HTN: Vitamins (2007)

Citation:
 
Study Design:
Class:
- Click here for explanation of classification scheme.
Quality Rating:
Research Purpose:
To determine the effect of vitamin C supplements on ambulatory blood pressure and plasma lipids.
Inclusion Criteria:
  • 60 to 80 years old
  • Non-smokers for over 10 years
  • No hx of vascular disease, i.e., stroke, MY, angina, peripheral vascular disease
  • Not taking prescribed medications including aspirin, non-steroidal anti-inflammatory drugs or vitamin supplements
  • Normotensive, hx of borderline HTN or newly diagnosed HTN, but never having received treatment.
Exclusion Criteria:
None specified.
Description of Study Protocol:

Recruitment

Subjects were recruited from general practice lists.

Design
  • Randomized placebo-controlled crossover study
  • Baselne measures of weight, BP, plasma ascorbic acid and lipids were conducted
  • Subjects were randomized to treatment or placebo for three months
  • After a one-week washout period, subjects were crossed over to the alternative treatment for three more months.   

Blinding Used

Treatment was doubly-blinded.

Intervention

250mg vitamin C twice daily for three months.

Statistical Analysis

  • A power analysis was conducted to obtain a power of 80% at the 5% significance level to detect changes in systolic BP of at least three mm Hg and HDL-C of at least 0.1mmol per L
  • Regression analysis was used to determine the effect of vitamin C on difference in BP and lipid levels between placebo and active phases of the study
  • Treatment periods, sex, weight change and baseline BP were variables included in the analysis. 
Data Collection Summary:
Timing of Measurements
  • Measurement of weight, BP and serum lipids were taken at baseline
  • BP was measured monthly during the study including at the end of each three-month study period
  • Plasma lipids and ascorbic acid were measured at the end of each three-month study period.

Dependent Variables

  • Systolic and diastolic BP measured in sitting position with a sphygomanometer 
  • Systolic and diastolic BP measured using home 24-hour ambulatory method with measures every 15 minutes
  • Plasma lipids including TC, LDL-C, and HDL-C.

Independent Variables

  • 250mg vitamin C taken as capsules twice daily (500mg total daily)
  • Matched placebo.
Description of Actual Data Sample:
  • Initial N: 40 (20 men)
  • Attrition (final N): 40; data from two participants demonstrated <10% change in plasma ascorbic acid from placebo to vitamin C phases of the study, however analysis with and without this data was not different.
  • Age: 72±4 years (mean±SD)
  • Ethnicity: Not discussed
  • Other relevant demographics: None discussed.
  • Anthropometrics: Weight decreased from baseline to intervention phases by 0.47kg (P=0.06), but there was no change beween placebo and vitamin C phases (73.2±12.7 vs. 73.2±12.9kg). 
  • Location: UK.
Summary of Results:

Mean BP During Each Phase of the Study (mean±SD)

All Subjects (N=40)
 
Baseline
Placebo
Vitamin C
BP Measured in Clinic
SBP
142±15
143±15
142±16
 
DBP
88±9
87±8
86±8
Ambulatory Day-time BP
SBP
135±15
136±18
134±14*
 
DBP
79±9
79±9
78±6
Night-time BP
SBP
122±15
122±14
122±14
 
DBP
68±9
68±7
68±7
HTN Subjects (N=17)
Ambulatory Day-time
SBP
149±10
150±7
146±8*
 
DBP
84±10
83±8
81±7
Normotensive Subjects (N=23) Ambulatory Night-time
SBP
125±9
125±8
125±9
 
DBP
75±6
75±5
76±4

*P≤0.05

Other Findings

  • Sitting clinic BP did not change between vitamin C and placebo phases
  • Daytime ambulatory SBP decreased by 2.0±5.2 mm Hg, 95% CI 0.0-3.9 mm Hg, following vitamin C supplementation
  • Plasma ascorbate levels during placebo and treatment phases or change in ascrobate between the phases was not associated with change in SBP
  • Increased baseline daytime BP was associated with greater decreases in BP following vitmain C supplementation (coefficient for SBP: 0.19, P=0.03, R2=15% and DBP coefficient: 0.20, P=0.02, R2=14%)
  • There was no difference between placebo and treatment groups for serum lipids , with the exception of an increase in HDL for women, following vitamin C supplementation, 0.08±0.11mmol, P=0.007.
Author Conclusion:
In older adults high intakes of vitamin C for three months may lower elevated systolic BP.
Funding Source:
University/Hospital: University of Leicester, Glenfield Hospital, University of Surrey (all UK)
Reviewer Comments:
  • Smoking, exercise, diet, ethnicity were not discussed
  • Measurement of compliance with the vitamin C supplement took place at baseline and completion of the three-month intervention phase by plasma ascorbic acid levels
  • Pill-counting was used, however this did not determine if the vitamin C was taken regularly during the entire treatment phase
  • A strength is the crossover design.
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? ???
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? 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? No
  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? No
  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? No
  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? ???
  10.2. Was the study free from apparent conflict of interest? Yes