EAL

HTN: Vitamins (2007)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To investigate the effects of a combination of daily dosage of 1000mg vitamin C, 800mg vitamin E and 10mg folate on markers of vascular function in young healthy male adults.

Inclusion Criteria:

Healthy
Normotensive
Caucasion
Male
18 to 25 years old
Discontuance of vitamin supplementation, if used, for at least two weeks before the study.

Exclusion Criteria:

Hypertension or any other chronic disease.

Description of Study Protocol:

Recruitment

No information given.

Design

Randomized, placebo controlled, 12-week trial
Subjects were randomly divided into two groups
Within two weeks, the subjects visited the research facility on two occasions to obtain baseline cardiovascular values
The cardiovascular measurements were taken in a resting, fasted state twice and a mean of the two measurements was used
Cardiovascular measurements included systolic BP, diastolic BP, mean blood pressure, heart rate, stroke volume, cardiac output, total peripheral resistance and arterial compliance
Body mass and height measurements, along with a general health questionnaire were completed
Subjects then followed daily supplementation with a placebo or vitamins (1,000mg vitamin C, 800mg vitamin E, 10mg folic acid) for 12 weeks
The resting cardiovascular measurements were taken again under the same conditions as the initial measurements.

Blinding Used

Placebo was used for the control group.

Intervention

Placebo given for 12 weeks to placebo group, vitamin supplementation given to treatment group for two weeks
Placebo and vitamins were divided into six tablets to be consumed daily with 3 in the morning and three in the evening.

Statistical Analysis

Dependent T-tests were used to determine significant differences between resting cardiovascular values before and after the intervention
Independent T-tests were used to test for differences between groups regarding age and body composition
Significance was determined at P<0.05.

Data Collection Summary:

Timing of Measurements

At baseline and following the 12-week intervention.

Dependent Variables

Variable One: SBP measured using a Finometer for 10 minutes in the morning in a rested, fasted state. This device takes continuous measurements with a return-to-flow systolic calibration. Means of measurements obtained during mintues five to seven were used. The meaurements were conducted twice at baseline and at follow-up and meaned. A previously described vascular unloading technique was used to provide reliable data, typically obtained from intra-arterial measurements. This method was used to obtain all dependent variables listed below.
Variable Two: DBP
Variable Three: MAP (mean blood pressure)
Variable Four: Stroke volume
Variable Five: Heart rate
Variable Six: Cardiac output
Variable Seven: Total peripheral resistance
Vairable Eight: Arterial compliance.

Independent Variables

Variable One: Placebo for 12 weeks
Variable Two: Vitamin supplementation for 12 weeks, consisting of 1000mg vitamin C, 800mg vitamin E, 10mg folic acid daily.

Description of Actual Data Sample:

Initial N: 38 (all males)

Attrition (final N): 31 (14 in placebo group, 17 in the vitamin group). Reasons for attrition were subjects not consuming at least 80% of the vitamin tablets or non-compliance with the schedule of the study protocol.
Age

Placebo group: 21.8 (20.8-22.8)
Vitamin group: 22.0 (20.7-23.3).

Ethnicity: Caucasian
Other relevant demographics: Six smokers in the placebo group, nine in the vitamin group
Anthropometrics: The groups were not different for height, body mass or BMI
Location: South Africa.

Summary of Results:

There was a sigificant decrease (P=0.03) in SBP in the vitamin (treatment) group
No statistically significant changes were observed within the other cardiovascular variables of the vitamin group, but possible beneficial decreases in DBP and increases in arterial compliance after 12 weeks of vitamin supplementation were indicated.

Changes Within the Vitamin (Treatment) Group Following 12 Weeks of Supplementation

Variable	Before, After Intervention and Change	Mean	95% CI	P-Value Between A&B
SBP (mmHg)	B	130.8	125.9-135.8
	A	123.8	119.6-127.9
	Change	-7.06	-11.12 to -3.01	0.03
DBP (mmHg)	B	79.1	75.5-82.6
	A	76.7	74.1-79.3
	Change	-2.39	-5.20-0.41	0.25
Arterial Compliance (mL/mmHg)	B	2.79	2.6-2.97
	A	2.85	2.70-3.00
	Change	0.06	-0.02-0.14	0.58

Changes within Placebo group following 12 weeks of intervention with p values for differences between Vitamin and Placebo groups

Variable	Before, After Intervention and Change	Mean	95% CI	P-Value Between A&B	P-Value Between Groups
SBP (mm Hg)	B	126.7	121.9-131.4		0.21
	A	125.6	120.8-130.5		0.53
	Change	-1.02	-5.92-3.87	0.75	0.04
DBP (mm Hg)	B	79.2	76.2-82.1		0.98
	A	78.4	76.0-80.9		0.31
	Change	-0.71	-4.08-3.70	0.69	0.41
Arterial Compliance (mL per mm Hg)	B	2.79	2.61-2.97		0.95
	A	2.85	2.70-3.00		0.59
	Change	0.06	-0.02-0.14	0.97	0.35

When the changes in SBP in the two groups were compared, the vitamin group showed a significantly greater decrease (0.04).

Author Conclusion:

Oral vitamin C, vitamin E and folate supplementation improved systolic blood pressure in young, healthy males.

Funding Source:

Government:	Technology and Human Resources for Industry Programme (South Africa)
University/Hospital:	North-West University

Reviewer Comments:

Strengths of the study were that compliance was measured by counting tablets weekly and that BP was measured for 10 continuous minutes twice at baseline and at the study's end under very controlled conditions
Unclear if subjects were excluded for not consuming at least 80% of placebo tablets
Dietary intake and exercise were not controlled
The sample size was small (14 in placebo group, 17 in treatment group).

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?	???
	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?	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?	???
	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?	???
	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.)	???
	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?	Yes
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?		No
	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)?	No
	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?	No
	8.7.	If negative findings, was a power calculation reported to address type 2 error?	No
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