HTN: Omega-3 Fatty Acids (2007)
Woodman RJ, Mori TA, Burke V, Puddey IB, Watts GF, Beilin LJ, Effects of purified eicosapentaenoic and docosahexaenoic acids on glycemic control, blood pressure, and serum lipids in type 2 diabetic patients wih treated hypertension, Am J Clin Nutr. 76: 1,007-1,015, 2002.
The objective was to study the independent effects of purified eicosapentaenoic acid(EPA) and docosahexaenoic acid (DHA) on glycemic control, blood pressure, heart rate and lipid metabolism in type 2 diabetic patients with treated hypertension.
- Men and post-menopausal women aged 40 to 75 years
- Have type 2 diabetes mellitus (defined as being treated with oral hypoglycemic medications or having a fasting glucose concentration above 7.0mmol per L or a non-fasting glucose concentration above 11.1mmol per L)
- Glycated hemoglobin under 9%
- Systolic BP above 115 and less than 180mm Hg; diastolic BP under 110mm Hg
- On antihypertensive medication for at least three months
- Not receiving insulin herapy
- BMI under 35
- Fasting serum cholesterol and triacylgycerols below 7.5mmol per L
- Usual consumption of not more than two fish meals per week, not taking fish oil supplements. Less than 40g ethanol per day.
- Recent history of heart disease, angina or recent surgery
- Recent history of myocardial infarction or stroke
- Significant liver or renal disease, macroproteinuria or symptomatic autonomic neuropathy
- Smoker or had smoked within the past two years
- Regular use of non-steroidal anti-inflammatory drugs.
Recruited from the general public by media advertising and screened for study criteria.
- Randomized double-bind clinical trial
- Baseline measurements were collected over three weeks and subjects were randomized to one of three groups stratified by sex, age and BMI
- Groups received either four-gram EPA, four-gram DHA or olive oil placebo as capsules daily for six weeks
- Subjects were instructed not to change diets, alcohol intake, level of physical activity or other lifestyle factors
- Diet records were kept, as well as records of weight, alcohol intake, changes in physical activity or medication during the intervention period
- Blood measurements and ambulatory blood pressure monitoring was conducted at baseline and at six weeks following initiation of intervention.
- Olive oil was used as a placebo
- Subjects and investigators were blinded to the treatment.
Subjects were randomized to one of three intervention groups to receive four-gram EPA capsules or four-gram DHA capsules or olive oil capsules daily for six weeks.Statistical Analysis
- General linear models were used to analyze for the effects of EPA or DHA, relative to those of olive oil after adjusting for baseline values
- Significance levels were adjusted for multiple comparisons by using the Bonferroni method
- P<0.05 was used for significance after adjustments for multiple comparisons.
Timing of Measurements
Measurements occured at baseline and at six weeks following intervention.
- Variable One: Systolic BP, diastolic BP and heart rate measured by a 24-hour ambulatory monitoring system
- Variable Two: Fasting glucose
- Variable Three: Fasting insuin
- Variable Four: Fasting C-peptide
- Variable Five: Glycated hemoglobin
- Variable Six: Insulin sensitivity index
- Variable Seven: Insulin secretion
- Variable Eight: Serum lipids and lipoproteins.
- Variable One: Daily capsules of four grams EPA
- Variable Two: Daily capsules of four grams DHA
- Variable Three: Daily capsules of four grams olive oil.
- Dietary intake
- Physical activity
- Alcohol intake
Attrition (final N)
- 51 (39 males randomized to 12 males in olive oil group, 14 males in EPA group, 13 males in DHA group; females were similarly randomized among groups)
- Five of the original subjects withdrew, due to changes in medication, two withdrew due to time commitments and one became ill
- For the hypertension analysis, additional subjects were removed
- One subject had a stroke and three were removed due to an insufficient number of valid readings during BP monitoring. Thus, the final N for hypertension analysis was 55.
- Olive oil group: 61.5±7.6 years
- EPA: 61.2±9.6
- DHA: 60.9±8.2 (means±SD).
Other Relevant Demographics
- BMI expressed per group
- Olive oil: 29.9±4.0
- EPA: 27.9±3.4
- DHA: 30.6±3.1 (means±SD).
- Waist to hip ratio per group
- Olive oil: 0.99±0.11
- EPA: 0.92±0.06
- DHA: 0.92±0.05 (means±SD).
- Report of results are limited to those that are significant and those related to hypertension
- No significant changes in diet and lifestyle occured during the intervention
- Plasma fatty acid levels reflected supplementation of the respective fatty acids
- Fasting serum glucose was higher at the end of the study, compared to baseline for the EPA (+1.40±0.29mmol per L), P<0.001, and the DHA groups (+0.98±0.29mmol per L), P<0.005. In comparison with the change in the olive oil group and adjusting for baseline values, both EPA and DHA resulted in greater increases in fastng glucose, P=0.002 for both groups.
- Adjusting for baseline values, fasting triacylglycerol fell 19% with EPA (P=0.022) and 15% with DHA (P=0.022), compared to the change observed in the olive oil group
- Compared to changes observed in the olive oil group, HDL2-cholesterol increased by 16% with EPA (P=0.026) and by 22% with DHA (P=0.05) and HDL3-cholesterol decreased by 11% with EPA (P=0.026). Total HDL was not affected by either intervention.
24-Hour BP (mm Hg) and Heart Rate (Beats per Minute) at Baseline and Post-Intervention
EPA Treatment Effect
DHA Treatment Effect
- Treatment effect represents changes compared to those in the olive oil group after adjustment for baseline values
- There were no significant treatment effects.
- Over six weeks, four grams of EPA or DHA per day caused a mild impairment in glycemic control in moderately obese type 2 diabetic patients with treated hypertension
- Additionally, these results suggest that purified EPA and DHA do not offer any substantial advantages over fish or mixed fish oil supplements, with respect to effects on glycemic control, lipids or sytolic and diastolic BP in hypertensive patients with type 2 diabetes.
|Government:||National Health and Research Council of Australia|
|In-Kind support reported by Industry:||Yes|
- Well-controlled study, however sample size is small.
- There was no effect on SBP, DBP or heart rate of EPA or DHA, compared to the olive oil placebo, though this is not reflected in the author's conclusion.
- The authors discuss possible reasons for the lack of antihypertensive effect in this study that was observed in their previous study in overweight, mildly hypercholesterolemic men
- Factors affecting the lack of effect in this study may be use of other medications, adequacy of glycemic control, increased BP variability in the diabetic patients causing indadequate statistical power and the use of olive oil as the placebo.
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?||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?||???|
|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?||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?||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?||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?||???|
|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?||Yes|
|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?||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?||???|
|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?||Yes|
|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?||???|
|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)?||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|