L-arginine and coronary outcomes
Bednarz B, Jaxa-Chamiec T, Gebalska J, Herbaczynska-Cedro K, Ceremuzynski L. L-arginine supplementation prolongs exercise capacity in congestive heart failure. Kardiol Pol. 2004, Apr; 60 (4): 348-353.
To investigate the effect of oral supplementation with L-arginine on exercise capacity and markers of oxidative stress in patients with mild to moderate CHF.
- New York Heart Association Class II to III heart failure
- Ejection fraction (EF) below 40%.
- Overt atherosclerotic peripheral disease
- Impairment of renal or liver function.
Patients with CHF admitted to the department of Cardiology at Grochowski Hospital because of exacerbation of their disease.
- Patients were randomized to L-arginine or placebo
- Blood was drawn from the antecubital vein and an exercise test was performed
- After seven-day treatment with L-arginine (three g orally, three times daily) or placebo (matching capsules of saccharum lactis), blood sampling and exercise test were repeated
- After seven days of wash-out, the treatment was crossed-over for another seven days when final blood samples and exercise tests were performed.
- Exercise tests were performed on Marquette CASE 12 treadmill exercise system, according to the modified Naughton protocol with increments of approximately one MET at each two-minute stage
- Tests were performed the same time of day under identidal conditions
- Patients were asked to exercise until fatigue or dyspnea forced them to stop.
Intervention (if applicable)
Seven-day treatment with L-arginine (three grams orally, three times daily) vs. placebo.
- Per author's statement, data are presented as mean ±SD
- Student's T-test was used for analysis of normally distributed data
- Wilcoxon signed ranks test based on analysis of median values was applied in case of abnormal distribution
- Statistical significance was defined as P<0.05.
[Reviewer's note: Data tables referred to in the text were not included in the article made available for review.]
Timing of Measurements
Baseline, then at seven-day intervals.
- Variable One: Total exercise time, calculated based on time to exhaustion
- Variable Two: Maximal work load, in METS (METS not defined)
- Variable Three: Serum urea, creatinine and electrolytes, by "routine laboratory methods"
- Variable Four: Lipid peroxides, by method of Buege and Aust
- Variable Five: Sulphydryl groups, by the method of Ellman
- Variable Six: Oxygen free radical production, by lucigenin-amplified chemiluminescence, using a whole blood lumi-aggregometer.
Oral administration of L-arginine: Three grams, three times a day for seven days.
Matching capsules of saccharum lactis for seven days.
- Initial N: 21 patients
- Attrition (final N): 17 patients
- Location: Poland.
[Reviewer's note: Data tables referred to in the text were not available for review.]
Authors found higher prolongation of exercise duration time after L-arginine than with placebo (99±106 vs. 70±99, P<0.05; units of measurement not defined, perhaps seconds).
- In patients with chronic stable CHF, oral supplementation with L-arginine prolongs exercise duration, which may be due to NO-induced peripheral vasodilatation
- The antioxidant properties of L-arginine have not been confirmed in this ex-vivo study.
- This was a well-designed study, which tested the effect of a feasible treatment on clinically-significant outcomes
- However, the lack of critical data tables referred to in the text made it difficult to evaluate this article fully.
The medications taken by the study subjects were not described, but a statement was made that medications were unchanged before and during the study.
Quality Criteria Checklist: Primary Research
|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|
|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?||N/A|
|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?||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?||???|
|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?||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%.)||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?||Yes|
|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?||Yes|
|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?||No|
|6.6.||Were extra or unplanned treatments described?||No|
|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?||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?||???|
|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)?||N/A|
|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?||N/A|
|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|