OMEGA-3 Interventions in Alcohol Dependence and Related Outcomes: A Systematic Review and Propositions

Author(s): José Carlos F. Galduróz*, Andréia Gomes Bezerra, Gabriel Natan Pires, Renata Pauluci, Ana Regina Noto

Journal Name: Current Neuropharmacology

Volume 18 , Issue 5 , 2020

Become EABM
Become Reviewer
Call for Editor

Graphical Abstract:


Background: Pharmacological treatment for alcohol dependence has only three approved drugs: disulfiram, naltrexone and acamprosate. The effects of these drugs are, however, limited, presenting several side effects and a modestly higher efficacy compared to placebo. The administration of omega-3 might bring new perspectives to relapse prevention.

Methods: This systematic review aimed to analyze the available literature, compiling the studies that used omega-3 to prevent relapse in alcohol dependents.

Results: The databases used were PubMed and Web of Science. We identified 2,231 studies and only five articles addressed the administration of omega-3 and alcoholism. Preclinical studies evaluating the effects of PUFAs related to chronic alcohol administration showed improvements in behavioral, cellular and molecular levels. The clinical trial yielded inconclusive results.

Conclusion: Despite the reduced number of studies, omega-3 interventions seem to be promising for controlling issues related to alcohol dependence.

Keywords: PUFAs, omega-3, ethanol, relapse, treatment, craving.

Zindel, L.R.; Kranzler, H.R. Pharmacotherapy of alcohol use disorders: seventy-five years of progress. J. Stud. Alcohol Drugs Suppl., 2014, 75(Suppl. 17), 79-88.
[] [PMID: 24565314]
McLellan, A.T.; Lewis, D.C.; O’Brien, C.P.; Kleber, H.D. Drug dependence, a chronic medical illness: implications for treatment, insurance, and outcomes evaluation. JAMA, 2000, 284(13), 1689-1695.
[] [PMID: 11015800]
Maisel, N.C.; Blodgett, J.C.; Wilbourne, P.L.; Humphreys, K.; Finney, J.W. Meta-analysis of naltrexone and acamprosate for treating alcohol use disorders: when are these medications most helpful? Addiction, 2013, 108(2), 275-293.
[] [PMID: 23075288]
Shi, Z.; Xie, Y.; Ren, H.; He, B.; Wang, M.; Wan, J.B.; Yuan, T.F.; Yao, X.; Su, H. Fish oil treatment reduces chronic alcohol exposure induced synaptic changes. Addict. Biol., 2019, 24(4), 577-589.
[] [PMID: 29569345]
Buydens-Branchey, L.; Branchey, M.; Hibbeln, J.R. Low plasma levels of docosahexaenoic acid are associated with an increased relapse vulnerability in substance abusers. Am. J. Addict., 2009, 18(1), 73-80.
[] [PMID: 19219668]
Umhau, J.C.; Zhou, W.; Thada, S.; Demar, J.; Hussein, N.; Bhattacharjee, A.K.; Ma, K.; Majchrzak-Hong, S.; Herscovitch, P.; Salem, N., Jr; Urish, A.; Hibbeln, J.R.; Cunnane, S.C.; Rapoport, S.I.; Hirvonen, J. Brain docosahexaenoic acid [DHA] incorporation and blood flow are increased in chronic alcoholics: a positron emission tomography study corrected for cerebral atrophy. PLoS One, 2013, 8(10), e75333
[] [PMID: 24098376]
Nervi, A.M.; Peluffo, R.O.; Brenner, R.R.; Leikin, A.I. Effect of ethanol administration on fatty acid desaturation. Lipids, 1980, 15(4), 263-268.
[] [PMID: 7374380]
Reitz, R.C. Relationship of the ocyl-CoA desaturase to certain membrane fatty acid changes induced by ethanol consumption. Proc. West. Pharmacol. Soc., 1984, 27, 247-249.
Nakamura, M.T.; Tang, A.B.; Villanueva, J.; Halsted, C.H.; Phinney, S.D. Selective reduction of delta 6 and delta 5 desaturase activities but not delta 9 desaturase in micropigs chronically fed ethanol. J. Clin. Invest., 1994, 93(1), 450-454.
[] [PMID: 8282819]
Yehuda, S. Omega-6/omega-3 ratio and brain-related functions. World Rev. Nutr. Diet., 2003, 92, 37-56.
[] [PMID: 14579682]
Das, U.N.; Fams, Long-chain polyunsaturated fatty acids in the growth and development of the brain and memory. Nutrition, 2003, 19(1), 62-65.
[] [PMID: 12507641]
Hermann, D.; Weber-Fahr, W.; Sartorius, A.; Hoerst, M.; Frischknecht, U.; Tunc-Skarka, N.; Perreau-Lenz, S.; Hansson, A.C.; Krumm, B.; Kiefer, F.; Spanagel, R.; Mann, K.; Ende, G.; Sommer, W.H. Translational magnetic resonance spectroscopy reveals excessive central glutamate levels during alcohol withdrawal in humans and rats. Biol. Psychiatry, 2012, 71(11), 1015-1021.
[] [PMID: 21907974]
Holmes, A.; Spanagel, R.; Krystal, J.H. Glutamatergic targets for new alcohol medications. Psychopharmacology (Berl.), 2013, 229(3), 539-554.
[] [PMID: 23995381]
Kalivas, P.W. The glutamate homeostasis hypothesis of addiction. Nat. Rev. Neurosci., 2009, 10(8), 561-572.
[] [PMID: 19571793]
Spanagel, R. Alcoholism: a systems approach from molecular physiology to addictive behavior. Physiol. Rev., 2009, 89(2), 649-705.
[] [PMID: 19342616]
Shiraishi, K.; Matsuzaki, S.; Itakura, M.; Ishida, H. Abnormality in membrane fatty acid compositions of cells measured on erythrocyte in alcoholic liver disease. Alcohol. Clin. Exp. Res., 1996, 20(1)(Suppl.), 56A-59A.
[] [PMID: 8659691]
Pita, M.L.; Rubio, J.M.; Murillo, M.L.; Carreras, O.; Delgado, M.J. Chronic alcoholism decreases polyunsaturated fatty acid levels in human plasma, erythrocytes, and platelets--influence of chronic liver disease. Thromb. Haemost., 1997, 78(2), 808-812.
[] [PMID: 9268176]
Varatharajalu, R.; Garige, M.; Leckey, L.C.; Reyes-Gordillo, K.; Shah, R.; Lakshman, M.J. Protective role of dietary curcumin in the prevention of the oxidative stress induced by chronic alcohol with respect to hepatic injury and antiatherogenic markers. Oxid. Med. Cell. Longev., 2016.
[] [PMID: 5017460]
Meehan, E.; Beaugé, F.; Choquart, D.; Leonard, B.E. Influence of an n-6 polyunsaturated fatty acid-enriched diet on the development of tolerance during chronic ethanol administration in rats. Alcohol. Clin. Exp. Res., 1995, 19(6), 1441-1446.
[] [PMID: 8749808]
Duffy, O.; Ménez, J.F.; Leonard, B.E. Attenuation of the effects of chronic ethanol administration in the brain lipid content of the developing rat by an oil enriched in gamma linolenic acid. Drug Alcohol Depend., 1992, 31(1), 85-89.
[] [PMID: 1330473]
Le-Niculescu, H.; Case, N.J.; Hulvershorn, L.; Patel, S.D.; Bowker, D.; Gupta, J.; Bell, R.; Edenberg, H.J.; Tsuang, M.T.; Kuczenski, R.; Geyer, M.A.; Rodd, Z.A.; Niculescu, A.B. Convergent functional genomic studies of ω-3 fatty acids in stress reactivity, bipolar disorder and alcoholism. Transl. Psychiatry, 2011, 1e, 4.
[] [PMID: 22832392]
Glen, I.; Glen, E.; MacDonnell, L. Possible pharmacologic approaches to the prevention and treatment of alcohol-related CNS impairment: results of a double blind trial of essential fatty acids.Pharmacological Treatments for Alcoholism; Littleton, J., Ed.; Croon-Helm: London, 1984.
Goldstein, D.B. Ethanol-induced adaptation in biological membranes. Ann. N. Y. Acad. Sci., 1987, 492, 103-111.
[] [PMID: 3474920]
Dyall, S.C. The role of omega-3 fatty acids in adult hippocampal neurogenesis. O.C.L., 2011, 18(5), 242-45.
Tian, C.; Fan, C.; Liu, X.; Xu, F.; Qi, K. Brain histological changes in young mice submitted to diets with different ratios of n-6/n-3 polyunsaturated fatty acids during maternal pregnancy and lactation. Clin. Nutr., 2011, 30(5), 659-667.
[] [PMID: 21459495]
Tanaka, K.; Farooqui, A.A.; Siddiqi, N.J.; Alhomida, A.S.; Ong, W.Y. Effects of docosahexaenoic Acid on neurotransmission. Biomol. Ther. (Seoul), 2012, 20(2), 152-157.
[] [PMID: 24116288]
Higgins, J.P.; Altman, D.G.; Gøtzsche, P.C.; Jüni, P.; Moher, D.; Oxman, A.D.; Savovic, J.; Schulz, K.F.; Weeks, L.; Sterne, J.A. Cochrane Statistical Methods Group. The Cochrane Collaboration's tool for assessing risk of bias in randomised trials. B.M.J., 2011, 18, 343,d5928.e
Hooijmans, C.R.; Rovers, M.M.; de Vries, R.B.; Leenaars, M.; Ritskes-Hoitinga, M.; Langendam, M.W. SYRCLE’s risk of bias tool for animal studies. BMC Med. Res. Methodol., 2014, 14, 43.
[] [PMID: 24667063]
Fogaça, M.N.; Santos-Galduróz, R.F.; Eserian, J.K.; Galduróz, J.C.F. The effects of polyunsaturated fatty acids in alcohol dependence treatment--a double-blind, placebo-controlled pilot study. BMC Clin. Pharmacol., 2011, 11, 10.
[] [PMID: 21787433]
Balaszczuk, V.; Salguero, J.A.; Villarreal, R.N.; Scaramuzza, R.G.; Mendez, S.; Abate, P. Hyperlocomotion and anxiety- like behavior induced by binge ethanol exposure in rat neonates. Possible ameliorative effects of Omega 3. Behav. Brain. Res., 2019, 17: 372, 112022.
He, J.; Huang, W.; Zheng, S.; Vigorito, M.; Chang, S.L. Effects of docosahexaenoic acid on locomotor activity in ethanol-treated HIV-1 transgenic rats. J. Neurovirol., 2018, 24(1), 88-97.
[] [PMID: 29260441]
Raabe, R.C.; Mathies, L.D.; Davies, A.G.; Bettinger, J.C. The omega-3 fatty acid eicosapentaenoic acid is required for normal alcohol response behaviors in C. elegans. PLoS One, 2014, 27,9(8), e105999
Simopoulos, A.P. An Increase in the omega-6/omega-3 fatty acid ratio increases the risk for obesity. Nutrients, 2016, 8(3), 128.
[] [PMID: 26950145]
Witkiewitz, K.; Litten, R.Z.; Leggio, L. Advances in the science and treatment of alcohol use disorder. Sci. Adv., 2019, 5(9), eaax4043
[] [PMID: 31579824]
Scaglia, N.; Chatkin, J.; Chapman, K.R.; Ferreira, I.; Wagner, M.; Selby, P.; Allard, J.; Zamel, N. The relationship between omega-3 and smoking habit: a cross-sectional study. Lipids Health Dis., 2016, 15, 61.
[] [PMID: 27004534]
Zaparoli, J.X.; Sugawara, E.K.; de Souza, A.A.; Tufik, S.; Galduróz, J.C. Omega-3 levels and nicotine dependence: a cross-sectional study and clinical trial. Eur. Addict. Res., 2016, 22(3), 153-162.
[] [PMID: 26570994]
Rabinovitz, S. Effects of omega-3 fatty acids on tobacco craving in cigarette smokers: A double-blind, randomized, placebo-controlled pilot study. J. Psychopharmacol. (Oxford), 2014, 28(8), 804-809.
[] [PMID: 24899596]
Buydens-Branchey, L.; Branchey, M.; McMakin, D.L.; Hibbeln, J.R. Polyunsaturated fatty acid status and relapse vulnerability in cocaine addicts. Psychiatry Res., 2003, 120(1), 29-35.
[] [PMID: 14500111]
Buydens-Branchey, L.; Branchey, M.; McMakin, D.L.; Hibbeln, J.R. Polyunsaturated fatty acid status and aggression in cocaine addicts. Drug Alcohol Depend., 2003, 71(3), 319-323.
[] [PMID: 12957349]
Buydens-Branchey, L.; Branchey, M.; Hibbeln, J.R. Associations between increases in plasma n-3 polyunsaturated fatty acids following supplementation and decreases in anger and anxiety in substance abusers. Prog. Neuropsychopharmacol. Biol. Psychiatry, 2008, 32(2), 568-575.
[] [PMID: 18060675]
Barbadoro, P.; Annino, I.; Ponzio, E.; Romanelli, R.M.; D’Errico, M.M.; Prospero, E.; Minelli, A. Fish oil supplementation reduces cortisol basal levels and perceived stress: a randomized, placebo-controlled trial in abstinent alcoholics. Mol. Nutr. Food Res., 2013, 57(6), 1110-1114.
[] [PMID: 23390041]
Pompili, M.; Longo, L.; Dominici, G.; Serafini, G.; Lamis, D.A.; Sarris, J.; Amore, M.; Girardi, P. Polyunsaturated fatty acids and suicide risk in mood disorders: A systematic review. Prog. Neuropsychopharmacol. Biol. Psychiatry, 2017, 74(74), 43-56.
[] [PMID: 27940200]
Bozzatello, P.; Rocca, P.; Mantelli, E.; Bellino, S. Polyunsaturated fatty acids: What is their role in treatment of psychiatric disorders? Int. J. Mol. Sci., 2019, 20(21), pii: E5257.

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2020
Published on: 19 May, 2020
Page: [456 - 462]
Pages: 7
DOI: 10.2174/1570159X18666200128120729
Price: $65

Article Metrics

PDF: 19