The effects of 90-day supplementation with the Omega-3 essential fatty acid docosahexaenoic acid (DHA) on cognitive function and visual acuity in a healthy aging population

Neurobiology of Aging 33 (2012) 824.e1– 824.e3 www.elsevier.com/locate/neuaging Negative results The effects of 90-day supplementation with the Omega-3 essential fatty acid docosahexaenoic acid (DHA) on cognitive function and visual acuity in a healthy aging population Con Stougha,*, Luke Downeya, Beata Silbera, Jenny Lloyda, Christina Kurea, Keith Wesnesa,b, David Camfielda a National Institute of Complementary Medicine (NICM) Collaborative Centre for Neurocognition, Brain Sciences Institute, Swinburne University of Technology b United BioSource Corporation, Goring-on-Thames, UK Received 13 October 2010; received in revised form 15 March 2011; accepted 22 March 2011 Abstract The omega-3 fatty acid docosahexaenoic acid (DHA) is essential for nervous system and retinal development and there is evidence to suggest that DHA deficiencies increase with normal aging. A triple-blind placebo-controlled randomized repeated-measures trial was conducted with 74 healthy participants, aged 45–77 years. Cognitive and visual acuity measures and plasma levels of DHA were determined at baseline and after 90 days of administration of either HiDHA® (Clover Corp., Sydney, NSW, Australia: 1000 mg of tuna oil; comprising 252 mg DHA, 60 mg EPA and 10 mg vitamin E) or placebo (1000 mg soybean oil). Ninety days of DHA supplementation was found to significantly raise both plasma DHA and total ␻-3 plasma levels in the treatment group, as well as significantly lower total ␻-6 levels. However, no significant effects of DHA supplementation on cognitive functioning were found. For participants with corrected vision, the group receiving DHA were found to have significantly better right eye visual acuity posttreatment in comparison with the placebo group (F(1,22) ⫽ 7.651; p ⫽ 0.011; partial ␩2 ⫽ 0.258). © 2012 Elsevier Inc. All rights reserved. Keywords: Essential fatty acids; Docosahexaenoic acid (DHA); Geriatrics; Dementia; Nutrition; Cognition; Visual Acuity 1. Introduction Docosahexaenoic acid (DHA) is a long chain ␻-3 polyunsaturated fatty acid (PUFA) which is commonly found in fish oils and constitutes more than 30% of the total phospholipid composition of plasma membranes in the brain (Gomez-Pinilla, 2008; Sinclair et al., 2002). Epidemiological and prospective cohort research has provided strong evidence to indicate that a diet high in fish and marine ␻-3 * Corresponding author at: National Institute of Complementary Medicine (NICM) Collaborative Centre for Neurocognition, Brain Sciences Institute, Swinburne University of Technology, PO Box 218 Hawthorn, Melbourne Victoria 3122, Australia. Tel.: ⫹61 3 9214 8167; fax: ⫹ 61 3 9214 5230. E-mail address: cstough@swin.edu.au (C. Stough). 0197-4580/$ – see front matter © 2012 Elsevier Inc. All rights reserved. doi:10.1016/j.neurobiolaging.2011.03.019 is linked to a lowered risk of cognitive decline and Alzheimer’s disease (AD) (Beydoun et al., 2007; Morris et al., 2005; Van Gelder et al., 2007). However, clinical evidence for the efficacy of DHA in ameliorating cognitive decline has not been without contention. In an extensive review of DHA clinical trials in dementia, Cunnane and colleagues (2009) concluded that there is currently greater evidence for DHA playing a preventive rather than curative role in dementia. Intervention studies that have investigated the cognitive benefits associated with DHA supplementation in healthy elderly individuals without evidence of dementia have also yielded mixed results; with some reporting modest cognitive improvements (Fontani et al., 2005; Johnson et al., 2008; YurkoMauro et al., 2010), while a large study by Van De Rest et 824.e2 C. Stough et al. / Neurobiology of Aging 33 (2012) 824.e1– 824.e3 al. (2008) reported no improvement. Further clinical trials to assess the efficacy of DHA in ameliorating normal agerelated cognitive decline in the elderly are warranted. Clinical research regarding possible beneficial effects of DHA in the visual system (see Nguyen et al., 2008) is also largely unexplored. See Supplementary data for a more detailed review. 2. Methods A randomized, triple-blind, placebo-controlled, repeatedmeasures design was employed to investigate the chronic effects of 252 mg per day DHA treatment in regards to plasma fatty acids levels, cognition, and visual acuity over a 90-day period in 74 healthy elderly participants aged between 45 and 80 years. Repeated measures analysis of variance (ANOVA) was used to analyze differences between placebo and DHA groups as well as time ⫻ treatment interactions. See Supplementary data for further details of methods. 3. Results A significant time ⫻ treatment interaction was observed for plasma DHA levels; while both groups had similar DHA levels at baseline, posttreatment the group receiving DHA supplementation was found to have significantly higher DHA levels in comparison with the placebo group (F(1,37) ⫽ 16.911; p ⬍ 0.001; partial ␩2 ⫽ 0.314). A significant time ⫻ treatment interaction was observed for right eye visual acuity in participants with corrected vision; while both groups had similar visual acuity at baseline, posttreatment the group receiving DHA supplementation was found to have significantly better visual acuity in comparison with the placebo group (F(1,22) ⫽ 7.651; p ⫽ 0.011, partial ␩2 ⫽ 0.258), reflecting a 3.94% improvement for the treatment group. For the Cognitive Drug Research (CDR) cognitive outcome measures as well as the CDR factor scores no significant between-group differences or interactions were observed. See Supplementary data for further details. There is the possibility that with a larger sample size significant cognitive effects associated with DHA supplementation may have been found. Similarly the possibility remains that significant cognitive effects may have been found if a higher dose of DHA or longer treatment duration was used; as was the case in the study of Yurko-Mauro et al. (2010) where increases in plasma DHA were considerably higher than those observed in the current study. Limitations of the current study include lack of apolipoprotein E (APOE)-␧4 genotyping (see Jofre-Monseny et al., 2008) and absence of indices of oxidized DHA (e.g., thiobarbituric acid reactive substances or malondialdehyde); information that would have aided in the analysis and interpretation of the results. The finding that 90-day DHA administration brought about an improvement to visual acuity in participants with corrected vision is encouraging. These findings lend support to previous research which has associated DHA with improved membrane function in the lens and retina (Johnson, 2005; Nguyen, et al., 2008) and better performance in brightness discrimination tasks (Ikemoto et al., 2001). In consideration of the high incidence of vision impairment in the elderly, and the increasing proportion of the population that makes up this demographic, this finding is worthy of further investigation (see Supplementary data for further discussion). Disclosure statement Prof Sinclair has worked as an expert scientific advisor to Clover Corporation. A grant of 50,000 Australian dollars was made from Clover Corporation to Prof Stough to assist in conducting this trial (this was less than 50% of the cost of the trial). The research study was approved by the institutional human research ethics committee and all participants provided written informed consent. Acknowledgements Clover Corporation partially financially supported the research undertaken and presented in this report. They have not provided any feedback on the manuscript. 4. Discussion Appendix A. Supplementary data The current findings are indicative of a lack of cognitive effects associated with 90 days DHA 252 mg per day supplementation within an elderly sample free from dementia. The CDR neuropsychological assessment battery has previously been found to be a particularly sensitive measure for the detection of changes to cognitive function associated with chronic nutraceutical and dietary interventions (see Ryan et al., 2008; Stough et al., 2008; Wesnes et al., 2000). For this reason, the lack of efficacy is more likely to be explained by other factors. Supplementary data associated with this article can be found, in the online version, at doi:10.1016/j.neurobiolaging. 2011.03.019. References Beydoun, M.A., Kaufman, J.S., Satia, J.A., Rosamond, W., Folsom, A.R, 2007. 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