EAL

HTN: Omega-3 Fatty Acids (2007)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

The purpose of this study was to investigate the effects of eicosapentaenoic acid (EPA) and of docosahexaenoic acid (DHA) on systemic arterial compliance (SAC) in dyslipidemic subjects.

Inclusion Criteria:

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.

Exclusion Criteria:

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.

Description of Study Protocol:

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:

Group One: Placebo
Group Two: EPA capsules
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:

Group One (placebo): Received four one-gram capsules daily of olive oil (0.28g oleic acid per day)
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)
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

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
Correlations were tested using a two-tailed Pearson product-moment correlation coefficeint (R)
P<0.05 was used to indicate significance.

Data Collection Summary:

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.

Description of Actual Data Sample:

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.

Summary of Results:

	Placebo Baseline	Placebo Week Seven	EPA Baseline	EPA Week Seven	DHA Baseline	DHA Week Seven	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.

Author Conclusion:

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.

Funding Source:

Industry:

F. Hoffman-La Roche (Switzerland)

Pharmaceutical/Dietary Supplement Company:

Reviewer Comments:

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
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