Magnesium and Metabolic Syndrome: A Dose-response Meta-analysis
Condition: Metabolic Syndrome X; Insulin Resistance Syndrome X; Metabolic Cardiovascular Syndrome; Dysmetabolic Syndrome X
MeSH terms: Microvascular Angina; Metabolic Syndrome; Insulin Resistance; Syndrome
Study type: Observational

Summary: 
      Magnesium is an essential mineral found in many foods; rich sources include whole grains,
      green leafy vegetables, coffee, and legumes. Magnesium is a critical cofactor in >300
      enzymatic reactions, including those related to energy metabolism. Reduced magnesium intake
      and serum concentrations have been detected, both cross-sectionally and prospectively,in type
      2 diabetes and insulin resistance, hypertension, dyslipidemia, and cardiovascular diseases.

      Different studies have reported inadequate magnesium intake and low serum magnesium
      concentrations may correlated also with metabolic syndrome, defined as a cluster of metabolic
      disorders including obesity, hypertension, dyslipidemia and impaired glucose tolerance or
      diabetes mellitus. Previous studies on this subject, however, reported contradicting results.
      Some investigations reported inadequate magnesium intake and low serum magnesium
      concentrations while others did not.

      To our knowledge, the epidemiological evidence on the relation between dietary magnesium
      intake and risk of metabolic syndrome has not yet been summarized.Therefore, the
      investigators will perform a systematic review and dose-response meta-analysis to assess the
      association between dietary and circulating magnesium level and risk of metabolic syndrome.
    

Detailed description: 
      Background: Increasing evidence has suggested inadequate magnesium intake and low serum
      magnesium concentrations may correlated with metabolic syndrome. However, whether or not
      dietary or circulating magnesium at usual intakes or concentrations influences risk of
      metabolic syndrome is inconsistent

      Objective:To our knowledge, the epidemiological evidence on the relation between dietary
      magnesium intake and risk of metabolic syndrome has not yet been summarized.Therefore, to
      improve evidence-based guidance for dietary guidelines, the investigators will perform a
      systematic review and dose-response meta-analysis to assess the association between dietary
      and circulating magnesium level and risk of metabolic syndrome.

      Design: The planning, conduct and reporting of the proposed meta-analyses will follow
      Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines.

      Data search and screening: The PubMed, Cochrane CENTRAL, and EMBASE databases via Elsevier
      will be searched using appropriate search terms.

      Study selection: Published articles will be included: Randomized, controlled studies,
      case-control studies, cross-sectional studies and cohort studies. All studies enrolled adults
      (age 18 years) and reported metabolic syndrome as the outcome of interest and magnesium
      intake or serum magnesium concentration as a risk factor or intervention. They reported
      adjusted risk ratios, including odds ratios, relative risks, hazard ratios with 95%
      confidence intervals (CIs), or they reported sufficient data to calculate these values for 3
      or more quantitative categories of dietary magnesium intake levels. They reported risk ratios
      with metabolic syndrome criteria according to the National Cholesterol Education Panel
      (NCEP), modified NCEP, American Heart Association/National Heart Lung and Blood Institute ,
      and harmonized definition . The investigators selected articles written in English that were
      published in their entirety.

      Data extraction: Titles and/or abstracts of studies retrieved using the search strategy will
      be screened independently by two review investigators to identify studies that potentially
      meet the inclusion criteria outlined above. The full text of these potentially eligible
      studies will be retrieved and independently assessed for eligibility by two investigators
      with disagreements being resolved by consensus. Data will be extracted from
      multivariate-adjusted models.

      Extracted information will included: first author's surname, publication year, name of the
      cohort study, study location (nation), years of follow-up (in case of cohort study design),
      sex, age, sample size (prevalence of metabolic syndrome and total number of participants),
      dietary magnesium intake(mg/day), serum magnesium concentration, covariates adjusted for in
      the multivariable analysis, and risk ratios with their 95% confidence intervals for each
      category of dietary magnesium intake and serum magnesium concentrations. The investigators
      will extract risk ratios that reflect the greatest degree of adjustment for potential
      confounders. The study investigator will assess the risk of bias in included studies using a
      tool for assessing the risk of bias for nonrandomized studies (RoBANs) which contain the
      following eight domains: comparability of groups, selection of participants, confounding
      variables, measurement of exposure, blinding of outcome assessment, adequacy of outcome
      assessment, incomplete outcome data and selective outcome reporting.

      Domains of RoBANs have the following characteristics:

      Comparability of groups: Selection bias caused by the inadequate selection of comparable
      groups.

      Selection of participants: Selection bias caused by the inadequate selection of participants.

      Measurement of exposure: Performance bias caused by the inadequate confirmation and
      consideration of confounding variable.

      Blinding of outcome assessments: Detection bias caused by the inadequate blinding of outcome
      assessments.

      Incomplete outcome data: Attrition bias caused by the inadequate handling of incomplete
      outcome data.

      Selective outcome reporting: Reporting bias caused by the selective reporting of outcome.

      Adequacy of outcome assessments: Performance bias caused by the inadequate confirmation of
      outcomes.

      RoBANS was developed to be used for the assessment of all study designs except for randomized
      controlled studies. RoBANS includes criteria for judging the risk of bias for each domain.
      Any discrepancies will be checked with the study investigator. A final copy of the form from
      each trial will be checked with the appropriate trial investigator for verification.

      Outcomes: The investigators will perform a two stage random-effects dose-risk meta-analysis
      to examine a linear dose-response relationship between dose of magnesium intake and metabolic
      syndrome using a generalized least-squares method taking into account random effects. This
      method constructs a covariance estimate for dose-specific log relative risks (RRs) within
      each study and then estimates the dose-response relation, accounting for between- and
      within-study variation. Reported hazard ratios and odds ratios were assumed to approximate
      RRs.

      For the dose-response meta-analysis, The investigators will generalized least-squares
      regression (GLST), which take into account the correlation between estimates for different
      expose level, to compute study-specific slopes. This method requires that the number of cases
      and controls (or person-years) and the RR with its variance estimate for at least three
      quantitative exposure categories were known. For studies that dose not provide this
      information, the investigators will estimate the dose-response slopes using variance-weighted
      least-squares regression (VWLS). Both the methods (GLST and VWLS) required median or mean
      intake for each category of intake level. For studies that report the concentrations as
      ranges of magnesium intake only, the investigators will estimate the midpoint in each
      category by calculating the average of the lower and upper bound. If the upper boundary for
      the highest category is not provided, the investigators will assume that the boundary has the
      same amplitude as the adjacent category. When the lowest category is open-ended, the
      investigators will set the lower boundary to the same amplitude as the adjacent category. In
      the case of different categorizations of magnesium intake and serum concentrations across
      studies, the investigators will choose the lowest level as the reference category. Dose
      responses of dietary magnesium intake will be standardized based on unweighted median
      differences between the highest and lowest quartile category medians across all studies.

      For the meta-analysis, the statistical heterogeneity between the studies will be assessed
      using the Q and I-squared statistics. For the Q statistic, heterogeneity was considered
      present if p < 0.1. The investigators will define low, moderate and high heterogeneity as
      I-squared values of 25%, 50% and 75%, respectively. Publication bias will be evaluated using
      Begg's test. In the presence of publication bias, the P values for Begg's test are less than
      0.05. The investigators will conduct sensitivity analyses to evaluate potential sources of
      heterogeneity in the analyses. The investigators will conduct subgroup meta-analyses
      according to the study design (cross-sectional study, cohort cohort or nested case-control
      study), study quality, definition of metabolic syndrome, gender, age, and geographic area of
      the study
    

Observational model: Cohort
Time perspective: Cross-Sectional
Sampling method: Probability Sample
Study population: 
        Adult population: 18 years old and older
      
Keywords: Meta-Analysis; Metabolic Syndrome; Magnesium; Dose Response Effect; Systematic Review