Effects of a Six-Month Multi-Ingredient Nutrition Supplement Intervention of Omega-3 Polyunsaturated Fatty Acids, vitamin D, Resveratrol, and Whey Protein on Cognitive Function in Older Adults: A Randomised, Double-Blind, Controlled Trial

  • Catherine MoranEmail author
  • A. Scotto di Palumbo
  • J. Bramham
  • A. Moran
  • B. Rooney
  • G. De Vito
  • B. Egan
Brief Report



To investigate the impact of a six-month multi-ingredient nutrition supplement intervention (Smartfish®), containing omega-3 polyunsaturated fatty acids (PUFAs), vitamin D, resveratrol, and whey protein, on cognitive function in Irish older adults.


Double-blind, randomised controlled trial ( NCT02001831). A quantitative, mixedmodel design was employed in which the dependent variable (cognitive function) was analysed with a between-subjects factor of group (placebo, intervention) and within-subjects factor of testing occasion (baseline, three-months, six-months).


Community-based intervention including assessments conducted at University College Dublin, Ireland.


Thirty-seven community-dwelling older adults (68-83 years; mean (x̅)= 75.14 years; standard deviation (SD)= 3.64; 18 males) with normal cognitive function (>24 on the Mini Mental State Examination) were assigned to the placebo (n= 17) or intervention (n= 20) via a block randomisation procedure.


Daily consumption for six-months of a 200mL liquid juice intervention comprising 3000mg omega-3 PUFAs [1500mg docosahexaenoic acid (DHA) and 1500mg eicosapentaenoic acid (EPA)], 10μg vitamin D3, 150mg resveratrol and 8g whey protein isolate. The placebo contained 200mL juice only.


A standardised cognitive assessment battery was conducted at baseline and follow-ups. Individual test scores were z-transformed to generate composite scores grouped into cognitive domains: executive function, memory, attention and sensorimotor speed. Motor imagery accuracy and subjective awareness of cognitive failures variables were computed from raw scores.


A hierarchical statistical approach was used to analyse the data; first, by examining overall cognitive function, then by domain, and then by individual test scores. Using mixed between-within subjects, analyses of variance (ANOVAs), no significant differences in overall cognitive function or composite cognitive domains were observed between groups over time. The only significant interaction was for Stroop Color-Word Time (p< 0.05). The intervention group demonstrated reduced task completion time at three- and six-month follow-ups, indicating enhanced performance.


The present nutrition intervention encompassed a multi-ingredient approach targeted towards improving cognitive function, but overall had only a limited beneficial impact in the older adult sample investigated. Future investigations should seek to establish any potential clinical applications of such targeted interventions with longer durations of supplementation, or in populations with defined cognitive deficits.

Key words

Cognitive failures executive function aging nutrition supplementation 

Abbreviations and Symbols


Analysis of Variance


Auditory Verbal Learning Test


Body Mass Index


Cognitive Failures Questionnaire


Controlled Oral Word Association




Docosahexaenoic acid


Eicosapentaenoic acid


Intervention Group


Motor Imagery


Mini Mental State Examination


Principal Investigator


Placebo Group


Polyunsaturated fatty acid


Randomised controlled trial


Standard deviation


Trail Making Test


Timed Up and Go


University College Dublin


Wechsler Adult Intelligence Scale III



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  1. 1.
    Johansson B. Memory and cognition in aging. In: Woods R, Clare L (eds) Handbook of the clinical psychology of aging, 2nd edn. John Wiley & Sons LTD, New York, 2008;pp 33–55.Google Scholar
  2. 2.
    Forte R, Boreham CA, Leite JC, De Vito G, Brennan L, Gibney ER, Pesce C. Enhancing cognitive functioning in the elderly:multicomponent vs resistance training. Clin Interv Aging 2013;8:19–27. doi:10.2147/CIA.S36514.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Sydenham E, Dangour AD, Lim WS. Omega 3 fatty acid for the prevention of cognitive decline and dementia. Cochrane Database of Syst Rev 2012;13(6):1–42. doi:10.1002/14651858.CD005379.pub3.Google Scholar
  4. 4.
    Gillette Guyonnet S, Abellan van Kan G, Andrieu S, Barberger Gateau P, Berr C, Bonnefoy M, Dartigues JF, de Groot L, Ferry M, Galan P, Hercberg S, Jeandel C, Morris MC, Nourhashemi F, Payette H, Poulain JP, Portet F, Roussel AM, Ritz P, Rolland Y, Vellas B. IANA task force on nutrition and cognitive decline with aging. J Nutr Health Aging 2007;11:132–152.PubMedGoogle Scholar
  5. 5.
    Barberger-Gateau P, Raffaitin C, Letenneur L, Berr C, Tzourio C, Dartigues JF, Alperovitch A. Dietary patterns and risk of dementia:the Three-City cohort study. Neurology 2007;69:1921–1930. doi:10.1212/01.wnl.0000278116.37320.52CrossRefPubMedGoogle Scholar
  6. 6.
    Hooijmans CR, Pasker-de Jong PC, de Vries RB, Ritskes-Hoitinga M. The effects of long-term omega-3 fatty acid supplementation on cognition and Alzheimer’s pathology in animal models of Alzheimer’s disease:a systematic review and meta-analysis. J Alzheimers Dis 2012;28:191–209. doi:10.3233/JAD-2011-111217.CrossRefPubMedGoogle Scholar
  7. 7.
    van Gelder BM, Tijhuis M, Kalmijn S, Kromhout D. Fish consumption, n-3 fatty acids, and subsequent 5-y cognitive decline in elderly men:the Zutphen Elderly Study. Am J Clin Nutr 2007;85:1142–1147.CrossRefPubMedGoogle Scholar
  8. 8.
    Engelhart MJ, Geerlings MI, Ruitenberg A, van Swieten JC, Hofman A, Witteman JC, Breteler MM. Diet and risk of dementia:does fat matter? The Rotterdam Study. Neurology 2001;59:1915–1921. doi:10.1212/01. WNL.0000038345.77753.46.CrossRefGoogle Scholar
  9. 9.
    Kalmijn S, Feskens EJ, Launer LJ, Kromhout D. Polyunsaturated fatty acids, antioxidants, and cognitive function in very old men. Am J Epidemiol 1997;145:33–41.CrossRefPubMedGoogle Scholar
  10. 10.
    Dangour AD, Allen E, Elbourne D, Faey N, Fletcher AE, Hardy P, Holder GE, Knight R, Letley L, Richards M, Uauy R. Effect of 2-y n-3 long-chain polyunsaturated fatty acid supplementation on cognitive function in older people:a randomised, double-blind, controlled trial. Am J Clin Nutr 2010;91:1725–1732. doi:10.3945/ajcn.2009.29121.CrossRefPubMedGoogle Scholar
  11. 11.
    Geleijnse J, Giltay E, & Kromhout D. Effects of n-3 fatty acids on cognitive decline:A randomised, double-blind, placebo-controlled decline in stable myocardial infarction patients. Alzheimers Dement 2012;8:278–287. doi:10.1016/j.jalz.2011.06.002.CrossRefPubMedGoogle Scholar
  12. 12.
    van de Rest O, Geleijnse JM, Kok FJ, van Staveren WA, Dullemeijer C, Olderikkert MGM, Beekman AT, de Groot CP. Effect of fish oil on cognitive performance in older subjects; A randomised, controlled trial. Neurology 2008;71:430–438. doi:10.1212/01.wnl.0000324268.45138.86.CrossRefPubMedGoogle Scholar
  13. 13.
    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;24:3059–3068. doi:10.1093/cercor/bht163.CrossRefPubMedGoogle Scholar
  14. 14.
    Külzow N, Witte VA, Kerti L, Grittner U, Schuchardt JP, Hahn A, Flöel A. Impact of omega-3 fatty acid supplementation on memory functions in healthy older adults. J Alzheimers Dis 2016;51:713–725. doi:10.3233/JAD-150886CrossRefPubMedGoogle Scholar
  15. 15.
    Buell JS, Dawson-Hughes B. Vitamin D and neurocognitive dysfunction:Preventing “D”ecline? Mol Aspects Med 2008;29:415–422. doi:10.1016/j. mam.2008.05.001.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Miller JW. Vitamin D and cognitive function in older adults. Are we concerned about vitamin D-mentia? Neurology 2010;74:13–15. doi:10.1212/WNL.0b013e3181c719a2.CrossRefPubMedGoogle Scholar
  17. 17.
    Llewellyn DJ, Lang IA, Langa KM, Muniz-Terrera G, Phillips CL, Cherubini, A, Ferrucci L, Melzer D. Vitamin D and risk of cognitive decline in elderly persons. Arch Inter Med 2010;170:1135–1141. doi:10.1001/archinternmed.2010.173.CrossRefGoogle Scholar
  18. 18.
    Slinin Y, Paudel ML, Taylor BC, Fink HA, Ishani A, Canales MT, Yaffe K, Barrett-Connor E, Orwoll ES, Shikany JM, Leblanc ES, Cauley JA, Ensrud KE, Osteoporotic Fractures in Men (MrOS) Study Research Group. 25-Hydroxyvitamin D levels and cognitive performance and decline in elderly men. Neurology 2010;74:33–41. doi:10.1212/WNL.0b013e3181c7197b.PubMedGoogle Scholar
  19. 19.
    Folstein MF, Folstein SE, McHugh PR. “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975;12:189–198. doi:10.1016/0022-3956(75)90026-6.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Army Individual Test Battery. Manual of directions and scoring. War Department, Adjutant General’s Office, Washington DC, 1944.Google Scholar
  21. 21.
    Laughlin GA, Kritz-Silverstein D, Bergstrom J, Reas ET, Jassal SK, Barrett-Connor E, McEvoy LK. Vitamin D insufficiency and cognitive function trajectories in older adults:The Rancho Bernardo study. J Alzheimers Dis 2017;58:871–883. doi:10.3233/JAD-161295.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Anekonda TS. Resveratrol-A boon for treating Alzheimer’s disease? Brain Res Rev 2006;52:316–326. doi:10.1016/j.brainresrev.2006.04.004.CrossRefPubMedGoogle Scholar
  23. 23.
    Bedalov A, Simon JA. Neuroscience. NAD to the rescue. Science 2004;305:954–955.PubMedGoogle Scholar
  24. 24.
    Parker JA, Arango M, Abderrahmane S, Lambert E, Tourette C, Catoire H, Neri C. Resveratrol rescues mutant polyglutamine cytotoxicity in nematode and mammalian neurons. Nat Genet 2005;37:349–350. doi:10.1038/ng1534.CrossRefPubMedGoogle Scholar
  25. 25.
    Walle T. Bioavailability of resveratrol. Ann N Y Acad Sci 2011;1215:9–15. doi:10.1111/j.1749-6632.2010.05842.x.CrossRefPubMedGoogle Scholar
  26. 26.
    Bauer JM, Verlaan S, Bautmans I, Brandt K, Donini LM, Maggio M, McMurdo ME, Mets T, Seal C, Wijers SL, Ceda GP, De Vito G, Donders G, Drey M, Greig C, Holmbäck U, Narici M, McPhee J, Poggiogalle E, Power D, Scafoglieri A, Schultz R, Sieber CC, Cederholm T. Effects of a vitamin D and leucineenriched whey protein nutritional supplement on measures of sarcopenia in older adults, the PROVIDE Study:A randomized, double-blind, placebocontrolled trial. J Am Med Dir Assoc 2015;16(9):740–747. doi:10.1016/j. jamda.2015.05.021.CrossRefPubMedGoogle Scholar
  27. 27.
    Weaver CM. Role of dairy beverages in the diet. Physiol Behav 100:2010;63–66. doi:10.1016/j.physbeh.2010.01.020.Google Scholar
  28. 28.
    Camfield DA, Owen L, Scholey AB, Pipingas A, Stough C. Dairy constituents and neurocognitive health in aging. Br J Nutr 2011;106:159–174. doi:10.1017/S0007114511000158.CrossRefPubMedGoogle Scholar
  29. 29.
    Greig CA, Young A, Skelton DA, Pippet E, Butler FM, Mahmud SM. Exercise studies with elderly volunteers. Age Ageing 1994;23:185–189. doi:10.1093/ageing/23.3.185.CrossRefPubMedGoogle Scholar
  30. 30.
    Beauchet O, Annweiler C, Assal F, Bridenbaugh S, Herrmann FR, Kressig RW, Allali G. Imagined Timed Up & Go test:A new tool to assess higher-level gait and balance disorders in older adults? J Neurol Sci 2010;294:103–106. doi:10.1016/j.jns.2010.03.021.CrossRefGoogle Scholar
  31. 31.
    Broadbent DE, Cooper PF, FitzGerald P, Parkes KR. The Cognitive Failures Questionnaire (CFQ) and its correlates. Brit J Clin Psychol 1982;21:1–16. doi:10.1111/j.2044-8260.1982.tb01421.x.CrossRefGoogle Scholar
  32. 32.
    Rey A. The clinical examination in psychology. Universitaires de France, Paris, 1964.Google Scholar
  33. 33.
    Stroop J. Studies of interference in serial verbal reactions. J Exp Psychol 1935;18:643–662. doi:10.1037/h0054651.CrossRefGoogle Scholar
  34. 34.
    Trenerry M, Crosson B, DeBoe J, Leber W. Stroop neuropsychological screening test manual. Psychological Assessment Resources (PAR), Adessa, Florida, 1989.Google Scholar
  35. 35.
    Benton AL, Hamsher KD. Multilingual aphasia examination. AJA Associates, Iowa City, Iowa, 1989.Google Scholar
  36. 36.
    Wechsler D. Wechsler adult intelligence scale, 3rd edn. Harcourt Assessment, San Antonio, Texas, 1997Google Scholar
  37. 37.
    Jennerod M. Mental imagery in the motor context. Neuropsychologia 1995;33:1419–1432. doi:10.1016/0028-3932(95)00073-C.CrossRefGoogle Scholar
  38. 38.
    Podsiadlo D, Richardson S. The timed “up and go”:a test of basic functional mobility for frail elderly persons. J Am Geriatr Soc 1991;39:142–148. doi:10.1111/j.1532-5415.1991.tb01616.x.CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Beauchet O, Launay CP, Sejdic E, Allali G, Annweiler C. Motor imagery of gait:a new way to detect mild cognitive impairment? J Neuroeng Rehabil 2014;11(66):1–7. doi:10.1186/1743-0003-11-66.Google Scholar
  40. 40.
    Vogel A, Stokholm J, Gade A, Andersen BB, Hejl AM, Waldemar G. Awareness of deficits in mild cognitive impairment and Alzheimer’s disease:Do MCI patients have impaired insight? Dement Geriatr Cogn Disord 2004;17(3):181–187. doi:10.1159/000076354.CrossRefPubMedGoogle Scholar
  41. 41.
    IBM SPSS Statistics. IBM SPSS statistics 20.0 for Windows/Apple Mac. SPSS Inc, Chicago, 2011.Google Scholar
  42. 42.
    Norman G. Likert scales, levels of measurement and the “laws of statistics”. Adv Health Sci Educ Theory Pract 2010;15:625–632. doi:10.1007/s10459-010-9222-y.CrossRefPubMedGoogle Scholar
  43. 43.
    Famenini S, Rigali EA, Olivera-Perez HM, Dang J, Chang MT, Halder R, Rao RV, Pellegrini M, Porter V, Bredesen D, Fiala M. Increased intermediate M1-M2 macrophage polarization and improved cognition in mild cognitive impairment patients on omega-3 supplementation. FASEB J 2017;31:148–160. doi:10.1096/fj.201600677RR.CrossRefPubMedGoogle Scholar

Copyright information

© Serdi and Springer Nature Switzerland AG 2018

Authors and Affiliations

  • Catherine Moran
    • 1
    • 3
    Email author
  • A. Scotto di Palumbo
    • 2
  • J. Bramham
    • 1
  • A. Moran
    • 1
  • B. Rooney
    • 1
  • G. De Vito
    • 2
  • B. Egan
    • 2
  1. 1.School of PsychologyUniversity College DublinDublinIreland
  2. 2.School of Public Health, Physiotherapy and Sports ScienceUniversity College DublinDublinIreland
  3. 3.School of Psychology, Trinity College Institute for NeuroscienceTrinity College Dublin, College GreenDublin 2Ireland

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