a close interplay between vitamins, EBV and ERV in the pathogenesis of MS. Here, we summarize the important data on vitamin D, including polymorphisms in genes related to vitamin D metabolism, EBV and ERV, in the pathogenesis of MS and create hypotheses regarding their interactions. Data indicate that vitamin D has a strong impact on viral infections and interferes with EBV infection, while EBV is capable of activating silent ERVs. We believe that EBV could be the missing link between vitamin D and ERV in MS pathogenesis.
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Supplementation with vitamin D in the COVID-19 pandemic?
Hadizadeh, F
Nutrition reviews. 2021;(2):200-208
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Abstract
The coronavirus disease 2019 (COVID-19) pandemic was declared a public health emergency of international concern by the World Health Organization. COVID-19 has high transmissibility and could result in acute lung injury in a fraction of patients. By counterbalancing the activity of the renin-angiotensin system, angiotensin-converting enzyme 2, which is the fusion receptor of the virus, plays a protective role against the development of complications of this viral infection. Vitamin D can induce the expression of angiotensin-converting enzyme 2 and regulate the immune system through different mechanisms. Epidemiologic studies of the relationship between vitamin D and various respiratory infections were reviewed and, here, the postulated mechanisms and clinical data supporting the protective role of vitamin D against COVID-19-mediated complications are discussed.
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EFFECTS OF VITAMIN D SUPPLEMENTATION DURING PREGNANCY ON NEWBORNS AND INFANTS: AN INTEGRATIVE REVIEW.
Dutra, LV, Souza, FIS, Konstantyner, T
Revista paulista de pediatria : orgao oficial da Sociedade de Pediatria de Sao Paulo. 2021;:e2020087
Abstract
OBJECTIVE To identify the effects of vitamin D supplementation during pregnancy on newborns and infants. DATA SOURCES The present study is an integrative review of literature based on clinical trials published in journals indexed in the PubMed and Web of Science databases. Two searches were carried out, starting with the association (and) of the health term "vitamin D" with "pregnancy". In the search for information, selection criteria were established, and there was no language limitation and year of publication. DATA SYNTHESIS The final selection resulted in 44 clinical trials, most of which were randomized and double blind, which were carried out in outpatient clinics, referral hospitals and universities, mainly in Europe. The samples studied were predominantly of newborns. In these 44 trials, 23 types of different doses of vitamin D during pregnancy, with different doses, regimens and times of use, and 14 different outcomes were studied in newborns (NB) and infants. Of the 44 studies performed, 35 showed statistically significant beneficial effects of vitamin D supplementation during pregnancy on newborns and infants compared to control groups. CONCLUSIONS Vitamin D supplementation during pregnancy for at least three months before delivery has the potential of positively influencing calcium metabolism, physical growth and immune system development in newborns and infants. However, there is insufficient knowledge to define the optimal dose and to guarantee the absence of possible long-term adverse effects.
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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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Can Optimum Solar Radiation Exposure or Supplemented Vitamin D Intake Reduce the Severity of COVID-19 Symptoms?
Abraham, J, Dowling, K, Florentine, S
International journal of environmental research and public health. 2021;(2)
Abstract
The foremost mortality-causing symptom associated with COVID-19 is acute respiratory distress syndrome (ARDS). A significant correlation has been identified between the deficiency in vitamin D and the risk of developing ARDS. It has been suggested that if we can reduce or modify ARDS in COVID-19 patients, we may significantly reduce the severity of COVID-19 symptoms and associated mortality rates. The increased mortality of dark-skinned people, who have a reduced UV absorption capacity, may be consistent with diminished vitamin D status. The factors associated with COVID-19 mortality, such as old age, ethnicity, obesity, hypertension, cardiovascular diseases, and diabetes, are all found to be linked with vitamin D deficiency. Based on this review and as a precautionary measure, it is suggested that the adoption of appropriate and safe solar exposure and vitamin D enriched foods and supplements should be considered to reduce the possible severity of COVID-19 symptoms. Safe sun exposure is deemed beneficial globally, specifically in low and middle-income countries, as there is no cost involved. It is also noted that improved solar exposure and vitamin D levels can reduce the impact of other diseases as well, thus assisting in maintaining general human well-being.