EAL

DFA: EPA/DHA and Cognitive Health (2011)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To evaluate the effect of fish oil supplementation on quality of life (QOL), including cognitive performance and depressive symptoms.

Inclusion Criteria:

≥65 years of age
Written informed consent.

Exclusion Criteria:

Score of greater than 16 on the Center for Epidemiological Studies Depression Scale (CES-D)
Score of less than 21 on Mini-Mental State Examination (MMSE)
Current or recent (less than four weeks) use of fish oil supplements
Intake of fish more than four times per week or more than 800mg of EPA-DHA from fish per day as estimated by fish consumption questionnaire
Current use of pharmacological antidepressants
Current use of medication for dementia
Consumption of more than four glasses of alcohol per day
80% adherence to capsule use during the two week placebo run-in period according to self report
≤65 years of age
No written informed consent.

Description of Study Protocol:

Recruitment

Recruited from independently living older Dutch population

Design

Primary outcomes were cognitive performance and depressive symptoms
Subjects randomized using computer-generated random numbers in stratified permuted blocks of size six
Stratification factors included age, sex, MMSE test score and CES-D test score
Intervention of one of the following for 26 weeks
- Daily dose of fish oil containing high dose EPA-DHA (about 1,800mg)
- Daily low dose EPA-DHA fish oil (about 400mg)
- Placebo dose of high oleic sunflower oil
QOL assessed using short version of World Health Organization QOL questionnaire (WHOQOL-BREF)
- Self-administered and checked for completeness by a research assistant at the study center at baseline and after 13 and 26 weeks of intervention.

Blinding

Subjects and investigators blinded to assigned treatment type

Intervention

Daily dose of EPA-DHA supplement for 26 weeks
- High dose of about 1,800mg: 1,093±17mg EPA and 847±23mg of DHA (roughly equivalent consuming eight portions of fish per week)
- Low dose of about 400mg: 226+3mg EPA and 176+4mg DHA (approximately equivalent to consuming one to two servings of oily fish per week)
- Placebo oil (high oleic sunflower oil)
- Capsules with fish oil or placebo oil were indistinguishable in appearance.

Statistical Analysis

Analysis performed on an intention-to-treat basis
To evaluate cognitive performance, a minimum sample size of 63 subjects per group were needed to detect a difference (power 80%)
To evaluate depressive symptoms, a minimum sample size of 85 subjects per group were needed to detect a difference (power 80%)
Two-sided P-value <0.05 considered statistically significant
Baseline characteristics of treatment groups were compared using one-way analysis of variance (ANOVA) or Kruskal-Wallis for continuous variables and chi-square for categorical variables
Differential changes in QOL between the three intervention groups were tested using ANOVA
Dunnett test used to compare mean changes within the treatment groups with that of the placebo group
Additional per-protocol analysis including adherent subjects only also performed
Post hoc analysis performed for subgroups of men and women separately.

Data Collection Summary:

Timing of Measurements

Self administered WHOQOL-BREF used to assess QOL at baseline and after 13 and 26 weeks of intervention
Fasting venous blood sample for determination of n-3 PUFAs collected at baseline and after 13 and 26 weeks of intervention
Information on medical history, drug use, alcohol consumption, smoking habits, educational level, marital status and physical activity level obtained using a questionnaire at baseline
Food frequency questionnaire to estimate fish intake in the previous three months administered at screening, baseline and after 13 and 26 weeks of intervention
Height measured at baseline and weight and waist circumference measured at each center visit.

Dependent Variables

Change in WHOQOL-BREF score

Independent Variables

EPA and DHA intake

Control Variables

Fish intake
Height
Weight
Waist circumference
Medical history
Drug use
Alcohol consumption
n-3 PUFAs from fasting venous blood sample
Smoking habits
Education level
Marital status
Physical activity level
Adherence to treatments.

Description of Actual Data Sample:

Initial N: 302 subjects (55% male)
Attrition (final N): 299 subjects
Age: Mean of 69.8 years
Ethnicity: Dutch, no further details discussed
Other relevant demographics:
Education level (low/middle/high percentage)
- High dose EPA/DHA: 10/54/35%
- Low dose EPA/DHA: 11/49/40%
- Placebo: 5/59/37
Anthropometrics:
- BMI
  - High dose EPA/DHA: 26.1±13kg/m²
  - Low dose EPA/DHA: 26.2±3.4kg/m²
  - Placebo: 26.5+3.9kg/m²
  - No significant difference between groups
Location: Netherlands.

Summary of Results:

Key Findings

Total baseline WHOQOL-BREF scores at baseline and after 13 and 26 weeks of intervention were comparable between the three groups
- High dose EPA/DHA: 110
- Low dose EPA/DHA: 107
- Placebo: 107
After 13 and 26 weeks of supplementation, neither fish oil groups showed better total WHOQOL-BREF scores or better scores on any of the four domains as compared to the placebo group
After 26 weeks, the mean difference in WHOQOL-BREF scores from placebo was -1.42 (95% CI= -3.4-0.57) in the high dose fish oil group and 0.02 (-1.95-1.99) in the low dose fish oil group
Exploratory analysis according to sex showed a significant change after 26 weeks in men in the high dose fish oil group with a mean difference from placebo of -3.28 (CI= -1.95= -5.85-0.71)
After 26 weeks, a significant difference in men in the high dose fish oil group was observed for the domain physical health (-1.0, 95% CI= -1.95 to -0.05) and for domain environment (-1.45, 95% CI= -2.55 to -0.35)

Quality of Life

1,800mg EPA/DHA

Mean (95% CI)

P-value

400mg EPA/DHA

Mean (95% CI)

P-value

WHOQOL-BREF Total Score
(possible range of 26-130)

Week 13

-0.98
(2.89-0.94)

0.42

-1.07
(-2.97-0.82)

0.35

WHOQOL-BREF Total Score
(possible range of 26-130)

Week 26

-1.42
(-3.40-0.57)

0.2

0.02
(-1.95-1.99)

1.0

Other Findings

Reasons for withdrawal from study
- Nine subjects did not complete study
  - Five subjects stopped due to gastrointestinal complaints
  - Two subjects stopped because participation was too burdensome
  - Two subjects died before the end of the intervention
Adherence to treatment
- Average adherence based on counts of returned capsules was high (99%, with only three subjects <80% based on individuals completing treatment).

Author Conclusion:

Study showed that daily supplementation with a low or high dose of EPA-DHA for 26 weeks had no effect on QOL in healthy older subjects. Adherence was excellent and did not differ between treatment groups. The dropout rate was low, at 3%, and cannot therefore explain the findings. More studies investigating the effects of n-3 PUFAs on QOL are warranted, especially in subjects with impaired QOL.

Funding Source:

Government:

Netherlands Organization for Health Research and Development

Reviewer Comments:

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.)	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.)	No
	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?	Yes
	6.6.	Were extra or unplanned treatments described?	Yes
	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?	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?	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?		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)?	Yes
	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?	Yes
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