EAL

HTN: Vitamins (2007)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To determine if supraphysiological levels of ascorbic acid attained by infusion in young and old healthy men modulates large elastic artery compliance and central blood pressure.
Also, to determine if oral vitamin C supplementation for 30 days had therapeutic benefits.

Inclusion Criteria:

Healthy males
Sedentary, non-obese, normotensive, free of cardiovascular disease
18 to 30 years of age for young group
60 to 79 years of age for the older group.

Exclusion Criteria:

Use of antioxidant supplements within six weeks of study recruitment
Use of medication within six weeks of study recruitment.

Description of Study Protocol:

Recruitment

Not discussed.

Design

Fasting for 12 hours preceded the study protocols
Protocol One: Acute infusion of a pharmacologic dose ascorbic acid (priming dose of 0.06g per kg fat-free mass followed by a drip infusion of 0.02g per kg FFM) delivered over 60 minutes
Protocol Two: Oral supplementation of 500mg per day vitamin C for 30 days, beginning at least 72 hours after Protocol One.

Blinding Used

None.

Intervention (if applicable)

Infusion of pharmacologic dose of vitamin C, followed by oral intake of 500mg per day of vitamin C for 30 days.

Statistical Analysis

ANOVA was used to determine difference between the two groups (young and old)
Repeated-measures ANOVA was used to determine effects of acute (infused) and chronic (oral) ascorbic acid administration
Univariate correlation analyses examined relations between variables of interest
Significance was set at P<0.05.

Data Collection Summary:

Timing of Measurements

Protocol One: Measurements of elastic artery compliance stiffness and BP were conducted before and after IV infusion of pharmacological dose of ascorbic acid
Protocol Two: Arterial compliance, stiffness and BP measurements were measured after intervention of 500mg per day of oral vitamin C supplementation for 30 days.

Dependent Variables

Protocols One and Two:

Brachial SBP and DBP, mm Hg, measured over the brachial artery with a semi-automated device
Carotid arterial compliance, measured by high-resolution ultrasonography
Arterial stiffness, measured by carotid AIx and aortic pulse wave velocity
Body composition, measured with DEXA
Plasma samples analyzed for venous ascorbic acid concentrations, oxidized LDL, catecholamines and endothelin-1.

Independent Variables

Protocol One: IV infusion of a priming bolus sof 0.06g per kg fat-free mass of vitamin C, followed by a drip infusion of 0.02g per kg FFM over 60 minutes
Protocol Two: Oral supplementation of time-released capsules of 500 mg vitamin C per day for 30 days.

Description of Actual Data Sample:

Initial N

25 men (13 "young" between the ages of 18 and 30 years, 12 "older" aged 60 to 79 years) completed Protocol One
Of these, 20 (10 young and 10 older) completed Protocol Two.

Attrition (Final N)

None discussed.

Age

"Young" group: 26±1 year (means±SE)
"Older" group: 63±2.

Ethnicity

None discussed.

Other Relevant Demographics

None discussed.

Anthropometrics

Height was not different between the younger and older groups
Weight was less for the younger group, 75±3kg vs. 84±3kg, P<0.05
Body fat percentage was less for the younger group, 17±2 vs. 28±3, P<0.05.

Location

Boulder, CO.

Summary of Results:

The groups were the same with respect to height, brachial SBP, heart rate, plasma HDL-C, insulin and glucose
Body weight, body fat percentage, brachial DBP, plasma total cholesterol, LDL-C and plasma oxidized LDL-C were greater in the older group (P<0.05).

Protocol One: Peripheral and Central BP at Baseline and During Ascorbic Acid Infusion

	Young Men Baseline	Young Men, Vitamin C Infusion	Older Men Baseline	Older Men, Vitamin C Infusion
Brachial SBP, mmHg	115±2	115±2	120±4	122±3
Brachial DBP, mmHg	65±2	64±2	73±2*	75±2*
Carotid SBP, mmHg	101±3	99±3	116±5*	115±5*

*P<0.05 vs. young men

Baseline carotid artery compliance was 43% lower (P<0.01, data not shown) and carotid BP was higher (see above) in older men.

Protocol Two: Peripheral and Central BP at Baseline and Following 30 Days of Ascorbic Acid Supplementation

	Young Men Baseline	Young Men, Vitamin C Supplementation	Older Men Baseline	Older Men, Vitamin C Supplementation
Brachial SBP, mmHg	113±1	112±2	120±4	119±4
Brachial DBP, mmHg	64±2	62±2	73±3*	72±3*
Carotid SBP, mmHg	98±2	97±4	116±6*	117±5*

*P<0.05 vs. young men.

Characteristics of the subset group (N=10) were not different from the whole group
Chronic ascorbic acid supplementation had no effect on BP, compared with baseline.

Author Conclusion:

Adverse changes in artery compliance and central BP with aging in healthy men are not mediated by ascorbic acid-sensitive oxidative stress and are not affected by short-term, moderate daily vitamin C supplementation. Thus, daily supplementation with 500mg vitamin C for one month had no effect on central arterial compliance, stiffness or BP in young or older men.

Funding Source:

Government:

NIH

Reviewer Comments:

No mention of weight change during the study, dietary intake, alcohol use or ethnicity was made
Small N, no control group, no blinding.

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.)	No
	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?		No
	4.1.	Were follow-up methods described and the same for all groups?	No
	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%.)	No
	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?		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.)	No
	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?		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?	???
	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?	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