Original Article

Brain-derived neurotrophic factor (BDNF) is increased by omega-3 fatty acids in coronary artery disease: a randomized, double-blind, placebo-controlled


Background: Cardiovascular disease is the most common cause of morbidity and mortality throughout the world. Diminution of brain-derived neurotrophic factor (BDNF) plays a chief role in the pathogenesis of coronary artery disease (CAD). One of the beneficial effects of omega-3 fatty acids is to modulate the secretion of BDNF. We aimed to evaluate the effects of omega-3 fatty acids supplementation on serum BDNF in men with CAD.
Methods: Forty-eight CAD patients were randomly assigned to either the omega-3 (n=24) or placebo (n=24) group. In the omega-3 group each subject received 4 omega-3 soft gels per day (720 mg eicosapentaenoic acid plus 480 mg docosahexaenoic acid), while each subject in the placebo group received 4 placebo soft gels (edible paraffin) for a period of 8 weeks. Serum BDNF, high-sensitivity C-reactive protein (hs-CRP), serum lipoproteins, anthropometric indices, body composition, food intake and physical activity were evaluated before and after intervention.
Results: Omega-3 fatty acids supplementation increased serum BDNF (p= 0.015), and did not cause significant modifications on the blood pressure, serum lipids with the exception of LDL, fasting blood glucose, anthropometric measurements and body composition (p > 0.05).
Conclusion: Omega-3 fatty acids supplementation significantly enhances serum BDNF in male patients who have CAD.

Niknam M, Paknahad Z, Maracy MR, Hashemi M.Dietary fatty acids and inflammatory markers in patients with coronary artery disease. AdvBiomed Res. 2014;3:148.

Lee B-J, Tseng Y-F, Yen C-H, Lin P-T. Effects ofcoenzyme Q10 supplementation (300 mg/day) onantioxidation and antiinflammation in coronaryartery disease patients during statins therapy: arandomized, placebo-controlled trial. Nutr J.2013;12(1):142.

Nurjono M, Tay YH, Lee J. The relationshipbetween serum brainderived neurotrophic factor(BDNF) and cardiometabolic indices inschizophrenia. Schizophrenia Research. 2014;157(1):244-8.

Kishi T, Hirooka Y, Nagayama T, Isegawa K,Katsuki M, Takesue K, et al. Calorie restrictionimproves cognitive decline via up-regulation ofbrain-derived neurotrophic factor. InternationalHeart Journal. Int Heart J. 2015;56(1):110-5.

Jiang H, Wang R, Liu Y, Zhang Y, Chen Z-Y.BDNF Val66Met polymorphism is associatedwith unstable angina. Clinica Chimica Acta.2009;400(1):3-7.

Karczewska-Kupczewska M, Strączkowski M,Adamska A, Nikołajuk A, Otziomek E, GórskaM, et al. Decreased serum brain derivedneurotrophic factor concentration in youngnonobese subjects with low insulin sensitivity.Clinical Biochemistry. 2011;44(10):817-20.

Jiang H, Liu Y, Zhang Y, Chen Z-Y. Associationof plasma brain-derived neurotrophic factor andcardiovascular risk factors and prognosis inangina pectoris. Biochemical and biophysicalresearch communications. 2011;11;415(1):99-103.

Okada S, Yokoyama M, Toko H, Tateno K,Moriya J, Shimizu I, et al. Brain-DerivedNeurotrophic Factor Protects Against CardiacDysfunction After Myocardial Infarction via aCentral Nervous System–Mediated Pathway.Arteriosclerosis, Thrombosis, and VascularBiology. 2012;32(8):1902-9.

Kadoya M, Koyama H, Kanzaki A, Kurajoh M,Hatayama M, Shiraishi J, et al. Plasma brainderivedneurotrophic factor and reverse dippingpattern of nocturnal blood pressure in patientswith cardiovascular risk factors. PloS One.2014;9(8):e105977.

Devaraj S, Tang R, Adams-Huet B, Harris A,Seenivasan T, de Lemos JA, et al. Effect of highdosealpha-tocopherol supplementation onbiomarkers of oxidative stress and inflammationand carotid atherosclerosis in patients withcoronary artery disease. Am J Clin Nutr.2007;86(5):1392-8.

Kromhout D, Yasuda S, Geleijnse JM,Shimokawa H. Fish oil and omega-3 fatty acids incardiovascular disease: do they really work? EurHeart J. 2012;33(4):436-43.

Calder PC. Omega‐3 polyunsaturated fatty acidsand inflammatory processes: nutrition orpharmacology? Br J Clin Pharmacol.2013;75(3):645-62.

Dhobale M. Neurotrophins: Role in adversepregnancy outcome. Int J Dev Neurosci.2014;37:8-14.

Fahnestock M, Marchese M, Head E, Pop V,Michalski B, Milgram WN, et al. BDNF increaseswith behavioral enrichment and an antioxidantdiet in the aged dog. Neurobiol Aging.2012;33(3):546-54.

Vetrivel U, Ravichandran SB, Kuppan K,Mohanlal J, Das UN, Narayanasamy A. Agonisticeffect of polyunsaturated fatty acids (PUFAs) andits metabolites on brain-derived neurotrophicfactor (BDNF) through molecular dockingsimulation. Lipids Health Dis. 2012 4;11(1):109.

Wu A, Ying Z, Gomez-Pinilla F.Docosahexaenoic acid dietary supplementationenhances the effects of exercise on ynapticplasticity and cognition. Neuroscience. 200826;155(3):751-9.

Lukiw WJ, Cui J-G, Marcheselli VL, Bodker M,Botkjaer A, Gotlinger K, et al. A role fordocosahexaenoic acid derived neuroprotectin D1in neural cell survival and Alzheimer disease. JClin Invest. 2005;115(10):2774.

Lee I-T, Lee W-J, Tsai I-C, Liang K-W, Lin S-Y,Wan C-J, et al. Brainderived neurotrophic factornot associated with metabolic syndrome butinversely correlated with vascular cell adhesionmolecule-1 in men without diabetes. Clin ChimActa. 2012;413(9):944-8.

Sekhri T, Kanwar RS, Wilfred R, Chugh P,Chhillar M, Aggarwal R, et al. Prevalence of riskfactors for coronary artery disease in an urbanIndian population. BMJ Open.2014;4(12):e005346.

Calabrese F, Rossetti AC, Racagni G, Gass P,Riva MA, Molteni R. Brain-derived neurotrophicfactor: a bridge between inflammation andneuroplasticity. Front Cell Neurosci. 2014;8:430.

Ferreira CF, Bernardi JR, Bosa VL, Schuch I, Goldani MZ, Kapczinski F, et al. Correlationbetween n-3 polyunsaturated fatty acidsconsumption and BDNF peripheral levels inadolescents. Lipids Health Dis. 2014 5;13(1):44.

Wu A, Ying Z, Gomez-Pinilla F. The salutaryeffects of DHA dietary supplementation oncognition, neuroplasticity, and membranehomeostasis after brain trauma. J eurotrauma.2011;28(10):2113-22.

Hjorth E, Zhu M, Toro VC, Vedin I, Palmblad J,Cederholm T, et al. Omega-3 fatty acids enhancephagocytosis of alzheimer's disease-relatedamyloid-β 42 by human microglia and decreaseinflammatory markers. J Alzheimers Dis.2013;35(4):697-713.

Bousquet M, Gibrat C, Saint-Pierre M, Julien C,Calon F, Cicchetti F. Modulation of brain-derivedneurotrophic factor as a potential neuroprotectivemechanism of action of omega-3 fatty acids in aparkinsonian animal model. ProgNeuropsychopharmacol Biol Psychiatry. 200913;33(8):1401-8.

Balogun KA, Cheema SK. The expression ofneurotrophins is differentially regulated byomega-3 polyunsaturated fatty acids at weaningand postweaning in C57BL/6 mice cerebralcortex. Neurochem Int. 2014;66:33-42.

Hashimoto M, Inoue T, Katakura M, Tanabe Y,Hossain S, Tsuchikura S, et al. Prescription n-3fatty acids, but not eicosapentaenoic acid alone,improve reference memory-related learning abilityby increasing brain-derived neurotrophic factorlevels in SHR. Cg-Lepr cp/NDmcr rats, ametabolic syndrome model. Neurochem Res.2013;38(10):2124-35.

Kumar YP, Srinivas GSS, Yadu Mitravinda E,Malla L, Rao AA. Agonistic approach of omega-3, omega-6 and its metabolites with BDNF: AnIn-silico study. Bioinformation. 2013;9(18):908.

Manni L, Nikolova V, Vyagova D, ChaldakovGN, Aloe L. Reduced plasma levels of NGF andBDNF in patients with acute coronary syndromes.Int J Cardiol. 2005 22;102(1):169-71.

IssueVol 2, No 1 (Winter 2016) QRcode
SectionOriginal Article(s)
Omega-3 fatty acids Eicosapentaenoic acid Docosahexaenoic acid Coronary artery disease Brain-derived neurotrophic factor

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How to Cite
Agh F, Mohammadzadeh Honarvar N, Djalali M, Nematipour E, Zarei M, Jafari Salim S, Samavat S, Javanbakht MH. Brain-derived neurotrophic factor (BDNF) is increased by omega-3 fatty acids in coronary artery disease: a randomized, double-blind, placebo-controlled. J Nutr Sci & Diet. 2016;2(1):2-8.