HTN: Vitamins (2007)

Citation:
 
Study Design:
Class:
- Click here for explanation of classification scheme.
Quality Rating:
Research Purpose:
To examine the role of vitamin C and several other antioxidants on blood pressure.
Inclusion Criteria:
  • Healthy males
  • Normotensive
  • 30 to 59 years of age.

 

Exclusion Criteria:
Anyone who had smoked within six months of recruitment.

 

Description of Study Protocol:

Recruitment

Recruited from Beltsville, MD area.

Design

  • One month of stabilization with 60mg vitamin C, followed by one month on a vitamin C deficient diet (nine mg vitamin C), followed by one month of a repletion diet (117mg vitamin C)
  • The depletion and repletion phases were then repeated
  • For the repletion phases subjects were randomized to receive vitamin C from either oranges, broccoli or a supplement.

Blinding Used

None.

Intervention

After stabilization and a month period of a vitamin C deficient diet, subjects received 117mg vitamin C from either oranges, broccoli or a supplement for one month along with a controlled diet.

Statistical Analysis

  • Multiple regression, ANOVA, T-tests and Pearson correlations used to analyze the effect of baseline vitamin C tissue stores on BP.
  • Significance defined at under 0.05 was used.

 

Data Collection Summary:

Timing of Measurements

  • Physical activity, stress, sickness were recorded daily
  • BP was measured at the end of the first repletion phase, the end of the second depletion phase and at the end of the second repletion phase (at Weeks Nine, 13, and 17)
  • Fasting blood was obtained every two weeks during the depletion phases and every week during the repletion phases for vitamin C assays.

Dependent Variables

  • SBP and DBP measured with a portable BP monitor after sitting for five minutes
  • Measurement was repeated three times with the average of the last two measures recorded 
  • Plasma assayed for vitamin C, carotenoids, retinol, selenium, cholesterol and alpha- and gamma-tocopherol.

Independent Variables

  • Diet containing nine mg per day of vitamin C (depletion phase)
  • Diet containing 117mg per day of vitamin C from oranges
  • Diet containing 117 mg per day of vitamin C from broccoli
  • 117mg per day of vitamin C from supplement with depletion diet
  • Energy intake adjusted to weekly to prevent weight gain or loss. 

Control Variables

  • Smoking
  • Alcohol consumption
  • Body weight
  • Physical activity.
Description of Actual Data Sample:
  • Initial N: 68 healthy men
  • Attrition (final N): 68 men
  • Age: 30 to 59 years old; mean, 40.6 years
  • Ethnicity: 57 whites, eight blacks, three Asians.

Anthropometrics

  • Mean weight: 80.9 kg (range 59.3 to 100.8kg)
  • Mean BMI: 25.7 (range 18.1 to 34.9)
  • Weights were stable throughout the study period

Location

Beltsville, MD.

 

Summary of Results:
  • Week Five (end of first depletion phase) plasma ascorbic acid and Week Nine (end of first repletion phase) DBP were more strongly correlated, R=-0.48, P<0.0001, than the Week Nine plasma ascorbic acid level and Week Nine DBP, R=-0.31, P<0.01
  • This is thought to be significant because the Week Five plasma ascorbic acid levels would reflect tissues stores remaining following the depletion phase.

Change in BP with Vitamin C Intake

 

Week Nine
End of depletion/repletion

Week 13
End of 2nd depletion

Week 17
End of 2nd repletion

DBP (mmHg)
Quartile 1 (low C)

76.4 76.6 75.6

DBP (mmHg)
Quartile 2-3

73.9 74.5 72.8

DBP (mmHg)
Quartile 4 (high C)

69.3* 69.9* 70.0

SBP (mmHg)
Quartile 1

122.8 122.4 123.4

SBP (mmHg)
Quartile 2-3

123.3 121.9 122.2

SBP (mmHg)
Quartile 4

118.8 117.7 118.0

Quartiles are defined by plasma ascorbic acid levels at Week Five and age adjusted means
*The highest plasma ascorbic acid levels had the lowest DBP at Week Nine (P=0.007), at Week 13 (P=0.02)

  • Differences in groups and changes over time for SBP were not significant. Therefore, subjects whose plasma ascorbic acid levels went down the most following depletion had the highest DBP one month later.
  • The source of vitamin C was not significant, P=0.89. 

Other Findings

  • Age, weight and BMI were positively associated with BP. This was significant for age and DBP, R=0.33, P=0.006.
  • Four of the subjects were hypertensive.
Author Conclusion:
  • Plasma vitamin C is inversely associated with blood pressure, even in healthy persons with normal blood pressure
  • Tissue stores of vitamin C may be important in regulating blood pressure
  • Low intake of antioxidant-rich fruits and vegetables may be one of the causes of hypertension
  • One fourth of the variance in DBP was accounted for by plasma vitamin C
  • Plasma vitamin C was also associated with SBP.
Funding Source:
University/Hospital: University of California at Berkeley
Reviewer Comments:
  • A part of a NCI and USDA funded larger study to look at several aspects of vitamin C metabolism
  • Even though SBP is included in author's conclusion, there was no statistical difference in SBP shown in data
  • Compliance was carefully measured with actual mg intake from foods analyzed. A metabolic kitchen with all food and drink was provided during the study period. Body weight was maintained. Smoking, alcohol consumption, body weight and physical activity were controlled for upon analysis and in study design.
  • Because a steady state was not reached during the depletion and repletion phases, the authors determined that changes in BP better reflected tissues stores.
  • The main outcome of the study was NOT change in BP at the of depletion and repletion for two reasons. First, BP was not measured until subjects had completed a full depletion-repletion cycle and second, stabilization or a plateau in plasma ascorbic acid had not been reached at the end of the repletion phases in 1/3 to 1/2 of subjects. Therefore, the main outcome was the effect of baseline ascorbic acid tissue stores on subsequent BP measures.
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? N/A
  3.1. Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT) N/A
  3.2. Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline? N/A
  3.3. Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.) N/A
  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? N/A
  4.1. Were follow-up methods described and the same for all groups? N/A
  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%.) N/A
  4.3. Were all enrolled subjects/patients (in the original sample) accounted for? N/A
  4.4. Were reasons for withdrawals similar across groups? N/A
  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? No
  5.1. In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate? No
  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.) ???
  5.3. In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded? No
  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? No
  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? No
  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? N/A
  6.6. Were extra or unplanned treatments described? N/A
  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? ???
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