Dangour AD, Allen E, Elbourne D, Fasey N, Fletcher AE, Hardy P et al.. 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

London School of Hygiene and Tropical Medicine, United Kingdom. <>
American Journal of Clinical Nutrition (Impact Factor: 6.77). 06/2010; 91(6):1725-32. DOI: 10.3945/ajcn.2009.29121
Source: PubMed


Increased consumption of n-3 (omega-3) long-chain polyunsaturated fatty acids (LC PUFAs), especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), may maintain cognitive function in later life.
We tested the hypothesis that n-3 LC PUFA supplementation would benefit cognitive function in cognitively healthy older people.
At total of 867 cognitively healthy adults, aged 70-79 y, from 20 general practices in England and Wales were randomly assigned into a double-blind controlled trial of daily capsules providing 200 mg EPA plus 500 mg DHA or olive oil for 24 mo. Treatment-allocation codes were obtained from a central computerized randomization service. Trained research nurses administered a battery of cognitive tests, including the primary outcome, the California Verbal Learning Test (CVLT), at baseline and 24 mo. Intention-to-treat analysis of covariance, with adjustment for baseline cognitive scores, age, sex, and age at leaving full-time education, included 748 (86%) individuals who completed the study.
The mean age of participants was 75 y; 55% of the participants were men. Withdrawals and deaths were similar in active (n = 49 and n = 9, respectively) and placebo (n = 53 and n = 8, respectively) arms. Mean (+/-SD) serum EPA and DHA concentrations were significantly higher in the active arm than in the placebo arm at 24 mo (49.9 +/- 2.7 mg EPA/L in the active arm compared with 39.1 +/- 3.1 mg EPA/L in the placebo arm; 95.6 +/- 3.1 mg DHA/L in the active arm compared with 70.7 +/- 2.9 mg DHA/L in the placebo arm). There was no change in cognitive function scores over 24 mo, and intention-to-treat analysis showed no significant differences between trial arms at 24 mo in the CVLT or any secondary cognitive outcome.
Cognitive function did not decline in either study arm over 24 mo. The lack of decline in the control arm and the relatively short intervention period may have limited our ability to detect any potential beneficial effect of fish oil on cognitive function in this study. The Older People And n-3 Long-chain polyunsaturated fatty acids (OPAL) Study was registered at as ISRCTN 72331636.

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Available from: Ricardo Uauy, Jan 29, 2016
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    • "Of these, three studied young adults of age 35 years or less [16] [17] [18]and two studied middle aged to elderly individuals [19] [20]. Dangour et al. reported no changes in cognitive measure such as the California Verbal Learning Test in 70–79 year old adults after providing an experimental treatment of 700 mg/d of EPA/DHA [19]. However, as the authors noted, over the 24 months period of the study, the subjects experienced no decline in cognitive function; thus, it does not seem possible to measure a benefit of a supplement on declining cognitive function [21]. "
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    ABSTRACT: A brief overview of the evidence for omega-3 fatty acids and, in particular, of docosahexaenoic acid (DHA), involvement in cognition and in dementia is given. Two studies are presented in this regard in which the key intervention is a DHA supplement. The fist, the MIDAS Study demonstrated that DHA can be of benefit for episodic memory in healthy adults with a mild memory complaint. The second, the ADCS AD trial found no benefit of DHA in the primary outcomes but found an intriguing benefit for cognitive score in ApoE4 negative allele patients. This leads to a consideration of the mechanisms of action and role of ApoE and its modulation by DHA. Given the fundamental role of ApoE in cellular lipid transport and metabolism in the brain and periphery, it is no surprise that ApoE affects n-3 PUFA brain function as well. It remains to be seen to what extent ApoE4 deleterious effect in AD is associated with n-3 PUFA-related cellular mechanisms in the brain and, more specifically, whether ApoE4 directly impairs the transport of DHA into the brain, as has been suggested.
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    • "In fact, several studies report little benefit of omega-3 intake on cognitive function (de Lorgeril et al., 1994; Pistell et al., 2010; Oksman et al., 2006), and initial randomized trials directly testing the effects of raised omega-3 intake have yielded only limited evidence of improved cognitive performance (Antypa et al., 2009; Chiu et al., 2008; Dangour et al., 2010; Fontani et al., 2005; Freund- Levi et al., 2006; Giltay et al., 2012; Rogers et al., 2008; Stonehouse et al., 2013; van de Rest et al., 2008). Some studies (Antypa et al., 2009; Bourre, 2004; Fontani et al., 2005; Gomez-Pinilla, 2008) suggest that associations between omega-3 and cognitive performance may be domain specific with some cognitive functions (i.e., executive functions) being more sensitive to omega-3 than others. "
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    ABSTRACT: Greater amounts of physical activity (PA) and omega-3 fatty acids have both been independently associated with better cognitive performance. Because of the overlapping biological effects of omega-3 fatty acids and PA, fatty acid intake may modify the effects of PA on neurocognitive function. The present study tested this hypothesis by examining whether the ratio of serum omega-6 to omega-3 fatty acid levels would moderate the association between PA and executive and memory functions in 344 participants (Mean age=44.42 years, SD=6.72). The Paffenbarger Physical Activity Questionnaire (PPAQ), serum fatty acid levels, and performance on a standard neuropsychological battery were acquired on all subjects. A principal component analysis reduced the number of cognitive outcomes to three factors: n-back working memory, Trail Making test, and Logical Memory. We found a significant interaction between PA and the ratio of omega-6 to omega-3 fatty acid serum levels on Trail Making performance and n-back performance, such that higher amounts of omega-3 levels offset the deleterious effects of lower amounts of PA. These effects remained significant in a subsample (n=299) controlling for overall dietary fat consumption. There were no significant additive or multiplicative benefits of higher amounts of both omega-3 and PA on cognitive performance. Our results demonstrate that a diet high in omega-3 fatty acids might mitigate the effect of lower levels of PA on cognitive performance. This study illuminates the importance of understanding dietary and PA factors in tandem when exploring their effects on neurocognitive health.
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    • "The first functional magnetic resonance imaging (fMRI) study in the omega-3 fatty acid research field (Mcnamara et al., 2010b) revealed that an 8-week DHA supplementation led to an increase in functional activation in the dorsolateral prefrontal brain regions during a sustained visual attention task (a simple continuous performance task) compared with presupplementation in healthy children aged 8 to 10 years. However, these cortical activation changes were not accompanied by a corresponding change in either accuracy or reaction times comparing pre-supplementation and post-supplementation testing sessions, a finding supported by other DHA intervention studies using near-infrared spectroscopy (Dullemeijer et al., 2007; Dangour et al., 2010; Stough et al., 2011; Jackson et al., 2012a; Benton et al., 2013). Less well-investigated are the effects on brain function of supplementation with EPA. "
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    ABSTRACT: The current study aimed to investigate the effects of eicosapentaenoic acid (EPA)-rich and docosahexaenoic acid (DHA)-rich supplementations on cognitive performance and functional brain activation. A double-blind, counterbalanced, crossover design, with a 30-day washout period between two supplementation periods (EPA-rich and DHA-rich) was employed. Functional magnetic resonance imaging scans were obtained during performance of Stroop and Spatial Working Memory tasks prior to supplementation and after each 30-day supplementation period. Both supplementations resulted in reduced ratio of arachidonic acid to EPA levels. Following the EPA-rich supplementation, there was a reduction in functional activation in the left anterior cingulate cortex and an increase in activation in the right precentral gyrus coupled with a reduction in reaction times on the colour-word Stroop task. By contrast, the DHA-rich supplementation led to a significant increase in functional activation in the right precentral gyrus during the Stroop and Spatial Working Memory tasks, but there was no change in behavioural performance. By extending the theory of neural efficiency to the within-subject neurocognitive effects of supplementation, we concluded that following the EPA-rich supplementation, participants' brains worked 'less hard' and achieved a better cognitive performance than prior to supplementation. Conversely, the increase in functional activation and lack of improvement in time or accuracy of cognitive performance following DHA-rich supplementation may indicate that DHA-rich supplementation is less effective than EPA-rich supplementation in enhancing neurocognitive functioning after a 30-day supplementation period in the same group of individuals. Copyright © 2014 John Wiley & Sons, Ltd.
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