Effect of omega 3 supplementation alone or associated in patients with Alzheimer's disease: a systematic literature review
DOI:
https://doi.org/10.34019/1982-8047.2019.v45.27797Keywords:
Brain, Alzheimer’s disease, Docosahexaenoic Acids; Fatty Acids, Unsaturated.Abstract
Introduction: Aging of the population is associated with an increased incidence of Alzheimer's disease (AD), which causes severe complications to the patient. Immunomodulatory nutrients such as polyunsaturated fatty acids (PUFAs) of the omega-3 (w-3) series may help improve the clinical picture of AD. Objective: To analyze the effect of supplementation of isolated or associated w-3 PUFAs in patients with AD. Material and methods: This is a systematic review of the scientific literature in the Pubmed and Science Direct databases, which included clinical trials in elderly people with probable and / or proven diagnosis of AD supplemented with isolated or associated PUFAS w-3, in English and with the following health descriptors (DECs): brain, Alzheimer's disease, fatty docosahexaenoic acid (DHA), polyunsaturated fatty acids (PUFA), older and elderly people and search term: eicosapentaenoic acid (EPA).The time cut of publications was delimited from 2006 to 2017. Results: a total of 10 clinical trials were selected, whose w-3 supplementation favored a smaller decline in the Mini Mental Status Examination (MMSE) score, delayed dysfunction, improved neuropsychiatric inventory (NPI) agitation, and improved depressive symptoms by the Montgomery-Asberg Depression Scale (MADRS). Significant changes were observed as increased appetite, weight, body mass index (BMI), EPA and DHA, as well as reductions in serum albumin levels, arachidonic acid (AA), myristic acid, interleukin-6 (IL-6), interleukin 1β (IL-1β), and granulocyte colony stimulating factor (G-CSF) and reduced clearance of prostaglandin F2α (PGF2α). Positive alterations have been reported in some genes and in others, reduction of their expression, besides hypomethylation of important genes. Conclusion: Supplementation of PUFAs w-3 had a positive effect in patients with mild to moderate AD.
Downloads
References
World Health Organization (WHO). World report on ageing and health. Geneve: WHO; 2015.
United Nations, Department of Economic and Social Affairs, Population Division. World population ageing. New York: United Nations; 2015.
Scazufca M, Cerqueira A, Menezes PR, Prince M, Vallada HP, Miyazaki MCOS et al. Investigações epidemiológicas sobre demência nos países em desenvolvimento. Revsp. 2002; 36(1):6. doi:10.1590/S0034-89102002000700018.
Woolley JD, Khan BK, Murthy NK, Miller BL, Rankin KP. The diagnostic challenge of psychiatric symptoms in neurodegenerative disease: rates of and risk factors for prior psychiatric diagnosis in patients with early neurodegenerative disease. J Clin Psychiatry. 2011; 72(2):126-33. doi: 10.4088/JCP.10m06382oli.
Alzheimer’s Disease International (ADI). Relatório sobre a doença de Alzheimer no mundo 2009: resumo executivo. Illinois: 2009.
Tosto G, Monsell SE, Hawes SE, Bruno G, Mayeux R. Progression of extrapyramidal signs in Alzheimer's disease: clinical and neuropathological correlates. J Alzheimers Dis. 2015; 49(4):1085-93. doi: 10.3233/JAD-150244.
Shoshan-Barmatz V, Nahon-Crystal E, Shteinfer-Kuzmine A, Gupta R. VDAC1, mitochondrial dysfunction, and Alzheimer’s disease. Pharmacol Res. 2018; 131(1):87-101. doi: 10.1016/j.phrs.2018.03.010.
Karch CM, Goate AM. Alzheimer’s disease risk genes and mechanisms of disease pathogenesis. Biol Psychiatry. 2015; 77(1):43-51. doi: 10.1016/j.biopsych.2014.05.006.
Taylor CA, Greenlund SF, McGuire LC, Lu H, Croft JB. Deaths from Alzheimer’s disease: United States, 1999-2014. MMWR Morb Mortal Wkly Rep. 2017; 66(1):521-6. doi: 10.15585/mmwr.mm6620a1.
Bua X-L, Jiaoa S-S, Lianb Y, Wanga Y-J. Perspectives on the tertiary prevention strategy for Alzheimer’s disease. Curr Alzheimer Res. 2016; 13(3):307-16. doi: 10.2174/1567205013666151215110114.
Anand R, Gill K D, Mahdi AA. Therapeutics of Alzheimer’s disease: past, present and future. Int J Neuropharmacol. 2014; 76(1):27-50. doi: 10.1016/j.neuropharm.2013.07.004.
Freund-Levi Y, Eriksdotter-Jönhagen M, Cederholm T, Basun H, Faxén-Irving G, Garlind A et al. Omega-3 fatty acid treatment in 174 patients with mild to moderate Alzheimer disease: omegAD study: a randomized double-blind trial. Arch Neurol. 2006; 63(10):1402-8.
Karimi M, Vedin I, Freund-Levi Y, Basun H, Faxén-Irving, Eriksdotter M et al. DHA-rich n–3 fatty acid supplementation decreases dna methylation in blood leukocytes: the omegAD study. Am J Clin Nutr. 2017; 106(4):1157-65. doi: 10.3945/ajcn.117.155648.
Vedin I, Cederholm T, Freund-Levi Y, Basun H, Garlind A, Irving GF et al. Effects of DHA-rich n-3 fatty acid supplementation on gene expression in blood mononuclear leukocytes: the OmegAD study. PLos One. 2012; 7(4): e35425. doi: 10.1371/journal.pone.0035425.
Youdim KA, Martin A, Joseph JA. Essential fatty acids and the brain: possible health implications. Int J Devl Neuroscience. 2000; 18(1):383-99.
Mc Namara RK, Asch RH, Lindquist DM, Krikorian R. Role of polyunsaturated fatty acids in human brain structure and function across the lifespan: an update on neuroimaging findings. PLEFA. 2018; 136(1):23-34. doi:10.1016/j.plefa.2017.05.001.
Hashimoto K. Role of soluble epoxide hydrolase in metabolism of pufas in psychiatric and neurological disorders. Front Pharmacol. 2019; 10(1):36. doi: 10.3389/fphar.2019.00036.
Layé S, Nadjar A, Joffre C, Bazinet RP. Anti-inflammatory effects of omega-3 fatty acids in the brain: physiological mechanisms and relevance to pharmacology. Pharmacol Rev. 2018; 70(1):12-38. doi: 10.1124/pr.117.014092.
Freund-Levi Y, Basun H, Cederholm T, Faxén-Irving G, Garlind A, Grut M et al. Omega-3 supplementation in mild to moderate Alzheimer's disease: effects on neuropsychiatric symptoms. Int J Geriatr Psychiatry. 2008; 23(2):161-9. doi: 10.1002/gps.1857. PMID: 17582225.
Irving GF, Freund-Levi Y, Eriksdotter-Jönhagen M, Basun H, Brismar K, Hjorth E et al. Omega-3 fatty acid supplementation effects on weight and appetite in patients with Alzheimer's disease: the omega-3 Alzheimer's disease study. J Am Geriatr Soc. 2009; 57(1):11-7. doi: 10.1111/j.1532-5415.2008.02055. x.
Vedin I, Cederholm T, Freund-Levi Y, Basun H, Hjorth E, Irving GF et al. Reduced prostaglandin F release from blood mononuclear leukocytes after oral supplementation of ω3 fatty acids: the OmegAD study. J Lipid Res. 2010; 51(5):1179-85. doi: 10.1194/jlr.M002667.
Freund-Levi Y, Vedin I, Cederholm T, Basun H, Faxén-Irving G, Eriksdotter M et al. J Intern Med. 2014; 275(4):428-36. doi: 10.1111/joim.12166.
Freund-Levi Y, Vedin I, Hjorth E, Basun H, Faxén Irving G, Schultzberg M et al. Effects of supplementation with omega-3 fatty acids on oxidative stress and inflammation in patients with Alzheimer's disease: the omegAD study. J Alzheimers Dis. 2014; 42(3):823-31. doi: 10.3233/JAD-132042. PMID: 24934544.
Wang X, Hjorth E, Vedin I, Eriksdotter M, Freund-Levi Y, Wahlund LO et al. Effects of n-3 FA supplementation on the release of proresolving lipid mediators by blood mononuclear cells: the OmegAD study. J Lipid Res. 2015; 56(3):674-81. doi: 10.1194/jlr. P055418.
Eriksdotter M, Vedin I, Falahati F, Freund-Levi Y, Hjorth E, Faxén-Irving G et al. Plasma fatty acid profiles in relation to cognition and ender in Alzheimer's disease patients during oral omega-3 fatty acid supplementation: the omegAD study. J Alzheimers Dis. 2015; 48(3):805-12. doi: 10.3233/JAD-150102.
Baranowska-Bosiacka I, Olszowski T, Gutowska I, Korbecki J, Rebacz-Maron E, Barczak K et al. Fatty acid levels alterations in THP-1 macrophages cultured with lead (Pb). J Trace Elem Med Biol. 2019; 52(1):222-31. doi: 10.1016/j.jtemb.2019.01.003.
Esposito G, Giovacchini G, Liow JS, Bhattacharjee AK, Greenstein D, Schapiro M et al. Imaging neuroinflammation in Alzheimer disease with radiolabeled arachidonic acid and pET. J Nucl Med. 2008; 49(9): 1414-21. doi:10.2967/jnumed.107.049619.
Lu Y, Nguyen PH, Sterpone F, Salsbury Jr FR, Derreumaux P. Amyloid-β (29-42) dimeric conformations in membranes rich in omega-3 and omega-6 polyunsaturated fatty acids. J Phys Chem B. 2019; 123(12):2687-96. doi: 10.1021/acs.jpcb.9b00431.
Zárate R, El Jaber-Vazdekis N, Tejera N, Pérez JA, Rodríguez C. Significance of long chain polyunsaturated fatty acids in human health. Clin Transl Med. 2017; 6(1):25. doi: 10.1186/s40169-017-0153-6.
Interim Summary of Conclusions and Dietary Recommendations on Total Fat & Fatty Acids. Joint FAO/WHO expert consultation on fats and fatty acids in human nutrition. 2008. [citado em 2008 dezembro] Disponível em: http://www.fao.org/ag/agn/nutrition/docs/Fats%20and%20Fatty%20Acids%20Summary.pdf.
Lundová T, Stambergová H, Zemanová L, Svobodová M, Havránková J et al. Human dehydrogenase/reductase (SDR family) member 8 (DHRS8): a description and evaluation of its biochemical properties. Mol Cell Biochem. 2016; 411(1-2):35-42. doi: 10.1007/s11010-015-2566-0.
Strittmatter WJ, Saunders AM, Schmechel D, Pericak-Vance M, Enghild J, Salvesen GS et al. Apolipoprotein E: high-avidity binding to beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease. Proc Natl Acad Sci USA. 1993; 90(5):1977-81.
Reinvang I, Espeseth T, Westlye LT. APOE-related biomarker profiles in non-pathological aging and early phases of Alzheimer's disease. Neurosci Biobehav Rev. 2013; 37(8):1322-35. doi: 10.1016/j.neubiorev.2013.05.006.
Ishibashi T, Yokota T, Satoh Y, Ichii M, Sudo T, Doi Y et al. Identification of MS4A3 as a reliable marker for early myeloid differentiation in human hematopoiesis. Biochem Biophys Res Commun. 2018; 495(3):2338-43. doi: 10.1016/j.bbrc.2017.12.117.
Huang YA, Zhou B, Wernig M, Südhof TC. ApoE2, apoe3, and apoe4 differentially stimulate app transcription and Aβ secretion. Cell. 2017; 26;168(3):427-41. e21. doi: 10.1016/j.cell.2016.12.044.
Kutok JL, Yang X, Folkerth R, Adra CN. Characterization of the expression of HTm4 (MS4A3), a cell cycle regulator, in human peripheral blood cells and normal and malignant tissues. J Cell Mol Med. 2011; 15(1):86-93. doi: 10.1111/j.1582-4934.2009.00925. x.
Vance RE. The NAIP/NLRC4 Inflammasomes. Curr Opin Immunol. 2015; 84-89. doi: 10.1016/j.coi.2015.01.010.
Ellen TP, Ke Q, Zhang P, Costa M. NDRG1, a growth and cancer related gene: regulation of gene expression and function in normal and disease states. Carcinogenesis. 2008; 29(1):2-8.
Srinivasan S, Selvan ST, Archunan G, Gulyas B, Padmanabhan. MicroRNAs: the next generation therapeutic targets in human diseases. Theranostics. 2013; 3(12):930-42. doi: 10.7150/thno.7026.
Pols MS, Klumperman J. Trafficking and function of the tetraspanin CD63. Exp Cell Res. 2009; 315(9):1584-92. doi: 10.1016/j.yexcr.2008.09.020.
Naguib A, Sandmann T, Yi F, Watts RJ, Lewcock JW, Dowdle WE. SUPT4H1 depletion leads to a global reduction in RNA. Cell Rep. 2019; 26(1):45-53. doi: 10.1016/j.celrep.2018.12.004.
Yin RH, Yu JT, Tan L. The role of SORL1 in Alzheimer's disease. Mol Neurobiol. 2015; 51(3):909-18. doi: 10.1007/s12035-014-8742-5.
Bertram L, Tanzi RE. The genetics of Alzheimer's disease. Prog Mol Biol Transl Sci. 2012; 107(1):79-100. doi: 10.1016/B978-0-12-385883-2.00008-4.
Chouliaras L, Rutten BP, Kenis G, Peerbooms O, Visser PJ, Verhey F et al. Epigenetic regulation in the pathophysiology of Alzheimer's disease. Prog Neurobiol. 2010; 90(4):498-510. doi: 10.1016/j.pneurobio.2010.01.002.
Liu X, Jiao B, Shen L. The epigenetics of Alzheimer’s disease: factors and therapeutic implications. Front Genet. 2018; 9(1):579. doi: 10.3389/fgene.2018.00579.
Mehler MF. Epigenetic principles and mechanisms underlying nervous system functions in health and disease. Prog Neurobiol. 2008; 86(4):305-41. doi: 10.1016/j.pneurobio.2008.10.001.
Di Francesco A, Arosio B, Falconi A, Micioni Di Bonaventura MV, Karimi M, Mari D et al. Global changes in DNA methylation in Alzheimer's disease peripheral blood mononuclear cells. Brain Behav Immun. 2015; 45(1):139-44. doi: 10.1016/j.bbi.2014.11.002.
Mrak RE, Griffin WS. Potential inflammatory biomarkers in Alzheimer's disease. J Alzheimers Dis. 2005; 8(4):369-75. PMID: 16556968.
Laske C, Stellos K, Stransky E, Leyhe T, Gawaz M. Decreased plasma levels of granulocyte-colony stimulating factor (G-CSF) in patients with early Alzheimer's disease. J Alzheimers Dis. 2009; 17(1):115-23. doi: 10.3233/JAD-2009-1017.
Sirin FB, Kumbul Doğuç D, Vural H, Eren I, Inanli I, Sütçü R et al. Plasma 8-isoPGF2α and serum melatonin levels in patients with minimal cognitive impairment and Alzheimer disease. Turk J Med Sci. 2015; 45(5):1073-7.
Casadesus G, Smith MA, Basu S, Hua J, Capobianco DE, Siedlak SL et al. Increased isoprostane and prostaglandin are prominent in neurons in Alzheimer disease. Mol Neurodegener. 2007; 22(1):2:2. doi: 10.1186/1750-1326-2-2.
Kim JY, Lee JW, Youn YJ, Ahn MS, Ahn SG, Yoo BS et al. Urinary levels of 8-iso-prostaglandin F2α and 8-hydroxydeoxyguanine as markers of oxidative stress in patients with coronary artery disease. Korean Circ J. 2012; 42(9):614-17.doi:10.4070/kcj.2012.42.9.614.
Yaffe K1 Kanaya A, Lindquist K, Simonsick EM, Harris T, Shorr RI et al. The metabolic syndrome, inflammation, and risk of cognitive decline. JAMA. 2004; 292(18):2237-42. doi: 10.1001/jama.292.18.2237.
Rocha NP, Martins LCA, Teixeira AL, Reis HJ. Processo inflamatório e neuroimunomodulação na doença de Alzheimer: revisão de literatura. Rev Neurocienc. 2011; 19(2):300-13.
Gonçalves, MV (editor). Caracterização da resposta imune periférica na doença de Alzheimer. 2012. [citado em 2012] disponível em: https://estudogeral.sib.uc.pt/bitstream/10316/25142/1/Caracteriza%C3%A7%C3%A3o%20da%20Resposta%20Imune%20Perif%C3%A9rica%20na%20Doen%C3%A7a%20de%20Alzheimer_Milene%20Vieira%20Gon%C3%A7alves.pdf.
Shang S, Yang YM, Zhang H, Tian L, Jiang JS, Dong YB et al. Intracerebral GM-CSF contributes to transendothelial monocyte migration in APP/PS1 Alzheimer's disease mice. J Cereb Blood Flow Metab. 2016; 36(11):1978-91. doi:10.1177/0271678X16660983.
Patricò D. The neurobiology of isoprostanes and Alzheimer’s disease. Biochim Biophys Acta. 2010; 1801(8): 930-3.doi: 10.1016/j.bbalip.2010.01.009.
Villeda SA, Luo J, Mosher KI, Zou B, Britschgi M, Bieri G et al. The ageing systemic milieu negatively regulates neurogenesis and cognitive function. Nature. 2011; 477(7362):90-4. doi: 10.1038/nature10357.
Reisberg B, Ferris SH, de Leon MJ, Crook T. The Global Deterioration Scale for assessment of primary degenerative dementia. Am J Psychiatry. 1982; 139(9):1136-9. doi: 10.1176/ajp.139.9.1136.
Garcia-Ptacek S, Eriksdotter M, Jelic V, Porta-Etessam J, Kåreholt I, Manzano Palomo S. Subjective cognitive impairment: towards early identification of Alzheimer disease. Neurología. 2016; 31(8):562-71. doi: 10.1016/j.nrl.2013.02.007.
Jonsson T, Atwal JK, Steinberg S, Snaedal J, Jonsson PV, Bjornsson S et al. A mutation in aap protects against Alzheimer's disease and age-related cognitive decline. Nature. 2012; 488(7409):96-9. doi: 10.1038/nature11283.
Prajapati KD, Sharma SS, Roy N. Current perspectives on potential role of albumin in neuroprotection. Rev Neurosci. 2011; 22(3):355-63. doi: 10.1515/RNS.2011.028.
Merlot AM, Kalinowski DS, Richardson DR. Unraveling the mysteries of serum albumin-more than just a serum protein. Front Physiol. 2014; 5(1):299. doi: 10.3389/fphys.2014.00299.
Besser LM1, Gill DP, Monsell SE, Brenowitz W, Meranus DH, Kukull W et al. Body mass index, weight change, and clinical progression in mild cognitive impairment and Alzheimer disease. Alzheimer Dis Assoc Disord. 2014; 28(1):36-43. doi: 10.1097/WAD.0000000000000005.
Ikeda M, Brown J, Holland A, Fukuhara R, Hodges J. Changes in appetite, food preference, and eating habits in frontotemporal dementia and Alzheimer's disease. J Neurol Neurosurg Psychiatry. 2002; 73(4):371-6. doi: 10.1136/jnnp.73.4.371.
Vidoni ED, Townley RA, Honea RA, Burns JM. Alzheimer disease biomarkers are associated with body mass index. Neurol. 2011; 77(21):1913-20. doi: 10.1212/WNL.0b013e318238eec1.
Daborg J, Andreasson U, Pekna M, Lautner R, Hanse E, Minthon L et al. Cerebrospinal fluid levels of complement proteins C3, C4 and CR1 in Alzheimer's disease. J Neural Transm. 2012; 119(7):789-97. doi: 10.1007/s00702-012-0797-8.
Ramos-Fernández E, Tajes M, Palomer E, Ill-Raga G, Bosch-Morató M, Guivernau B et al. Posttranslational nitro-glycative modifications of albumin in Alzheimer's disease: implications in cytotoxicity and amyloid-β peptide aggregation. J Alzheimers Dis. 2014; 40(3):643-57. doi: 10.3233/JAD-130914.
Kai K, Hashimoto M, Amano K, Tanaka H, Fukuhara R, Ikeda M et al. Relationship between eating disturbance and dementia severity in patients with Alzheimer's disease. PLoS One. 2015; 10(8): e0133666. doi: 10.1371/journal.pone.0133666.
Brock F, Bettinelli LA, Dobner T, Stobbe JC, Pomatti G, Telles CT. Prevalence of hypoalbuminemia and nutritional issues in hospitalized elders. [citado em 2019 Maio] Rev Latino-Am Enfermagem. 2016; 24: e2736. Disponível em: http://www.scielo.br/pdf/rlae/v24/es_0104-1169-rlae-24-02736.pdf. doi: http://dx.doi.org/10.1590/1518-8345.0260.2736.
Casati M, Boccardi V, Ferri E, Bertagnoli L, Bastiani P, Ciccone S, et al. Vitamin E and Alzheimer’s disease: the mediating role of cellular aging. Aging Clin Exp Res. 2019. doi: 10.1007/s40520-019-01209-3.
Traber MG, Stevens JF. Vitamins C and E: beneficial effects from a mechanistic perspective. Free Radic Biol Med. 2011; 51(5):1000-13. doi: 10.1016/j.freeradbiomed.2011.05.017.
Direção-Geral da Saúde (DGS). Programa Nacional para a Promoção da Alimentação Saudável: Nutrição e doença de Alzheimer. Lisboa: DGS; 2015.
Faludi AA, Izar MCO, Saraiva JFK, Chacra APM, Bianco HT, Afiune Neto A et al. Atualização da diretriz brasileira de dislipidemias e prevenção da aterosclerose – 2017. Arq Bras Cardiol. 2017; 109(2Supl.1):1-76.
Downloads
Published
How to Cite
Issue
Section
License
Cessão de Primeira Publicação à HU Revista
Os autores mantém todos os direitos autorais sobre a publicação, sem restrições, e concedem à HU Revista o direito de primeira publicação, com o trabalho licenciado sob a Licença Creative Commons Attribution que permite o compartilhamento irrestrito do trabalho, com reconhecimento da autoria e crédito pela citação de publicação inicial nesta revista, referenciando inclusive seu DOI.