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Effects of multi-domain intervention on intrinsic capacity in older adults: A systematic review of randomized controlled trials (RCTs).
Liao, X, Shen, J, Li, M
Experimental gerontology. 2023;174:112112
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With the increase of age, the physiological reserve of the elderly decreases, which leads to the increase of physical vulnerability and the decrease of anti-stress ability, showing a series of frailty manifestations. Intrinsic capacity (refers to the comprehensive capacity of all physical and mental capacities of an individual) is central to maintaining function in older adults, and maintaining optimal intrinsic capacity is important to promote healthy aging. The aim of this study was to assess randomised controlled trials of multidomain interventions to further validate their effectiveness in the maintenance and enhancement of function in older adults, and to formulate strategies for preventive care and clinical practice. This study was a systematic review and meta-analysis of twenty-five publications. Results showed that multi-domain interventions can improve indicators of vital domains in older adults and integrate to optimise intrinsic capacity (refers to the comprehensive capacity of all physical and mental capacities of an individual) through potential interaction mechanisms. Authors concluded that because older adults may not be able to receive overly complex interventions due to limitations in their integrative abilities, the involvement of older adults and the sustainability of interventions should be considered before implementing them.
Abstract
Intrinsic capacity is central to the maintenance of function in older adults, and maintaining optimal intrinsic capacity is of great importance to promote healthy aging. The purpose of this systematic review and meta-analysis was to analyze the impact of multi-domain interventions on intrinsic capacity in older adults, intervention components, and potential interactions between components. A total of 6740 published articles were screened until August 2022, and the review included 25 randomized controlled trials that analyzed populations, interventions, control groups, and outcomes. The meta-analysis showed improvements in the primary outcome indicators in the intervention group compared to the control group. These included increased scores on the Mini-Mental State Examination as an indicator of cognitive function, decreased scores on the Geriatric Depression Scale (GDS-15) as an indicator of psychological ability and increased scores on the Short Physical Performance Battery (SPPB) as an indicator of physical performance, with only the SPPB indicator analyzed showing greater heterogeneity. Significant improvements were also seen in the secondary indicators Time-to-Walk Test (TUG), gait speed, Chair Stand Test (CST), grip strength values and BMI. There was insufficient data for the Mini Nutritional Assessment (MNA) as an indicator of vitality to conduct a meta-analysis. Studies were of moderate to high quality. The results of this review indicate that multi-domain interventions can maintain the level of intrinsic capacity in older adults and are equally effective in older adults with declining self-care abilities.
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Inverse Association Between Serum 25-Hydroxyvitamin D and Nonalcoholic Fatty Liver Disease.
Yuan, S, Larsson, SC
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2023;21(2):398-405.e4
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The prevalence of non-alcoholic fatty liver disease (NAFLD) is projected to increase due to the obesity epidemic, rise in diabetes prevalence, and other factors. An inverse association between serum 25-hydroxyvitamin D [S-25(OH)D], a clinical marker of vitamin D status, and NAFLD has been observed in several cross-sectional and case-control studies. The aim of this study was to determine the association between S-25(OH)D and NAFLD. This study is a 2-sample Mendelian randomisation study based on summary-level data of genome-wide association analyses on S-25(OH)D levels, NAFLD, and liver enzymes. Results show an inverse genetic correlation of S-25(OH)D with NAFLD and certain liver enzymes and an inverse association of genetically predicted S-25(OH)D with risk of NAFLD in European individuals. Authors conclude that vitamin D may play a role in NAFLD prevention. However, further studies are needed in order to confirm the causal effect of NAFLD on lowering S-25(OH)D levels.
Abstract
BACKGROUND & AIMS Serum 25-hydroxyvitamin D [S-25(OH)D] and nonalcoholic fatty liver disease (NAFLD) are correlated in many observational studies, whereas the causality of this association is uncertain, especially in European populations. We conducted a bidirectional Mendelian randomization study to determine the association between S-25(OH)D and NAFLD. METHODS Seven and 6 independent genetic variants associated with S-25(OH)D and NAFLD at the genome-wide-significance level, respectively, were selected as instrumental variables. Summary-level data for S-25(OH)D were obtained from the Study of Underlying Genetic Determinants of Vitamin D and Highly Related Traits consortium including 79,366 individuals. Summary-level data for NAFLD were available from a genome-wide association meta-analysis (1483 cases and 17,781 controls), the FinnGen consortium (894 cases and 217,898 controls), and the UK Biobank study (275 cases and 360,919 controls). Summary-level data for 4 liver enzymes were obtained from the UK Biobank. RESULTS There were genetic correlations of S-25(OH)D with NAFLD and certain liver enzymes. Genetically predicted higher levels of S-25(OH)D were consistently associated with a decreased risk of NAFLD in the 3 sources. For a 1-SD increase in genetically predicted S-25(OH)D levels, the combined odds ratio of NAFLD was 0.78 (95% confidence interval [CI], 0.69 to 0.89). Genetically predicted higher levels of S-25(OH)D showed a borderline association with aspartate aminotransferase levels (change -1.17; 95% CI, -1.36 to 0.01). Genetic predisposition to NAFLD was not associated with S-25(OH)D (change 0.13; 95% CI, -1.26 to 0.53). CONCLUSIONS Our findings have clinical implications as they suggest that increased vitamin D levels may play a role in NAFLD prevention in European populations.
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Effects of vitamin D treatment on thyroid function and autoimmunity markers in patients with Hashimoto's thyroiditis-A meta-analysis of randomized controlled trials.
Jiang, H, Chen, X, Qian, X, Shao, S
Journal of clinical pharmacy and therapeutics. 2022;47(6):767-775
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Hashimoto's thyroiditis (HT), also called chronic lymphocytic thyroiditis, is the most prevalent organ-specific autoimmune disorder as well as the most common cause of thyroid hypofunction. The main purpose of HT treatment is the control of hypothyroidism, including oral administration of a synthetic hormone to achieve normal circulating thyrotropin levels. The aim of this study was to review the association between vitamin D treatment in patients with HT by assessing patients’ serum circulating 25-hydroxyvitamin D - 25(OH)D - level to evaluate whether a change occurs in the course of disease. This study is a systematic review and meta-analysis of seven cohorts of patients from six studies (3 prospective cohort studies and 3 randomised controlled trials). Results show that vitamin D might significantly increase the serum 25(OH)D levels and produce changes in thyroid peroxidase antibodies titres. However, there wasn't a significant association between serum vitamin D supplementation and the levels of thyroid-stimulating hormone, thyroglobulin antibodies, free triiodothyronine and free thyroxine. Authors conclude that their findings suggest that vitamin D is not associated with the function of the thyroid in patients with HT. Thus, further well-designed randomised controlled trials with sufficient sample sizes investigating the effect of vitamin D on thyroid function are still warranted.
Abstract
INTRODUCTION Recent evidence suggested that vitamin D deficiency was associated with Hashimoto's thyroiditis (HT) pathogenesis and thyroid hypofunction. This study aimed to investigate whether vitamin D supplementation would be effective in the prevention and progression of hypothyroidism in patients with HT. METHODS PubMed, Embase and the Cochrane library were searched for randomized controlled trials (RCTs) and prospective cohort studies published from inception to August 2021. RESULTS A total of 7 cohorts of patients from six clinical trials with 258 patients with HT were included. Significant difference was found (WMD = 19.00, 95% CI: 12.43, 25.58, p < 0.001; I2 = 90.0%, pheterogeneity < 0.001) between the vitamin D group and control group in serum 25-hydroxyvitamin D level. And the combined results indicated vitamin D supplementation significantly reduced the level of thyroid peroxidase antibodies (TPO-Ab) compared to the control group (WMD = -158.18, 95% CI: -301.92, -14.45, p = 0.031; I2 = 68.8%, pheterogeneity = 0.007). Whereas no significant differences were found on the levels of thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxine (FT4) compared to the control group (p > 0.05). WHAT IS NEW AND CONCLUSION Our study demonstrated that vitamin D treatment might significantly increase the serum 25(OH)D levels and produce changes in TPO-Ab titres. No significant association was found between serum vitamin D treatment and the levels of TG-Ab, TSH, FT3 and FT4, suggesting that vitamin D is not associated with the function of the thyroid in patients with HT.
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Prognostic and Therapeutic Role of Vitamin D in COVID-19: Systematic Review and Meta-analysis.
Dissanayake, HA, de Silva, NL, Sumanatilleke, M, de Silva, SDN, Gamage, KKK, Dematapitiya, C, Kuruppu, DC, Ranasinghe, P, Pathmanathan, S, Katulanda, P
The Journal of clinical endocrinology and metabolism. 2022;107(5):1484-1502
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Vitamin D is implicated in optimum function of the immune system. Its deficiency has been linked to susceptibility to respiratory infections. It is postulated that vitamin D deficiency/insufficiency is also associated with COVID-19. The aim of this study was to determine the association between vitamin D deficiency/insufficiency and susceptibility to COVID-19, its severity, mortality and role of vitamin D in its treatment. This study is a systematic review and meta-analysis of seventy-six publications. Results show increased odds of developing COVID-19, progression to severe COVID-19 and death in people with vitamin D deficiency/insufficiency. In fact, people who developed COVID-19, severe COVID-19 and fatal disease had lower 25-hydroxy vitamin D concentration compared to people without COVID-19 or non-severe COVID-19 or non-fatal COVID-19 respectively. Authors conclude that Vitamin D deficiency/insufficiency may increase the risk of developing COVID-19 infection and susceptibility to more severe disease.
Abstract
PURPOSE Vitamin D deficiency/insufficiency may increase the susceptibility to coronavirus disease 2019 (COVID-19). We aimed to determine the association between vitamin D deficiency/insufficiency and susceptibility to COVID-19, its severity, mortality, and role of vitamin D in its treatment. METHODS We searched CINAHL, Cochrane library, EMBASE, PubMED, Scopus, and Web of Science up to May 30, 2021, for observational studies on association between vitamin D deficiency/insufficiency and susceptibility to COVID-19, severe disease, and death among adults, and, randomized controlled trials (RCTs) comparing vitamin D treatment against standard care or placebo, in improving severity or mortality among adults with COVID-19. Risk of bias was assessed using Newcastle-Ottawa scale for observational studies and AUB-KQ1 Cochrane tool for RCTs. Study-level data were analyzed using RevMan 5.3 and R (v4.1.0). Heterogeneity was determined by I2 and sources were explored through prespecified sensitivity analyses, subgroup analyses, and meta-regressions. RESULTS Of 1877 search results, 76 studies satisfying eligibility criteria were included. Seventy-two observational studies were included in the meta-analysis (n = 1 976 099). Vitamin D deficiency/insufficiency increased the odds of developing COVID-19 (odds ratio [OR] 1.46; 95% CI, 1.28-1.65; P < 0.0001; I2 = 92%), severe disease (OR 1.90; 95% CI, 1.52-2.38; P < 0.0001; I2 = 81%), and death (OR 2.07; 95% CI, 1.28-3.35; P = 0.003; I2 = 73%). The 25-hydroxy vitamin D concentrations were lower in individuals with COVID-19 compared with controls (mean difference [MD] -3.85 ng/mL; 95% CI, -5.44 to -2.26; P ≤ 0.0001), in patients with severe COVID-19 compared with controls with nonsevere COVID-19 (MD -4.84 ng/mL; 95% CI, -7.32 to -2.35; P = 0.0001) and in nonsurvivors compared with survivors (MD -4.80 ng/mL; 95% CI, -7.89 to -1.71; P = 0.002). The association between vitamin D deficiency/insufficiency and death was insignificant when studies with high risk of bias or studies reporting unadjusted effect estimates were excluded. Risk of bias and heterogeneity were high across all analyses. Discrepancies in timing of vitamin D testing, definitions of severe COVID-19, and vitamin D deficiency/insufficiency partly explained the heterogeneity. Four RCTs were widely heterogeneous precluding meta-analysis. CONCLUSION Multiple observational studies involving nearly 2 million adults suggest vitamin D deficiency/insufficiency increases susceptibility to COVID-19 and severe COVID-19, although with a high risk of bias and heterogeneity. Association with mortality was less robust. Heterogeneity in RCTs precluded their meta-analysis.
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Effects of Vitamin D Serum Level on Morbidity and Mortality in Patients with COVID-19: A Systematic Review and Meta-Analysis.
Hu, Y, Kung, J, Cave, A, Banh, HL
Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques. 2022;25:84-92
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COVID-19 caused by SARS-CoV-2 infection is associated with severe acute respiratory syndrome resulting from the excessive inflammatory response at 5-7 days. It has been shown that low Vitamin D serum concentration is associated with increased pneumonia and viral respiratory infections. The aim of this study was to determine the clinical effects of Vitamin D serum concentration in COVID-19 patients. This study is a systematic review and meta-analysis of 20 studies. Results show that Vitamin D serum concentration was not statistically associated with mortality and ICU admission, ventilator support requirement, and length of hospital stay. Authors conclude that additional randomized controlled trials are required to provide a specific supplemental vitamin dose and Vitamin D serum concentration.
Abstract
PURPOSE It has been shown that low Vitamin D serum concentration is associated with increased pneumonia and viral respiratory infections. Vitamin D is readily available, inexpensive, and easy to administer to subjects infected with COVID-19. If effective in reducing the severity of COVID-19, it could be an important and feasible therapeutic intervention. METHODS We performed a systematic review and meta-analysis of the literature to determine the effects of Vitamin D serum concentration on mortality and morbidity in COVID-19 patients. The primary objectives were to determine if Vitamin D serum concentration decrease mortality, ICU admissions, ventilator support, and length of hospital stay in COVID-19 patients. RESULTS A total of 3572 publications were identified. Ultimately, 20 studies are included. A total of 12,806 patients aged between 42 to 81 years old were analyzed. The pooled estimated RR for mortality, ICU admission, ventilator support and length of hospital stay were 1.49 (95% CI: 1.34, 1.65), 0.87 (95% CI: 0.67, 1.14), 1.29 (95% CI: 0.79, 1.84), and 0.84 (95% CI -0.45, 2.13). CONCLUSION There is no statistical difference in mortality, ICU admission rate, ventilator support requirement, and length of hospital stay in COVID-19 patients with low and high Vitamin D serum concentration.
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Meta-Analysis of Effects of Nutritional Intervention Combined with Calcium Carbonate D3 Tablets on Bone Mineral Density, Bone Metabolism, and Curative Effect in Patients with Osteoporosis.
Ni, H, Zhang, S, Niu, X, Dai, S
Contrast media & molecular imaging. 2022;2022:3670007
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Osteoporosis is characterised by reduced bone mineral density and changes in bone metabolism, which may increase the risk of bone fractures. Elderly people are more at risk of developing osteoporosis. A calcium carbonate D3 tablet combined with nutritional intervention is commonly recommended by health professionals for the treatment of osteoporosis in the elderly. In this meta-analysis, 10 Chinese literature, 7 high-quality literature and 3 low-quality research were examined to determine the effect of nutritional intervention with calcium carbonate D3 tablets on changes in bone mineral density and bone metabolism in osteoporosis patients. Nutritional intervention in combination with calcium carbonate tablet supplementation showed significant efficacy compared to the use of a single drug. In the combined intervention group, osteocalcin levels, serum alkaline phosphatase levels, serum calcium levels, blood phosphorus levels, and bone mineral density were significantly higher than those in the monotherapy group. This study provides healthcare professionals with an opportunity to gain a better understanding of the efficacy of nutritional intervention coupled with calcium carbonate D3 supplementation on osteocalcin levels, serum alkaline phosphatase levels, serum calcium levels, blood phosphorus levels, and bone mineral density in osteoporosis patients. The validity of the data and the clinical utility of different combinations of therapeutic strategies require further robust research.
Abstract
To investigate the changes in bone mineral density, bone metabolism, and efficacy of nutritional intervention combined with calcium carbonate D3 tablets in patients with osteoporosis, a RevMan 5.2 software meta-analysis was conducted in this study. According to the therapeutic direction of nutritional intervention combined with calcium carbonate D3 tablets for osteoporosis patients, relevant literature were searched in Wanfang Medical, CNKI, VIP, and PubMed literature databases at home and abroad. Keywords included bone mineral density, bone metabolism, blood calcium (Ca), blood phosphorus (P), osteocalcin (OC), bone mineral density (BMD), serum alkaline phosphatase (ALP), efficacy, osteoporosis, and nutritional intervention. Literature that met the criteria were deleted, and meta-analysis was performed using RevMan 5.2 software. The results indicate that a total of 10 Chinese literature were included. Compared with the monotherapy group, the clinical efficacy, osteocalcin, BMD, alkaline phosphatase, calcium, and phosphorus were significantly higher in the combination group (P < 0.05). Based on calcium carbonate D3, treatment combined with nutritional intervention can enhance the clinical efficacy, bone metabolism, and bone mineral density of patients with osteoporosis, and nutritional intervention combined with calcium carbonate D3 tablets is a feasible program to promote the recovery of patients with osteoporosis.
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Vitamin D and miscarriage: a systematic review and meta-analysis.
Tamblyn, JA, Pilarski, NSP, Markland, AD, Marson, EJ, Devall, A, Hewison, M, Morris, RK, Coomarasamy, A
Fertility and sterility. 2022;118(1):111-122
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Miscarriage causes significant physical and psychological harm. Vitamin D deficiency (low serum levels of 25- hydroxyvitamin D) is a major global health concern, with pregnant women and those planning pregnancy at increased risk. The aim of this study was to evaluate the association between vitamin D status and pregnancy loss, including spontaneous miscarriage and recurrent miscarriage. This study is a systematic review and meta-analysis of ten studies (6 where observational studies and 4 interventional studies). Results show that women who were vitamin D deficient were at significantly increased risk of miscarriage compared with those who were vitamin D replete. This association was maintained when women with insufficient levels were included, with a biologic gradient evident. Authors conclude that new evidence-based interventions are required for women at risk of miscarriage.
Abstract
OBJECTIVE To investigate whether a significant association between vitamin D status and the risk of miscarriage or recurrent miscarriage (RM) exists. DESIGN Systematic review and meta-analysis. SETTING Not applicable. PATIENT(S): Women with miscarriage and RM. INTERVENTION(S): We searched the Ovid MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature, and Cochrane Central Register of Controlled Trials from database inception to May 2021. Randomized and observational studies investigating the association between maternal vitamin D status and miscarriage and/or vitamin D treatment and miscarriage were included. MAIN OUTCOME MEASURE(S): The primary outcome was miscarriage or RM, with vitamin D status used as the predictor of risk. Whether vitamin D treatment reduces the risk of miscarriage and RM was also assessed. RESULT(S): Of 902 studies identified, 10 (n = 7,663 women) were included: 4 randomized controlled trials (n = 666 women) and 6 observational studies (n = 6,997 women). Women diagnosed with vitamin D deficiency (<50 nmol/L) had an increased risk of miscarriage compared with women who were vitamin D replete (>75 nmol/L) (odds ratio, 1.94; 95% confidence interval, 1.25-3.02; 4 studies; n = 3,674; I2 = 18%). Combined analysis, including women who were vitamin D insufficient (50-75 nmol/L) and deficient (<50 nmol/L) compared with women who were replete (>75 nmol/L), found an association with miscarriage (odds ratio, 1.60; 95% confidence interval, 1.11-2.30; 6 studies; n = 6,338; I2 = 35%). Although 4 randomized controlled trials assessed the effect of vitamin D treatment on miscarriage, study heterogeneity, data quality, and reporting bias precluded direct comparison and meta-analysis. The overall study quality was "low" or "very low" using the Grading of Recommendations, Assessment, Development and Evaluations approach. CONCLUSION(S): Vitamin D deficiency and insufficiency are associated with miscarriage. Whether preconception treatment of vitamin D deficiency protects against pregnancy loss in women at risk of miscarriage remains unknown. REGISTRATION NUMBER CRD42021259899.
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Systematic review and meta-analysis of candidate gene association studies of benign prostate hyperplasia.
Lin, L, Li, P, Liu, X, Xie, X, Liu, L, Singh, AK, Singh, HN
Systematic reviews. 2022;11(1):60
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Benign prostatic hyperplasia (BPH) is a non-malignant enlargement of the prostate which can cause urinary dysfunction and may affect the quality of life of patients. Polymorphism in several genes has been linked to the high susceptibility of BPH. The aim of this study was to analyse genetic variations in important genes towards the susceptibility of BPH. This study is a systematic review and meta-analysis of twenty-three case-control studies (11 for CYP17 [gene], 10 for VDR - vitamin D receptor [a member of the steroid/ thyroid hormone receptor family] and 4 for ACE - angiotensin-converting enzyme [component of the renin–angiotensin system] polymorphisms). The sample size in each study ranged from 20 to 588 participants. Results show that genetic polymorphism in the ACE gene was significantly associated with the risk of BPH when compared with control subjects. Whereas there was a negative association for the polymorphism located in VDR and CYP17 genes with the risk of BPH. Authors conclude that larger studies with prospective data and larger sample sizes are required.
Abstract
BACKGROUND Benign prostate hyperplasia (BPH) is the most common urological problem in elderly males. Recent studies have reported polymorphism in various metabolic genes in BPH. However, their association with the susceptibility of BPH is still inconsistent. Here, we systematically reviewed and performed a meta-analysis of CYP17, VDR, and ACE genes to determine their precise association with the risk of BPH. METHODS A comprehensive literature search for published studies on candidate gene associations involving vitamin D receptor (VDR), angiotensin-converting enzyme (ACE), and CYP17 genes with the risk of BPH was done up to April 2020 in PubMed, Scopus, Cochrane Central Register of Controlled Trials (CENTRAL), and Google Scholar databases. Fixed/random effects models were used to estimate the odd's ratio (OR) and 95% confidence intervals (CIs). Begg's funnel plot was used to assess the potential for publication bias. RESULTS We found a total of 23 studies containing 3461 cases and 3833 controls for these gene polymorphisms. A significant association of ACE gene polymorphism was observed under the recessive (II vs. ID + DD) model for BPH susceptibility compared to control subjects (overall OR = 1.67, 95% CI = 1.03-2.73). Similar trends were observed for ACE gene polymorphism in Caucasian (OR = 6.18, 95% CI = 1.38-27.68) and Asian (OR = 1.42, 95% CI = 0.99-2.03) populations under study. No significant association was observed in VDR and CYP17 gene polymorphisms in any dominant or recessive models. CONCLUSION Significant OR demonstrated the implication of ACE gene polymorphism in the proliferation of prostate tissue, which in turn is associated with BPH susceptibility. However, prospective studies at large scale and sample size are needed to confirm the current findings.
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Micronutrients Deficiency, Supplementation and Novel Coronavirus Infections-A Systematic Review and Meta-Analysis.
Wang, MX, Gwee, SXW, Pang, J
Nutrients. 2021;13(5)
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Coronaviruses are a family of enveloped RNA viruses capable of infecting both humans and animals. A robust immune system has general protective effects against disease infection and severity. Micronutrients are shown to be fundamental in strengthening and maintaining immune function. The aim of this study was to systematically assess the associations between micronutrient supplementation or deficiency, with novel coronavirus incidence and its associated severity. This study is a systematic review and meta-analysis of 19 studies. Only literature on COVID-19 induced by SARS-CoV-2 were recovered from the systematic search. Results demonstrate significantly reduced odds of COVID-19 incidence, and ICU admissions or severe/critical disease onset in individuals without micronutrient deficiency. Authors conclude that integrating micronutrients into the prevention and therapeutic management of COVID-19 may complement nonpharmaceutical interventions to reduce the risk of transmission and disease severity in an unvaccinated population.
Abstract
BACKGROUND Micronutrients play roles in strengthening and maintaining immune function, but their supplementation and/or deficiency effects on respiratory tract infections are inconclusive. This review aims to systematically assess the associations between micronutrient supplementation or deficiency, with novel coronavirus incidence and disease severity. METHODS Systematic literature searches conducted in five electronic databases identified 751 unique studies, of which 33 studies (five supplementation studies, one supplementation and deficiency study, and 27 deficiency studies) were eventually included in this review. Proportions of incidence and severity outcomes in each group, and adjusted summary statistics with their relevant 95% confidence intervaIs (CI) were extracted. Data from 19 studies were pooled in meta-analysis using the generic inverse variance method. FINDINGS A total of 360,346 patients across 16 countries, with a mean age between 32 and 87.7 years, were involved across 33 studies. All studies were on COVID-19 infections. In individuals without micronutrient deficiency, there was a significant reduction on odds of COVID-19 incidence (pooled OR: 0.37, 95% CI: 0.18, 0.78), and ICU admissions or severe/critical disease onset when combined as a severity outcome (pooled OR: 0.26, 95% CI: 0.08, 0.89). Insignificant protective effects were observed on other outcome measures, namely mortality, ICU admission, progression to respiratory-related complications, severe/critical disease onset or requiring respiratory support and hospitalization rate. CONCLUSION The absence of micronutrient deficiency significantly reduced COVID-19 incidence and clinical deterioration in hospitalized patients. Usage of micronutrients as prophylaxis and complementary supplement in therapeutic management of COVID-19 patients may be a promising and cost-effective approach warranting in-depth investigation.
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Vitamin D supplementation to prevent acute respiratory infections: individual participant data meta-analysis.
Martineau, AR, Jolliffe, DA, Greenberg, L, Aloia, JF, Bergman, P, Dubnov-Raz, G, Esposito, S, Ganmaa, D, Ginde, AA, Goodall, EC, et al
Health technology assessment (Winchester, England). 2019;23(2):1-44
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Low blood levels of vitamin D have been linked to an increased risk of colds, flu and chest infections, collectively termed ‘acute respiratory infections’ (ARIs). The main aim of this study was to determine the overall effect of vitamin D supplementation on the risk of ARI and serious adverse events. The study is a systemic review which included randomised, double-blind, placebo-controlled trials of supplementation with vitamin D3 or vitamin D2 of any duration for analysis. Authors obtained raw data on a total of 10,933 people from 25 trials. Results indicate that vitamin D supplementation reduced the risk of having at least one ARI. Furthermore, vitamin D had greater protective effects when it was given daily or weekly to people with the lowest vitamin D levels: the risk of having at least one ARI was reduced from 60% to 32% in these individuals. Authors conclude that their findings add to the body of evidence supporting the introduction of public health measures, such as food fortification, to improve vitamin D status in settings in which profound vitamin D deficiency is common.
Abstract
BACKGROUND Randomised controlled trials (RCTs) exploring the potential of vitamin D to prevent acute respiratory infections have yielded mixed results. Individual participant data (IPD) meta-analysis has the potential to identify factors that may explain this heterogeneity. OBJECTIVES To assess the overall effect of vitamin D supplementation on the risk of acute respiratory infections (ARIs) and to identify factors modifying this effect. DATA SOURCES MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, ClinicalTrials.gov and the International Standard Randomised Controlled Trials Number (ISRCTN) registry. STUDY SELECTION Randomised, double-blind, placebo-controlled trials of supplementation with vitamin D3 or vitamin D2 of any duration having incidence of acute respiratory infection as a prespecified efficacy outcome were selected. STUDY APPRAISAL Study quality was assessed using the Cochrane Collaboration Risk of Bias tool to assess sequence generation, allocation concealment, blinding of participants, personnel and outcome assessors, completeness of outcome data, evidence of selective outcome reporting and other potential threats to validity. RESULTS We identified 25 eligible RCTs (a total of 11,321 participants, aged from 0 to 95 years). IPD were obtained for 10,933 out of 11,321 (96.6%) participants. Vitamin D supplementation reduced the risk of ARI among all participants [adjusted odds ratio (aOR) 0.88, 95% confidence interval (CI) 0.81 to 0.96; heterogeneity p < 0.001]. Subgroup analysis revealed that protective effects were seen in individuals receiving daily or weekly vitamin D without additional bolus doses (aOR 0.81, 95% CI 0.72 to 0.91), but not in those receiving one or more bolus doses (aOR 0.97, 95% CI 0.86 to 1.10; p = 0.05). Among those receiving daily or weekly vitamin D, protective effects of vitamin D were stronger in individuals with a baseline 25-hydroxyvitamin D [25(OH)D] concentration of < 25 nmol/l (aOR 0.30, 95% CI 0.17 to 0.53) than in those with a baseline 25(OH)D concentration of ≥ 25 nmol/l (aOR 0.75, 95% CI 0.60 to 0.95; p = 0.006). Vitamin D did not influence the proportion of participants experiencing at least one serious adverse event (aOR 0.98, 95% CI 0.80 to 1.20; p = 0.83). The body of evidence contributing to these analyses was assessed as being of high quality. LIMITATIONS Our study had limited power to detect the effects of vitamin D supplementation on the risk of upper versus lower respiratory infection, analysed separately. CONCLUSIONS Vitamin D supplementation was safe, and it protected against ARIs overall. Very deficient individuals and those not receiving bolus doses experienced the benefit. Incorporation of additional IPD from ongoing trials in the field has the potential to increase statistical power for analyses of secondary outcomes. STUDY REGISTRATION This study is registered as PROSPERO CRD42014013953. FUNDING The National Institute for Health Research Health Technology Assessment programme.