HTN: Omega-3 Fatty Acids (2007)
Nestel P, Shige H, Pomeroy S, et al, The n-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid increase systemic arterial compliance in humans. Am J Clin Nutr. 2002, 76: 326-330.

- 40 to 69 years old
- Post-menopausal, if female
- BMI between 25 and 29
- One or more of the following:
- Total lasma cholesterol over 5.5mmol per L
- Triacylglycerol over two mmol
- HDL-C under 1.0mmol per L for men; under 1.2mmol per L for women.
- Smoking
- Alcohol consumption of over four drinks per day
- Refusal to suspend hormone replacement therapy for women; vitamin and other supplements or antilipidemic or antihpertensive therapy
- Refusal to comply with dietary requirements of avoiding fish and plant n-3 fatty acid foods
- Metabolic disorders such as diabetes.
Recruitment
Not specified.
Design
Randomized controlled trial with a two-week familiarization period in which study instructions were provided to subjects followed by randomization to one of three groups:
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Group One: Placebo
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Group Two: EPA capsules
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Group Three: DHA capsules.
The intervention phase was seven weeks in duration, with measuremens taken at the beginning and end of the intervention.
Blinding Used
Double-blinding.
Intervention
Seven-week intervention as follows:
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Group One (placebo): Received four one-gram capsules daily of olive oil (0.28g oleic acid per day)
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Group Two (EPA): Received four one-gram capsules daily, comprised of 85% fatty acids, 76% EPA, 1.7% DHA, 3.1% eicosatetraenoic acid (3.04g EPA per day)
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Group Three (DHA): Received four one-gram capsules daily, comprised of 70.7% GHA, 4.1% EPA, 13.2% DPA (2.84g DHA plus 0.52g DPA per day).
Subjects were instructed regarding background diet, physical activity and alcohol intake.
Statistical Analysis
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Repeated-measures analysis of variance was used with a group x time interaction (before and after intervention) to test for changes in the levels of the variables over the period of treatment being equal for the three treatments
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Correlations were tested using a two-tailed Pearson product-moment correlation coefficeint (R)
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P<0.05 was used to indicate significance.
Timing of Measurements
Measurements were taken in the morning at the beginning and end of the seven-week intervention phase.
Dependent Variables
- Variable One: Sysemic arterial compliance (SAC) was estimated using the area method utilizing measurement of aortic blood flow and associated driving pressure to derive an estimated compliance; determined using the formula, SAC=Ad/[R(Ps-Pd)], where Ad is the area under the BP diastolic decay curve from end systole to end diastole, R is the total peripheral resistance, Ps is the end-systolic BP and Pd is the end-diastolic BP
- Variable Two: Blood pressure (BP) measured automatically at frequent intervals during the measurement of SAC
- Variable Three: Plasma total cholesterol, triacylglycerol, HDL-C, using standard methods.
Independent Variables
- Placebo of olive oil
- 3.04g EPA
- 2.84g DHA plus 0.52g DPA.
Control Variables
Olive oil (placebo) used as control.
- Initial N: 41
- Attrition (final N): 38 (17 females)
- Age
- Placebo group: 61±9 years
- EPA group: 57±7
- DHA group: 55±6.
- Ethnicity: Not described
- Other relevant demographics: None given
- Anthropometrics: There was no difference between the groups.
|
Placebo Group |
EPA Group |
DHA Group |
Weight at baseline (kg) |
80±14 |
80±9 |
77±10 |
Weight at end (kg) |
80±14 |
81±9 |
78±10 |
Mean±SD.
Location
Melbourne, Australia.
|
Placebo |
Placebo |
EPA |
EPA |
DHA |
DHA |
P-Value |
SAC |
0.150±0.08 |
0.150±0.08 |
0.149±0.06 |
0.203±0.06* |
0.147±0.05 |
0.187±0.07 |
0.043 |
SBP |
132±27 |
130±19 |
126±19 |
121±21 |
126±18 |
122±15 |
0.90 |
DBP |
77±14 |
77±9 |
74±8 |
72±6 |
74±8 |
74±9 |
|
SAC in units; BP in mm Hg; means±SD; P-values are group x time interaction ANOVA across all three groups
*Significantly different from placebo, P=0.028
- There was a trend toward lowering SBP that was not statistically significant.
Other Findings
- There was a substantial decrease in triacylglycerols with both EPA and DHA, P=0.013
- HDL-C tended to increase with both EPA and DHA, but also increased in the placebo group and changes were not statistically significant.
- The major finding was improvement of SAC in dyslipidemic individuals with n-3 fatty acid supplementation by 36% in the EPA group and 27% in the DHA group
- The authors state that the clinical importance of these findings are in the relationship of less SAC and increased cardiovascular risk from hypertension and diabetes.
Industry: |
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- Major focus of the study was on sysemic arterial compliance, however this is based on the fact that SAC is a factor affecting blood pressure and thus, a potential cardiovascular risk
- Compliance was determined with food diaries and plasma fatty acids
- Body weights increased approximately one kg in Groups Two and Three, however the change was not significant
- Demographics were not specified for the subjects, blinding was not specified other than use of the placebo and SAC is not generally a focus of clinical practitioners giving this paper a neutral rating.
Quality Criteria Checklist: Primary Research
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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? | No | |
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? | 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? | ??? | |
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? | N/A | |
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? | 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? | 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)? | ??? | |
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? | No | |
10.1. | Were sources of funding and investigators' affiliations described? | No | |
10.2. | Was the study free from apparent conflict of interest? | Yes | |