Rapid Review Alert June 14, 2012
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 In EPA & DHA Research
Abstract (as published)

Background: Evidence from observational studies suggests that diets high in omega-3 long-chain PUFAs may protect people from cognitive decline and dementia. The strength of this potential protective effect has recently been tested in randomized controlled trials.

Objectives: To assess the effects of omega-3 PUFA supplementation for the prevention of dementia and cognitive decline in cognitively healthy older people.

Search Methods: We searched ALOIS- the Cochrane Dementia and Cognitive Improvement Group’s Specialized Register on 6 April 2012 using the terms: “omega 3”, PUFA, “fatty acids”, “fatty acid”, fish, linseed, eicosapentaenoic, docosahexaenoic.

Selection Criteria: Randomised controlled trials of an omega-3 PUFA intervention which was provided for a minimum of six months to participants aged 60 years and over who were free from dementia or cognitive impairment at the beginning of the study. Two review authors independently assessed all trials.

Data Collection and Analysis: The review authors sought and extracted data on incident dementia, cognitive function, safety and adherence, either from published reports or by contacting the investigators for original data. Data were extracted by two review authors. We calculated mean difference (MD) or standardised mean differences (SMD) and 95% confidence intervals (CI) on an intention-to-treat  basis, and summarized narratively information on safety and adherence.

Main Results: Information on cognitive function at the start of a study was available on 4080 participants randomised in three trials. Cognitive function data were available on 3536 participants at final follow-up. 

In two studies participants received gel capsules containing either omega-3 PUFA (the intervention) or olive or sunflower oil (placebo) for six or 24 months. In one study, participants received margarine spread for 40 months; the margarine for the intervention group contained omega-3 PUFA. Two studies had cognitive health as their primary outcome; one study of cardiovascular disease included cognitive health as an additional outcome.

None of the studies examined the effect of omega-3 PUFA on incident dementia. In two studies involving 3221 participants there was no difference between the omega-3 and placebo group in mini-mental state examination score at final follow-up (following 24 or 40 months of intervention);MD-0.07 (95%CI -0.25 to 0.10). In two studies involving 1043 participants, other tests of cognitive function such as word learning, digit span and verbal fluency showed no beneficial effect of omega-3 PUFA supplementation. Participants in both the intervention and control groups experienced either small or no cognitive declines during the studies.

The main reported side-effect of omega-3 PUFA supplementation was mild gastrointestinal problems. Overall, minor adverse events were reported by fewer than 15%of participants, and reports were balanced between intervention groups. Adherence to the intervention was on average over 90% among people who completed the trials. All three studies included in this review are of high methodological quality.

ConclusionsDirect evidence on the effect of omega-3 PUFA on incident dementia is lacking. The available trials showed no benefit of omega-3 PUFA supplementation on cognitive function in cognitively healthy older people. Omega-3 PUFA supplementation is generally well tolerated with the most commonly reported side-effect being mild gastrointestinal problems.

Further studies of longer duration are required. Longer-term studies may identify greater change in cognitive function in study participants which may enhance the ability to detect the possible effects of omega-3 PUFA supplementation in preventing cognitive decline in older people.
Rapid Review Alert
Sudden cardiac death
O-3s & Cognitive Decline

Review of:

Sydenham E Dangour AD and Lim WS (2012). Omega 3 fatty acid for the prevention of cognitive decline and dementia. Cochrane Database Syst Rev Issue 6. Art. No.: CD005379. DOI: 10.1002/14651858.CD005379.pub3.

GOED Take-Away

News headlines that Omega-3s don’t provide brain benefits are based on gross misinterpretations of a recently published review of three studies conducted in cognitively healthy older people. The authors correctly conclude that “further studies of longer duration are required.” 

What Else Should You Know? 

  • Apolipoprotein E4 (Apo E4) is a risk factor for cognitive decline and those individuals with two E4 alleles, which means they are homozygous, are at increased risk for developing cognitive decline. These are the individuals that should be included in trials on cognitive decline. Clinical trials not screening for Apo E4 are destined for failure because they are likely to be grossly underpowered.
  • The MIDAS5 (Memory Improvement With Docosahexaenoic Acid Study), published in 2010, demonstrated that 24 week supplementation with 900 mg/d DHA improved learning and memory function in age-related cognitive decline.
  • For one reason or another, of the three studies included in the review, none appropriately assessed the effects of O-3 supplementation for the prevention of dementia and cognitive decline in the population of interest.  
    1) OPAL1 (Older People And omega-3 Long-chain polyunsaturated fatty acids): This study was designed to test the hypothesis that EPA+DHA supplementation would slow cognitive decline. The primary shortcoming of this study is that there was an absence of cognitive decline over 24 months in the total sample which suggests that a longer follow-up period was needed. OPAL’s principal investigator, Alan Dangour, co-authored the Cochrane Review which could be perceived as a conflict of interest.
    2) Alpha Omega Trial2,3 cohort analysis: In this study, the treatment group received less than 400 mg EPA + DHA per day which is considered too low a dose to demonstrate any cognitive benefits. Also, cognition was a secondary outcome measurement. See Aug 31, 2010 Rapid Review Alert for more information on this study. 
    3) MEMO4 (Mental health in Elderly Maintained with Omega-3): This study was underpowered with 300 subjects. 

Suggested Citation

Global Organization for EPA and DHA Omega-3s (2012). Omega-3s & Cognitive Decline [Peer commentary on the paper “Omega 3 fatty acid for the prevention of cognitive decline and dementia” by Sydenham E Dangour AD and Lim WS (2012). Cochrane Database Syst Rev. Issue 6. Art. No.: CD005379. DOI: 10.1002/14651858.CD005379.pub3.].


  1. Dangour AD Allen E Elbourne D Fasey N Fletcher AE Hardy P Holder GE Knight R Letley L Richards M and Uauy R (2010). Effect of 2-y n-3 long-chain polyunsaturated fatty acid supplementation on cognitive function in older people: a randomized, double-blind, controlled trial. Am J Clin Nutr 91:1725–1732.
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  3. Kromhout D Giltay EJ and Geleijnse JM for the Alpha Omega Trial Group (2010). n-3 fatty acids and cardiovascular events after myocardial infarction. N Eng J Med 363:2015–2026.
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