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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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Renal complications and quality of life in postsurgical hypoparathyroidism: a case-control study.
Mazoni, L, Matrone, A, Apicella, M, Saponaro, F, Borsari, S, Pardi, E, Cosci, B, Biagioni, I, Rossi, P, Pacciardi, F, et al
Journal of endocrinological investigation. 2022;(3):573-582
Abstract
PURPOSE Conventional therapy (calcium and activated vitamin D) does not restore calcium homeostasis in patients with chronic hypoparathyroidism (HypoPT) and is associated with renal complications and reduced quality of life (QoL). The aim of this study was to evaluate in a case-control, cross-sectional study, the rate of renal complications and QoL in two sex- and age-matched cohort of patients with differentiated thyroid cancer with (n = 89) and without (n = 89) chronic post-operative HypoPT (PoHypoPT) and their relationship with the biochemical control of the disease. METHODS Serum and urinary parameters, renal ultrasound and QoL were assessed by SF-36 and WHO-5 questionnaires. RESULTS Forty-three (48.3%) PoHypoPT patients reported symptoms of hypocalcemia. Twenty-six (29.2%) patients were at target for all 6 parameters, 46 (51.6%) for 5. The most frequently unmet targets were gender-specific 24-h urinary calcium (44.9%) and serum calcium (37.1%). Serum phosphate, magnesium and 25(OH)D were in the normal range in > 90% of patients. Renal calcifications were found in 26 (29.2%) patients, with no correlation with 24-h urinary calcium. eGFR did not differ between patients and controls. Conversely, patients had a significant higher rate of renal calcifications and a lower SF-36, but not WHO-5, scores. SF-36 scores did not differ between PoHypoPT patients who were, or not, hypocalcemic. CONCLUSIONS Our study shows that the rate of renal calcifications was higher in patients with PoHypoPT than in those without. This finding, together with the reduced QoL and the presence of hypocalcemic symptoms in about half patients, underscores that the treatment of chronic HypoPT with conventional therapy is suboptimal.
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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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Effects of Vitamin D on Respiratory Function and Immune Status for Patients with Chronic Obstructive Pulmonary Disease (COPD): A Systematic Review and Meta-Analysis.
Yang, H, Sun, D, Wu, F, Xu, X, Liu, X, Wang, Z, Zhou, L
Computational and mathematical methods in medicine. 2022;:2910782
Abstract
BACKGROUND Many studies have demonstrated that vitamin D has clinical benefits when used to treat patients with chronic obstructive pulmonary disease (COPD). However, most of these studies have insufficient samples or inconsistent results. The aim of this meta-analysis was to evaluate the effects of vitamin D therapy in patients with COPD. METHODS We performed a comprehensive retrieval in the following electronic databases: PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang Data, and Chinese Scientific Journals Database (VIP). Two trained reviewers identified relevant studies, extracted data information, and then assessed the methodical quality by the Cochrane risk of bias assessment tool, independently. Then, the meta-analyses were conducted by RevMan 5.4, binary variables were represented by risks ratio (RR), and continuous variables were represented by mean difference (MD) or standardized mean difference (SMD) to assess the efficacy of vitamin D therapy in patients with COPD. Then, publication bias assessment was conducted by funnel plot analysis. Finally, the quality of evidence was assessed by the GRADE system. RESULTS A total of 15 articles involving 1598 participants were included in this study. The overall results showed a statistical significance of vitamin D therapy in patients with COPD which can significantly improve forced expiratory volume in 1 second (FEV1) (MD: 5.69, 95% CI: 5.01-6.38,P < 0.00001,I2 = 51%) and FEV1/FVC (SMD:0.49, 95% CI: 0.39-0.60,P < 0.00001,I2 = 84%); and serum 25 (OH)D (SMD:1.21, 95% CI:1.07-1.34,P < 0.00001,I2 = 98%) also increase CD3+ Tcells (MD: 6.67, 95% CI: 5.34-8.00,P < 0.00001,I2 = 78%) and CD4+ T cells (MD: 6.00, 95% CI: 5.01-7.00,P < 0.00001,I2 = 65%); and T lymphocyte CD4+/CD8+ ratio (MD: 0.41, 95% CI: 0.20-0.61,P = 0.0001,I2 = 95%) obviously decrease CD8+ Tcells(SMD: -0.83, 95% CI: -1.05- -0.06,P < 0.00001,I2 = 82%), the times of acute exacerbation (RR: 0.40, 95% CI: 0.28-0.59,P < 0.00001,I2 = 0%), and COPD assessment test (CAT) score (MD: -3.77, 95% CI: -5.86 - -1.68,P = 0.0004,I2 = 79%). CONCLUSIONS Our analysis indicated that vitamin D used in patients with COPD could improve the lung function (FEV1 and FEV1/FVC), the serum 25(OH)D, CD3+ T cells, CD4 + T cells, and T lymphocyte CD4+/CD8+ ratio and reduce CD8+ T cells, acute exacerbation, and CAT scores.
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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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Effect of Application of Treadmill Training on Metabolic Control and Vitamin D Level in Saudi Patients with Type 2 Diabetes Mellitus.
El Askary, A, Shafie, A, Almehmadi, M, Allam, HH, Elsayyad, LK, Hassan, AF, Althobaiti, BB, Khalifa, MM, Saber, T, Alharthi, AH, et al
Computational and mathematical methods in medicine. 2022;:3059629
Abstract
BACKGROUND Diabetes mellitus type 2 and vitamin D deficiency are both prevalent in the Saudi Arabia. Vitamin D deficiency treatment with supplements carries a risk of intoxication. AIM: The present study is aimed at elucidating the effect of exercise on modulation of metabolic status and vitamin D level in patients with type 2 diabetes mellitus (T2DM). METHODS A sum of 110 type 2 diabetic patients were voluntarily enrolled for the present investigation by dividing them into two separate groups (55 individuals for each group), the diabetic study group and diabetic control group. The diabetic study group was engaged in the training program using treadmill exercise. Laboratory parameters were monitored before and after the training program. RESULTS There were significant elevation in the diabetic study group compared to diabetic control group regarding postexercise vitamin D level, high-density lipoprotein (HDL) (p value ≤ 0.001, 0.045; respectively). In addition, triglycerides, low-density lipoprotein (LDL), glycosylated hemoglobin (HbA1C), and homeostatic model assessment-insulin resistance (HOMA-IR) were significantly decreased (p value < 0.001 for all mentioned parameters). Moreover, there were significant higher level in postexercise parameters as compared to preexercise level in the diabetic study group. CONCLUSION The exercise training program improved the metabolic control and vitamin D level after three months of intervention.
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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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Association between maternal vitamin D levels and risk of adverse pregnancy outcomes: a systematic review and dose-response meta-analysis.
Zhao, R, Zhou, L, Wang, S, Xiong, G, Hao, L
Food & function. 2022;(1):14-37
Abstract
Epidemiological studies have investigated the associations between vitamin D and the risk of adverse pregnancy outcomes; however, the results are conflicting and dose-response relationships remain to be confirmed. This study aimed to summarize previous studies on the associations of vitamin D levels with the risk of gestational diabetes mellitus (GDM), pre-eclampsia (PE), gestational hypertension (GH), and caesarean section (C-section), and to clarify the dose-response trends. PubMed, Embase, Scopus, and Web of Science were searched to identify eligible articles. A total of 69 prospective observational studies including cohort studies, case-cohort studies, or nested case-control studies were included in the current systematic review, of which 68 studies were available for meta-analysis. Compared with the lowest level, the highest level of 25(OH)D was significantly associated with a lower risk of GDM (RR: 0.76; 95% CI: 0.66-0.87), PE (RR: 0.74; 95% CI: 0.60-0.90;), and GH (RR: 0.87; 95% CI: 0.79-0.97); however, no significant relationship was found for C-section (RR: 1.00; 95% CI: 0.90-1.12). There was significant between-study heterogeneity for GDM (I2 = 69.2%; Pheterogeneity < 0.001), PE (I2 = 52.0%; Pheterogeneity = 0.001), and C-section (I2 = 59.1%; Pheterogeneity < 0.001), while no heterogeneity was found for GH (I2 = 0.0%; Pheterogeneity = 0.676). For each 25 nmol L-1 increase in 25(OH)D, the pooled RR was 0.92 (95% CI: 0.86-0.97) for GDM and 0.89 (95% CI: 0.84-0.94) for PE, respectively. Notably, the dose-response analysis showed a non-linear relationship between maternal 25(OH)D levels and the risk of PE (Pnon-linearity = 0.009). Our meta-analysis provides further scientific evidence of the inverse association between 25(OH)D levels and the risk of GDM, PE, and GH, which may be useful for the prevention of pregnancy complications. However, more evidence from prospective studies is needed regarding the dietary intake of vitamin D during pregnancy.
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Vitamin D and nonalcoholic fatty liver disease in children: a randomized controlled clinical trial.
El Amrousy, D, Abdelhai, D, Shawky, D
European journal of pediatrics. 2022;(2):579-586
Abstract
Vitamin D is reported to have anti-inflammatory and insulin-sensitizing effects, yet vitamin D effects on hepatic fat content in children with nonalcoholic fatty liver disease (NAFLD) are not studied sufficiently. We aimed to evaluate the role of vitamin D supplementation on the hepatic fat content and NAFLD progression in children. This randomized controlled clinical trial was performed on 109 children with biopsy-proven NAFLD; only 100 patients completed the study. Patients were randomly assigned into two groups: the treatment group who received 2000 IU/day vitamin D for 6 months and the control group who received a placebo. Anthropometric measurements, vitamin D levels, aspartate aminotransferase (AST), alanine aminotransferase (ALT), total cholesterol (TC), serum triglyceride (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), fasting blood glucose (FBG), fasting blood insulin level (FBI), homeostasis model assessment of insulin resistance (HOMA-IR), and serum calcium level were measured at the beginning and the end of the study. Liver biopsy was taken before and at the end of the study for all included children. There was a significant improvement of the hepatic steatosis and lobular inflammation by liver biopsy in the treatment group after treatment. However, there was no significant effect on the hepatocyte ballooning or hepatic fibrosis. There were significant decrease of AST, ALT, TG, LDL, FBG, FBI, and HOMA-IR and significant increase of vitamin D levels and HDL in the treatment group compared to the placebo group (P < 0.05).Conclusion: Vitamin D supplementation was found to be beneficial in the treatment of NAFLD in children.Trial registration: www.pactr.org , PACTR201710002634203. What is Known: • Nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease in pediatrics. • Several studies reported a negative association between low serum vitamin D level and grades of NAFLD. What is New: • Vitamin D supplementation has significantly decreased hepatic steatosis and lobular inflammation and improved the grades of NAFLD in children, confirmed by liver biopsy, but no effect on hepatocyte ballooning or fibrosis was observed. • Adjuvant vitamin D supplementation is recommended in children with NAFLD.
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Aging Men With Insufficient Vitamin D Have a Higher Mortality Risk: No Added Value of its Free Fractions or Active Form.
Dejaeger, M, Antonio, L, Bouillon, R, Moors, H, Wu, FCW, O'Neill, TW, Huhtaniemi, IT, Rastrelli, G, Forti, G, Maggi, M, et al
The Journal of clinical endocrinology and metabolism. 2022;(3):e1212-e1220
Abstract
CONTEXT Low total 25-hydroxyvitamin D (25(OH)D) has been associated with mortality. Whether vitamin D in its free form or 1,25-dihydroxyvitamin D (1,25(OH)2D), provide any additional information is unclear. OBJECTIVE To determine what level of 25(OH)D is predictive for mortality and if free 25(OH)D or 1,25(OH) 2 D concentrations have any added value. METHODS This prospective cohort comprised 1915 community-dwelling men, aged 40 to 79 years. Intervention included determination of association of total and free 25(OH)D and 1,25(OH) 2 D concentrations with survival status. Vitamin D results were grouped into quintiles. For total 25(OH)D, specific cutoff values were also applied. Cox proportional hazard models were used adjusted for center, body mass index, smoking, alcohol, physical activity, season of blood sample, kidney function, and number of comorbidities. RESULTS A total of 469 (23.5%) men died during a mean follow-up of 12.3 ± 3.4 years. Compared to those with normal vitamin D values (> 30 µg/L), men with a total 25(OH)D of less than 20 µg/L had an increased mortality (hazard ratio [HR] 2.03 [95% CI, 1.39-2.96]; P < .001). Likewise, men in the lowest 3 free 25(OH)D quintiles (< 4.43 ng/L) had a higher mortality risk compared to the highest quintile (HR 2.09 [95% CI, 1.34-3.25]; P < .01). Mortality risks were similar across all 1,25(OH)2D and vitamin D binding protein quintiles. CONCLUSION Aging men with vitamin D deficiency have a 2-fold increased mortality risk. Determinations of either the free fractions of vitamin D or measurement of its active form offer no additional information on mortality risks.