HTN: Garlic (2007)

Citation:
 
Study Design:
Class:
- Click here for explanation of classification scheme.
Quality Rating:
Research Purpose:

To further clarify the effect of dried garlic powder tablets on blood lipids, blood pressure and arterial stiffness as assessed by pulse wave velocity.

Inclusion Criteria:
Healthy, normo-lipidemic, non-smoking and smoking men and women, aged 40 to 60 years.
Exclusion Criteria:
Use of lipid or blood pressure-lowering medication, anticoagulation medication, use of contraceptives, more than four hours of intensive physical exercise per week, in-study infectious disease (plasma C-reactive protein above 10mg per dL). 
Description of Study Protocol:
  • Recruitment: Mainly recruited from university employees in Copenhagen, Denmark, but also from the general public in May and June 1999
  • Design: Randomized controlled trial 
  • Blinding used: Double-blind
  • Intervention: Subjects were stratified according to gender and smoking status and randomized by drawing numbers to either dried garlic powder or placebo for 12 weeks.

Statistical Analysis

  • Based on a power of 80% to detect a significant difference in total serum cholesterol concentration of 10% (P=0.05, two-sided), a sample size of 35 in each group were required
  • 75 participants were recruited to allow for dropouts
  • Data were analyzed with non-parametric methods
  • Statistical differences between baseline and end-study paired data were assessed by Wilcoxon signed ranked test and between-group differences (unpaired data) by Mann-Whitney U test
  • Significance levels were two-sided
  • Categorical data at baseline were analyzed with a chi-square test.
Data Collection Summary:

Timing of Measurements

  • Subjects had measurements at baseline and after 12 weeks of garlic or placebo. 

Dependent Variables

  • Fasting blood samples were analyzed for serum total cholesterol, HDL-cholesterol, triacylglycerol and C-reactive protein concentrations
  • Serum LDL-cholesterol calculated by Friedewald's formula 
  • Blood pressure measured with automated sphygmomanometer
  • Arterial stiffness assessed by pulse wave velocity. 

Independent Variables

  • Two tablets twice daily of dried garlic powder [10.8mg alliin (3-(2-propenylsulfinyl)-L-alanine) per day, corresponding to about three garlic cloves] or placebo for 12 weeks; compliance assessed through leftover pill counts.
  • Dietary intakes assessed at baseline and later in study, using portion size aids and same data collector 
  • Participants not allowed to consume other dietary supplements apart from one daily multivitamin tablet and were not allowed to consume more than two garlic cloves per week
  • Participants asked not to change dietary, smoking or physical activity habits during the study. 

Control Variables

Smoking status.
Description of Actual Data Sample:

Initial N

75 subjects.

Attrition (final N)

  • 62 subjects eligible for per-protocol analysis (83% completion)
    • 30 in garlic group (12 male, 18 female)
    • 32 in placebo group (12 male, 20 female)
  • 12 withdrew for reasons such as change of working hours, use of medicine, illness, fear of instruments, intolerance of tablets or no reason and one was excluded for high C-reactive protein levels.   
Age
  • Garlic group mean age: 49.6±5.5 years
  • Placebo group mean age: 50.9±4.6 years. 

Ethnicity

Not mentioned. 

Other Relevant Demographics

  • Six smokers in garlic group
  • Eight smokers in placebo. 

Anthropometrics

There were no significant differences between groups at baseline.

Location

Denmark.

Summary of Results:

  Median Change, Garlic Median Change, Placebo P-value
Change in Total Cholesterol (mmol/L)

 0.05

-0.12

0.38

Change in HDL-C (mmol/L)

 0.05

 0.03

 0.41

Change in LDL-C (mmol/L)

 0.01

-0.15

0.21

Change in Total Triacylglycerol (mmol/L)

 -0.08

0.03

0.07

Change in SBP (mm Hg)

2.0

3.0

0.90

Change in DBP (mm Hg)

0.0

0.5

0.73

Change in PWV (m/s)

 0.11

 0.15

 0.88

Other Findings

  • During the intervention period, there was a tendency toward a slight decrease in body weight in the garlic group (P=0.08), but not in the placebo group (P=0.73)
  • No significant inter-treatment group differences in dietary intake were observed
  • Compliance was very high: 95% of pills were consumed and 95% of subjects consumed all of their pills
  • No significant differences between the garlic and placebo groups were detected for any of the outcome measures
  • However, garlic powder was associated with a near significant decrease (12%) in triacylglycerol concentration (P=0.07), but it was found to be dependent on baseline triacylglycerol concentration (R=-0.41, P=0.03)
  • HDL-cholesterol concentration increased significantly in the garlic group (P=0.03), but no significant treatment difference was demonstrated.
Author Conclusion:
  • In conclusion, garlic powder tablets have no clinically relevant impact on fasting serum LDL and HDL concentrations and blood pressure, whereas a modest triacylglycerol-lowering effect cannot be excluded in middle-aged, normo-lipidemic individuals
  • The anti-atherosclerotic effect of garlic may be linked to risk markers other than blood lipids, such as an effect on endothelial function and arterial stiffness or improvement of resistance of LDL to oxidation, rather than lowering of total cholesterol and triacylglycerol concentrations as formerly thought
  • More research is obviously needed to clarify the effect of garlic on risk markers of CVD other than cholesterol levels.
Funding Source:
Reviewer Comments:
  • Power calculation done
  • Compliance was very high
  • Authors note unsuccessful participant blinding due to odor of garlic pills.
Quality Criteria Checklist: Primary Research
Relevance Questions
  1. Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population group? (Not Applicable for some epidemiological studies) Yes
  2. Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about? Yes
  3. Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice? Yes
  4. Is the intervention or procedure feasible? (NA for some epidemiological studies) Yes
 
Validity Questions
1. Was the research question clearly stated? Yes
  1.1. Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified? Yes
  1.2. Was (were) the outcome(s) [dependent variable(s)] clearly indicated? Yes
  1.3. Were the target population and setting specified? Yes
2. Was the selection of study subjects/patients free from bias? Yes
  2.1. Were inclusion/exclusion criteria specified (e.g., risk, point in disease progression, diagnostic or prognosis criteria), and with sufficient detail and without omitting criteria critical to the study? Yes
  2.2. Were criteria applied equally to all study groups? Yes
  2.3. Were health, demographics, and other characteristics of subjects described? Yes
  2.4. Were the subjects/patients a representative sample of the relevant population? Yes
3. Were study groups comparable? Yes
  3.1. Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT) Yes
  3.2. Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline? Yes
  3.3. Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.) Yes
  3.4. If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis? N/A
  3.5. If case control study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable.) N/A
  3.6. If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")? N/A
4. Was method of handling withdrawals described? Yes
  4.1. Were follow-up methods described and the same for all groups? Yes
  4.2. Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.) Yes
  4.3. Were all enrolled subjects/patients (in the original sample) accounted for? Yes
  4.4. Were reasons for withdrawals similar across groups? Yes
  4.5. If diagnostic test, was decision to perform reference test not dependent on results of test under study? N/A
5. Was blinding used to prevent introduction of bias? Yes
  5.1. In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate? Yes
  5.2. Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.) Yes
  5.3. In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded? N/A
  5.4. In case control study, was case definition explicit and case ascertainment not influenced by exposure status? N/A
  5.5. In diagnostic study, were test results blinded to patient history and other test results? N/A
6. Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described? Yes
  6.1. In RCT or other intervention trial, were protocols described for all regimens studied? Yes
  6.2. In observational study, were interventions, study settings, and clinicians/provider described? N/A
  6.3. Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect? Yes
  6.4. Was the amount of exposure and, if relevant, subject/patient compliance measured? Yes
  6.5. Were co-interventions (e.g., ancillary treatments, other therapies) described? Yes
  6.6. Were extra or unplanned treatments described? Yes
  6.7. Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups? Yes
  6.8. In diagnostic study, were details of test administration and replication sufficient? N/A
7. Were outcomes clearly defined and the measurements valid and reliable? Yes
  7.1. Were primary and secondary endpoints described and relevant to the question? Yes
  7.2. Were nutrition measures appropriate to question and outcomes of concern? Yes
  7.3. Was the period of follow-up long enough for important outcome(s) to occur? Yes
  7.4. Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures? Yes
  7.5. Was the measurement of effect at an appropriate level of precision? Yes
  7.6. Were other factors accounted for (measured) that could affect outcomes? Yes
  7.7. Were the measurements conducted consistently across groups? Yes
8. Was the statistical analysis appropriate for the study design and type of outcome indicators? Yes
  8.1. Were statistical analyses adequately described and the results reported appropriately? Yes
  8.2. Were correct statistical tests used and assumptions of test not violated? Yes
  8.3. Were statistics reported with levels of significance and/or confidence intervals? Yes
  8.4. Was "intent to treat" analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)? N/A
  8.5. Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)? Yes
  8.6. Was clinical significance as well as statistical significance reported? Yes
  8.7. If negative findings, was a power calculation reported to address type 2 error? Yes
9. Are conclusions supported by results with biases and limitations taken into consideration? Yes
  9.1. Is there a discussion of findings? Yes
  9.2. Are biases and study limitations identified and discussed? Yes
10. Is bias due to study's funding or sponsorship unlikely? Yes
  10.1. Were sources of funding and investigators' affiliations described? Yes
  10.2. Was the study free from apparent conflict of interest? Yes