Supplementation with oil rich in eicosapentaenoic acid, but not in docosahexaenoic acid, improves global cognitive function in healthy, young adults: results from randomized controlled trials

Michael J Patan, David O Kennedy, Cathrine Husberg, Svein Olaf Hustvedt, Philip C Calder, Julie Khan, Joanne Forster, Philippa A Jackson, Michael J Patan, David O Kennedy, Cathrine Husberg, Svein Olaf Hustvedt, Philip C Calder, Julie Khan, Joanne Forster, Philippa A Jackson

Abstract

Background: Evidence regarding the effects of the omega-3 (ɷ-3) PUFAs (n-3 PUFAs) DHA and EPA on cognition is lacking.

Objectives: We investigated whether supplementation with oils rich in EPA or DHA improves cognition, prefrontal cortex (PFC) hemoglobin (Hb) oxygenation, and memory consolidation.

Methods: Healthy adults (n = 310; age range: 25-49 y) completed a 26-wk randomized controlled trial in which they consumed either 900 mg DHA/d and 270 mg EPA/d (DHA-rich oil), 360 mg DHA/d and 900 mg EPA/d (EPA-rich oil), or 3000 mg/d refined olive oil (placebo). Cognitive performance and memory consolidation were assessed via computerized cognitive test battery. PFC Hb oxygenation was measured using near infrared spectroscopy (NIRS).

Results: Both global accuracy and speed improved with EPA-rich oil compared with placebo and DHA-rich oil [EPA vs. placebo accuracy: estimated marginal mean (EMM) = 0.17 (95% CI: 0.09, 0.24) vs. EMM = 0.03 (95% CI = -0.04, 0.11); P = 0.044; EPA vs. placebo speed: EMM = -0.15 (95% CI: -0.22, -0.07) vs. EMM = 0.03 (95% CI: -0.05, 0.10); P = 0.003]. Accuracy of memory was improved with EPA compared with DHA [EMM = 0.66 (95% CI: 0.26, 1.06) vs. EMM = -0.08 (95% CI: -0.49, 0.33); P = 0.034]. Both EPA- and DHA-rich oils showed trends towards reduced PFC oxygenated Hb (oxy-Hb) compared with placebo [placebo: EMM = 27.36 µM (95% CI: 25.73, 28.98); DHA: EMM = 24.62 µM (95% CI: 22.75, 26.48); P = 0.060; EPA: EMM = 24.97 µM (95% CI: 23.35, 26.59); P = 0.082].

Conclusions: EPA supplementation improved global cognitive function and was superior to the oil enriched with DHA. Interpreted within a neural efficiency framework, reduced PFC oxygenated Hb suggests that n-3 PUFAs may be associated with increased efficiency.These trials were registered in the clinical trials registry (https://ichgcp.net/clinical-trials-registry/NCT03158545" title="See in ClinicalTrials.gov">NCT03158545, NCT03592251, NCT02763514.

Keywords: cognition; docosahexaenoic acid; eicosapentaenoic acid; memory; n-3 polyunsaturated fatty acids; self-micro-emulsifying.

© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.

Figures

FIGURE 1
FIGURE 1
CONSORT flow diagram. *Data from the sleep subsample are published elsewhere (24). CONSORT, Consolidated Standards of Reporting Trials; NIRS, near infrared spectroscopy.
FIGURE 2
FIGURE 2
Estimated marginal means ± SEs from LMM analysis for post-dose (A) global accuracy (average standardized % accuracy scores across all cognitive tasks), (B) global speed (average standardized reaction time across all cognitive tasks), and (C) accuracy of memory (average standardized % accuracy across all the memory tasks). *P < 0.05. LMM, linear mixed model.
FIGURE 3
FIGURE 3
Estimated marginal means ± SEs from LMM analysis for word recognition RT during the learning trials. *P < 0.05. LMM, linear mixed model; RT, reaction time.
FIGURE 4
FIGURE 4
Estimated marginal means ± SEs from LMM analysis for post-dose quantities (µM) of oxy-Hb, in the right PFC, during the serial subtraction tasks. In the right hemisphere, placebo vs, DHA-rich (P = 0.060); placebo vs, EPA-rich (P = 0.082). LMM, linear mixed model; Oxy-Hb, oxygenated hemoglobin; PFC, prefrontal cortex.
FIGURE 5
FIGURE 5
Pearson's bivariate correlations during the serial subtraction tasks between oxy-Hb quantities (µM) in the right PFC and n–3 index at baseline (n = 78) and week 26 (n = 75). Oxy-Hb, oxygenated hemoglobin; PFC, prefrontal cortex.

References

    1. Masana MF, Koyanagi A, Haro JM, Tyrovolas S. n-3 Fatty acids, Mediterranean diet and cognitive function in normal aging: a systematic review. Exp Gerontol. 2017;91:39–50.
    1. Adjepong M, Yakah W, Harris WS, Annan RA, Pontifex MB, Fenton JI. Whole blood n-3 fatty acids are associated with executive function in 2-6-year-old northern Ghanaian children. J Nutr Biochem. 2018;57:287–93.
    1. Pot GK, Prynne CJ, Roberts C, Olson A, Nicholson SK, Whitton C, Teucher B, Bates B, Henderson H, Pigott Set al. . National Diet and Nutrition Survey: fat and fatty acid intake from the first year of the rolling programme and comparison with previous surveys. Br J Nutr. 2012;107(3):405–15.
    1. Rangel-Huerta OD, Gil A. Effect of omega-3 fatty acids on cognition: an updated systematic review of randomized clinical trials. Nutr Rev. 2018;76(1):1–20.
    1. Stonehouse W. Does consumption of LC omega-3 PUFA enhance cognitive performance in healthy school-aged children and throughout adulthood? Evidence from clinical trials. Nutrients. 2014;6(7):2730–58.
    1. Cooper RE, Tye C, Kuntsi J, Vassos E, Asherson P. Omega-3 polyunsaturated fatty acid supplementation and cognition: a systematic review and meta-analysis. J Psychopharmacol. 2015;29(7):753–63.
    1. Meldrum SJ, Smith MA, Prescott SL, Hird K, Simmer K. Achieving definitive results in long-chain polyunsaturated fatty acid supplementation trials of term infants: factors for consideration. Nutr Rev. 2011;69(4):205–14.
    1. Yurko-Mauro K, Alexander DD, Van Elswyk ME. Docosahexaenoic acid and adult memory: a systematic review and meta-analysis. PLoS One. 2015;10(3):e0120391. doi: 10.1371/journal.pone.0120391.
    1. Maki KC, Palacios OM, Buggia MA, Trivedi R, Dicklin MR, Maki CE. Effects of a self–micro-emulsifying delivery system formulation versus a standard ω-3 acid ethyl ester product on the bioavailability of eicosapentaenoic acid and docosahexaenoic acid: a study in healthy men and women in a fasted state. Clin Ther. 2018;40(12):2065–76.
    1. West AL, Kindberg GM, Hustvedt SO, Calder PC. A novel self-micro-emulsifying delivery system enhances enrichment of eicosapentaenoic acid and docosahexaenoic acid after single and repeated dosing in healthy adults in a randomized trial. J Nutr. 2018;148(11):1704–15.
    1. Bauer I, Hughes M, Rowsell R, Cockerell R, Pipingas A, Crewther S, Crewther D. Omega-3 supplementation improves cognition and modifies brain activation in young adults. Hum Psychopharmacol Clin Exp. 2014;29(2):133–44.
    1. Bauer I, Crewther DP, Pipingas A, Rowsell R, Cockerell R, Crewther SG. Omega-3 fatty acids modify human cortical visual processing—a double-blind, crossover study. PLoS One. 2011;6(12):e28214. doi: 10.1371/journal.pone.0028214.
    1. Bauer I, Crewther S, Pipingas A, Sellick L, Crewther D. Does omega-3 fatty acid supplementation enhance neural efficiency? A review of the literature. Hum Psychopharmacol Clin Exp. 2014;29(1):8–18.
    1. Konagai C, Yanagimoto K, Hayamizu K, Han L, Tsuji T, Koga Y. Effects of krill oil containing n-3 polyunsaturated fatty acids in phospholipid form on human brain function: a randomized controlled trial in healthy elderly volunteers. Clin Intervent Aging. 2013;8:1247–57.
    1. Howe PRC, Evans HM, Kuszewski JC, Wong RHX. Effects of long chain omega-3 polyunsaturated fatty acids on brain function in mildly hypertensive older adults. Nutrients. 2018;10(10):1413. doi: 10.3390/nu10101413.
    1. Jackson PA, Reay JL, Scholey AB, Kennedy DO. DHA-rich oil modulates the cerebral haemodynamic response to cognitive tasks in healthy young adults: a near infrared spectroscopy pilot study. Br J Nutr. 2012;107(8):1093–8.
    1. Jackson PA, Reay JL, Scholey AB, Kennedy DO. Docosahexaenoic acid-rich fish oil modulates the cerebral hemodynamic response to cognitive tasks in healthy young adults. Biol Psychol. 2012;89(1):183–90.
    1. Jackson PA, Deary ME, Reay JL, Scholey AB, Kennedy DO. No effect of 12 weeks' supplementation with 1 g DHA-rich or EPA-rich fish oil on cognitive function or mood in healthy young adults aged 18–35 years. Br J Nutr. 2012;107(8):1232–43.
    1. Stonehouse W, Conlon CA, Podd J, Hill SR, Minihane AM, Haskell C, Kennedy D. DHA supplementation improved both memory and reaction time in healthy young adults: a randomized controlled trial. Am J Clin Nutr. 2013;97(5):1134–43.
    1. Dalton A, Wolmarans P, Witthuhn RC, van Stuijvenberg ME, Swanevelder SA, Smuts CM. A randomised control trial in schoolchildren showed improvement in cognitive function after consuming a bread spread, containing fish flour from a marine source. Prostaglandins Leukotrienes Essent Fatty Acids. 2009;80(2-3):143–9.
    1. Yurko-Mauro K, McCarthy D, Rom D, Nelson EB, Ryan AS, Blackwell A, Salem N, Stedman M, Beneficial effects of docosahexaenoic acid on cognition in age-related cognitive decline. Alzheimers Dementia. 2010;6(6):456–64.
    1. Dangour AD, Allen E, Elbourne D, Fasey N, Fletcher AE, Hardy P, Holder GE, Knight R, Letley L, Richards M. 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. 2010;91(6):1725–32.
    1. Kuelzow N, Witte AV, Kerti L, Grittner U, Schuchardt JP, Hahn A, Floeel A. Impact of omega-3 fatty acid supplementation on memory functions in healthy older adults. J Alzheimers Dis. 2016;51(3):713–25.
    1. Patan MJ, Kennedy DO, Husberg C, Hustvedt SO, Calder PC, Middleton B, Khan J, Forster J, Jackson PA. Differential Effects of DHA-and EPA-rich oils on sleep in healthy young adults: a randomized controlled trial. Nutrients. 2021;13(1):248.
    1. Salthouse TA. When does age-related cognitive decline begin?. Neurobiol Aging. 2009;30(4):507–14.
    1. Benisek D, Bailey-Hall E, Oken H, Masayesva S, Arterburn L. Validation of a simple food frequency questionnaire as an indicator of long chain omega-3 intake. Inform. 2002;96.
    1. Jackson PA, Husberg C, Hustvedt S-O, Calder PC, Khan J, Avery H, Forster J, Kennedy DO. Diurnal rhythm of plasma EPA and DHA in healthy adults. Prostaglandins Leukotrienes Essent Fatty Acids. 2020;154:102054.
    1. Fisk HL, West AL, Childs CE, Burdge GC, Calder PC. The use of gas chromatography to analyze compositional changes of fatty acids in rat liver tissue during pregnancy. J Vis Exp. 2014;(85):e51445.
    1. Hoshi Y. Functional near-infrared spectroscopy: current status and future prospects. J Biomed Opt. 2007;12(6):062106.
    1. Holz J, Piosczyk H, Landmann N, Feige B, Spiegelhalder K, Riemann D, Nissen C, Voderholzer U. The timing of learning before night-time sleep differentially affects declarative and procedural long-term memory consolidation in adolescents. PLoS One. 2012;7(7):e40963.
    1. Holz J, Piosczyk H, Feige B, Spiegelhalder K, Baglioni C, Riemann D, Nissen C. EEG sigma and slow-wave activity during NREM sleep correlate with overnight declarative and procedural memory consolidation. J Sleep Res. 2012;21(6):612–9.
    1. Krueger C, Tian L. A comparison of the general linear mixed model and repeated measures ANOVA using a dataset with multiple missing data points. Biol Res Nurs. 2004;6(2):151–7.
    1. Drton M, Plummer M. A Bayesian information criterion for singular models. J Roy Stat Soc B Stat Method. 2017;79(2):323–80.
    1. Jackson PA, Reay JL, Scholey AB, Kennedy DO. Docosahexaenoic acid-rich fish oil modulates the cerebral hemodynamic response to cognitive tasks in healthy young adults. Biol Psychol. 2012;89(1):183–90.
    1. Roy A, Bhaumik DK, Aryal S, Gibbons RD. Sample size determination for hierarchical longitudinal designs with differential attrition rates. Biometrics. 2007;63(3):699–707.
    1. Causse M, Chua Z, Peysakhovich V, Del Campo N, Matton N. Mental workload and neural efficiency quantified in the prefrontal cortex using fNIRS. Sci Rep. 2017;7(1):1–15.
    1. Eid M, Gollwitzer M, Schmitt M. Statistik und Forschungsmethoden Lehrbuch. Weinheim (Germany):Beltz; 2011.
    1. Chiu C-C, Su K-P, Cheng T-C, Liu H-C, Chang C-J, Dewey ME, Stewart R, Huang S-Y. The effects of omega-3 fatty acids monotherapy in Alzheimer's disease and mild cognitive impairment: a preliminary randomized double-blind placebo-controlled study. Prog Neuropsychopharmacol Biol Psychiatry. 2008;32(6):1538–44.
    1. Nishihira J, Tokashiki T, Higashiuesato Y, Willcox DC, Mattek N, Shinto L, Ohya Y, Dodge HH. Associations between serum omega-3 fatty acid levels and cognitive functions among community-dwelling octogenarians in Okinawa, Japan: the KOCOA study. J Alzheimers Dis. 2016;51(3):857–66.
    1. Witte AV, Kerti L, Hermannstädter HM, Fiebach JB, Schreiber SJ, Schuchardt JP, Hahn A, Flöel A. Long-chain omega-3 fatty acids improve brain function and structure in older adults. Cereb Cortex. 2014;24(11):3059–68.
    1. Chen CT, Liu Z, Bazinet RP. Rapid de-esterification and loss of eicosapentaenoic acid from rat brain phospholipids: an intracerebroventricular study. J Neurochem. 2011;116(3):363–73.
    1. Neubauer AC, Fink A. Intelligence and neural efficiency: measures of brain activation versus measures of functional connectivity in the brain. Intelligence. 2009;37(2):223–9.
    1. Calder PC. Very long-chain n-3 fatty acids and human health: fact, fiction and the future. Proc Nutr Soc. 2018;77(1):52–72.
    1. Dyall S, Mandhair H, Fincham R, Kerr D, Roche M, Molina-Holgado F. Distinctive effects of eicosapentaenoic and docosahexaenoic acids in regulating neural stem cell fate are mediated via endocannabinoid signalling pathways. Neuropharmacology. 2016;107:387–95.
    1. Aryal S, Hussain S, Drevon CA, Nagelhus E, Hvalby Ø, Jensen V, Walaas SI, Davanger S. Omega-3 fatty acids regulate plasticity in distinct hippocampal glutamatergic synapses. Eur J Neurosci. 2019;49(1):40–50.
    1. Stark KD, Van Elswyk ME, Higgins MR, Weatherford CA, Salem N Jr. Global survey of the omega-3 fatty acids, docosahexaenoic acid and eicosapentaenoic acid in the blood stream of healthy adults. Prog Lipid Res. 2016;63:132–52.. doi: 10.1016/j.plipres.2016.05.001.
    1. Kuszewski JC, Wong RHX, Howe PRC. Effects of long-chain omega-3 polyunsaturated fatty acids on endothelial vasodilator function and cognition—are they interrelated?. Nutrients. 2017;9(5):487. doi: 10.3390/nu9050487.
    1. de Groot RH, Emmett R, Meyer BJ. Non-dietary factors associated with n-3 long-chain PUFA levels in humans—a systematic literature review. Br J Nutr. 2019;121(7):793–808.

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