ABSTRACT
CONTEXT: Over the last decade, vitamin D has emerged as a risk determinant for type 2 diabetes and vitamin D supplementation has been hypothesized as a potential intervention to lower diabetes risk. Recently, several trials have reported on the effect of vitamin D supplementation on diabetes prevention in people with prediabetes. EVIDENCE ACQUISITION: A comprehensive literature review was performed using PubMed, Embase, and ClinicalTrials.gov to identify: (1) recent meta-analyses of longitudinal observational studies that report on the association between blood 25-hydroxyvitamin D (25[OH]D) level and incident diabetes, and (2) clinical trials of adults with prediabetes that have reported on the effect of vitamin D supplementation on incident diabetes. EVIDENCE SYNTHESIS: Longitudinal observational studies report highly consistent associations between higher blood 25(OH)D levels and a lower risk of incident diabetes in diverse populations, including populations with prediabetes. Trials in persons with prediabetes show risk reduction in incident diabetes with vitamin D supplementation. In the 3 large trials that were specifically designed and conducted for the prevention of diabetes, vitamin D supplementation, when compared with placebo, reduced the risk of developing diabetes by 10% to 13% in persons with prediabetes not selected for vitamin D deficiency. CONCLUSIONS: Results from recent trials are congruent with a large body of evidence from observational studies indicating that vitamin D has a role in modulating diabetes risk. Participant-level meta-analysis of the 3 largest trials should provide a more refined estimate of risk reduction and identify patient populations that are likely to benefit the most from vitamin D supplementation.
Subject(s)
Diabetes Mellitus, Type 2/prevention & control , Prediabetic State/drug therapy , Vitamin D/administration & dosage , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/epidemiology , Dietary Supplements , Humans , Longitudinal Studies , Observational Studies as Topic/statistics & numerical data , Prediabetic State/epidemiology , Risk Factors , Vitamin D/bloodABSTRACT
OBJECTIVE: To analyze clinical studies on correlations between Traditional Chinese Medicine (TCM) body constitution types and diseases published in the past 10 years, and to provide an evidence base to support the use of such correlations for health maintenance and disease prevention. METHODS: We searched five databases for the period April 2009 to December 2019: China National Knowledge Infrastructure Database, Wanfang Database, China Science and Technology Journal Database, PubMed and Embase. Three types of observational studies on correlation between constitution types and diseases were included: cross-sectional, case-control and cohort studies. Descriptive statistical methods were employed for data analysis. RESULTS: A total of 1639 clinical studies were identified: 1452 (88.59%) cross-sectional studies, 115 (7.02%) case-control studies and 72 (4.39%) cohort studies covering 30 regions of China and five other countries (Malaysia, South Korea, Singapore, Thailand and France). The collection of studies comprised 19 disease categories and 333 different diseases. The 10 most commonly studied diseases were hypertension, diabetes, stroke, coronary atherosclerotic heart disease (CAHD), sleep disorders, neoplasm of the breast, dysmenorrhea, fatty liver disease, chronic viral hepatitis B and dyslipidemia. We found high distributions for each biased constitution type in different patient populations as follows: Qi-deficiency constitution in stroke, diabetes, chronic obstructive pulmonary disease, acquired immunodeficiency syndrome and hypertension; Yang-deficiency constitution in female infertility, osteoporosis, irritable bowel syndrome, gonarthrosis and dysmenorrhea; Yin-deficiency constitution in hypertension, diabetes, constipation, female climacteric states and osteoporosis; phlegm- dampness constitution in hypertension, stroke, fatty liver disease, diabetes and metabolic syndrome; damp-heat constitution in acne, chronic gastritis, chronic viral hepatitis B, human papillomavirus infection and hyperuricemia; blood-stasis constitution in CAHD, endometriosis and stroke; Qi-stagnation constitution in hyperplasia and neoplasms of the breast, insomnia, depression and thyroid nodules; and inherited-special constitution in asthma and allergic rhinitis. CONCLUSION: Eight biased TCM constitutions were closely related to specific diseases, and could be used to guide individualized prevention and treatment. More rigorously designed studies are recommended to further verify the constitution-disease relationship.
Subject(s)
Drug Therapy , Drugs, Chinese Herbal/therapeutic use , Observational Studies as Topic/statistics & numerical data , Humans , Medicine, Chinese Traditional , Treatment OutcomeSubject(s)
Betacoronavirus , Biomedical Research/standards , Coronavirus Infections/epidemiology , Ethics Committees, Research/standards , Pneumonia, Viral/epidemiology , Practice Guidelines as Topic/standards , Research Design/standards , Antiviral Agents/therapeutic use , Biomedical Research/statistics & numerical data , COVID-19 , China/epidemiology , Consent Forms/standards , Consent Forms/statistics & numerical data , Containment of Biohazards/standards , Coronavirus Infections/diagnosis , Coronavirus Infections/therapy , Humans , Interferon-alpha/therapeutic use , Medicine, Chinese Traditional/adverse effects , Observational Studies as Topic/statistics & numerical data , Pandemics , Pneumonia, Viral/diagnosis , Pneumonia, Viral/therapy , Research Design/statistics & numerical data , SARS-CoV-2 , Sample Size , Time Factors , World Health OrganizationABSTRACT
BACKGROUND: Gastric electrical stimulation (GES) for treating gastroparesis symptoms is controversial. METHODS: We studied 319 idiopathic or diabetic gastroparesis symptom patients from the Gastroparesis Clinical Research Consortium (GpCRC) observational studies: 238 without GES and 81 with GES. We assessed the effects of GES using change in GCSI total score and nausea/vomiting subscales between baseline and 48 weeks. We used propensity score methods to control for imbalances in patient characteristics between comparison groups. KEY RESULTS: GES patients were clinically worse (40% severe vs. 18% for non-GES; P < .001); worse PAGI-QOL (2.2. vs. 2.6; P = .003); and worse GCSI total scores (3.5 vs. 2.8; P < .001). We observed improvements in 48-week GCSI total scores for GES vs. non-GES: improvement by ≥ 1-point (RR = 1.63; 95% CI = (1.14, 2.33); P = .01) and change from enrollment (difference = -0.5 (-0.8, -0.3); P < .001). When adjusting for patient characteristics, symptom scores were smaller and not statistically significant: improvement by ≥ 1-point (RR = 1.29 (0.88, 1.90); P = .20) and change from the enrollment (difference = -0.3 (-0.6, 0.0); P = .07). Of the individual items, the nausea improved by ≥ 1 point (RR = 1.31 (1.03, 1.67); P = .04). Patients with GCSI score ≥ 3.0 tended to improve more than those with score < 3.0. (Adjusted P = 0.02). CONCLUSIONS AND INFERENCES: This multicenter study of gastroparesis patients found significant improvements in gastroparesis symptoms among GES patients. Accounting for imbalances in patient characteristics, only nausea remained significant. Patients with greater symptoms at baseline improved more after GES. A much larger sample of patients is needed to fully evaluate symptomatic responses and to identify patients likely to respond to GES.
Subject(s)
Electric Stimulation Therapy , Gastroparesis/therapy , Adolescent , Adult , Aged , Databases, Factual/statistics & numerical data , Diabetic Neuropathies/physiopathology , Diabetic Neuropathies/therapy , Electric Stimulation Therapy/instrumentation , Electric Stimulation Therapy/methods , Electrodes, Implanted , Female , Gastric Emptying , Gastroparesis/etiology , Gastroparesis/physiopathology , Humans , Male , Middle Aged , Nausea/etiology , Nausea/prevention & control , Observational Studies as Topic/statistics & numerical data , Propensity Score , Registries , Retrospective Studies , Severity of Illness Index , Treatment Outcome , Vomiting/etiology , Vomiting/prevention & control , Young AdultABSTRACT
BACKGROUND: Weight loss interventions for obesity, such as bariatric surgery, are associated with reductions in bone mineral density and may increase the risk of fractures. We undertook a systematic review and meta-analysis of bariatric surgery and lifestyle weight management programs (WMPs) with fracture outcomes. METHODS: We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials from 1966 to 2018, and our trial registry of WMP randomized controlled trials (RCTs). We included RCTs, non-randomized trials, and observational studies of bariatric surgery, and RCTs of WMPs. Studies had follow-up ≥ 12 months, mean group body mass index ≥ 30 kg/m2. The primary outcome measure was incidence of any type of fracture in participants, and the secondary outcome was weight change. We used random effects meta-analysis for trial data. RESULTS: Fifteen studies were included. Three small trials provided short-term evidence of the association between bariatric surgery and participants with any fracture (365 participants; RR 0.82; 95% CI 0.29 to 2.35). Four out of six observational studies of bariatric surgery demonstrated significantly increased fracture risk. Six RCTs of WMPs with 6214 participants, the longest follow-up 11.3 years, showed no clear effect on any type of fracture (RR 1.04; 95% CI 0.91 to 1.18), although authors of the largest RCT reported an increased risk of frailty fracture by their definition (RR 1.40; 95% CI 1.04 to 1.90). CONCLUSION: Bariatric surgery appears to increase the risk of any fracture; however, longer-term trial data are needed. The effect of lifestyle WMPs on the risk of any fracture is currently unclear.
Subject(s)
Bariatric Surgery , Fractures, Bone/epidemiology , Obesity, Morbid/epidemiology , Obesity, Morbid/therapy , Weight Loss/physiology , Weight Reduction Programs , Adult , Bariatric Surgery/adverse effects , Bariatric Surgery/methods , Bariatric Surgery/statistics & numerical data , Body Mass Index , Bone Density/physiology , Controlled Clinical Trials as Topic/statistics & numerical data , Female , Fractures, Bone/etiology , Humans , Life Style , Nutrition Therapy , Obesity, Morbid/surgery , Observational Studies as Topic/statistics & numerical data , Randomized Controlled Trials as Topic/statistics & numerical data , Weight Reduction Programs/methods , Weight Reduction Programs/statistics & numerical dataABSTRACT
BACKGROUND: Worldwide, placenta-related complications contribute to adverse pregnancy outcomes, such as pre-eclampsia, fetal growth restriction and preterm birth, with implications for the future health of mothers and offspring. The placenta develops in the periconception period and forms the interface between mother and embryo/fetus. An unhealthy periconceptional maternal lifestyle, such as smoking, alcohol and under- and over-nutrition, can detrimentally influence placental development and function. OBJECTIVE AND RATIONALE: The impact of maternal lifestyle on placental health is largely unknown. Therefore, we aim to summarize the evidence of the impact of periconceptional maternal lifestyle on clinical features and biomarkers of placental development and function throughout pregnancy. SEARCH METHODS: A comprehensive search in Medline, Embase, Pubmed, The Cochrane Library Web of Science and Google Scholar was conducted. The search strategy included keywords related to the maternal lifestyle, smoking, alcohol, caffeine, nutrition (including folic acid supplement intake) and body weight. For placental markers throughout pregnancy, keywords related to ultrasound imaging, serum biomarkers and histological characteristics were used. We included randomized controlled trials and observational studies published between January 2000 and March 2017 and restricted the analysis to singleton pregnancies and maternal periconceptional lifestyle. Methodological quality was scored using the ErasmusAGE tool. A protocol of this systematic review has been registered in PROSPERO International prospective register of systematic reviews (PROSPERO 2016:CRD42016045596). OUTCOMES: Of 2593 unique citations found, 82 studies were included. The median quality score was 5 (range: 0-10). The findings revealed that maternal smoking was associated with lower first-trimester placental vascularization flow indices, higher second- and third-trimester resistance of the uterine and umbilical arteries and lower resistance of the middle cerebral artery. Although a negative impact of smoking on placental weight was expected, this was less clear. Alcohol use was associated with a lower placental weight. One study described higher second- and third-trimester placental growth factor (PlGF) levels after periconceptional alcohol use. None of the studies looked at caffeine intake. Adequate nutrition in the first trimester, periconceptional folic acid supplement intake and strong adherence to a Mediterranean diet, were all associated with a lower resistance of the uterine and umbilical arteries in the second and third trimester. A low caloric intake resulted in a lower placental weight, length, breadth, thickness, area and volume. Higher maternal body weight was associated with a larger placenta measured by ultrasound in the second and third trimester of pregnancy or weighed at birth. In addition, higher maternal body weight was associated with decreased PlGF-levels. WIDER IMPLICATIONS: Evidence of the impact of periconceptional maternal lifestyle on placental health was demonstrated. However, due to poorly defined lifestyle exposures and time windows of investigation, unstandardized measurements of placenta-related outcomes and small sample sizes of the included studies, a cautious interpretation of the effect estimates is indicated. We suggest that future research should focus more on physiological consequences of unhealthy lifestyle during the critical periconception window. Moreover, we foresee that new evidence will support the development of lifestyle interventions to improve the health of mothers and their offspring from the earliest moment in life.
Subject(s)
Fertilization/physiology , Life Style , Placentation/physiology , Pregnancy Complications/physiopathology , Pregnancy Outcome , Biomarkers/blood , Female , Humans , Infant, Newborn , Male , Observational Studies as Topic/statistics & numerical data , Placenta/physiopathology , Pregnancy , Pregnancy Complications/etiology , Pregnancy Outcome/epidemiology , Pregnancy Trimester, First/physiology , Randomized Controlled Trials as Topic/statistics & numerical dataABSTRACT
Randomized clinical trials are considered as the preferred design to assess the potential causal relationships between drugs or other medical interventions and intended effects. For this reason, randomized clinical trials are generally the basis of development programs in the life cycle of drugs and the cornerstone of evidence-based medicine. Instead, randomized clinical trials are not the design of choice for the detection and assessment of rare, delayed and/or unexpected effects related to drug safety. Moreover, the highly homogeneous populations resulting from restrictive eligibility criteria make randomized clinical trials inappropriate to describe comprehensively the safety profile of drugs. In that context, observational studies have a key added value when evaluating the benefit-risk balance of the drugs. However, observational studies are more prone to bias than randomized clinical trials and they have to be designed, conducted and reported judiciously. In this article, we discuss the strengths and limitations of randomized clinical trials and of observational studies, more particularly regarding their contribution to the knowledge of medicines' safety profile. In addition, we present general recommendations for the sensible use of observational data.
Subject(s)
Drug Evaluation, Preclinical/methods , Drug-Related Side Effects and Adverse Reactions/diagnosis , Observational Studies as Topic , Randomized Controlled Trials as Topic , Drug-Related Side Effects and Adverse Reactions/epidemiology , Evidence-Based Medicine , Humans , Observational Studies as Topic/methods , Observational Studies as Topic/statistics & numerical data , Randomized Controlled Trials as Topic/methods , Randomized Controlled Trials as Topic/statistics & numerical data , Research Design , Risk AssessmentSubject(s)
Black or African American/statistics & numerical data , Chronic Disease/epidemiology , Emergencies/epidemiology , Ergocalciferols/administration & dosage , Hospitalization/statistics & numerical data , Adult , Aged , Aged, 80 and over , Chronic Disease/ethnology , Cost of Illness , Dietary Supplements/adverse effects , Dose-Response Relationship, Drug , Emergency Service, Hospital/statistics & numerical data , Ergocalciferols/adverse effects , Humans , Male , Middle Aged , Observational Studies as Topic/statistics & numerical data , Randomized Controlled Trials as Topic/statistics & numerical dataABSTRACT
PURPOSE: The generalisability of randomised controlled trials (RCTs) may be limited by restrictive entry criteria or by their experimental nature. Observational research can provide complementary findings but is prone to bias. Employing propensity score matching, to reduce such bias, we compared the real-life effect of cinacalcet use on all-cause mortality (ACM) with findings from the Evaluation of Cinacalcet Therapy to Lower Cardiovascular Events (EVOLVE) RCT in chronic haemodialysis patients. METHODS: Incident adult haemodialysis patients receiving cinacalcet, recruited in a prospective observational cohort from 2007-2009 (AROii; n = 10,488), were matched to non-exposed patients regardless of future exposure status. The effect of treatment crossover was investigated with inverse probability of censoring weighted and lag-censored analyses. EVOLVE ACM data were analysed largely as described for the primary composite endpoint. RESULTS: AROii patients receiving cinacalcet (n = 532) were matched to 1790 non-exposed patients. The treatment effect of cinacalcet on ACM in the main AROii analysis (hazard ratio 1.03 [95% confidence interval (CI) 0.78-1.35]) was closer to the null than for the Intention to Treat (ITT) analysis of EVOLVE (0.94 [95%CI 0.85-1.04]). Adjusting for non-persistence by 0- and 6-month lag-censoring and by inverse probability of censoring weight, the hazard ratios in AROii (0.76 [95%CI 0.51-1.15], 0.84 [95%CI 0.60-1.18] and 0.79 [95%CI 0.56-1.11], respectively) were comparable with those of EVOLVE (0.82 [95%CI 0.67-1.01], 0.83 [95%CI 0.73-0.96] and 0.87 [95%CI 0.71-1.06], respectively). CONCLUSIONS: Correcting for treatment crossover, we observed results in the 'real-life' setting of the AROii observational cohort that closely mirrored the results of the EVOLVE RCT. Persistence-corrected analyses revealed a trend towards reduced ACM in haemodialysis patients receiving cinacalcet therapy.
Subject(s)
Calcimimetic Agents/therapeutic use , Cinacalcet/therapeutic use , Hyperparathyroidism/drug therapy , Kidney Failure, Chronic/mortality , Observational Studies as Topic/statistics & numerical data , Renal Dialysis/adverse effects , Adult , Aged , Bias , Calcimimetic Agents/administration & dosage , Calcium/blood , Cinacalcet/administration & dosage , Female , Humans , Hyperparathyroidism/etiology , Kidney Failure, Chronic/complications , Kidney Failure, Chronic/therapy , Logistic Models , Male , Middle Aged , Mortality/trends , Phosphorus/blood , Propensity ScoreABSTRACT
BACKGROUND: Some epidemiological studies have suggested that vitamin E intake reduces the risk of pancreatic cancer; however, this conclusion has not been supported by all the published studies. We conducted a meta-analysis to assess the relationship between vitamin E intake and the risk of pancreatic cancer by combining the results from published articles. MATERIAL/METHODS: We searched the published studies that reported the relationship between vitamin E intake and pancreatic cancer risk using the PubMed, Web of Science, and Embase databases through December 31st, 2014. Based on a fixed-effects or random-effects model, the RR and 95% CI were used to assess the combined risk. RESULTS: In total, 10 observational studies (6 case-control studies and 4 cohort studies) were included. The overall RR (95% CI) of pancreatic cancer for the highest vs. the lowest level of vitamin E intake was 0.81 (0.73, 0.89). We found little evidence of heterogeneity (I2=19.8%, P=0.255). In the subgroup analyses, we found an inverse association between vitamin E intake and pancreatic cancer risk both in the case-control and cohort studies. Additionally, this inverse association was not modified by different populations. CONCLUSIONS: In our meta-analysis, there was an inverse association between vitamin E intake and the risk of pancreatic cancer. A high level of vitamin E might be a protective factor for populations at risk for pancreatic cancer.
Subject(s)
Anticarcinogenic Agents , Antioxidants/physiology , Observational Studies as Topic/statistics & numerical data , Pancreatic Neoplasms/epidemiology , Vitamin E/physiology , Adult , Aged , Aged, 80 and over , Anticarcinogenic Agents/administration & dosage , Antioxidants/administration & dosage , Asia/epidemiology , Case-Control Studies , Cohort Studies , Dietary Supplements , Europe/epidemiology , Female , Humans , Male , Middle Aged , Pancreatic Neoplasms/prevention & control , Research Design , Risk , Risk Factors , Sample Size , United States/epidemiology , Vitamin E/administration & dosage , Young AdultABSTRACT
We reviewed recent scientific evidence regarding the effects of multivitamin/mineral (MVM) supplements on risk of chronic diseases, including cancer, cardiovascular disease, and age-related eye diseases. Data from randomized controlled trials (RCTs) and observational, prospective cohort studies were examined. The majority of scientific studies investigating the use of MVM supplements in chronic disease risk reduction reported no significant effect. However, the largest and longest RCT of MVM supplements conducted to date, the Physicians' Health Study II (PHS II), found a modest and significant reduction in total and epithelial cancer incidence in male physicians, consistent with the Supplémentation en Vitamines et Minéraux Antioxydants (SU.VI.MAX) trial. In addition, PHS II found a modest and significant reduction in the incidence of nuclear cataract, in agreement with several other RCTs and observational, prospective cohort studies. The effects of MVM use on other subtypes of cataract and age-related macular degeneration remain unclear. Neither RCTs nor prospective cohort studies are without their limitations. The placebo-controlled trial design of RCTs may be inadequate for nutrient interventions, and residual confounding, measurement error, and the possibility of reverse causality are inherent to any observational study. National surveys show that micronutrient inadequacies are widespread in the US and that dietary supplements, of which MVMs are the most common type, help fulfill micronutrient requirements in adults and children.
Subject(s)
Dietary Supplements/statistics & numerical data , Observational Studies as Topic/statistics & numerical data , Randomized Controlled Trials as Topic/statistics & numerical data , Trace Elements/therapeutic use , Vitamins/therapeutic use , Aging , Cardiovascular Diseases/prevention & control , Chronic Disease , Eye Diseases/prevention & control , Female , Humans , Male , Neoplasms/prevention & control , Prospective Studies , Trace Elements/administration & dosage , Treatment Outcome , Vitamins/administration & dosageABSTRACT
INTRODUCTION: Folic acid (FA) supplementation is recommended worldwide in the periconceptional period for the prevention of neural tube defects. Due to its involvement in a number of cellular processes, its role in other pregnancy outcomes such as miscarriage, recurrent miscarriage, low birth weight, preterm birth (PTB), preeclampsia, abruptio placentae, and stillbirth has been investigated. PTB is a leading cause of perinatal mortality and morbidity; therefore its association with FA supplementation is of major interest. The analysis of a small number of randomized clinical trials (RCTs) has not found a beneficial role of FA in reducing the rate of PTBs. AIM OF THE STUDY: The aim of this review was to examine the results from recent observational studies about the effect of FA supplementation on PTB. MATERIALS AND METHODS: We carried out a search on Medline and by manual search of the observational studies from 2009 onwards that analyzed the rate of PTB in patients who received supplementation with FA before and/or throughout pregnancy. RESULTS: The results from recent observational studies suggest a slight reduction of PTBs that is not consistent with the results from RCTs. Further research is needed to better understand the role of FA supplementation before and during pregnancy in PTB.
Subject(s)
Dietary Supplements/statistics & numerical data , Folic Acid/administration & dosage , MEDLINE/statistics & numerical data , Observational Studies as Topic/statistics & numerical data , Pregnancy/drug effects , Premature Birth/epidemiology , Premature Birth/prevention & control , Adolescent , Adult , Female , Humans , Middle Aged , Prevalence , Risk Factors , Treatment Outcome , Young AdultABSTRACT
BACKGROUND: The iodine status of the French population has been improved since 1952. As iodine requirements increase during pregnancy, the World Health Organization recommended in 2005 systematic iodine supplementation for pregnant women. Our work tried to assess the benefits and risks of iodine supplementation during pregnancy. METHODS: We reviewed the international literature from 1991 to 2011 and consulted the main references databases. Keywords were combined with boolean operators AND and OR. Selected studies were assessed with Consort grid. RESULTS: Among 226 papers, 99 were original articles. After analysis, 13 studies were included in this review. A favorable trend toward iodine supplementation from pregnancy desire to the end of pregnancy was observed. Iodine supplementation may prevent psychomotor and neuro-intellectual disorders. CONCLUSION: Iodine status of pregnant women could be improved before pregnancy by more widespread use of iodized salt and iodine-enriched bread in French households. A randomized controlled trial is recommended to confirm the benefit of iodine supplementation.
Subject(s)
Deficiency Diseases/drug therapy , Iodine/deficiency , Iodine/therapeutic use , Pregnancy Complications/drug therapy , Clinical Trials as Topic/statistics & numerical data , Deficiency Diseases/epidemiology , Dietary Supplements/adverse effects , Female , Humans , Observational Studies as Topic/statistics & numerical data , Pregnancy , Pregnancy Complications/epidemiology , Risk Assessment , Severity of Illness IndexABSTRACT
CONTEXT: Increasing evidence has suggested an association between blood vitamin D levels and metabolic syndrome. OBJECTIVE: Our objective was to determine the relationship between blood vitamin D status and metabolic syndrome in the general adult population, using a dose-response meta-analysis. DATA SOURCE: We searched the PubMed, EMBASE, Web of Science, and Cochrane Library databases through July 2013 to identify relevant studies. STUDY SELECTION: Observational studies, reporting risk ratios with a 95% confidence interval (CI) for metabolic syndrome in ≥3 categories of blood 25-hydroxyvitamin D [25(OH)D] levels, were selected. DATA EXTRACTION: Data extraction was performed independently by 2 authors, and the quality of the studies was evaluated using the risk of bias assessment tool for nonrandomized studies. DATA SYNTHESIS: The pooled odds ratio of metabolic syndrome per 25 nmol/L increment in the serum/plasma 25(OH)D concentration was 0.87 (95% CI = 0.83-0.92, I(2) = 85%), based on 16 "cross-sectional studies" and 1.00 (95% CI = 0.98-1.02, I(2) = 0%) for 2 "cohort and nested case-control studies." The dose-response meta-analysis showed a generally linear, inverse relationship between 25(OH)D levels and metabolic syndrome in the cross-sectional studies (P for linear trend < .001). CONCLUSIONS: Blood vitamin D levels were associated with a risk of metabolic syndrome in cross-sectional studies but not in longitudinal studies. Randomized, clinical trials will be necessary to address the issue of causality and to determine whether vitamin D supplementation is effective for the prevention of metabolic syndrome.