N-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFAs) have positive effect on cognitive function with mild cognitive impairment (MCI) is still controversial. The aim for this meta-analysis was to assess the scientific evidence published in the last 10 years on the effects of n-3 LC-PUFAs intake on MCI patients to explore whether n-3 LC-PUFAs have positive effective. A comprehensive literature search was developed using the Google Scholar, EMBASE, and PubMed database. The pooled effect for all studies was calculated using random-effects model. And the terms of weighted mean difference (WMD) with 95% confidence interval (CI) was pooled and indicated the effects. Heterogeneity was assessed by I2 statistics. A total of seven randomized clinical trials involving 213 cases of intervention and 221 cases of placebo were included in this analysis. Compared with placebo, n-3 LC-PUFAs supplements effectively improved cognition in elders with MCI (WMD = 0.85, 95% CI: 0.04–1.67, Z = 2.05, P = 0.04). Slight heterogeneity was detected across studies. Our results provided further evidence that n-3 LC-PUFAs may have beneficial effect in elderly with MCI.
Subscribe to Journal
Get full journal access for 1 year
only $53.83 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
Winblad B, Amouyel P, Andrieu S, Ballard C, Brayne C, Brodaty H, et al. Defeating Alzheimer's disease and other dementias: a priority for European science and society. Lancet Neurol. 2016;15:455–532.
Alzheimer’s Disease International. World Alzheimer report 2016. Alzheimer’s Disease International; 2016. https://www.alz.co.uk/research/WorldAlzheimerReport2016.pdf.
2018 Alzheimer’s disease facts and figures. Alzheimers Dement. 2018;14:367–429. https://doi.org/10.1016/j.jalz.2018.02.001.
Roberts R, Knopman DS. Classification and epidemiology of MCI. Clin Geriatr Med. 2013;29:753–72.
Ronald C, Petersen P, Mild MD. Cognitive impairment. Am Acad Neurol. 2016;22:404–18.
Cederholm T, Salem N Jr, Palmblad J. ω-3 fatty acids in the prevention of cognitive decline in humans. Adv Nutr. 2013;4:672–6.
Dangour AD, Allen E, Elbourne D, Fletcher A, Richards M, Uauy R. Fish consumption and cognitive function among older people in the UK: Baseline data from the OPAL study. J Nutr, Health Aging. 2009;13:198–202.
Van de Rest O, Wang Y, Barnes LL, Tangney C, Bennett DA, Morris MC. APOE ε4 and the associations of seafood and long-chain omega-3 fatty acids with cognitive decline. Neurology. 2016;86:2063–70.
Lee LK, Shahar S, Chin AV, Yusoff NA. et al. Docosahexaenoic acid-concentrated fish oil supplementation in subjects;with mild cognitive impairment (MCI): a 12-month randomised,;double-blind, placebo-controlled trial. Psychopharmacology. 2013;225:605–12.
Rondanelli M, Opizzi A, Faliva M, Mozzoni M, Antoniello N, Cazzola R, et al. Effects of a diet integration with an oily emulsion of DHA-phospholipids containing melatonin and tryptophan in elderly patients suffering from mild cognitive impairment. Nutritional Neurosci. 2012;15:46–54.
Hashimoto M, Yamashita K, Kato S, Tamai T, Tanabe Y, Mitarai M, et al. Beneficial effects of daily dietary omega-3 polyunsaturated fatty acid supplementation on age-related cognitive decline in elderly Japanese with very mild dementia: a 2-year randomized, double-blind, placebo-controlled trial. J Aging Res Clin Pract. 2012;1:193–201.
Phillips MA, Childs CE, Calder PC, Rogers PJ. No effect of omega-3 fatty acid supplementation on cognition and mood in individuals with cognitive impairment and probable Alzheimer's disease: a randomised controlled trial. Int J Mol Sci. 2015;16:24600–13.
Mahmoudi MJ, Hedayat M, Sharifi F, Mirarefin M, Nazari N, Mehrdad N, et al. Effect of low dose ω-3 poly unsaturated fatty acids on cognitive status among older people: a double-blind randomized placebo-controlled study. J Diabetes Metab Disord. 2014;13:34.
Rangel-Huerta OD, Gil A. Effect of omega-3 fatty acids on cognition: an updated systematic review of randomized clinical trials. Nutr Rev. 2017;76:1–20.
Moher D, Shamseer L, Clarke M, Ghersi D, Liberati A, Petticrew M, et al. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Syst Rev. 2015;4:1.
Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003;327:557–60.
Zhang Y, Chen J, Qiu J, Li Y, Wang J, Jiao J. Intakes of fish and polyunsaturated fatty acids and mild-to-severe cognitive impairment risks: a dose-response meta-analysis of 21 cohort studies. Am J Clin Nutr. 2016;103:330–40.
Kotani S, Sakaguchi E, Warashina S, Matsukawa N, Ishikura Y, Kiso Y, et al. Dietary supplementation of arachidonic and docosahexaenoic acids improves cognitive dysfunction. Neurosci Res. 2006;56:159–64.
Yurkomauro K, Alexander DD, Elswyk MEV. Docosahexaenoic acid and adult memory: a systematic review and meta-analysis. Plos ONE 2015;10:e0120391.
Zhang XW, Hou WS, Li M, Tang ZY. Omega-3 fatty acids and risk of cognitive decline in the elderly: a meta-analysis of randomized controlled trials. Aging Clin Exp Res. 2016;28:165–6.
Bazan NG, Molina MF, Gordon WC. Docosahexaenoic acid signalolipidomics in nutrition: significance in aging, neuroinflammation, macular degeneration, Alzheimer's, and other neurodegenerative diseases. Annu Rev Nutr. 2011;31:321–51.
Samieri C, Maillard P, Crivello F, Proustlima C, Peuchant E, Helmer C, et al. Plasma long-chain omega-3 fatty acids and atrophy of the medial temporal lobe. Neurology. 2012;79:642–50.
Petursdottir AL, Farr SA, Morley JE, Banks WA, Skuladottir GV. Effect of dietary n-3 polyunsaturated fatty acids on brain lipid fatty acid composition, learning ability, and memory of senescence-accelerated mouse. J Gerontol. 2008;63:1153–60.
Fotuhi M, Mohassel P, Yaffe K. Fish consumption, long-chain omega-3 fatty acids and risk of cognitive decline or Alzheimer disease: a complex association. Nat Clin Pract Neurol. 2009;5:140–52.
Rundblad A, Holven KB, Ottestad I, Myhrstad MC, Ulven SM. High-quality fish oil has a more favourable effect than oxidised fish oil on intermediate-density lipoprotein and LDL subclasses: a randomised controlled trial. Br J Nutr. 2017;117:1291–8.
Morris MC, Tangney CC. Dietary fat composition and dementia risk. Neurobiol Aging. 2014;35 Suppl 2:S59–64.
Quinn JF, Rema R, Thomas RG, Karin YM, Nelson EB, Christopher VD, et al. Docosahexaenoic acid supplementation and cognitive decline in Alzheimer disease: a randomized trial. JAMA. 1903;304:1903–11.
Daiello LA, Gongvatana A, Dunsiger S, Cohen RA, Ott BR. Association of fish oil supplement use with preservation of brain volume and cognitive function. Alzheimers Dement J Alzheimers Assoc. 2015;11:226–35.
Chouinard-Watkins R, Rioux-Perreault C, Fortier M, Tremblay-Mercier J, Zhang Y, Lawrence P, et al. Disturbance in uniformly 13C-labelled DHA metabolism in elderly human subjects carrying the apoE ε4 allele. Br J Nutr. 2013;110:1751–9.
Yurko-Mauro K, Mccarthy D, Rom D, Nelson EB, Ryan AS, Blackwell A, et al. Beneficial effects of docosahexaenoic acid on cognition in age-related cognitive decline. Alzheimer's Dement. 2010;6:456–64.
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. 2010;91:1725–32.
Bo Y, Zhang X, Wang Y, You J, Cui H, Zhu YW. The n-3 polyunsaturated fatty acids supplementation improved the cognitive function in the chinese elderly with mild cognitive impairment: a double-blind randomized controlled trial. Nutrients. 2017;9:54.
Sterne JAC, Harbord RM. Funnel plots in meta-analysis. Stata J. 2004;4:127–41.
Baleztena J, Ruiz-Canela M, Sayon-Orea C, Pardo M, Añorbe T, Gost JI, et al. Association between cognitive function and supplementation with omega-3 PUFAs and other nutrients in≥5 years old patients: a randomized multicenter study. Plos One. 2018;13:e0193568.
Chih-Chiang C, Kuan-Pin S, Tsung-Chi C, Hsing-Cheng L, Ching-Jui C, Dewey ME, et al. 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;32:1538–44.
This study was supported by the National Natural Science Foundation of China (nos: 81673277 and 81973154). We thank the reviewers for helpful suggestions.
Conflict of interest
The authors declare that they have no conflict of interest.
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
Cite this article
Zhang, X., Han, H., Ge, X. et al. Effect of n-3 long-chain polyunsaturated fatty acids on mild cognitive impairment: a meta-analysis of randomized clinical trials. Eur J Clin Nutr (2019) doi:10.1038/s41430-019-0544-4