EAL

HTN: Vitamins (2007)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To determine whether short-term oral supplementation with vitamin C reduces oxidative stress, improves endothelial function and lowers blood pressure in patients with uncomplicated Type II diabetes.

Inclusion Criteria:

Uncomplicated Type II diabetes controlled by diet or oral hypoglycemic drugs

Exclusion Criteria:

Systolic blood pressure (SBP) >160mm Hg and or diastolic blood pressure (DBP) >90mm Hg
Hypercholesterolemia (TC>7.0mmol/L)
Proteinuria
Significantly impaired renal function
Clinical evidence of neuropathy or atherosclerosis.

Description of Study Protocol:

Recruitment: Patients meeting criteria were recruited from the diabetes clinic at St Thomas Hospital in London
Design: Parallel-group, double-blind placebo-controlled trial with subjects randomized to either a placebo group or vitamin C supplemented group
Blinding used: Double-blinding is stated however specifics are not discussed.

Intervention (if applicable)

Vitamin C group received 500mg vitamin C three times daily (1.5g total per day) for three weeks
Placebo group received a placebo daily for three weeks.

Statistical Analysis

Differences in baseline characteristics between the two groups were analyzed using chi square and student's unpaired T-test
ANOVA was used to test for differences between the vitamin C and placebo groups in the changes from baseline for 8-epi-prostaglandin F (to assess oxidative stress), BP, and the change in reflection index and forearm blood flow (endothelial function tests)
When a difference between groups was significant, a paired T-test analyzed whether the change from baseline in each group was significant
All tests were two-tailed and P<0.05 was considered significant.

Data Collection Summary:

Timing of Measurements

Measurements were determined at the beginning of the study and three weeks later.

Dependent Variables

Blood pressure measured after supine rest for 30 minutes
Endothelial function assessed in the peripheral vasculature
Serum total cholesterol, triacylglycerols, HDL-cholesterol and glucose measured using standard methods.

Independent Variables

Vitamin C (1.5g per day) or placebo for three weeks.

Description of Actual Data Sample:

Initial N: 35 (12 women)
Attrition (final N): None described
Age: 56.6±1.2 (SEM) placebo group; 55.5±1.8 years Vitamin C group
Ethnicity: Not mentioned
Other relevant demographics: Not mentioned
Anthropometrics: BMI 30.2±1.2 placebo group; 27.9±1.5 Vitamin C group; no difference between groups
Location: London, UK

Summary of Results:

Variables	Placebo Group (N=17)	Vitamin C Group (N=18)	Statistical Significance of Group Difference
Systolic BP (mm Hg)	Baseline: 138±4 Post-tx: 136±4	Baseline: 141±5 Post-tx: 141±5	Not significant; P not given
Diastolic BP (mm Hg)	Baseline: 76±3 Post-tx: 77±3	Baseline: 80±2 Post-tx: 81±3	Not significant; P not given

Other Findings

Digital volume pulse (a measure of endothelial function) was similar in the placebo and Vitamin C groups
The 95% CI for decreases in BP following Vitamin C were 11 and four mm Hg for systolic and diastolic BP, respectively
The 95% CI for an increase in digital volume pulse using reflection index in response to albuterol following Vitamin C was 4%
Forearem blood flow responses to infusion of acetyllcholine and nitroprusside were similar before and after treatment in both groups
Plasma 8-epi-PGF was measured to determine difference in oxidative stress before and after treatment with no difference resulting between groups or baseline.

Author Conclusion:

Treatment with Vitamin C (1.5 grams daily) for three weeks does not significantly improve oxidative stress, blood pressure or endothelial function in patients with Type II diabetes.

Funding Source:

University/Hospital:

Hammersmith Hospital, Rayne Institute, St. Thomas Hospital, Kings College (all UK)

Reviewer Comments:

Changes in weight, activity, ethnicity, diet were not determined during the study
A small (under four mHg) change in diastolic BP was seen in the Vitamin C group that did not reach statistical significance is mentioned, however not supported by data presented
Plasma ascorbate measured pre- and post-treatment was significantly different from baseline in both groups.

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?		???
	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?	No
	2.4.	Were the subjects/patients a representative sample of the relevant population?	???
3.	Were study groups comparable?		???
	3.1.	Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT)	No
	3.2.	Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline?	???
	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?	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?	Yes
	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?		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?	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?		???
	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)?	No
	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?		???
	10.1.	Were sources of funding and investigators' affiliations described?	No
	10.2.	Was the study free from apparent conflict of interest?	Yes