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HTN: Magnesium (2015)

Citation:
Dickinson HO, Nicolson D, Campbell F, Cook JV, Beyer FR, Ford GA, Mason J. Magnesium supplementation for the management of primary hypertension in adults (Review). Cochrane Database of Systematic Reviews. 2006; 3. Art. No.: CD004640. DOI: 10.1002/14651858.CD004640.pub2. PubMed ID: 16856052
 
Study Design:
Meta-analysis or Systematic Review
Class:
M - Click here for explanation of classification scheme.
Quality Rating:
Positive POSITIVE: See Quality Criteria Checklist below.
Research Purpose:
To evaluate the effects of magnesium supplementation as treatment for primary hypertension in adults.
Inclusion Criteria:
  • RCTs of parallel or crossover design comparing magnesium supplementation with placebo, no treatment or usual care
  • Crossover restricted to two interventions and two treatment periods
  • Treatment and follow-up eight weeks or longer
  • Participants older than 18 years
  • SBP 140mm Hg or higher
  • DBP 85mm Hg or higher
  • SBP and DBP reported at end of follow-up
  • Types of interventions:
    • Oral magnesium supplements
    • Dietary interventions manipulating only magnesium intake.
Exclusion Criteria:
  • Pregnancy
  • Anti-hypertensive medication that changed during study
  • Magnesium supplementation combined with other interventions.
Description of Study Protocol:

Recruitment

Databases searched for RCTs:
  • Cochrane Library (2004, Issue 1)
  • Medline (2000 to January 9, 2004)
  • EMBASE (1999 to 2003)
  • Science Citation Index (1982 to 2003)
  • ISI Proceedings (1999 to 2003)
  • Clinical Trials.gov
  • Current Controlled Trials
  • CAB abstracts (to end July 2005).

Design 

  • Systematic review
  • Meta-analysis.

Blinding Used

Not applicable, implied with blood pressure measurements.

Interventions

  • Magnesium intake from diet or supplements vs. placebo
  • RCTs of parallel or crossover design
  • Intervention period of eight weeks or more
  • Crossover trials restricted to designs with two interventions and two treatment periods.

Statistical Analysis

  • Trials were aggregated in separate meta-analyses for crossover and parallel designs; these were combined if the same meta-analysis did not show heterogeneity
  • Mean differences weighted according to precision of each trial and combined in meta-analyses using a random effects model to estimate an overall pooled weighted mean difference and its 95% confidence interval
  • Heterogeneity assessed using the I2 statistic
  • Sub-group analyses:
    • Participants in active treatment arm received higher (higher than 15mmol per day) and lower (15mmol or less per day) doses of Mg
    • Participants' mean baseline SBP higher (higher than 150mm Hg) and lower (150mm Hg or less)
    • Percentage of male participants (50% or less, more than 50%).
  • Sensitivity analyses excluding trials that did not report adequate concealment of allocation; blinding of both participants and treatment providers; sufficient information to allow estimation of the SD of the treatment effect
  • Post-hoc analyses excluding one trial with very different results from others
  • Other post-hoc analyses:
    • Evaluation of the effect of Mg supplementation on serum Mg
    • Meta-regressions to evaluate whether the effect of Mg supplementation on BP varied with dose of Mg, percentage of male participants or baseline BP.
Data Collection Summary:

Dependent Variables

  • Death from all causes
  • CHD events (fatal or non-fatal strokes, excluding TIAs if possible)
  • SBP at end of follow-up
  • DBP at end of follow-up.

Independent Variables

Magnesium intake from diet or supplements vs. placebo.
 
Description of Actual Data Sample:

Initial N

  • N=304 potential references
  • N=27 for detailed evaluation.

Attrition (final N)

N=12 trials representing 545 subjects, approximately 45% male.

Age

Overall mean age of 54 years (range of 20 years to 77 years).

Ethnicity

Reported only in two trials.

Location

Most trials conducted in Europe and Australia, but one was conducted in the United States and one in Japan.

 

Summary of Results:

Key Findings

  • Overall mean BP at baseline: 148/91mm Hg
  • Range of SBP at baseline: 143mm Hg to 173mm Hg
  • Range of DBP at baseline: 88mm Hg to 97mm Hg
  • Mean dose Mg supplement: 17mmol per day (range of 10mmol to 40mmol)
  • Two trials reported statistically significant reduction in SBP and DBP in those receiving Mg supplementation compared to placebo
  • Two trials reported statistically significant reduction in DBP alone
  • Meta-analysis of nine parallel trials:
    • Mean difference between Mg supplemented and placebo:
      • SBP: 0.3mm Hg (95% CI: -4.2 to 4.8); I2=70%
      • DBP: -2.0mm Hg (95% CI: -4.1 to 0.1); I2=60%.
  • Meta-analysis of three crossover trials:
    • Mean difference between Mg supplements vs. control:
      • SBP: -3.5mm Hg (95% CI: -5.5 to -1.5); I2=0%
      • DBP: -2.0mm Hg (95% CI: -3.1 to -1.0); I2=0%.
  • Single meta-analysis including all trials:
    • Mean difference between Mg supplements vs. control:
      • SBP: -1.3mm Hg (95% CI: -4.0 to 1.5); I2=67%
      • DBP: -2.2mm Hg (95% CI: -3.4 to -0.9); I2=47%.
    • Heterogeneity was not accounted for by Mg dose or initial BP, although higher net reductions in trials with higher dose (more than 15mmol per day) and with higher initial BP, but differences not significant
    • Heterogeneity of DBP was significant for trials that had a higher percentage of men, but not SBP.
Author Conclusion:
Evidence in favor of a causal association between magnesium supplementation and blood pressure reduction is weak,  and small significant reductions observed are likely due to bias.
Funding Source:
Other: Not specified
Reviewer Comments:
Quality Criteria Checklist: Review Articles
Relevance Questions
  1. Will the answer if true, have a direct bearing on the health of patients? Yes
  2. Is the outcome or topic something that patients/clients/population groups would care about? Yes
  3. Is the problem addressed in the review one that is relevant to dietetics practice? Yes
  4. Will the information, if true, require a change in practice? Yes
 
Validity Questions
  1. Was the question for the review clearly focused and appropriate? Yes
  2. Was the search strategy used to locate relevant studies comprehensive? Were the databases searched and the search termsused described? Yes
  3. Were explicit methods used to select studies to include in the review? Were inclusion/exclusion criteria specified andappropriate? Wereselectionmethods unbiased? Yes
  4. Was there an appraisal of the quality and validity of studies included in the review? Were appraisal methodsspecified,appropriate, andreproducible? Yes
  5. Were specific treatments/interventions/exposures described? Were treatments similar enough to be combined? Yes
  6. Was the outcome of interest clearly indicated? Were other potential harms and benefits considered? Yes
  7. Were processes for data abstraction, synthesis, and analysis described? Were they applied consistently acrossstudies and groups? Was thereappropriate use of qualitative and/or quantitative synthesis? Was variation in findings among studies analyzed? Were heterogeneity issued considered? If data from studies were aggregated for meta-analysis, was the procedure described? Yes
  8. Are the results clearly presented in narrative and/or quantitative terms? If summary statistics are used, are levels ofsignificance and/or confidence intervals included? Yes
  9. Are conclusions supported by results with biases and limitations taken into consideration? Are limitations ofthe review identified anddiscussed? Yes
  10. Was bias due to the review's funding or sponsorship unlikely? Yes