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8. Clinical trials of DHA supplementation and brain function
N-3 LCPUFAs supplementation is recommended worldwide for feto-maternal and maternal-childhood growth and development, and cognitive function of the child(Carlson et al. , 2013, Julvez et al. , 2016, Koletzko et al. , 2007, Parra-Cabrera et al. , 2011). DHA supplementation improved pregnancy outcome, gestation, reduction in early preterm and very low birth weight, childhood visual and psychomotor development (Carlson et al., 2013, Shulkin et al. , 2018).
Several clinical studies were reported on n-3 LCPUFAs and mental disorders.
Some of these clinical trials and their health outcomes are presented in Table - 4. Most of the clinical studies did not show any significant effects of DHA supplementation(Sun et al., 2018). Differences in methodologies, the sample size, dietary habit, selection criteria, age, choice and dosage of LCPUFAs (EPA, or DHA, or a combination of EPA+DHA) and the duration of the intervention are mostl possibly responsible for inconclusive results(Sun et al., 2018).
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22 9. Conclusions
The optimal structure and function of the brain are critical for quality of life, productivity and individual growth. DHA and its metabolites influence the brain’s development, structure and functions, signaling pathways, receptor function, and enzyme activities. All these functionalities are critical for optimum brain physiology throughout the lifespan. In order to achieve these functionalities, sustained supply of DHA is required well before conception, during the gestation period, adolescence, adulthood and adult life. Therefore, maintaining optimal levels of DHA in the brain are likely to be required throughout the lifespan by obtaining preformed DHA via dietary or supplementation. Several studies suggest that the consumption of DHA leads to many inherent positive physiological and behavioral effects, however further clinical trials are required to assess different clinical outcomes, including mental health status and quality of life.
Conflicts of Interest:
The authors declare no conflict of interest.
Acknowledgements
This study was supported in part by the Thune Holst Foundation, Oslo, Norway References:
Agriculture UDo. EPA and DHA Content of Fish Species. Appendix G2. 2005.
Aïd S, Vancassel S, Poumès-Ballihaut C, Chalon S, Guesnet P, Lavialle M. Effect of a diet-induced n-3 PUFA depletion on cholinergic parameters in the rat hippocampus.
Journal of Lipid Research. 2003;44:1545-51.
Albert BB, Derraik JG, Cameron-Smith D, Hofman PL, Tumanov S, Villas-Boas SG, et al. Fish oil supplements in New Zealand are highly oxidised and do not meet label content of n-3 PUFA. Sci Rep. 2015;5:7928.
Anderson E, Taylor D. Stressing the heart of the matter: re-thinking the mechanisms underlying therapeutic effects of n-3 polyunsaturated fatty acids. F1000 Medicine Reports. 2012;4:13.
Anderson GJ, Neuringer M, Lin DS, Connor WS. Can prenatal N-3 fatty acid deficiency be completely reversed after birth? Effects on retinal and brain biochemistry and visual function in rhesus monkeys. Pediatric Research. 2005;58:865-72.
Journal Pre-proof
23 Ariel A, Li PL, Wang W, Tang WX, Fredman G, Hong S, et al. The docosatriene protectin D1 is produced by T H 2 skewing promotes human T cell via lipid raft clustering. Journal of Biological Chemistry. 2005;280:43079-86.
Ariel A, Serhan CN. New lives given by cell death: Macrophage differentiation following their encounter with apoptotic leukocytes during the resolution of inflammation. Frontiers in Immunology2012. p. 4.
Authority EFS. Scientific Opinion on the substantiation of health claims related to docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA). EFSA Journal. 2011;8:10.
Balas L, Durand T. Dihydroxylated E,E,Z-docosatrienes. An overview of their synthesis and biological significance. Progress in Lipid Research. 2016;61:1-18.
Basak S, Das MK, Duttaroy AK. Fatty acid-induced angiogenesis in first trimester placental trophoblast cells: possible roles of cellular fatty acid-binding proteins. Life Sci. 2013;93:755-62.
Bauer I, Hughes M, Rowsell R, Cockerell R, Pipingas A, Crewther S, et al. Omega-3 supplementation improves cognition and modifies brain activation in young adults.
Human Psychopharmacology. 2014;29:133-44.
Bazan NG. Neuroprotectin D1 (NPD1): a DHA-derived mediator that protects brain and retina against cell injury-induced oxidative stress. Brain pathology (Zurich, Switzerland). 2005;15:15267-78.
Bazan NG. Cell survival matters: docosahexaenoic acid signaling, neuroprotection and photoreceptors. Trends in Neurosciences2006. p. 263-71.
Bazan NG, Molina MF, Gordon WC. Docosahexaenoic Acid Signalolipidomics in Nutrition: Significance in Aging, Neuroinflammation, Macular Degeneration, Alzheimer's, and Other Neurodegenerative Diseases. Annual Review of Nutrition.
2011;31:321-51.
Bazinet RP, Layé S. Polyunsaturated fatty acids and their metabolites in brain function and disease. Nature Reviews Neuroscience2014. p. 771-85.
Bisicchia E, Sasso V, Catanzaro G, Leuti A, Besharat ZM, Chiacchiarini M, et al.
Resolvin D1 Halts Remote Neuroinflammation and Improves Functional Recovery after Focal Brain Damage Via ALX/FPR2 Receptor-Regulated MicroRNAs. Molecular Neurobiology. 2018;55:6894-905.
Bos DJ, Oranje B, Veerhoek ES, Van Diepen RM, Weusten JMH, Demmelmair H, et al. Reduced Symptoms of Inattention after Dietary Omega-3 Fatty Acid Supplementation in Boys with and without Attention Deficit/Hyperactivity Disorder.
Neuropsychopharmacology. 2015;40:2298-306.
Boudrault C, Bazinet RP, Ma DWL. Experimental models and mechanisms underlying the protective effects of n-3 polyunsaturated fatty acids in Alzheimer's disease. Journal of Nutritional Biochemistry2009. p. 1-10.
Bourre JM. Dietary omega-3 Fatty acids and psychiatry: mood, behaviour, stress, depression, dementia and aging. The journal of nutrition, health & aging. 2005;9.
Bozzatello P, Brignolo E, De Grandi E, Bellino S. Supplementation with Omega-3 Fatty Acids in Psychiatric Disorders: A Review of Literature Data. Journal of Clinical Medicine. 2016;5:8.
Bradbury J. Docosahexaenoic acid (DHA): An ancient nutrient for the modern human brain. Nutrients. 2011;3:529-54.
Brenna JT, Carlson SE. Docosahexaenoic acid and human brain development:
Evidence that adietary supply is needed for optimal development. Journal of Human Evolution. 2014;77:99-106.
Journal Pre-proof
24 Burdge GC, Jones AE, Wootton SA. Eicosapentaenoic and docosapentaenoic acids are the principal products of α-linolenic acid metabolism in young men. British Journal of Nutrition. 2002;88:355-63.
Burdge GC, Wootton SA. Conversion of α-linolenic acid to eicosapentaenoic, docosapentaenoic and docosahexaenoic acids in young women. British Journal of Nutrition. 2002;88:411-20.
Calandria JM, Marcheselli VL, Mukherjee PK, Uddin J, Winkler JW, Petasis NA, et al.
Selective survival rescue in 15-lipoxygenase-1-deficient retinal pigment epithelial cells by the novel docosahexaenoic acid-derived mediator, neuroprotectin D1. Journal of Biological Chemistry. 2009;284:17877-82.
Calder PC. Omega-3 polyunsaturated fatty acids and inflammatory processes: Nutrition or pharmacology? British Journal of Clinical Pharmacology. 2013;75:645-62.
Calder PC. The DHA content of a cell membrane can have a significant influence on cellular behaviour and responsiveness to signals. Annals of Nutrition and Metabolism.
2016;69:8-21.
Calderon F, Kim HY. Docosahexaenoic acid promotes neurite growth in hippocampal neurons. Journal of Neurochemistry. 2004;90:979-88.
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. Journal of Nutritional Biochemistry. 2005;16:538-46.
Cao DH, Xu JF, Xue RH, Zheng WF, Liu ZL. Protective effect of chronic ethyl docosahexaenoate administration on brain injury in ischemic gerbils. Pharmacology Biochemistry and Behavior. 2004;79:651-9.
Carlson SE, Colombo J, Gajewski BJ, Gustafson KM, Mundy D, Yeast J, et al. DHA supplementation and pregnancy outcomes. Am J Clin Nutr. 2013;97:808-15.
Carver JD, Benford VJ, Han B, Cantor AB. The relationship between age and the fatty acid composition of cerebral cortex and erythrocytes in human subjects. Brain Research Bulletin. 2001;56:79-85.
Chalon S. Omega-3 fatty acids and monoamine neurotransmission. Prostaglandins Leukotrienes and Essential Fatty Acids. 2006;75:259-69.
Chan JP, Wong BH, Chin CF, Galam DLA, Foo JC, Wong LC, et al. The lysolipid transporter Mfsd2a regulates lipogenesis in the developing brain. PLoS Biol.
2018;16:e2006443.
Chapkin RS, Mcmurray DN, Davidson LA, Patil BS, Fan YY, Lupton JR. Bioactive dietary long-chain fatty acids: Emerging mechanisms of action. British Journal of Nutrition2008. p. 1152-7.
Chen CT, Liu Z, Ouellet M, Calon F, Bazinet RP. Rapid β-oxidation of eicosapentaenoic acid in mouse brain: An in situ study. Prostaglandins Leukotrienes and Essential Fatty Acids. 2009;80:157-63.
Chen HF, Su HM. Exposure to a maternal n-3 fatty acid-deficient diet during brain development provokes excessive hypothalamic-pituitary-adrenal axis responses to stress and behavioral indices of depression and anxiety in male rat offspring later in life. Journal of Nutritional Biochemistry. 2013;24:70-80.
Chilton FH, Murphy RC, Wilson BA, Sergeant S, Ainsworth H, Seeds MC, et al. Diet-gene interactions and PUFA metabolism: A potential contributor to health disparities and human diseases. Nutrients2014. p. 1993-2022.
Coti Bertrand P, O'Kusky JR, Innis SM. Maternal dietary (n-3) fatty acid deficiency alters neurogenesis in the embryonic rat brain. The Journal of nutrition. 2006;136:1570-5.
Journal Pre-proof
25 Crane DI. Revisiting the neuropathogenesis of Zellweger syndrome. Neurochem Int.
2014;69:1-8.
Cunnane SC, Chouinard-Watkins R, Castellano CA, Barberger-Gateau P.
Docosahexaenoic acid homeostasis, brain aging and Alzheimer's disease: Can we reconcile the evidence? Prostaglandins Leukotrienes and Essential Fatty Acids.
2013;88:61-70.
D'Addario C, Micioni Di Bonaventura MV, Pucci M, Romano A, Gaetani S, Ciccocioppo R, et al. Endocannabinoid signaling and food addiction. Neuroscience and Biobehavioral Reviews2014. p. 203-24.
Dalli J, Winkler JW, Colas RA, Arnardottir H, Cheng CYC, Chiang N, et al. Resolvin D3 and aspirin-triggered resolvin D3 are potent immunoresolvents. Chemistry and Biology. 2013;20:188-201.
Davis BC, Kris-Etherton PM. Achieving optimal essential fatty acid status in vegetarians: Current knowledge and practical implications. American Journal of Clinical Nutrition2003.
De Petrocellis L, Melck D, Bisogno T, Milone A, Di Marzo V. Finding of the endocannabinoid signalling system in Hydra, a very primitive organism: Possible role in the feeding response. Neuroscience. 1999;92:377-87.
Diep QN, Touyz RM, Schiffrin EL. Docosahexaenoic acid, a peroxisome proliferator-activated receptor-α ligand, induces apoptosis in vascular smooth muscle cells by stimulation of p38: Mitogen-activated protein kinase. Hypertension. 2000;36:851-5.
Duttaroy AK. Transport mechanisms for long-chain polyunsaturated fatty acids in the human placenta. American Journal of Clinical Nutrition2000.
Duttaroy AK. Transport of fatty acids across the human placenta: a review. Prog Lipid Res. 2009;48:52-61.
Duttaroy AK. Docosahexaenoic acid supports feto-placental growth andprotects cardiovascular and cognitive function: A mini review. Eur J Lipid Sci Technol.
2016;118:1439-49.
Duvall MG, Levy BD. DHA- and EPA-derived resolvins, protectins, and maresins in airway inflammation. European Journal of Pharmacology. 2016;785:144-55.
Dyall SC. Long-chain omega-3 fatty acids and the brain: A review of the independent and shared effects of EPA, DPA and DHA. Frontiers in Aging Neuroscience2015. p.
52.
EFSAReport. EFSA Panel on Dietetic Products NaA. Scientific opinion on the tolerable upper intake level of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and docosapentaenoic acid (DPA). EFSA Journal.10:2815.
Farooqui A. n-3 Fatty Acid-Derived Lipid Mediators in the Brain: New Weapons Against Oxidative Stress and Inflammation. Current Medicinal Chemistry.
2012;19:532-43.
Forsyth S, Gautier S, Salem N. Global estimates of dietary intake of docosahexaenoic acid and arachidonic acid in developing and developed countries. Annals of Nutrition and Metabolism. 2016;68:258-67.
Francos-Quijorna I, Santos-Nogueira E, Gronert K, Sullivan AB, Kopp MA, Brommer B, et al. Maresin 1 Promotes Inflammatory Resolution, Neuroprotection, and Functional Neurological Recovery After Spinal Cord Injury. The Journal of Neuroscience. 2017;37:11731-43.
García-Sastre A. XLessons from lipids in the fight against influenza. Cell2013. p. 22-3.
Gladine C, Laurie J-C, Giulia C, Dominique B, Corinne C, Nathalie H, et al.
Neuroprostanes, produced by free-radical mediated peroxidation of DHA, inhibit the
Journal Pre-proof
26 inflammatory response of human macrophages. Free Radical Biology and Medicine.
2014;75:S15-S25.
Goustard-Langelier B, Guesnet P, Durand G, Antoine JM, Alessandri JM. n-3 and n-6 Fatty acid enrichment by dietary fish oil and phospholipid sources in brain cortical areas and nonneural tissues of formula-fed piglets. Lipids. 1999;34:5-16.
Green P, Glozman S, Weiner L, Yavin E. Enhanced free radical scavenging and decreased lipid peroxidation in the rat fetal brain after treatment with ethyl docosahexaenoate. Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids. 2001;1532:203-12.
Groeger AL, Cipollina C, Cole MP, Woodcock SR, Bonacci G, Rudolph TK, et al.
Cyclooxygenase-2 generates anti-inflammatory mediators from omega-3 fatty acids.
Nature Chemical Biology. 2010;6:433-41.
Grossfield A, Feller SE, Pitman MC. A role for direct interactions in the modulation of rhodopsin by -3 polyunsaturated lipids. Proceedings of the National Academy of Sciences. 2006;103:4888-93.
Hashimoto M, Hossain S, Agdul H, Shido O. Docosahexaenoic acid-induced amelioration on impairment of memory learning in amyloid β-infused rats relates to the decreases of amyloid β and cholesterol levels in detergent-insoluble membrane fractions. Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids.
2005;1738:91-8.
Hennebelle M, Balasse L, Latour A, Champeil-Potokar G, Denis S, Lavialle M, et al.
Influence of omega-3 fatty acid status on the way rats adapt to chronic restraint stress.
PLoS ONE. 2012;7:e42142.
Hibbeln JR. Fish consumption and major depression [9]. Lancet1998. p. 1213.
Hoffman DR, Hughbanks-Wheaton DK, Pearson NS, Fish GE, Spencer R, Takacs A, et al. Four-year placebo-controlled trial of docosahexaenoic acid in X-linked retinitis pigmentosa (DHAX trial): a randomized clinical trial. JAMA Ophthalmol.
2014;132:866-73.
Hoffman DR, Hughbanks-Wheaton DK, Spencer R, Fish GE, Pearson NS, Wang YZ, et al. Docosahexaenoic Acid Slows Visual Field Progression in X-Linked Retinitis Pigmentosa: Ancillary Outcomes of the DHAX Trial. Invest Ophthalmol Vis Sci.
2015;56:6646-53.
Hong S, Tjonahen E, Morgan EL, Lu Y, Serhan CN, Rowley AF. Rainbow trout (Oncorhynchus mykiss) brain cells biosynthesize novel docosahexaenoic acid-derived resolvins and protectins - Mediator lipidomic analysis. Prostaglandins and Other Lipid Mediators. 2005;78:107-16.
Huang LH, Chung HY, Su HM. Docosahexaenoic acid reduces sterol regulatory element binding protein-1 and fatty acid synthase expression and inhibits cell proliferation by inhibiting pAkt signaling in a human breast cancer MCF-7 cell line.
BMC Cancer. 2017;17:890.
Innis SM. Essential fatty acids in growth and development. Progress in Lipid Research1991. p. 39-103.
Innis SM. Dietary omega 3 fatty acids and the developing brain. Brain Research2008.
p. 35-43.
Innis SM. Dietary (n-3) Fatty Acids and Brain Development. The Journal of Nutrition.
2018;137:855-9.
Insua MF, Garelli A, Rotstein NP, German OL, Arias A, Politi LE. Cell cycle regulation in retinal progenitors by glia-derived neurotrophic factor and docosahexaenoic acid.
Investigative Ophthalmology and Visual Science. 2003;44:2235-44.
Journal Pre-proof
27 Jaremka LM, Derry HM, Bornstein R, Prakash RS, Peng J, Belury MA, et al. Omega-3 supplementation and loneliness-related memory problems: Secondary analyses of a randomized controlled trial. Psychosomatic Medicine. 2014;76:650-8.
Johnsen GM, Basak S, Weedon-Fekjaer MS, Staff AC, Duttaroy AK. Docosahexaenoic acid stimulates tube formation in first trimester trophoblast cells, HTR8/SVneo.
Placenta. 2011;32:626-32.
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 mo. Am J Clin Nutr.
2007;85:1572-7.
Julvez J, Mendez M, Fernandez-Barres S, Romaguera D, Vioque J, Llop S, et al.
Maternal Consumption of Seafood in Pregnancy and Child Neuropsychological Development: A Longitudinal Study Based on a Population With High Consumption Levels. Am J Epidemiol. 2016;183:169-82.
Kawakita E, Hashimoto M, Shido O. Docosahexaenoic acid promotes neurogenesis in vitro and in vivo. Neuroscience. 2006;139:991-7.
Kiecolt-Glaser JK, Belury MA, Andridge R, Malarkey WB, Glaser R. Omega-3 supplementation lowers inflammation and anxiety in medical students: A randomized controlled trial. Brain, Behavior, and Immunity. 2011;25:1725-34.
Kiliaan A, Königs A. Critical appraisal of omega-3 fatty acids in attention-deficit/hyperactivity disorder treatment. Neuropsychiatric Disease and Treatment.
2016;Volume 12:1869-82.
Kim J, Carlson ME, Watkins BA. Docosahexaenoyl ethanolamide improves glucose uptake and alters endocannabinoid system gene expression in proliferating and differentiating C2C12 myoblasts. Frontiers in Physiology. 2014;5.
Kinney JW, Bemiller SM, Murtishaw AS, Leisgang AM, Salazar AM, Lamb BT.
Inflammation as a central mechanism in Alzheimer's disease. Alzheimers Dement (N Y). 2018;4:575-90.
Kitajka K, Puskas LG, Zvara A, Hackler L, Barcelo-Coblijn G, Yeo YK, et al. The role of n-3 polyunsaturated fatty acids in brain: Modulation of rat brain gene expression by dietary n-3 fatty acids. Proceedings of the National Academy of Sciences.
2002;99:2619-24.
Klein CP, Sperotto NDM, Maciel IS, Leite CE, Souza AH, Campos MM. Effects of D-series resolvins on behavioral and neurochemical changes in a fibromyalgia-like model in mice. Neuropharmacology. 2014;86:57-66.
Koletzko B, Cetin I, Brenna JT, Perinatal Lipid Intake Working G, Child Health F, Diabetic Pregnancy Study G, et al. Dietary fat intakes for pregnant and lactating women. Br J Nutr. 2007;98:873-7.
Kuda O. Bioactive metabolites of docosahexaenoic acid. Biochimie2017. p. 12-20.
Laugero KD, Smilowitz JT, German JB, Jarcho MR, Mendoza SP, Bales KL. Plasma omega 3 polyunsaturated fatty acid status and monounsaturated fatty acids are altered by chronic social stress and predict endocrine responses to acute stress in titi monkeys.
Prostaglandins Leukotrienes and Essential Fatty Acids. 2011;84:71-8.
Lauritzen L, Brambilla P, Mazzocchi A, Harsløf LBS, Ciappolino V, Agostoni C. DHA effects in brain development and function. Nutrients2016. p. 6.
Lengqvist J, Mata de Urquiza A, Bergman A-C, Willson TM, Sjövall J, Perlmann T, et al. Polyunsaturated Fatty Acids Including Docosahexaenoic and Arachidonic Acid Bind to the Retinoid X Receptor α Ligand-binding Domain. Molecular & Cellular Proteomics. 2004;3:692-703.
Journal Pre-proof
28 Li Q, Wang M, Tan L, Wang C, Ma J, Li N, et al. Docosahexaenoic acid changes lipid composition and interleukin-2 receptor signaling in membrane rafts. Journal of Lipid Research. 2005;46:1904-13.
Lim JY, Park C-K, Hwang SW. Biological Roles of Resolvins and Related Substances in the Resolution of Pain. BioMed Research International. 2015;2015.
Lima-Garcia JF, Dutra RC, Da Silva KABS, Motta EM, Campos MM, Calixto JB. The precursor of resolvin D series and aspirin-triggered resolvin D1 display anti-hyperalgesic properties in adjuvant-induced arthritis in rats. British Journal of Pharmacology. 2011;164:278-93.
Lin PY, Su KP. A meta-analytic review of double-blind, placebo-controlled trials of antidepressant efficacy of omega-3 fatty acids. Journal of Clinical Psychiatry.
2007;68:1056-61.
Liu A, Lin Y, Terry R, Nelson K, Bernstein PS. Role of long-chain and very-long-chain polyunsaturated fatty acids in macular degenerations and dystrophies. Clin Lipidol.
2011;6:593-613.
Lu HC, MacKie K. An introduction to the endogenous cannabinoid system. Biological Psychiatry2016. p. 516-25.
Lucas M, Dewailly É, Blanchet C, Gingras S, Holub BJ. Plasma omega-3 and psychological distress among Nunavik Inuit (Canada). Psychiatry Research.
2009;167:266-78.
Lukiw WJ, Cui JG, Marcheselli VL, Bodker M, Botkjaer A, Gotlinger K, et al. A role for docosahexaenoic acid-derived neuroprotectin D1 in neural cell survival and Alzheimer disease. Journal of Clinical Investigation. 2005;115:2774-83.
Lupien SJ, McEwen BS, Gunnar MR, Heim C. Effects of stress throughout the lifespan on the brain, behaviour and cognition. Nature Reviews Neuroscience2009. p. 434-45.
Maes M, Christophe A, Bosmans E, Lin A, Neels H. In humans, serum polyunsaturated fatty acid levels predict the response of proinflammatory cytokines to psychologic stress. Biological Psychiatry. 2000;47:910-20.
Makrides M, Gibson RA, McPhee AJ, Collins CT, Davis PG, Doyle LW, et al.
Neurodevelopmental outcomes of preterm infants fed high-dose docosahexaenoic acid:
a randomized controlled trial. JAMA. 2009;301:175-82.
Marangell LB, Martinez JM, Zboyan HA, Kertz B, Kim HFS, Puryear LJ. A double-blind, placebo-controlled study of the omega-3 fatty acid docosahexaenoic acid in the treatment of major depression. American Journal of Psychiatry. 2003;160:996-8.
Masoodi M, Kuda O, Rossmeisl M, Flachs P, Kopecky J. Lipid signaling in adipose tissue: Connecting inflammation & metabolism. Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids2015. p. 503-18.
McEwen BS. Stress, sex, and neural adaptation to a changing environment:
Mechanisms of neuronal remodeling. Annals of the New York Academy of Sciences.
2010;1204:E38-E59.
McNamara RK. DHA Deficiency and Prefrontal Cortex Neuropathology in Recurrent Affective Disorders. The Journal of Nutrition. 2010;140:864-8.
McNamara RK, Hahn CG, Jandacek R, Rider T, Tso P, Stanford KE, et al. Selective Deficits in the Omega-3 Fatty Acid Docosahexaenoic Acid in the Postmortem Orbitofrontal Cortex of Patients with Major Depressive Disorder. Biological Psychiatry. 2007;62:17-24.
Metherel AH, Irfan M, Klingel SL, Mutch DM, Bazinet RP. Compound-specific isotope analysis reveals no retroconversion of DHA to EPA but substantial conversion of EPA to DHA following supplementation : a randomized control trial. American Journal of Clinical Nutrition. 2019:1-9.
Journal Pre-proof
29 Mita R, Beaulieu MJ, Field C, Godbout R. Brain Fatty Acid-binding Protein and ω-3/ω-6 Fatty Acids. Journal of Biological Chemistry. 2010;285:37005-15.
Mori TA, Burke V, Puddey IB, Watts GF, O'Neal DN, Best JD, et al. Purified eicosapentaenoic and docosahexaenoic acids have differential effects on serum lipids and lipoproteins, LDL particle size, glucose, and insulin in mildly hypedipidemic men.
American Journal of Clinical Nutrition. 2000a;71:1085-94.
Mori TA, Watts GF, Burke V, Hilme E, Puddey IB, Beilin LJ. Differential effects of eicosapentaenoic acid and docosahexaenoic acid on vascular reactivity of the forearm microcirculation in hyperlipidemic, overweight men. Circulation. 2000b;102:1264-71.
Morita M, Kuba K, Ichikawa A, Nakayama M, Katahira J, Iwamoto R, et al. The lipid mediator protectin D1 inhibits influenza virus replication and improves severe influenza. Cell. 2013;153:112-25.
Mulder KA, King DJ, Innis SM. Omega-3 fatty acid deficiency in infants before birth identified using a randomized trial of maternal DHA supplementation in pregnancy.
PLoS ONE. 2014;9:e83764.
Murray CJL, Lopez A. A comprehensive assessment of mortality and disability from disease, injures and risk factors in 1990 and projected to 2020. The Global Burden of Disease1996.
Myhrstad MC, Ottestad I, Gunther CC, Ryeng E, Holden M, Nilsson A, et al. The PBMC transcriptome profile after intake of oxidized versus high-quality fish oil: an explorative study in healthy subjects. Genes Nutr. 2016;11:16.
Neff LM, Culiner J, Cunningham Rundles S, Seidman C, Meehan D, Maturi J, et al.
Algal Docosahexaenoic Acid Affects Plasma Lipoprotein Particle Size Distribution in Overweight and Obese Adults. The Journal of Nutrition. 2010;141:207-13.
Algal Docosahexaenoic Acid Affects Plasma Lipoprotein Particle Size Distribution in Overweight and Obese Adults. The Journal of Nutrition. 2010;141:207-13.