Docosahexaenoic acid supplementation: a need or a commercial hype?


  • Harish Kumar Department of Psychiatry,MAMC, Agroha, Hisar, Haryana, India
  • M. C. Gupta Department of Pharmacology,Pt BDS PGIMS, Rohtak,Haryana,India
  • Sonal Dogra Medical Officer, HCMS,Rohtak, Haryana, India
  • Rajneesh Kumar Joshi NARI, Pune, Maharashtra,India


Docosahexaenoic acid, δ-linolenic acid, Eicosapentaenoic acid


Docosahexaenoic acid (DHA) is an important component of the brain and is essential critical for optimal brain health and function. With revealing of its beneficial effects on cognitive function, neurological, cardiovascular system and anti-inflammatory benefits, DHA has recently gained huge attention. As a result, the market is stocked with products supplemented with DHA claiming various health benefits. This review attempts to elucidate the current findings of DHA supplementation as a pharmacological agent with both preventive and therapeutic value.


Connor WE, Neuringer M, Reisbick S. Essential fatty acids: the importance of n-3 fatty acids in the retina and brain. Nutr Res. 1992;50:21-9.

Lai L, Kang JX, Li R, Wang J, Witt W, Yong HY, et al. Generation of cloned transgenic pigs rich in omega-3 fatty acids. Nat Biotechnol. 2006;24:435-7. [DOI via Crossref]

Harper M, Thom E, Klebanoff MA, Thorp J Jr, Sorokin Y, Varner MW, et al. Omega-3 fatty acid supplementation to prevent recurrent preterm birth: a randomized controlled trial. Obstet Gynecol. 2010;115:234-42. [DOI via Crossref]

Roman AS, Schreher J, Mackenzie AP, Nathanielsz PW. Omega-3 fatty acids and decidual cell prostaglandin production in response to the inflammatory cytokine IL-1beta. Am J Obstet Gynecol. 2006;95:1693-9. [DOI via Crossref]

Ramakrishnan U, Stein AD, Parra-Cabrera S, Wang M, Imhoff-Kunsch B, Juarezarquez S, et al. Effects of docosahexaenoic acid supplementation during pregnancy on gestational age and size at birth: randomized, double-blind, placebo-controlled trial in Mexico. Food Nutr Bull. 2010;31:S108-16.

Judge MP, Harel O, Lammi-Keefe CJ. Maternal consumption of a docosahexaenoic acid-containing functional food during pregnancy: benefit for infant performance on problem-solving but not on recognition memory tasks at age 9 months. Am J Clin Nutr. 2007;85:1572-7.

Dunstan JA, Simmer K, Dixon G, Prescott SL. Cognitive assessment of children at age 2(1/2) years after maternal fish oil supplementation in pregnancy: a randomised controlled trial. Arch Dis Child Fetal Neonatal Ed. 2008;93:F45-50. [DOI via Crossref]

Bush RA, Malnoe A, Reme CE, Williams TP. Dietary deficiency of N-3 fatty acids alters rhodopsin content and function in the rat retina. Invest Ophthalmol Vis Sci. 1994;35(1):91-100.

US Department of Agriculture and US Department of Health. Dietary Guidelines for Americans. Washington, DC: U.S. Government Printing Office; 2010.

McGahon BM, Martin DS, Horrobin DF, Lynch MA. Age-related changes in synaptic function: analysis of the effect of dietary supplementation with omega-3 fatty acids. Neuroscience. 1999;94(1):305-14. [DOI via Crossref]

Fujita S, Ikegaya Y, Nishikawa M, Nishiyama N, Matsuki N. Docosahexaenoic acid improves long-term potentiation attenuated by phospholipase A(2) inhibitor in rat hippocampal slices. Br J Pharmacol. 2001;132(7):1417-22. [DOI via Crossref]

Kitajka K, Puskas LG, Zvara A, Hackler L Jr, Barceló-Coblijn G, Yeo YK, et al. The role of omega-3 polyunsaturated fatty acids in brain: modulation of rat brain gene expression by dietary omega-3 fatty acids. Proc Natl Acad Sci USA. 2002;99(5):2619-24. [DOI via Crossref]

Cao D, Xue R, Xu J, Liu Z. Effects of docosahexaenoic acid on the survival and neurite outgrowth of rat cortical neurons in primary cultures. J Nutr Biochem. 2005;16(9):538-46. [DOI via Crossref]

De la Presa OS, Innis SM. Docosahexaenoic and arachidonic acid prevent a decrease in dopaminergic and serotoninergic neurotransmitters in frontal cortex caused by a linoleic and alpha-linolenic acid deficient diet in formula-fed piglets. J Nutr. 1999;129(11):2088-93.

Delion S, Chalon S, Guilloteau D, Besnard JC, Durand G. Alpha-Linolenic acid dietary deficiency alters age-related changes of dopaminergic and serotoninergic neurotransmission in the rat frontal cortex. J Neurochem. 1996;66(4):1582-91. [DOI via Crossref]

Habeck C, Stern Y. Alzheimer's disease neuroimaging initiative. Multivariate data analysis for neuroimaging data: overview and application to Alzheimer's disease. Cell Biochem Biophys. 2010;58:53-67. [DOI via Crossref]

Sodeberg M, Edlund C, Kristensson K, Dallner G. Fatty acid composition of brain phospholipids in aging and in Alzheimr´s disease. Lipids. 1991;26:421-5. [DOI via Crossref]

Bazan NG. Neuroprotectin D1-mediated anti-inflammatory and survival signaling in stroke, retinal degenerations, and Alzheimer's disease. J Lipid Res. 2009;50 Suppl:400-5. [DOI via Crossref]

Freund-Levi Y, Eriksdotter-Jonhagen M, Cederholm T, Basun H, Faxén-Irving G, Garlind A. Omega-3 fatty acid treatment in 174 patients with mild to moderate Alzheimer disease: OmegAD study. Arch Neurol. 2006;63:1402-8. [DOI via Crossref]

Boston PF, Bennett A, Horrobin DF, Bennett CN. Ethyl-EPA in Alzheimer's disease - A pilot study. Prostaglandins Leukot Essent Fatty Acids. 2004;71:341-6. [DOI via Crossref]

Whalley LJ, Deary IJ, Starr JM, Wahle KW, Rance KA, Bourne VJ, et al. n-3 fatty acid erythrocyte membrane content, APOE varepsilon, and cognitive variation: an observational follow-up study in late adulthood. Am J Clin Nutr. 2008;87:449-54.

Kiecolt-Glaser JK, Belury MA, Porter K, Beversdorf DQ, Lemeshow S, Glaser R, et al. Depressive symptoms, omega-6: omega-3 fatty acids, and inflammation in older adults. Psychosom Med. 2007;69(3):217-24. [DOI via Crossref]

Lee TH, Mencia-Huerta JM, Shih C, Corey EJ, Lewis RA, Austen KF. Effects of exogenous arachidonic, eicosapentaenoic, and docosahexaenoic acids on the generation of 5-lipoxygenase pathway products by ionophore-activated human neutrophils. J Clin Invest. 1984;74:1922-33. [DOI via Crossref]

Huan M, Hamazaki K, Sun Y, Itomura M, Liu H, Kang W, et al. Suicide attempt and omega-3 fatty acid levels in red blood cells: a case control study in China. Biol Psychiatry. 2004;56(7):490-6. [DOI via Crossref]

Sublette ME, Hibbeln JR, Galfalvy H, Oquendo MA, Mann JJ. Omega-3 polyunsaturated essential fatty acid status as a predictor of future suicide risk. Am J Psychiatry. 2006;163(6):1100-2. [DOI via Crossref]

Noga JT, Hyde TM, Herman MM, Spurney CF, Bigelow LB, Weinberger DR, et al. Glutamate receptors in the postmortem striatum of schizophrenic, suicide, and control brains. Synapse. 1997;27(3):168-76. [DOI via Crossref]

Hogyes E, Nyakas C, Kiliaan A, Farkas T, Penke B, Luiten PG, et al. Neuroprotective effect of developmental docosahexaenoic acid supplement against excitotoxic brain damage in infant rats. Neuroscience. 2003;119(4):999-1012. [DOI via Crossref]

Kamphuis MH, Geerlings MI, Tijhuis MAR, Kalmijn S, Grobbee DE, Kromhout D. Depression and cardiovascular mortality: a role for n-3 fatty acids? Am J Clin Nutr. 2006;84:1513-7.

Su KP, Huang SY, Chiu CC, Shen WW. Omega-3 fatty acids in major depressive disorder: a preliminary double-blind, placebo controlled trial. Eur Neuropsychopharmacol. 2003;13:267-71. [DOI via Crossref]

Rees AM, Austin MP, Parker GB. Omega-3 fatty acids as treatment for perinatal depression: randomized double-blind placebo-controlled trial. Aust N Z Psychiatry. 2008;42:199-205. [DOI via Crossref]

Stevens L, Zhang W, Peck L, Kuczek T, Grevstad N, Mahon A, et al. EFA supplementation in children with inattention, hyperactivity, and other disruptive behaviors. Lipids. 2003;38:1007-21. [DOI via Crossref]

Hirayama S, Hamazaki T, Terasawa K. Effect of docosahexaenoic acid-containing food administration on symptoms of attention-deficit/hyperactivity disorder — A placebo-controlled double-blind study. Eur J Clin Nutr. 2004;58:467-73. [DOI via Crossref]

Voigt RG, Llorente AM, Jensen CL, Fraley JK, Berretta MC, Heird WC. A randomized, double-blind, placebo-controlled trial of docosahexaenoic acid supplementation in children with attention-deficit/ hyperactivity disorder. J Pediatr. 2001;139:189-96. [DOI via Crossref]

Kris-Etherton PM, Harris WS, Appel LJ. Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease. Arterioscler Thromb Vasc Biol. 2003;23:20-30. [DOI via Crossref]

Davidson MH. Mechanisms for the hypotriglyceridemic effect of marine omega-3 fatty acids. Am J Cardiol. 2006;98:27i-33. [DOI via Crossref]

Yamamoto H, Yoshimura H, Noma M, Suzuki S, Kai H, Tajimi T, et al. Improvement of coronary vasomotion with eicosapentaenoic acid does not inhibit acetylcholine-induced coronary vasospasm in patients with variant angina. Jpn Circ J. 1995;59:608-16. [DOI via Crossref]

Sanders TA, Gleason K, Griffin B, Miller GJ. Influence of an algal triacylglycerol containing docosahexaenoic acid (22:6n-3) and docosapentaenoic acid (22:5n-6) on cardiovascular risk factors in healthy men and women. Br J Nutr. 2006;95:525-31. [DOI via Crossref]

Franceschini G. An omega-3 polyunsaturated fatty acid concentrate increases plasma high-density lipoprotein 2 cholesterol and paraoxonase levels in patients with familial combined hyperlipidemia. Metabolism. 2004;53:153-8. [DOI via Crossref]

Ferrier LK, Caston LJ, Leeson S, Squires J, Weaver BJ, Holub BJ. Alpha-linolenic acid- and docosahexaenoic acid-enriched eggs from hens fed flaxseed: influence on blood lipids and platelet phospholipid fatty acids in humans. Am J Clin Nutr. 1995;62:81-6.

Schubert R, Kitz R, Beermann C, Rose MA, Baer PC, Zielen S, et al. Influence of low-dose polyunsaturated fatty acids supplementation on the inflammatory response of healthy adults. Nutrition. 2007;23:724-30. [DOI via Crossref]

Bloomer RJ, Larson DE, Fisher-Wellman KH, Galpin AJ, Schilling BK. Effect of eicosapentaenoic and docosahexaenoic acid on resting and exercise-induced inflammatory and oxidative stress biomarkers: a randomized, placebo controlled, cross-over study. Lipids Health Dis. 2009;8:36. [DOI via Crossref]

Bouwens M, van de Rest O, Dellschaft N, Bromhaar MG, de Groot LC, Geleijnse JM, et al. Fish-oil supplementation induces antiinflammatory gene expression profiles in human blood mononuclear cells. Am J Clin Nutr. 2009;90:415-24. [DOI via Crossref]

Micallef MA, Garg ML. Anti-inflammatory and cardioprotective effects of n-3 polyunsaturated fatty acids and plant sterols in hyperlipidemic individuals. Atherosclerosis. 2009;204:476-82. [DOI via Crossref]

Endres S, Ghorbani R, Kelley VE, Georgilis K, Lonnemann G, van der Meer JW, et al. The effect of dietary supplementation with n-3 polyunsaturated fatty acids on the synthesis of interleukin-1 and tumor necrosis factor by mononuclear cells. N Engl J Med. 1989;320:265-71. [DOI via Crossref]

Mori TA, Woodman RJ, Burke V, Puddey IB, Croftt KD, Beilin LJ. Effect of eicosapentaenoic acid and docosahexaenoic acid on oxidative stress and inflammatory markers, in treated-hypertensive type 2 diabetic subjects. Free Rad Biol Med. 2003;35:772-81. [DOI via Crossref]

Kris-Etherton PM, Harris WS, Appel LJ. Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease. Circulation. 2002;106:2747-57. [DOI via Crossref]

Tavazzi L, Maggioni AP, Marchioli R, Barlera S, Franzosi MG, Latini R, et al. Effect of n-3 polyunsaturated fatty acids in patients with chronic heart failure (the GISSI-HF trial): a randomised, double-blind, placebo-controlled trial. Lancet. 2008;372:1223-30. [DOI via Crossref]

Gajos G, Rostoff P, Undas A, Piwowarska W. Effects of polyunsaturated omega-3 fatty acids on responsiveness to dual antiplatelet therapy in patients undergoing percutaneous coronary intervention: the OMEGA-PCI (OMEGA-3 fatty acids after PCI to modify responsiveness to dual anti-platelet therapy) study. J Am Coll Cardiol. 2010;55:1671-8. [DOI via Crossref]

Mori TA, Bao DQ, Burke V, Puddey IB, Beilin LJ. Docosahexaenoic acid but not eicosapentaenoic acid lowers ambulatory blood pressure and heart rate in humans. Hypertension. 1999;34:253-60. [DOI via Crossref]

Ergas D, Eilat E, Mednlovic S, Sthoeger ZM. n-3 fatty acids and the immune system in autoimmunity. Isr Med Assoc J. 2002;4:34-8.

Metcalf RG, Sanders P, James MJ, Cleland LG, Young GD. Effect of dietary n-3 polyunsaturated fatty acids on the inducibility of ventricular tachycardia in patients with ischemic cardiomyopathy. Am J Cardiol. 2008;101:758-61. [DOI via Crossref]

Rose DP, Connolly JM, Rayburn J, Coleman M. Influence of diets containing eicosapentaenoic or docosahexaenoic acid on growth and metastasis of breast cancer cells in nude mice. J Natl Cancer Inst. 1995;87:587-92. [DOI via Crossref]

Tang DG, Guan KL, Li L, Honn KV, Chen YQ, Rice RL, et al. Suppression of W256 carcinosarcoma cell apoptosis by arachidonic acid and other polyunsaturated fatty acids. Int J Cancer. 1997;72:1078-87. [DOI via Crossref]

Connor KM, Sangiovanni JP, Lofqvist C, Aderman CM, Chen J, Higuchi A, et al. Increased dietary intake of ω-3-polyunsaturated fatty acids reduces pathological retinal angiogenesis. Nat Med. 2007;13(7):868-73. [DOI via Crossref]

Spite M, Norling LV, Summers L, Yang R, Cooper D, Petasis NA, et al. Resolvin D2 is a potent regulator of leukocytes and controls microbial sepsis. Nature. 2009;461:1287-91. [DOI via Crossref]

Jin Y, Arita M, Zhang Q, Saban DR, Chauhan SK, Chiang N, et al. Anti- angiogenesis effect of the novel anti-inflammatory and pro-resolving lipid mediators. Invest Ophthalmol Vis Sci. 2009; 50(4):4743-52. [DOI via Crossref]

Krauss-Etschmann S, Hartl D, Rzehak P, Heinrich J, Shadid R, Del Carmen Ramirez Tortosa M, et al. Decreased cord blood IL-4, IL-13, and CCR4 and increased TGF-beta levels after fish oil supplementation of pregnant women. J Allergy Clin Immunol. 2008;121:464-70e6.

Goldberg RJ, Katz J. A meta-analysis of the analgesic effects of omega-3 polyunsaturated fatty acid supplementation for inflammatory joint pain. Pain. 2007;129:210-23. [DOI via Crossref]

Norris JM, Yin X, Lamb MM, Barriga K, Seifert J, Hoffman M, et al. Omega-3 polyunsaturated fatty acid intake and islet autoimmunity in children at increased risk for type 1 diabetes. JAMA. 2007;298:1420-8. [DOI via Crossref]

Aksoy Y, Aksoy H, Altinkaynak K, Aydin HR, Ozkan A. Sperm fatty acid composition in subfertile men. Prostaglandins Leukot Essent Fatty Acids. 2006;75:75-9. [DOI via Crossref]

Kim HH, Cho S, Lee S, Kim KH, Cho KH, Eun HC, et al. Photoprotective and anti-skin aging effects of eicosapentaenoic acid in human skin in vivo. J Lipid Res. 2006;47:921-30. [DOI via Crossref]

Harris WS, Gonzales M, Laney N, Sastre A, Borkon AM. Effects of omega-3 fatty acids on heart rate in cardiac transplant recipients. Am J Cardiol. 2006;98:1393-5. [DOI via Crossref]

Lagarde M, Calzada C, Guichardant M, Vericel E. Dose-effect and metabolism of docosahexaenoic acid: pathophysiological relevance in blood platelets. Prostaglandins Leukot Essent Fatty Acids. 2013;88(1):49-52. [DOI via Crossref]

Guillot N, Caillet E, Laville M, Calzada C, Lagarde M, Vericel E. Increasing intakes of the long-chain omega-3 docosahexaenoic acid: effects on platelet functions and redox status in healthy men. FASEB J. 2009;23:2909-16. [DOI via Crossref]

Rice TW, Wheeler AP, Thompson BT, DeBoisblanc BP, Steingrub J, Rock P, et al. Enteral omega-3 fatty acid, gamma-linolenic acid, and antioxidant supplementation in acute lung injury. JAMA. 2011;306:1574-81. [DOI via Crossref]

Serini S, Fasano E, Piccioni E, Cittadini AR, Calviello G. Dietary N-3 polyun-saturated fatty acids and the paradox of their health benefits and potential harmful effects. Chem Res Toxicol. 2011;24:2093-105. [DOI via Crossref]

Palozza P, Sgarlata E, Luberto C, Piccioni E, Anti M, Marra G, et al. N-3 fatty acids induce oxidative modifications in human erythrocytes depending ondose and duration of dietary supplementation. Am J Clin Nutr. 1996;64:297-304.

Taneja A, Singh H. Challenges for the delivery of long-chain N-3 fatty acids in functional foods. Ann Rev Food Sci Technol. 2012;3:105-23. [DOI via Crossref]




How to Cite

Kumar, H., Gupta, M. C., Dogra, S., & Joshi, R. K. (2017). Docosahexaenoic acid supplementation: a need or a commercial hype?. International Journal of Basic & Clinical Pharmacology, 3(2), 285–291. Retrieved from



Review Articles