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Vitamin D and multiple health outcomes: umbrella review of systematic reviews and meta-analyses of observational studies and randomised trials.

ABSTRACT: OBJECTIVE:To evaluate the breadth, validity, and presence of biases of the associations of vitamin D with diverse outcomes. DESIGN:Umbrella review of the evidence across systematic reviews and meta-analyses of observational studies of plasma 25-hydroxyvitamin D or 1,25-dihydroxyvitamin D concentrations and randomised controlled trials of vitamin D supplementation. DATA SOURCES:Medline, Embase, and screening of citations and references. ELIGIBILITY CRITERIA:Three types of studies were eligible for the umbrella review: systematic reviews and meta-analyses that examined observational associations between circulating vitamin D concentrations and any clinical outcome; and meta-analyses of randomised controlled trials assessing supplementation with vitamin D or active compounds (both established and newer compounds of vitamin D). RESULTS:107 systematic literature reviews and 74 meta-analyses of observational studies of plasma vitamin D concentrations and 87 meta-analyses of randomised controlled trials of vitamin D supplementation were identified. The relation between vitamin D and 137 outcomes has been explored, covering a wide range of skeletal, malignant, cardiovascular, autoimmune, infectious, metabolic, and other diseases. Ten outcomes were examined by both meta-analyses of observational studies and meta-analyses of randomised controlled trials, but the direction of the effect and level of statistical significance was concordant only for birth weight (maternal vitamin D status or supplementation). On the basis of the available evidence, an association between vitamin D concentrations and birth weight, dental caries in children, maternal vitamin D concentrations at term, and parathyroid hormone concentrations in patients with chronic kidney disease requiring dialysis is probable, but further studies and better designed trials are needed to draw firmer conclusions. In contrast to previous reports, evidence does not support the argument that vitamin D only supplementation increases bone mineral density or reduces the risk of fractures or falls in older people. CONCLUSIONS:Despite a few hundred systematic reviews and meta-analyses, highly convincing evidence of a clear role of vitamin D does not exist for any outcome, but associations with a selection of outcomes are probable.

SUBMITTER: Theodoratou E

PROVIDER: S-EPMC3972415 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Observational studies, randomized controlled trials (RCTs), and Mendelian randomization (MR) studies have yielded inconsistent results on the associations of vitamin D concentrations with multiple health outcomes. In the present umbrella review we aimed to evaluate the effects of low vitamin D concentrations and vitamin D supplementation on multiple health outcomes. We summarized current evidence obtained from meta-analyses of observational studies that examined associations between vitamin D concentrations and multiple health outcomes, meta-analyses of RCTs that investigated the effect of vitamin D supplementation on multiple health outcomes, and MR studies that explored the causal associations of vitamin D concentrations with various diseases (international prospective register of systematic reviews PROSPERO registration number CRD42018091434). A total of 296 meta-analyses of observational studies comprising 111 unique outcomes, 139 meta-analyses of RCTs comprising 46 unique outcomes, and 73 MR studies comprising 43 unique outcomes were included in the present umbrella review. Twenty-eight disease outcomes were identified by both meta-analyses of observational studies and MR studies. Seventeen of these reported disease outcomes had consistent results, demonstrating that lower concentrations of vitamin D were associated with a higher risk for all-cause mortality, Alzheimer's disease, hypertension, schizophrenia, and type 2 diabetes. The combinations of consistent evidence obtained by meta-analyses of observational studies and MR studies together with meta-analyses of RCTs showed that vitamin D supplementation was associated with a decreased risk for all-cause mortality but not associated with the risk for Alzheimer's disease, hypertension, schizophrenia, or type 2 diabetes. The results indicated that vitamin D supplementation is a promising strategy with long-term preventive effects on multiple chronic diseases and thus has the potential to decrease all-cause mortality. However, the current vitamin D supplementation strategy might not be an efficient intervention approach for these diseases, suggesting that new strategies are highly needed to improve the intervention outcomes.

Project description:Objective To map the diverse health outcomes associated with serum uric acid (SUA) levels.Design Umbrella review.Data sources Medline, Embase, Cochrane Database of Systematic Reviews, and screening of citations and references.Eligibility criteria Systematic reviews and meta-analyses of observational studies that examined associations between SUA level and health outcomes, meta-analyses of randomised controlled trials that investigated health outcomes related to SUA lowering treatment, and Mendelian randomisation studies that explored the causal associations of SUA level with health outcomes.Results 57 articles reporting 15 systematic reviews and144 meta-analyses of observational studies (76 unique outcomes), 8 articles reporting 31 meta-analyses of randomised controlled trials (20 unique outcomes), and 36 articles reporting 107 Mendelian randomisation studies (56 unique outcomes) met the eligibility criteria. Across all three study types, 136 unique health outcomes were reported. 16 unique outcomes in meta-analyses of observational studies had P<10-6, 8 unique outcomes in meta-analyses of randomised controlled trials had P<0.001, and 4 unique outcomes in Mendelian randomisation studies had P<0.01. Large between study heterogeneity was common (80% and 45% in meta-analyses of observational studies and of randomised controlled trials, respectively). 42 (55%) meta-analyses of observational studies and 7 (35%) meta-analyses of randomised controlled trials showed evidence of small study effects or excess significance bias. No associations from meta-analyses of observational studies were classified as convincing; five associations were classified as highly suggestive (increased risk of heart failure, hypertension, impaired fasting glucose or diabetes, chronic kidney disease, coronary heart disease mortality with high SUA levels). Only one outcome from randomised controlled trials (decreased risk of nephrolithiasis recurrence with SUA lowering treatment) had P<0.001, a 95% prediction interval excluding the null, and no large heterogeneity or bias. Only one outcome from Mendelian randomisation studies (increased risk of gout with high SUA levels) presented convincing evidence. Hypertension and chronic kidney disease showed concordant evidence in meta-analyses of observational studies, and in some (but not all) meta-analyses of randomised controlled trials with respective intermediate or surrogate outcomes, but they were not statistically significant in Mendelian randomisation studies.Conclusion Despite a few hundred systematic reviews, meta-analyses, and Mendelian randomisation studies exploring 136 unique health outcomes, convincing evidence of a clear role of SUA level only exists for gout and nephrolithiasis.

Project description:BackgroundSleep is closely related to various diseases. Several meta-analyses have provided evidence of sleep and cancer, and yet the credibility of this evidence has not been comprehensively quantified. Thus, we conducted an umbrella review to quantify the evidence for systematic reviews and meta-analyses of observational studies on sleep characteristics (sleep duration, sleep quality, napping, bedtime, and wake-up time) and cancer-related outcomes.MethodsPubMed, Web of Science (Core Collection), and Embase databases were searched from inception until 29 July 2022. Assessment of Multiple Systematic Reviews, version 1, was used to evaluate the methodological quality of each eligible systematic review or meta-analysis. For each association, the summary effect with a 95% confidence interval was evaluated by fixed and random effects models. The 95% prediction interval, heterogeneity, small-study effects, and excess significance bias were also evaluated. Evidence of the associations from systematic reviews and meta-analyses was ranked based on the established criteria of published literature as convincing, highly suggestive, suggestive, weak, or non-significant.ResultsThe umbrella review identified thirty meta-analyses on the aforementioned associations from six articles. The methodological quality of five articles was high or moderate. Suggestive evidence was found for associations between long sleep duration and a 21% increased risk of colorectal cancer, a 9% increased all-cancer mortality and a 65% increased mortality of lung cancer, and associations between short sleep duration and a 21% increased mortality of lung cancer. Additionally, the evidence of associations between short sleep duration and lung cancer mortality was upgraded to convincing, and between long sleep duration and lung cancer mortality was upgraded to highly suggestive, among the population reporting 24 h sleep duration.ConclusionAbnormal sleep duration might be linked to several adverse cancer-related outcomes.

Project description:Background and Aims: The associations between dietary carbohydrate and diverse health outcomes remain controversial and confusing. To summarize the existing evidence of the association between dietary carbohydrate intake and diverse health outcomes and to evaluate the credibility of these sources of evidence. We performed this umbrella review of evidence from meta-analyses of observational studies. Methods: PubMed, Embase, Web of Science databases, and manual screening of references up to July 2020 were searched. Systematic reviews with meta-analyses of observational studies in humans investigating the association between dietary carbohydrate intake and multiple health outcomes were identified. We assessed the evidence levels by using summary effect sizes, 95% prediction intervals, between-study heterogeneity, evidence of small-study effects, and evidence of excess significance bias for each meta-analysis. Results: We included 43 meta-analyses of observational research studies with 23 health outcomes, including cancer (n = 26), mortality (n = 4), metabolic diseases (n = 4), digestive system outcomes (n = 3), and other outcomes [coronary heart disease (n = 2), stroke (n = 1), Parkinson's disease (n = 1), and bone fracture (n = 2)]. This umbrella review summarized 281 individual studies with 13,164,365 participants. Highly suggestive evidence of an association between dietary carbohydrate intake and metabolic syndrome was observed with adjusted summary odds ratio of 1.25 [95% confidence interval (CI) 1.15-1.37]. The suggestive evidences were observed in associations of carbohydrate consumption with esophageal adenocarcinoma (0.57, 95% CI = 0.42-0.78) and all-cause mortality (adjusted summary hazard ratio 1.19, 95% CI = 1.09-1.30). Conclusions: Despite the fact that numerous systematic reviews and meta-analyses have explored the relationship between carbohydrate intake and diverse health outcomes, there is no convincing evidence of a clear role of carbohydrate intake. However, there is highly suggestive evidence suggested carbohydrate intake is associated with high risk of metabolic syndrome, suggestive evidence found its association with increased risk of all-cause mortality and decreased risk of esophageal adenocarcinoma. Systematic Review Registration: CRD42020197424.

Project description:BackgroundOmega-3 polyunsaturated fatty acids are known to be associated with numbers of health benefits, and which can be uptake from fish. The aim of this study was to evaluate the current evidence of associations between consumption of fish and diverse health outcomes. Here, we performed an umbrella review to summarize the breadth, strength, and validity of the evidence derived from meta-analyses and systematic reviews of fish consumption on all health outcomes.MethodsThe methodological quality of the included meta-analyses and the quality of the evidence were assessed by the Assessment of Multiple Systematic Reviews (AMSTAR) and the grading of recommendations, assessment, development, and evaluation (GRADE) tools, respectively. The umbrella review identified 91 meta-analyses with 66 unique health outcomes, of which 32 outcomes were beneficial, 34 showed nonsignificant associations and only one was harmful (myeloid leukemia).ResultsA total of 17 beneficial associations [all-cause mortality, prostate cancer mortality, cardiovascular disease (CVD) mortality, esophageal squamous cell carcinoma (ESCC), glioma, non-Hodgkin lymphoma (NHL), oral cancer, acute coronary syndrome (ACS), cerebrovascular disease, metabolic syndrome, age-related macular degeneration (AMD), inflammatory bowel disease (IBD), Crohn's disease (CD), triglycerides, vitamin D, high-density lipoprotein (HDL)-cholesterol, and multiple sclerosis (MS)], and eight nonsignificant associations [colorectal cancer (CRC) mortality, esophageal adenocarcinoma (EAC), prostate cancer, renal cancer, ovarian cancer, hypertension, ulcerative colitis (UC), and rheumatoid arthritis (RA)] were evaluated as moderate/high quality of evidence. According to dose-response analyses, consumption of fish, especially fatty types, seems generally safe at one-two servings per week and could exert protective effects.ConclusionsFish consumption is often associated with a variety of health outcomes, both beneficial and harmless, but only about 34% of the associations were graded as based on a moderate/high quality of evidence, and additional multicenter high quality randomized controlled trials (RCTs) with a large sample size are needed to verify these findings in the future.

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Vitamin D and multiple health outcomes: umbrella review of systematic reviews and meta-analyses of observational studies and randomised trials.

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