Effect of fish-oil supplementation on mental well-being in older subjects: a randomized, double-blind, placebo-controlled trial

Background:  Conflicting studies exist as to whether or not a low intake of fish, or n-3 polyunsaturated fatty acids (PUFAs), is associated with depressed mood.

Objective:  The objective of the study was to investigate the effects of PUFAs (EPA and DHA) on mental well- being in older subjects.

Methods:  The study was a randomized double-blind placebo controlled trial that took place at Wageningen University in Netherlands.  302 independently living participants, age 65 and older, were randomly assigned to receive a high or low dose of EPA + DHA or placebo.  Exclusion criteria were:  Score greater than 16 on the Center for Epidemiologic Studies Depression Scale (CES-D), a score of < 21 points on the mini-mental state examination (MMSE), current or recent use of fish oil supplements, current use of antidepressant or dementia medications, serious liver disease, consumption of > 4 glasses of alcohol a day, inability to participate as judged by a medical doctor, an allergy to fish, problems swallowing, current or recent participation in another clinical trial, and an intake of fish > 4 times a week or consumption of >800mg EPA+DHA from fish. Participants received a daily dose of either 400mg EPA + DHA, or 1800mg EPA + DHA or a placebo containing sunflower oil for 26 weeks.  Changes in mental well-being were assessed as the primary outcome using the CES-D, the Montgomery-Asberg Depression Rating Scale (MADRS), the short version of the Geriatric Depression Rating Scale (GDS-15) and the Hospital Anxiety and Depression Scale (HADS-A) questionnaires.  The questionnaires were completed at baseline and after 13 and 26 weeks. A subgroup of 104 patients was contacted at weeks 17 and 21 for telephone interviews and an additional CES-D was performed along with the Dutch version of the Profile of Mood States Short form (s-POMS).  A minimum sample size of 85 participants per treatment group was required to detect 80% power, 2-sided alpha = 0.05.

Results:  After weeks 13 and 26, there were no significant changes in the fish oil group compared with the placebo group for any of the measures of mental well-being.  Total scores for the additional CES-D scores and the s-POMS components (depression, fatigue, tension and loss of vigor) were not significantly different between the intervention groups but at week 21 scores for the mood component of anger were lower (P=0.01) in the low dose fish oil group.  Adherence to treatment was high and compliance was confirmed by a change in the proportion of EPA + DHA in plasma cholesteryl esters.

Strengths:  The execution and rationale of the study were appropriate.  The success of blinding was determined at the end of the study.  Primary and secondary outcome measures were clearly defined and the questionnaires that were used were validated. 

Weaknesses:  The study was to determine the effect of fish oil on mental well-being, however the questionnaires were designed to assess depressive symptoms in depressed individuals and not mental well-being in a non-depressed population.  The study should have excluded participants with optimal CES-D scores of less than 5, their inclusion might have made it more difficult to detect a change.  There was no power assigned to the secondary outcomes measured in the subgroup population of 104 participants.  

Conclusion:  Fish oil supplementation showed no effect on mental well-being as assessed by depression questionnaires in a non-depressed population, but further studies are needed to determine their effectiveness on depressed patients and depressed moods.

Van de Rest O, Geleijinse JM, Kok FJ, Van Staveren WA, Hoefnagels WH, et al.  Effect of fish-oil supplementation on mental well-being in older subjects: a randomized, double-blind, placebo-controlled trial.  Am J Clin Nutr 2008;88:707-713.

Nereah Wakala, Pharm D. Candidate