Mahabaleshwar V Hegde Anand Arvind Zanwar Sharad P Adekar Editors Omega-3 Fatty Acids Keys to Nutritional Health 123 Omega-3 Fatty Acids Mahabaleshwar V Hegde Anand Arvind Zanwar Sharad P Adekar Editors Omega-3 Fatty Acids Keys to Nutritional Health 123 Editors Mahabaleshwar V Hegde Center for Innovation in Nutrition Health Disease, IRSHA Medical College Campus Bharati Vidyapeeth Deemed University Dhankawadi, Pune, Maharashtra India Sharad P Adekar Department of IRB Affairs Western Institutional Review Board Inc Puyallup, WA USA Anand Arvind Zanwar Center for Innovation in Nutrition Health Disease, IRSHA Medical College Campus Bharati Vidyapeeth Deemed University Dhankawadi, Pune, Maharashtra India ISBN 978-3-319-40456-1 DOI 10.1007/978-3-319-40458-5 ISBN 978-3-319-40458-5 (eBook) Library of Congress Control Number: 2016943867 © Springer International Publishing Switzerland 2016 This work is subject to copyright All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed The use of general descriptive names, registered names, trademarks, service marks, etc in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use The publisher, the authors and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication Neither the publisher nor the authors or the editors give a warranty, express or implied, with respect to the material contained herein or for any errors or omissions that may have been made Printed on acid-free paper This Springer imprint is published by Springer Nature The registered company is Springer International Publishing AG Switzerland Preface This book, “Omega-3 Fatty acids: Keys to Nutritional Health,” is the product of our sincere effort, to provide scientific evidence for the extraordinary power of nature’s wonder molecules —omega-3-fatty acids Chapters by experts in different specific aspects of omega-3 fatty acids for human health, have been presented to our wide spread readers, nutritionists, dieticians, clinicians, and all health conscious readers and health professionals There is no exaggeration if we state that man owes his very existence on this planet to omega-3 fatty acids, as these molecules are largely responsible for the creation human brain It is the brain that gives man the extraordinary power to sense the nature and its environment and enable him to adapt, to live in more comfort Omega-3 fatty acids, besides being the hardware of the brain, take active part in almost every aspect of life reactions in health and disease Our Chap on “Nutrition, Life, Disease, and Death” narrates the importance of supply of all essential nutrients in adequate quantities including omega-3 fatty acids and Chap 36 of Dr M Jeganathan on “Role of Antioxidants” which are also needed not only as anti-stress, anti-aging nutrient, but also to prevent oxidation of omega-3 fatty acids in human body’s hostile environment It is unequivocally established that recent rise in the incidences and severity of several diseases, including diabetes, heart disease, obesity, pregnancy complications, alzheimer, psoriasis and aging, can be primarily attributed to the paucity of omega-3 fatty acids in modern human diet Hence, “Bring Back Omega-3 Fatty acid into Food Chain” has been aglobal cry Therefore, our Chap on “Flax Biovillage” and Chap 3, “Linseed Agriculture” by Dr P.K Singh aim at unleashing the power of linseed, for omega-3 nutritional security Chap 21 by Dr Scott Doughman presents a case of “Microalgae oil” and Dr Rafael Zarate’s in Chap 9, that of “marine algae,”as safe and effective vegetarian food Authors argue that different biotechnological approaches can boost fatty acid yield in microalgae, and thereby, microalgae may become important attractive, continuous, sustainable good omega-3 source, to satisfy the increasing world demand In Chap 34, Georgia Lenihan-Geels discusses the prospects of bioengineering of plant seed oils for docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), algae aquaculture and enhancement of LC-PUFA in meat, and dairy products through plant-derived livestock feeds In addition to increase the world omega-3 supply, for actually attaining omega-3 nutritional security and better health for one and all, another attractive complementary strategy is to fortify food, resourcing omega-3 fatty acid from flaxseed, marine algae, or fish oil sources Manohar Panse in Chap 8, while discussing the “Omega-3 fatty acid Food Fortification,” also highlights the importance of compliance of regulatory guidelines, required for marketing such products Further, Manohar Panse has also discussed Development of omega-3 eggs in Chap and World Market of Omega Fatty Acids in Chap Most importantly, the pharmacokinetics of safety of omega-3 fatty acids has been reviewed by Dr Juan Tamargo in Chap 39 Dr Puranik in Chap 10 describes omega-3 oil emulsion that prevents lipid peroxidation and also offers not only increased stability and shelf life but also better bioavailability In our Chap on “Omega-3 Milk,” with our colleague Dr P.B Ghorpade and Dr S.L Bodhankar, we narrate the importance of incorporating omega-3 fatty acid in milk and its utility for human health v vi The major problem today is the severe imbalance of the two essential fatty acids namely omega-3 and omega-6 fatty acids Omega-3 fatty acids being primarily anti-inflammatory and omega-6 being proinflammatory, too much omega-6 and very little of omega-3 fatty acids in modern human diet, the disease-prone inflammatory pathway is dominant in the modern man Dr Kadooin in Chap 15 discusses how omega-3 to omega-6 ratios can be manipulated in oilseeds to achieve balance of omega-3 and omega-6 fatty acids Most interesting thought-provoking chapters (Chaps 27–32) have been provided by Robert Brown His concern about the linoleic acid/alpha-linolenic acid imbalance and its influence on various aspects of ill health today is evident from the inferences drawn by him One of the major well-acknowledged effects of omega-3 fatty acids are their ability to prevent heart diseases Dr Manohar Garg in Chap discusses how omega-3 fatty acids control hyperlipidemia; Dr Jubbin Jacob in Chap 37, cardiovascular disorder; Dr Quian Gao in Chap 25, cardiovascular events; and Dr Sang Lee in Chap 33, Myocardial Infarction Dr Sayed Ahmed in Chap 11, discusses the mechanism by which EPA- and DHA-derived eicosanoids and lipid mediators contain chronic inflammation and prevent degenerative diseases Effects of omega-3 fatty acids on immune system in reducing the pathological manifestation especially in diseases related to inflammation, allergy, and autoimmunity have been discussed by Dr Sudha Gangal in Chap 26 Dr Vikas Kumar in Chap 38 on Psoriasis, a multifaceted autoimmune disorder discusses the potential benefits of omega-3 fatty acid, their metabolites, and the mechanisms involved in psoriasis treatment Role of omega-3 fatty acids in mitochondrial diseases and its profound effects on muscle, brain, heart, liver, nerves, eyes, ears, kidney functions, involvement in CVD, and diabetes have been discussed by Dr S Katyare in Chap 17 Dr Katyare in chapter on diabetes shows the link between omega-3 fatty acids in diabetic complications, neuropathy, retinopathy, nephropathy, and angiopathy, and the beneficial effect of omega-3 fatty acid supplementation in Chap 16, and Dr Katyare further in Chap 18 on Alzheimer argues that omega-3 fatty acid supplementation may be safe and prophylactic for Alzheimer's disease Oxidative stress and inflammation are the major mechanism that contributes to the pathogenesis of degenerative diseases including neurotraumatic, neurodegenerative, and neuropsychiatric diseases Dr Akhlaq A Farooqui, in Chap 19, concludes that increased consumption of omega-3 fatty acids may result in retardation of oxidative stress and neuroinflammation due to the production of resolvins, neuroprotectins, and maresins Dr Tassos Georgiou in Chap 20 on the role of omega-3 fatty acids on eye health describes how omega-3 fatty acid supplementation can result in regression in some type of retinopathies, including age-related macular degeneration, macular dystrophies, and also some form of drying eye Importance of omega-3 fatty acids in maternal nutrition in growing fetus, reducing the risk of adverse pregnancy outcome, has been reviewed in Chap 35, by Dr Sadhana Joshi Dr Gabriel Fernandes, in Chap 40, describes effect of fish oils on pain resolution, achieving prolonged disease free life Obesity leads to several chronic morbidities including type diabetes, atherosclerosis, and hypertension, which are major components of the metabolic syndrome In chapter 14, Dr Maria J Morena Aliaga reviews randomized controlled trials that evaluate the effect of supplementation of EPA and DHA on weight loss, insulin sensitivity, lipid metabolism, blood pressure, and inflammation in subjects with metabolic syndrome characteristics Dr Lindsay Brown in Chap 13 describes linseed as a functional food for the management of obesity He concludes that there is considerable evidence that the constituents in flaxseed especially ALA and probably also secoisolariciresinol diglucoside and fiber to a lesser extent, either separately or combined, can be defined as functional food, as they may improve the multiorgan changes induced by obesity Preface Preface vii Decrease in the brain DHA content causes number of neurobiological effects including depression Dr Beth Levantin in Chap 22 discusses the evidences that support the involvement of decreased brain omega-3 fatty acids in the etiology of postpartum depression and other depressive disorders and their implications in prevention and treatment Dr Julio Ochoa in Chap 23 summarizes the role of omega-3 fatty acids in bone health and turnover In Chap 24, Dr Julio Ochoa summarizes the interactive role of Fe and DHA in physiologicaland nutritional deficiency situations, revealing that DHA stimulates Fe metabolism In Chap 12 on cancer, we discuss the anticancer action of omega-3 fatty acids that may counter the proinflammatory, proangiogenic, and prometastaic and cell proliferative actions of AA eicosanoids and induce apoptosis It is no wonder that omega-3 fatty acids are very crucial for our health as they constitute the functional structural component of the membrane and also the precursors of hundreds of eicosanoids and lipid mediators controlling thousands of reactions in human body Therefore, it is not surprising that the omega-3 deficiency has wide range of adverse effects on different organs and tissues aggravating each and every disease Therefore, the book also focuses on the means of urgently bringing back omega-3 fatty acids into food chain These aspects have been very well illustrated by the contributory authors and co-authors of the chapters of the book We would like to profusely thank them all, being the part of this useful exercise Finally, volume editors would like to extend their appreciation to Springer and their staff for providing professional platform for communication with the experts in the field BVDU, Pune, India BVDU, Pune, India Puyallup, WA, USA Mahabaleshwar V Hegde Anand Arvind Zanwar Sharad P Adekar Acknowledgments The role of Ms Michele Aiello—developmental editor, in regularly communicating with contributing authors, in attending to required technical corrections, and persuading authors to keep deadline, was most important for the successful completion of the book We thank her We also thank Ms Samantha Lonuzzi—assistant editor, Clinical Medicine springer sciences— for her help in every aspect for completion of the book We are also thankful to former editors Ms Amanda Quinn and Ms Jonna Perey with whom we started this project We are grateful to Ms Sudeshana Das—production editor—at Scientific Publishing Services for his help in manuscript proofreading process till final publication of book We would like to express deep gratitude to Prof Dr Shivajirao S Kadam—honorable vice chancellor of Bharati Vidyapeeth Deemed University (BVDU), Prof S.F Patil—Executive Director Research BVDU, Dr Ulhas Wagh-—former director, and Dr A.C Mishra—the current director of Interactive Research School for Health affairs, BVDU, Pune, for their unstinted support and encouragement for successful completion of the book Lastly, we would like to express heartfelt thanks to our family members for their understanding and support Prof Mahabaleshwar V Hegde M.Sc., Ph.D Dr Anand A Zanwar M.Pharm., Ph.D Dr Sharad P Adekar M.D., Ph.D ix Contents Nutrition, Life, Disease, and Death Mahabaleshwar V Hegde, Anand Arvind Zanwar, and Sharad P Adekar Flax Bio-village Concept Mahabaleshwar V Hegde, Anand Arvind Zanwar, and Prakash B Ghorpade 11 Status Paper on Linseed/Flax Agriculture P.K Singh 21 Omega-3 Milk Anand Arvind Zanwar, Yogesh S Badhe, Subhash L Bodhankar, Prakash B Ghorpade, and Mahabaleshwar V Hegde 45 Omega-3 Egg Manohar L Panse, Shripad P Atakare, Mahabaleshwar V Hegde, and Shivajirao S Kadam 51 Omega-3 Polyunsaturated Fatty Acids and Hyperlipidaemias J.J.A Ferguson, C.B Dias, and M.L Garg 67 World Market of Omega-3 Fatty Acids Manohar L Panse and Shital D Phalke 79 Fortification of Food with Omega-3 Fatty Acids Manohar L Panse and Shital D Phalke 89 Importance of Polyunsaturated Fatty Acids from Marine Algae 101 Rafael Zárate, Nabil el Jaber-Vazdekis, and Raquel Ramírez-Moreno 10 Emulsions of Omega-3 Fatty Acids for Better Bioavailability and Beneficial Health Effects 127 Sarang S Puranik 11 Omega-3 Fatty Acids in Inflammatory Diseases 141 Salma Mukhtar Mir, Sanjit Kanjilal, and Syed Ubaid Ahmed 12 Omega-3 Fatty Acids in Cancer: Insight into the Mechanism of Actions in Preclinical Cancer Models 157 Asavari A Joshi, Mahabaleshwar V Hegde, and Sharad P Adekar 13 Linseed as a Functional Food for the Management of Obesity 173 Siti Raihanah Shafie, Hemant Poudyal, Sunil K Panchal, and Lindsay Brown 14 Role of Omega-3 Fatty Acids in Metabolic Syndrome 189 Ana Elsa Huerta, Laura M Laiglesia, Leyre Martínez-Fernández, and Maria J Moreno-Aliaga 15 Balancing Omega-6: Omega-3 Ratios in Oilseeds 203 Tejas P Chirmade, Smrati Sanghi, Ashwini V Rajwade, Vidya S Gupta, and Narendra Y Kadoo xi xii 16 Omega-3 Fatty Acids and Diabetic Complications 221 A.V Mali, S.S Bhise, and Surendra S Katyare 17 Omega-3 Fatty Acids and Mitochondrial Functions 229 Surendra S Katyare and A.V Mali 18 Omega-3 Fatty Acids and Alzheimer’s Disease 235 Santosh D Devkar and Surendra S Katyare 19 Prevention of Oxidative Stress by Omega-3 Fatty Acids in the Brain 239 Akhlaq A Farooqui and Tahira Farooqui 20 Role of Omega-3 Fatty Acids for Eye Health 251 Tassos Georgiou and Ekatherine Prokopiou 21 DHA-Rich Algae Oil Is a Safe and Effective Vegetarian Source of Omega-3 263 Scott Doughman, Sreerama Krupanidhi, and C.B Sanjeevi 22 Role of n-3 (Omega-3) Polyunsaturated Fatty Acids in Postpartum Depression: Mechanisms and Implications for Prevention and Treatment 267 Beth Levant 23 Influence of Omega-3 Fatty Acids on Bone Turnover 285 Javier Díaz-Castro, Naroa Kajarabille, Mario Pulido-Morán, Jorge Moreno-Fernández, Magdalena López-Frías, and Julio J Ochoa 24 Interactions Between Omega-3 Fatty Acids and Iron 293 Julio J Ochoa, Mario Pulido-Morán, Silvia Hijano, Naroa Kajarabille, Jorge Moreno-Fernández, and Javier Díaz-Castro 25 Role of Omega-3 Fatty Acid in Major Cardiovascular Events—A Current View 301 Yanting Wen and Qian Gao 26 Modulation of Immune Response by Omega-3 in Health and Disease 307 Sudha Gangal 27 The Linoleic-to-Linolenic Dietary Intake Ratio: The Fundamental Implications of Imbalance and Excess Looked at from Both a Functional and an Evolutionary Perspective: An Overview 321 Robert Andrew Brown 28 Bioactive Oxidised Products of Omega-6 and Omega-3, Excess Oxidative Stress, Oxidised Dietary Intake and Antioxidant Nutrient Deficiencies, in the Context of a Modern Diet 349 Robert Andrew Brown 29 In a Western Dietary Context Excess Oxidised Linoleic Acid of Dietary and Endogenous Origin by Over-Activation of PPAR Gamma so Immune and Inflammatory Pathways, and through Cardiolipin Damage, Increases Cardiovascular Risk 385 Robert Andrew Brown 30 Linoleic Acid and Alpha-Linolenic Acid Have Central Roles in Brain Energy Substrate Provision, Endogenous Lipid Production, Immune and Repair Function, via Peroxisomal Beta-Oxidation-Related Pathways? 413 Robert Andrew Brown Contents 596 44 45 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Carr MJ, McAlexander MA Prostaglandin-induced activation of nociceptive neurons via direct interaction with transient receptor potential A1 (TRPA1) Mol Pharmacol 2008;73(2):274–81 Yen YT, Tu PH, Chen CJ, Lin YW, Hsieh ST, Chen CC Role of acid-sensing ion channel in sub-acute-phase inflammation Molecular Pain 2009;5:1 Riera CE, Huising MO, Follett P, Leblanc M, Halloran J, Van Andel R, et al TRPV1 pain receptors regulate longevity and metabolism by neuropeptide signaling Cell 2014;157(5):1023– 36 Nobre ME, Correia AO, Borges Mde B, Sampaio TM, Chakraborty SA, Goncalves Dde O, et al Eicosapentaenoic acid and docosahexaenoic acid exert anti-inflammatory and antinociceptive effects in rodents at low doses Nutr Res 2013;33(5):422– 33 Dyuizen IV, Manzhulo IV, Ogurtsova OS, Lamash NE, Latyshev NA, Kas’yanov SV Specific features of analgesic effect of docosahexaenoic acid in rats with neuropathic pain syndrome Bull Exp Biol Med 2014;156(5):699–701 Ko GD, Nowacki NB, Arseneau L, Eitel M, Hum A Omega-3 fatty acids for neuropathic pain: case series Clinic J Pain 2010;26 (2):168–72 Xu ZZ, Berta T, Ji RR Resolvin E1 inhibits neuropathic pain and spinal cord microglial activation following peripheral nerve injury J Neuroimmune Pharmacol Off J Soc NeuroImmune Pharmacol 2013;8(1):37–41 Xu ZZ, Liu XJ, Berta T, Park CK, Lu N, Serhan CN, et al Neuroprotectin/protectin D1 protects against neuropathic pain in mice after nerve trauma Ann Neurol 2013;74(3):490–5 Figueroa JD, Cordero K, Serrano-Illan M, Almeyda A, Baldeosingh K, Almaguel FG, et al Metabolomics uncovers dietary omega-3 fatty acid-derived metabolites implicated in anti-nociceptive responses after experimental spinal cord injury Neuroscience 2013;255:1–18 Ramsden CE, Faurot KR, Zamora D, Suchindran CM, Macintosh BA, Gaylord S, et al Targeted alteration of dietary n-3 and n-6 fatty acids for the treatment of chronic headaches: a randomized trial Pain 2013;154(11):2441–51 Rizos EC, Ntzani EE, Bika E, Kostapanos MS, Elisaf MS Association between omega-3 fatty acid supplementation and risk of major cardiovascular disease events: a systematic review and meta-analysis JAMA 2012;308(10):1024–33 125 Shaikh NA, Yantha J, Shaikh S, Rowe W, Laidlaw M, Cockerline C, et al Efficacy of a unique omega-3 formulation on the correction of nutritional deficiency and its effects on cardiovascular disease risk factors in a randomized controlled VASCAZEN ((R)) REVEAL Trial Mol Cell Biochem 2014;396(1–2):9–22 126 Nigam A, Talajic M, Roy D, Nattel S, Lambert J, Nozza A, et al Fish oil for the reduction of atrial fibrillation recurrence, inflammation, and oxidative stress J Am Coll Cardiol 2014;64 (14):1441–8 127 Macchia A, Grancelli H, Varini S, Nul D, Laffaye N, Mariani J, et al Omega-3 fatty acids for the prevention of recurrent symptomatic atrial fibrillation: results of the FORWARD (Randomized trial to assess efficacy of PUFA for the maintenance of sinus rhythm in persistent atrial fibrillation) trial J Am Coll Cardiol 2013;61(4):463–8 128 Salari Sharif P, Asalforoush M, Ameri F, Larijani B, Abdollahi M The effect of n-3 fatty acids on bone biomarkers in Iranian postmenopausal osteoporotic women: a randomized clinical trial Age 2010;32(2):179–86 129 Martin-Bautista E, Munoz-Torres M, Fonolla J, Quesada M, Poyatos A, Lopez-Huertas E Improvement of bone formation biomarkers after 1-year consumption with milk fortified with eicosapentaenoic acid, docosahexaenoic acid, oleic acid, and selected vitamins Nutr Res 2010;30(5):320–6 130 Lappe J, Kunz I, Bendik I, Prudence K, Weber P, Recker R, et al Effect of a combination of genistein, polyunsaturated fatty acids and vitamins D3 and K1 on bone mineral density in postmenopausal women: a randomized, placebo-controlled, double-blind pilot study Eur J Nutr 2013;52(1):203–15 131 Kremer JM, Lawrence DA, Petrillo GF, Litts LL, Mullaly PM, Rynes RI, et al Effects of high-dose fish oil on rheumatoid arthritis after stopping nonsteroidal antiinflammatory drugs Clinical and immune correlates Arthritis Rheum 1995;38 (8):1107–14 132 Farina EK, Kiel DP, Roubenoff R, Schaefer EJ, Cupples LA, Tucker KL Protective effects of fish intake and interactive effects of long-chain polyunsaturated fatty acid intakes on hip bone mineral density in older adults: the Framingham Osteoporosis Study Am J Clinic Nutr 2011;93(5):1142–51 133 Virtanen JK, Mozaffarian D, Willett WC, Feskanich D Dietary intake of polyunsaturated fatty acids and risk of hip fracture in men and women Osteoporos Int A journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA 2012;23 (11):2615–24 134 Jarvinen R, Tuppurainen M, Erkkila AT, Penttinen P, Karkkainen M, Salovaara K, et al Associations of dietary polyunsaturated fatty acids with bone mineral density in elderly women Eur J Clin Nutr 2012;66(4):496–503 Index Note: Page numbers followed by f and t refer to figures and tables, respectively A Acetabularia acetabulum, 103 Acetyl coenzyme A (ACoA) alternate potential fuel products of, 420 insulin regulated by, 444 synthesis inside plasmid, 205–206, 206f Acid sphingomyelinase (ASM), 222–223 Adenosine triphosphate (ATP), Adhesion and omega-3 fatty acids role in, 164–165 Adhesion molecules, expression of, 309 Adipose tissue accretion, linoleic acid’s role in, 434–436, 435f, 436f composition of plasma nutrients by, 445 half-life of, 444–445 LA rich diets effect on, 431–433, 431f, 432f Age-related macular degeneration (AMD), 251–254 current research in, 253 dry, 253 observational studies in, 253–254, 254f para-inflammation in, 252 pathogenesis of, 251–252 treatment options for, 252–253 wet, 254 Aging antioxidants role in, 507 disorders, fish oil fatty acids for, 585–594 Agrotis ipsilon Hfn., 37 Ahiflower oil, 87 Albumin, as transport mechanism, 390 Alcohol concentration, effect on emulsion formation, 133 Algal oil, 85, 86 Allostasis–homeostasis–stress integration, 7–8 Alpha-linolenic acid (ALA), 12, 13–14, 45, 46, 80, 321, 351 absorption of, 387–388, 388f and cancer, 373–374, 374f chemical structure of, 174f, 514f delivery of, 387 phosphatidylcholine for, 388–389, 388f desaturase function, 354–355 dietary absence of, 440, 440f balance of, 421–423 effect on brain function, 410 digestion of, 387 as essential nutrients, 351 evolutionary importance of anoxic environment, 327–331, 328f conditions of existence, 322 light and energy, 324–326, 325f, 326f light-protective evolutionary niches, 326–327 organised structure, 331–332 womb and cradle of life, 322–324 feed efficiency in livestock, 440 in human fat tissue, 439 in humans, 344, 351–352 limited capacity of antioxidants, 356–357, 357–359f linseed, 24 in mammals, 344 marine algae, 113t mechanisms of action, 178–179 metabolism, 440 in monogastrics, 439 and non-alcoholic fatty liver disease, 440 omega-3-eggs, 54–59, 56t omega-6 oxylipins, negative effects of, 356–357, 357–359f oxidative overload, 355–356 oxidised products, physiological relevance of, 358–362 COX and LOX 12/15 enzymes, 360–362 CTP450 enzymes, 362 multiple pathways, 358–359 and 13HODE, 359–360 oxylipins, 360 photo-oxidation products, 360 sensitivity, 358 peroxisomal beta-oxidation of, 439–440, 451–461 peroxisomes, 451–461 pharmacology and therapeutic benefits of, 174–178 physiological consequences of, 352–354, 353f in plants cardiolipin, 342–343 chiral lipid forms, 344 COX, 341 energy production and storage, 341 eukaryotes, conservation of gene pathways in, 339–340 galactolipids and phosphatidylcholine, 340 immune system and predator defence, 342 light sensing, 343–344 LOX, 341 oxidised derivatives and signaling systems, 342 peroxisomes, 340–341 photosynthesis and UV protection, 340 reproduction and fast storage, 342 in structural brain lipids, 414 thermogenesis, 440 uptake and usage by brain, 414–415 uptake pathways of, 387 © Springer International Publishing Switzerland 2016 M.V Hegde et al (eds.), Omega-3 Fatty Acids, DOI 10.1007/978-3-319-40458-5 599 600 and vascular disease, 406 vesicles, 332–339, 335–338f Alternaria blight disease development, 39 management, 39 Alzheimer’s disease (AD), 235–236 lipid composition imbalance and, 423 omega-3 fatty acids role in, 236–237 β-Amyloid protein, 236 Anagallis arvensis, 36 Angiogenesis, omega-3 fatty acids role in, 164–165 Animal feed, omega-3 fatty acids, 85 Animal studies See also Rabbits; Rodents obesity, 178 omega-3 fatty acids role in cancer, 167 Anther culture, 27, 30 Antigen-presenting cells (APCs), 309 Antihypertensive drugs, drug interaction, 575 Anti-inflammatory effect, of dietary omega-3, 308–309 Antioxidants natural, 502 role in human health, 501–508, 508f aging, 507 cancer, 505–506 cardiovascular diseases, 502–504, 503f, 505f chronic kidney disease, 504–505, 505f diabetes mellitus, 504, 505f neurodegenerative diseases, 506–507 obesity, 507 sources of, 502 Antiplatelet agents, drug interaction, 573–574 Apolipoprotein E polymorphisms, 73–74 Apoptosis, omega-3 fatty acids role in, 164 APPswe (Tg2576) transgenic mouse model, 236 Aquaculture, 480–481 Arabinoxylans, structure of, 182f Arachidonic acid (ARA), 47, 48, 85 -derived lipid mediators in brain, chemical structures of, 241f enzymatic and non-enzymatic, 242–243 marine algae, 113t Archean, 324–327, 330 Ardeola grayii, 37 Arrhythmias fish oil fatty acids for, 589–590 omega-3 fatty acids effect on, 519 Arrhythmogenic right ventricular dysplasia (ARVD), 394 Asthma, 147, 150t, 312 Astrocytes, 415–416, 417 Autophagy, B Baby food, 95 Bakery, 94 B-cell inhibitors, for rheumatoid arthritis, 145, 147 Beta oxidation , 341 See also Peroxisomal beta-oxidation mobilisation of fats out of adipose tissue and, 434 of n-3 PUFA, 566 peroxisomal DHA, 455 preferred substrates for, 454 protection of long-chain fats in brain, 417 regulation of insulin, and, 444 to support mitochondrial ATP production, 458–459 use of, 439–440 Beverages, 95 Index Biological evolution, 3–4 Birds, 16, 456 omega-3 enrichment to, benefits of, 18, 58–59 Bleeding complications, omega-3 fatty acids and, 569–571 Blood pressure, in metabolic syndrome, 198 Bone density, 288 Bone health, fish oil fatty acids for, 590–591, 592–693t Bone remodeling inflammation and, 286–287 omega-3 fatty acids, negative effect of, 289 oxidative stress and, 286–287 Bone resorption, 285–289 Bone turnover, 285–289 breast cancer and, 288–289 Bornetia secundiflora, 114 Brain mitochondria, 416 omega-3 fatty acids role in, 235 sensitivity to oxidative stress, 421 Breads, 94 Breast-feeding, 572–573 Breast milk, polyunsaturated percentage content of, 407 Bud fly (Dasyneura lini Barnes), 36 C Cadra cautella Walk, 36 Cancer, 372–374 alpha-linolenic acid, 373–374, 374f antioxidants role in, 505–506 breast, and bone turnover, 288–289 epithelial tissues, role of, 372 linoleic acid and, 373–374, 374f omega-3 fatty acids role in, 157–168 adhesion and angiogenesis, 164–165 animal studies, 167 apoptosis, 164 combination with chemotherapeutic agents and drug resistance, 165–167 immunomodulation, 165, 166f inflammation, 161–163, 162f limitless cell proliferation, 164 lipid peroxidation, 159–160, 161f lipid rafts and signal transduction, physicochemical properties of, 163, 164f metastasis, 165 OLR1 and, 372 relationship with LA oxidised products, 372 Canola, omega-3 enrichment, 57 Carbohydrate metabolism, in metabolic syndrome, 193–197, 194–197t Carcinogenesis, omega-3 fatty acids and, 571 Cardiac arrhythmias, 302 Cardiolipin, 342–343, 366–368 damage, 400–401, 401f mitochondrial function of, 421–422 Cardiovascular diseases (CVD) antioxidants role in, 502–504, 503f, 505f mitochondrial dysfunction and, 231 monosaturated fat and, 404–406 omega-3 fatty acids role in, 513–524, 516f, 520–521t adverse effects of, 523–524 dosage recommendations, 523t pharmacological preparations and dosages, 523 supplementation, 312–313 saturated fat and, 403–404, 404f, 405f Cardiovascular protection, omega-3 PUFA in, 301–302 Index Catalase (CAT), 371, 501 Cathartolinum, 22 Caulerpa, 106 Caulerpa racemosa, 114 Caulerpa veravalnensis, 114 CD36, 395–396 Census of Marine Life, 103 Chaetomorpha sp., 114 Chemical evolution, 3–4 Chenopodium album, 36 Chewable softgels, 83–84 Chia seeds, 80 Chiococca, 22 Chiral lipid forms, 344 Chiral oxylipin products, 365 Chlamydomonas, 106 Chlamydomonas reinhardtii, 117–119 Chlorella, 106 Chlorella minutissima, 120 Chlorella pyrenoidosa, 119 Chocolates, 96–97 Cholesterol lowering eggs, 62 Chondrus, 105 Chronic degenerative disease, Chronic kidney disease (CKD) antioxidants role in, 504–505, 505f omega-3 fatty acids effect on, 521–522, 522f Chylomicrons, lipid delivery to fat cells by, 433 Cladophora albida, 114 Clinical nutrition, omega-3 fatty acids, 85–86 Coacervation, 132–133 Coccinella septempunctata Linn, 37 Coconut fat, 403 Codex alimentarius, and human nutrition, 108–109 Codium fragile, 115 Cone dystrophies, 256 Confectionary, 96–97 Conjugated linoleic acid (CLA)-enriched eggs, 61–62 Corallina pilulifera, 115 Coralline, 105 Corcyra cephalonica, 36 Coronary heart disease (CHD), 53, 302 CPT1 enzymes, 416, 417–418 Crassostrea gigas, 111 Crypthecodinium cohnii, 111 CTP450 enzymes, 362 Cultivars, linseed, 24, 31 Cuscuta sp., 32, 36, 38, 40 Cyanidioschyzon merolae, 116 Cyclooxygenases (COX), 161–163 alpha-linolenic acid, 341 linoleic acid, 341 12/15 enzymes, 360–362 role in oxidative stress reduction, 397 Cystoseira hakodatensis, 115 Cystoseira indica, 114 Cytochrome p450 (CYP450), 161 Cytokine inhibitors, for rheumatoid arthritis, 145 Cytokines, pro-inflammatory, 309 Cytoplasmic fatty acid pool, 209 D Dairy products, 94–95 Dasylinum, 22 Deoxyribonucleic acid (DNA), 3–4, 601 Desaturation, in fatty acid biosynthesis, 208 Designer eggs, 61–62 Diabetes mellitus (DM) antioxidants role in, 504, 505f gestational, 492 omega-3 fatty acids effect on, 313–314, 516–517, 517t Diabetic cardiomyopathy, 223–224 Diabetic mitochondria, 231–232 Diabetic nephropathy, 222 Diabetic neuropathy, 225 Diabetic retinopathy, 222–223 Diacylglycerol (DAG) de novo synthesis of, 209 PC-derived, synthesis of, 209 TAG synthesis from, 209–210 Dicrurus adsimilis, 37 Diet and Reinfarction Trial (DART), 468 Diet–heart hypothesis, 406 Dietary absence of alpha-linolenic acid, 440, 440f Dietary fibre, linseed, 24 Dietary supplement, omega-3 fatty acids, 83–84 Diets ALA deficiency in, 366 fat content in, 554–555 high-fat preindustrilised, 407 low-fat, 406 and nutrition, 229 ω-6 and ω-3 fatty acids in, 204–205 alternative origins for, 475–483 phosphatidylcholine composition, 388 supplementation in old population, 311 on pregnancy and lactation in relation to infant allergies, 311 and Western disease, 374 Digestion absorption, 5–6 Dilution test, 134 Disease of civilisation, See also individual diseases Docosahexaenoic acid (DHA), 12, 45–47, 80–81 biotransformation pathways of, 567f in brain, 422–423 interaction with iron during gestation, 296 marine algae, 109–113, 113t metabolism, enzymatic and non-enzymatic mediators of, 244–246, 244–246f omega-3-eggs, 54–59, 56t, 61, 62 prevention of neuroinflammation by, 246–247 for psoriasis resolvins and protectins, 534, 534t role of, 533t -rich algae oil, 263–266 in pregnancy and development, 264–265 supplementation, 264 role in human brain evolution, vesicle membrane, 334, 336f Drug interactions, of omega-3 fatty acids, 573–576 E Ectopic gene expression, promoters of, 214, 215t Eggs compared with omega-3-eggs, 53t global production, 52–54 health benefits of, 52 nutritional content, 52 Eicosanoid metabolism, iron and, 296–297, 297f Eicosapentaenoic acid (EPA), 12, 14, 15, 45, 80–81 602 biotransformation pathways of, 567f marine algae, 109–113, 113t metabolism, enzymatic and non-enzymatic mediators of, 243–244 omega-3-eggs, 54–59, 56t prevention of neuroinflammation by, 246–247 for psoriasis resolvins, 534, 534t role of, 533t Elasmus sp., 37 Embryo rescue technique, 31 Emulsifiers high-molecular weight, 130–131 low molecular weight, 130 Emulsion bioavailability of, 135 characterisation of dilution test, 134 limpidity test, 134 long-term stability, 134 microscopic examination, 134 peroxides and degradation product detection, 134 repeated freezing and thawing, 134 rheological properties, 134 size determination, 133 stability assessment test, 134 staining test, 134 stress testing using centrifugation, 134 thermal stability, determination of, 134 visual inspection, physical appearance by, 133 definition of, 128 formation, factors affecting alcohol concentration, 133 hydrophobic chain length of surfactant, 133 ionic strength, 133 oil properties, 133 pH, 133 salt concentration, 133 microencapsulation of, 131 coacervation, 132–133 extrusion, 133 fluidised bed drying, 132 freeze-drying (lyophilisation), 132 spray drying, 131–132 preparation methods, 129–130 Endothelial health, in metabolic syndrome, 198 Endothelial progenitor cells (EPCs), 222 Enterocyte, Fe absorption pathways in, 294f Entropy, 2–3, 3f Epithelial tissues, role in cancer, 372 Escherichia coli, 571 acetyl-CoA synthetase (ACS), 119 TE gene tesA, 120 E-selectin, 141 Essential amino acids (EAA), 40, 52 Essential fatty acids (EFAs), 11, 47, 94, 141, 487 alpha-linolenic acid (ALA), 80 breast milk, 45 and diabetic neuropathy, 225 EPA and DHA, 80–81 in human nutrition (see also Long-chain polyunsaturated fatty acids (LCPUFAs)), 46 linseed, 24 Eukaryotes, conservation of gene pathways in, 339–340 Eurytoma sp., 37 Extrusion, 133 Eye health, omega-3 fatty acids role in, 251–258 Index age-related macular degeneration, 251–254, 254f cone dystrophies, 256 macular dystrophies, 256, 256f polyunsaturated fatty acids, 241 retinitis pigmentosa, 254–255 severe dry eyes, 256–258, 257f, 258f Stargardt disease, 255–256 F Farnesol X receptor (FXR), 69–70 Fat deposition, fructose synergy with, 442–444 FAT1 See CD36 Fat-1 transgenic mouse model, 167 Fatty acids classification of, 514f essential (see Essential fatty acids (EFAs)) non-esterified free, 69 omega-3 (see Omega-3 fatty acids) omega-6 (see Omega-6 fatty acids) terrestrial plants, 106–108, 107f between tissues, trafficking of, 70 Fatty acyl chain elongation, termination of, 208 Fish feeds, 480–481 omega-3 enrichment, 57 Fish oil fatty acids for aging disorders, 585–594 bone health, 590–591, 592–693t clinical evidence, 587–589, 588–589t mechanism of action, 586–587 pain, 591, 594–595 and cardiovascular health, 586 arrhythmia, 589–590 Fish oil versus omega-3-eggs, 55–56 Flax Bio-village Concept (FBC), 11–18, 17f Flax lignin, pharmaceutical applications of, 17–18 Flaxseeds, 15–16 omega-3 enrichment, 57 Fluidised bed drying, 132 Formula milk, 46 Fortification, 46–47, 89–99 to combat micronutrient malnutrition, advantages of, 90–91 guidelines for, 91–92 industry-driven, 91 national food law and, 91 omega-3, 92 policy, 91 safety of, 92–93 Fortified products baby food and pediatric juices, 95 beverages and juices, 95 breads and bakery, 94 confectionary and chocolates, 96–97 dairy products, 94–95 infant formula, 97–98 market of, 93–94 meats and meat products, 95–96 omega-3 beneficiaries of, 98 market drivers of, 98 market restraints for, 98 omega-3 eggs, 90, 95 prepared products, 96 Free radicals, 7, 239–240 Freeze-drying (lyophilisation), 132 Index Fructose synergy, with LA and fat deposition, 442–444 Fumaria parviflora, 36 Functional foods obesity and, 173 omega-3 fatty acids, 83 and public health, 11–12 G Galactolipids, 340, 377–378 Gamma linolenic acid (GLA), 31 diabetic nephropathy, 222 in flax seeds, 40 marine algae, 113t Gelidium, 105 Gender differences, in hyperlipidemia, 74 Generally Recognized as Safe (GRAS), 129 Gestation, iron–DHA interaction during, 296 Gestational diabetes mellitus (GDM), 492 Glial death, PPAR gamma-induced, 420 Glucose, in refined food, 442–443 Glutathione, 370–371 Glutathione peroxidase (GPx), 501 Glutathione reductase (GRx), 501 Gracilaria, 105 Gracilaria debilis, 114 Gracilaria dura, 114, 115–116 Gracilaria gracilis, 115 Gracilaria tenuistipitata, 115 Gracilaria vermiculophylla, 116 Gracilaria wattii, 114 Grateloupia turuturu, 115 H Habitat loss, 476–477 Halopteris scoparia, 114 Haploid technique, 27, 30 HDL-ch fraction, effects on metabolic syndrome, 198 Healthy donors, omega-3 fatty acid supplementation effect on, 311 Heart failure, omega-3 fatty acids effect on, 519 Helicoverpa armigera Hubn., 37 Hepatocyte nuclear factor-4α (HNF-4α), 69 Herbal-enriched eggs, 62 High-density lipoprotein (HDL) as antioxidant transport for oxidised phospholipids and cholesterol, 401–403, 402f cholesterol (HDL-ch), 71 High-molecular-weight emulsifiers, 130–131 High-pressure homogeniser, 129 Himanthalia elongata, 115 Homeostasis–allostasis–stress integration, 7–8 Human fat tissue, alpha-linolenic acid in, 439 Human genome project, 4-Hydroxynonenal (4HNE), 128342, 363–364 9-Hydroxyoctadecadienoic acid (9HODE), 359–360, 368 13-Hydroxyoctadecadienoic acid (13HODE), 340, 342–344, 359–360, 378, 434, 437, 441, 443 -related oxidised stress, and damage to vascular membranes, 397–398 Hyperlipidemia, 67–68 n-3 PUFA efficacy in, factors affecting apolipoprotein E polymorphisms, 73–74 gender differences, 74 Hypocaloric diets, for metabolic syndrome, 193, 191–192t 603 I Immune response, long-chain fatty acids and, 307–308 Immune system, 307 components, omega-3 PUFA effect on, 308–310 inflammation in, 141–142, 142f Immunoglobulin-enriched eggs, 62 Immunomodulation, omega-3 fatty acids role in, 165, 166f Impaired glucose metabolism (IGM), 303 Inducible nitric oxide synthase (iNOS), 352, 361, 365, 366, 371, 372 peroxisome peroxide production in conjunction with, 458 -related NO catalase inhibition, 443 Industry-driven fortification, 91 Infant formula fortified products, 97–98 omega-3 fatty acids, 85 Inflammation and bone remodeling, 286–287 in immune system, 141–142, 142f neuroinflammation, 246–247 omega-3 fatty acids role in, 161–163, 162f omega-3 PUFA effect on, 308–309 PUFA’s role in, 142–143 Inflammatory bowel disease (IBD), 147, 148–149t, 312 Inflammatory diseases, omega-3 fatty acids in, 141–151, 144f, 145t asthma, 147, 150t, 312 diabetes, 313–314 exerting effect on cell signaling pathways, 143 multiple sclerosis, 150, 314 inflammatory bowel diseases, 147, 148–149t, 312 lipid mediator patterns, altering, 143–145 membrane's physical properties, altering, 143 psoriasis, 312 rheumatoid arthritis, 145–147, 146t, 312 systemic lupus erythematosus, 314 Inflammatory markers, effects on metabolic syndrome, 198–199 Ingredients, 4f Insulin by melonyl CoA and ACoA, 444 resistance, beta-cell related, 443–444 Integrated disease management, for linseed, 38–40, 38t Integrated pest management, for linseed, 36–37 Intercellular adhesion molecule-1 (ICAM-1), 141 Interspecific hybridisation, linseed, 22–23, 31 Intrauterine growth restriction (IUGR), 492 Ionic strength, effect on emulsion formation, 133 Iron absorption pathways, in enterocyte, 294f and eicosanoid metabolism, 296–297, 297f interaction with DHA during gestation, 296 with omega-3 fatty acids, 295–296 metabolism, 293–294 Irrigated ecosystem, 32–33 Ischemic heart disease (IHD), 517–518 Isocaloric diets, for metabolic syndrome, 191–193, 191–192t Isochrysis galbana, 112 Isochrysis sp., 112 Isochrysis zhangjiangensis, 112 J Juices, 95 K Krill, 81 604 omega-3 market, 81–82 omega-3 world market for ingredients, 82–83 for application segment (see Krill, application segment) Krill, application segment clinical nutrition, 85–86 infant formula, 85 pet and animal feed, 85 pharmaceuticals, 84 omega-3 therapeutic potential, 84–85 supplements and functional foods, 83 soft gels, 83–84 L Lactation DHA and, 97–98, 268 omega-3 diet supplementation effect on, 311 Laminaria, 105 Laminaria digitata, 115 Laminaria hyperborean, 114 Laurencia filiformis, 114–115 Laurencia intricata, 114–115 LDL-ch fraction, effects on metabolic syndrome, 198 Lignans, 15 flax lignan, 17–18 linseed, 24 Limitless cell proliferation, 164 Limpidity test, 134 Linastrum, 22 Linola, 24 Linoleic acid (LA), 12, 321, 351, 385 absorption of, 387–388, 388f age of menarche, 354 brain maturation, 354 and cancer, 373–374, 374f to control reproductive capacity and function, 352 delivery of, 387–390 desaturase function, 354–355 dietary balance of, 421–423 dietary oxidised, 398–400, 399f digestion of, 387 as enabler and controller of reproductive capacity, 351 as essential nutrients, 351 evolutionary importance of anoxic environment, 327–331, 328f conditions of existence, 322 light and energy, 324–326, 325f, 326f light-protective evolutionary niches, 326–327 organised structure, 331–332 womb and cradle of life, 322–324 export from liver, and non-alcoholic fatty liver disease, 390–391 fructose synergy with, 442–444 in humans, 344, 351–352 in mammals, 344 marine algae, 113t and non-alcoholic fatty liver disease, 440 oxidative overload, 355–356 oxidised products, physiological relevance of, 358–362 and 13HODE, 359–360 COX and LOX 12/15 enzymes, 360–362 CTP450 enzymes, 362 multiple pathways, 358–359 oxylipins, 360 photo-oxidation products, 360 sensitivity, 358 Index peroxisomes, 451–461 physiological consequences of, 352–354, 353f in plants cardiolipin, 342–343 chiral lipid forms, 344 COX, 341 energy production and storage, 341 eukaryotes, conservation of gene pathways in, 339–340 galactolipids and phosphatidylcholine, 340 immune system and predator defence, 342 light sensing, 343–344 LOX, 341 oxidised derivatives and signaling systems, 342 peroxisomes, 340–341 photosynthesis and UV protection, 340 reproduction and fast storage, 342 puberty, 354 rich diets effect on adipose tissue, 431–433, 431f, 432f native versus westernised, 430–431 role in adipose tissue accretion, 434–436, 435f, 436f in structural brain lipids, 414 uptake pathways of, 387 vesicles, 332–339, 335–338f Linseed, 15–16, 21–42 agriculture to health and wealth, convergence of, 17 cake, 24–25 centre of origin, 21 composition, 174 crop description floral biology, 23 importance, 21–22 nutritional values, 23–25 origin, 21 scientific name and species relationship, 22–23 cultivars, 24, 31 cultivation special initiatives, 41–42 zones, 25 comparative analysis, 25, 26–27t export–import status, 25, 27t varietal development, 25, 28–30t, 31t yield gap, 25 climatic requirement, 25 gene pool, 23 genetic potentiality advancement, 25, 27, 30–32 seed scenario, 32 good crop production practices, 32–36 agronomical practices, 34t cropping systems, 34, 35t harvesting calendar, 35t irrigated ecosystem, 32–33 rainfed ecosystem, 32 soil and moisture management, 34, 36 utera system, 32 history of, 173 integrated nutrient management biological control, 37 chemical control, 37–38 harvesting, drying and threshing, 36 integrated disease management, 38–40, 38t integrated pest management, 36–37 IPM schedule, 37 linseed bud fly, 37 post-harvest technology, 36 sowing time and intercropping, 37 Index weed management, 36 interspecific hybridisation, 22–23, 31 mucilage, isolation and therapeutic effects of dietary fibre from, 181–182 as neglected crop, 16 for obesity management, 170–183 oil, isolation of, 174 products, 40–41 vitamins and minerals in, 176t Linseed bud fly, 37 Linum africanum, 22 Linum angustifolium, 21, 22 Linum austriacum, 31 Linum bienne, 21, 23 Linum corymbiferum, 22 Linum decumbens, 22 Linum grandiflorum, 22 Linum mysorense, 22 Linum perenne, 22, 31 Linum spp., 21–23 Linum strictum, 22 Linum usitatissimum, 21, 22 Linustatin, chemical structure of, 176f Lipid metabolism, in metabolic syndrome, 197–198 Lipid peroxidation mitochondrial membrane, 160 omega-3 fatty acids role in, 159–160, 161f Lipid rafts, physicochemical properties of, 163, 164f Lipids and cardiac function, 386 and cardiovascular health, 386 delivery of, and oxidised substrate to heart, 395–396 functional and behavioral imbalances of, 424–425 oxidised material and cellular detritus delivery to fat cells, 433–434 Lipoprotein lipase (LPL) activity, 69 Lipoxygenases (LOX), 161, 163 alpha-linolenic acid, 341 linoleic acid, 341 12/15 enzymes, 360–362 alpha-linolenic acid as competitive marker for, 441 role during brain damage or injury, 422 role in oxidative stress reduction, 397 Liver X receptor-alpha (LXRα), 69 Liver X receptors (LXR), 268 Long-chain fatty acids, and immune response, 307–308 Long-chain polyunsaturated fatty acids (LCPUFAs), 487–488 biosynthesis of, 488 enzymes in plant seeds, heterologous expression of, 214, 215t enzymes for, 212 pathway, 213, 213f maternal, 487–494 fetal development, 493–494 fetal status, 488 fetus through placenta, transport of, 491, 491f in placental growth and development, 490–491 inadequacy/insufficiency, consequences of, 491–493 initiation of labor, 489–490, 490f intake/status, 488 length of gestation, 490 metabolism, 488 recommendations for, 494 role of, 488–491, 490f pathway in plants, 212 in psoriasis, 531–537 challenges to delivery, 536 DHA-derived resolvins and protectins, 533, 534t 605 EPA and DHA, role of, 533t EPA-derived resolvins, 534, 534t immunosuppression, 534–536 nanomedicine, scope of, 536–537 pathophysiology, 532 pharmacotherapy, 532–533, 532f Low-density lipoprotein (LDL) Cholesterol (LDL-ch), 70–71 combined with n-3 PUFA, 72–73 concentration, 70–71 delivery of fat-soluble antioxidant to fat tissue, 432–433 lipids oxidised material and cellular detritus to fat cells by, 433–434 as evolutionary lipid supply mechanism, 391–394, 392f, 393f LA-related oxidative stress to cardiovascular disease, 396–397 as LA transporter to vascular epithelial cells, 391 liver output, 391 MRFA PUFA and saturate fat content of, 391 particle size, 71, 71f plasma, 391 via receptors sweep and regulate levels of oxidised product in blood, 400 very low-density lipoprotein, 69 Low molecular weight emulsifiers, 130 Lutein-enriched eggs, 61 Lymphocytes antibody production, 310 NK and LAK cells activity, 310 proliferation, 309 regulatory T cells, 310 Lymphokine-activated killer (LAK) cell activity, 310 Lyophilisation, 132 Lysophosphatidylcholine, 367 use in food processing, 369 M Macrocystis, 101 Macrophages, 441 Macular dystrophies, 256, 256f Malonaldehyde (MDA), 128, 342, 364 Malonyl acyl carrier protein (ACP), 206–207, 207f condensation with, 207–208 Malonyl-CoA CPTIA Randle cycle-related blocking, 444 formation, 206–207, 207f insulin regulated by, 444 Mammals, 212 alpha-linolenic acid, 344, 576 intake of LA and ALA in, 430–431 linoleic acid, 344 peroxisomes, 458 MAPK cascade, for psoriasis, 535–536 Marine algae environment, 102–106 omega-3 enrichment, 57 polyunsaturated fatty acids from, 101–121 biotechnology, 116–120, 117f codex alimentarius and human nutrition, 108–109 seaweeds, 109t terrestrial plants, 106–108, 107f Marker-assisted selection (MAS), 30–31 MCAD deficiency disorder, 419 Meat products, 95–96 Meats, 95–96 606 Medium chain triglyceride (MCT), 394 Melilotus spp., 36 Menochilus sexmaculatus Fabr, 37 Metabolic syndrome obesity and, 189 omega-3 fatty acids role in, 189–200 blood pressure and endothelial health, 198 carbohydrate metabolism, 193–197, 194–197t future perspectives of, 199–200 inflammatory markers, 198–199 lipid metabolism, 197–198 weight loss and body composition, 191–193, 191–192t Metal toxin accumulation, 477 Metastasis, omega-3 fatty acids role in, 165 Microemulsion system, types of, 128–129 Microencapsulation of emulsion, 131 coacervation, 132–133 extrusion, 133 fluidised bed drying, 132 freeze-drying (lyophilisation), 132 omega-3 fatty acids, 135 spray drying, 131–132 Micronutrient malnutrition (MNM), fortification as strategy to combat, 90–91 Micronutrients, Mitochondria, 394 brain, 416 long-chain lipid access to, by CPTIA malonyl-CoA Randle cycle-related blocking, 444 Mitochondrial diseases (MDs), omega-3 fatty acids and, 229–232 cardiovascular diseases, 231 diabetes, 231–232 neurodegenerative diseases, 230–231 Mitochondrial energy coupling impairment, 230 Mitochondrial membrane lipid peroxidation, 160 Mitochondrial phospholipids, 231 Moisture management, for linseed, 34, 36 Monogastrics, alpha-linolenic acid in, 439 Monosaturated fat, and cardiovascular disease, 404–406 Multiple sclerosis (MS), 150, 151t, 314 Mutagenesis, omega-3 fatty acids and, 571 Myocardial infarction, omega-3 fatty acids effect on, 465–472 clinical trials, 466–467t intervention studies, 468–471 meta-analysis, 471 N NADH+, 4, 229 NADPH+, 4, 206, 208, 244 Nannochloropsis, 101, 118 fatty acids, 110 Nannochloropsis limnetica, 110 Nannochloropsis oculata, 110 Nanomedicine, for psoriasis, 536–537 National food law, and fortification, 91 Natural killer (NK) cell activity, 310 Neurodegenerative diseases antioxidants role in, 506–507 mitochondrial dysfunction and, 230–231 omega-3 fatty acids role in, 235 Neurofibrillary tangles (NFT), 236 Neuroinflammation, 273, 275–276 prevention by EPA and DHA, 246–247 Nitrogen-related (nitrous) oxidation products, 365–366 Nitzschia laevis, 113 Index Non-alcoholic fatty liver disease (NAFLD), 390–391, 440 Non-esterified free fatty acids (NEFAs), 69 Non-puerperal depression, 268–269 Nuclear factor kappa B (NFκB), 146 activation, for psoriasis, 536 Nutraceuticals, 79–80, 81 Nutrition, 2–3 O Obesity antioxidants role in, 507 functional and, 173 management, linseed for, 170–183 and metabolic syndrome, 190 oxidative stress and, 433, 440–442 Odontelloa aurita, 110–111 Oil properties, effect on emulsion formation, 133 Oilseeds, balancing omega-6:omega-3 ratios in, 203–216 acetyl-CoA synthesis inside plasmid, 205–206, 206f biotechnological approaches, 211–216 choice of, 214 condensation with malonyl-ACP, 207–208 energy requirement, 206 future prospects of, 216 importance of, 204–205 malonyl acyl carrier protein, 206–207, 207f malonyl-CoA formation, 206–207, 207f oil accumulation during seed development, 210–211 potential hurdles in, 215–216, 215f Rubisco, role of, 208–209, 209f triacylglycerol formation, 209–210 synthesis, 209–211 in vegetable oils, 204t Older population, omega-3 diet supplementation effect on, 311 Oleate (OA), 209 OLR1 activated by oxidised LDL, 395–396 and cancer, 372 Omega-3-chicken, 11, 12, 14–17 fortification, 95–96 Omega-3-eggs, 11, 12, 14–17, 51–62 advantages of, 55 commercial aspects of, 59–61 commercial poultry feed for, 59 compared with regular eggs, 53t designer eggs, 61–62 enrichment to birds, benefits of, 58–59 feed for enrichment, 56, 56t fish oil versus, 55–56 fortification, 95 health benefits of, 55 means to improve oxidative stability and quality of, 59 quality characteristics, production parameters and, 57–58 resources for enrichment fish, 57 marine algae, 57 plants, 56–57 Omega-3 fatty acids, 1, 2, 5, adverse effects of, 570–573, 570t and Alzheimer’s disease, 235–237 biochemistry of, 513–516 and bone turnover, 285–289 and cancer, 157–168 and cardiovascular diseases, 513–524 Index and diabetic complications, 221–226 in diet, alternative origins for, 475–483 drug interactions, 573–576 edible and anti-nutrients, 16 effect on health, 310–311 and eye health, 251–258 fortification, 89–99 health benefits of, 54 and inflammatory diseases, 141–151 linseed, 24 and metabolic syndrome, 189–200 metabolism, 294–295 microencapsulation of emulsion, 135 and mitochondrial functions, 229–232 mechanism of action, 514–516 and myocardial infarction, 465–472 role in public health, 12–15, 13f awareness of importance of, 16–17 stability of, 16 therapeutic potential, 84–85 types and sources of, 80–81 world market of, 79–87 application segment, 83–86 clinical nutrition, 85–86 infant formula, 85 ingredients, 82–83 new emerging market, 86–87 pet and animal feed, 85 Omega-3 index, 6–7 of cardiovascular health, 522–523 Omega-3-milk, 11, 12, 14–17, 45–48 biofortification of, 46–47 role in human health, 47–48 Omega-3 polyunsaturated fatty acids (n-3 PUFA), 54, 55 as alternative to oily fish, 478–480 animal sources of, 481–482 beta-oxidation of, 566 blood lipids, 68–73 combination therapies, 72–73 combined with natural therapies, 73 dietary sources and metabolism, 68 digestion of, 544–546, 545f distribution of, 558–566, 563f efficacy in hyperlipidemia, factors affecting apolipoprotein E polymorphisms, 73–74 gender differences, 74 excretion of, 569 macro and microalgae sources of, 482 maternal status by pregnancy and lactation, modulation of, 268 metabolism of, 566–569 oral bioavailability of, 546–558, 547–548t, 550t, 556t and postpartum depression, 267–276 regulation of, 267–268 structure of, 68 synthesis pathways of, 542–544, 543f TG-lowering effects of, 69–70, 70f Omega-6 fatty acids, 5, 7, 47, 54 See also Gamma linoleic acid (GLA) intake of vegetarians and nonvegetarians, 12, 13f linseed, 24, 40 and omega-3 acids, biotechnological approaches, 211–212 osteoblastogenesis, 287–288 pro-inflammatory nature, 586 Origin of life, 3–4 Osteoprotegerin (OPG), 285 Ostreococcus tauri, 116, 118 Overfishing, 476–477 607 Oxidation of foods, 368–369 Oxidation of PUFAs, 127–128 Oxidative DNA damage, 369–370 Oxidative stress, 7, and bone remodeling, 286–287 brain sensitivity to, 421 and DNA damage, 371 management of, 3f and obesity, 433, 440–442 by omega-3 fatty acids in brain, prevention of, 239–247 ARA-derived metabolism, 242–243 DHA metabolism, 244–246, 244–246f enzymatic and non-enzymatic mediators of, 243 EPA metabolism, 243–244 factors contributing to, 240f signal transduction process, 242f oxylipins, 355 PPAR peroxisomal activation, impact of, 420 reduction by LOX12/15 and COX, 385 Oxidised linoleic acid, and cardiovascular disease, 386 Oxo-HODE, 436, 440, 452 Oxygen, for life and death, 3f Oxylipins chiral oxylipin products, 365 4HNE, 363–364 linoleic acid, 360, 362–366, 363f, 397–398, 398f MDA, 364 nitrogen-related (nitrous) oxidation products, 365–366 oestrogen desaturase and cardiovascular disease, 365 omega-3 oxylipins, 364 oxidative stress, implications of, 355 oxidised product, metabolic sensing and pathway preference for, 366 PPAR gamma and alpha activators, 365 role during brain damage or injury, 422 TRVP1 pain pathways, 364–365 P Pain, fish oil fatty acids for, 591, 594–595 Palmaria palmata, 114, 115 Palmitic acid (PA), 209 as peroxisomal substrate, 419–420 uptake and usage by brain, 414–415 Pavlova lutheri, 111–112 Pediatric juices, 95 Peripheral arterial disease (PAD), 302–303 Peroxisomal beta-oxidation of alpha-linolenic acid, 439–440 carbon removal cycle, shortening, 454 combined with blood–brain barrier, 455 energetic advantages, 455 functional roles of, 454 mitochondrial damage during oxidative stress, 454 products to support mitochondrial ATP production, capacity of, 458–460 proliferation and/or increased size in activity, 455–456 restrictions on DHA beta-oxidation, 455 Peroxisomal dysfunction-related cardiac impairment, 394–395 Peroxisomal pathway substrates to fuel Inuit with CPT1A variant, 417–418 to fuel neonate brains, 418–419 Peroxisome proliferator-activated receptors (PPARs), 69, 146, 268 alpha activation, 383, 407, 421, 438–439 activation, by energy deficit, 456–457 608 activators, 365 and Alzheimer’s disease, 423–424 and beta-cell-related insulin resistance, 443–444 energy production, 459 roles of, 453 alpha-related peroxisomes, 421 delta and beta-cell-related insulin resistance, 443–444 role in brain antioxidant protection, 421 gamma activation of, 438–439, 456 activators, 365, 441, 453 and Alzheimer’s disease, 423–424 and beta-cell-related insulin resistance, 443–444 cellular creation maintenance and repair, 458 -induced glial death, 420 master adipogenic controller, 436–438, 437f, 438f peroxisomal activation, impact on oxidative stress, 420 roles of, 420 Peroxisomes, 340–341, 451–461 antioxidant production capacity, 457 basic feature and role of, 452–453 and calories, 459–460 fat oxidation rates, 453–454 functional role of, 454 importance of, 394–395 MCT production by, 394 oxygen recycling by, 394 peroxide production in conjunction with iNOS, 458 role in brain function, 416 stored linoleic acid, impact of, 461 thermogenesis temperature adoption and hibernation, 460 Pet feed, omega-3 fatty acids, 85 Peyssonnelia sp., 114 pH, effect on emulsion formation, 133 Phaeodactylum, 101 Phaeodactylum tricornutum, 110, 116–118 Phagocytosis, omega-3 PUFA effect on, 308–309 Phalaris minor, 36 Pharmaceuticals market, omega-3 fatty acids, 84 Phase inversion method, 129 Phase titration method, 129 Phosphatidylcholine, 340, 366–368 for delivery of lipids and choline, 388–389, 388f importance to lipoprotein membranes, 377 Pi bond, 325, 333, 334, 337–339 Plant sterols, 73 Plants -based fat-soluble antioxidants, 405 cardiolipin, 342–343 energy production and storage, 341 enzymes LOX and COX, 341 galactolipids and phosphatidylcholine, 340 immune system and predator defence, 342 light sensing, precursor to vision, 343–344 omega-3 enrichment, 56–57 oxidised derivatives and signaling systems, 342 peroxisomes, 340–341 photosynthesis and UV protection, 340 reproduction and fat storage, 342 sources of omega-3 PUFA as an alternative to oily fish, 478–479 arabidopsis, 479 Camelina sativa, 479–480 echium oil, 479 Index flaxseed, 479 rapeseed, 480 soybean, 479 terrestrial and fatty acids, 106–108 Polarisation, 327 Pollution, 477 Polyunsaturated fatty acids (PUFAs), 101–121 marine algae from biotechnology, 116–120, 117f codex alimentarius and human nutrition, 108–109 seaweeds, 109t terrestrial plants, 106–108, 107f oxidation of, 127–128 role in eye health, 251 inflammation, 142–143 Porphyra, 105 Porphyridium sp., 57 Postpartum depression, n-3 PUFA role in, 267–276 clinical trials, 269–273, 270–271t, 272t neurobiology and behavior, 273–276 non-puerperal depression, 268–269 Powdery mildew disease development, 39 management, 39–40 Preeclampsia, 493 Pregnancy DHA-rich algae oil, supplementation of, 264–265 omega-3 diet supplementation effect on, 311 Prepared products, 96 Preterm labor, 491–492 Protein kinase C (PKC) activation, for psoriasis, 534, 535f Protein–sugar–lipid crosslinking, 369 Protoplast fusion technique, 31 Psoriasis, LCPUFA role in, 531–537 challenges to delivery, 536 DHA-derived resolvins and protectins, 533, 534t EPA -derived resolvins, 534, 534t and DHA, role of, 533t immunosuppression, 534–536 nanomedicine, scope of, 536–537 omega-3 diet supplementation effect on, 312 pathophysiology, 532 pharmacotherapy, 532–533, 532f Public health, functional foods and, 11–12 Purslane, 80 Q Quality characteristics, of eggs, 57–58 Quality of life, functional foods, 11–12 Quality of omega-3 eggs, 59 R Rabbits See also Animal studies secoisolariciresinol diglucoside, actions of, 180–181 Rainfed ecosystem, 32 Reactive nitrogen species (RNS), 7, Reactive oxygen species (ROS), 5, 7, Receptor-activated nuclear kappa-β ligand (RANKL), 285–287 Red blood cell deformability, omega-3 fatty acids and, 225 Redox, Index Regulatory T cells, 310 Reproduction studies, 572 Retinitis pigmentosa (RP), 254–255 current research in, 255 Retinoid X receptor-alpha (RXRα), 69 Retinoid X receptors (RXR), 268 Rheumatoid arthritis, 145–147, 146t, 312 RNA, Rodents See also Animal studies secoisolariciresinol diglucoside, actions of, 180–181 Rubisco, role in fatty acid biosynthesis, 208–209, 209f Rust disease development, 40 management, 40 S Saccharina latissima, 115 Salt concentration, effect on emulsion formation, 133 Sargassum horneri, 115 Sargassum vulgare, 114 Saturated fat as beta-oxidation fuel substrate, protecting, 417 and cardiovascular disease, 403–404, 404f, 405f Schizochytrium, 101, 112, 113, 119, 263 Schizochytrium limacinum, 112 Seaweeds, marine algae, 109t, 114–116, 116t Secoisolariciresinol diglucoside (SDG), 24 actions in rodents and rabbits, 180–181 isolation from linseed, 179–180 pharmacology of, 179–180 structure of, 175f therapeutic benefits in humans, 177 Severe dry eyes, 256–258, 257f, 258f Short-term fasting, benefits of, 395 Signal transduction, physicochemical properties of, 163, 164f Softgels, 83 chewable, 83–84 Soil management, for linseed, 34, 36 Sonication method, 130 Spray drying, 131–132 Squid, 87 Staining test, 134 Stargardt disease, 255 current research in, 255–256 Statins, drug interaction, 575 Stearate (SA), 209 Stearidonic acid (SDA), 87 marine algae, 113t Stearoyl-CoA desaturase (SCD1), and Alzheimer’s disease, 423 Sterol regulatory element-binding proteins (SREBP), 69 Sulphur metabolism, 330 Superoxide dismutase (SOD), 501 Surfactant’s hydrophobic chain length, effect on emulsion formation, 133 Survival of the sickest, Syllinum, 22 Synechococcus elongates, 118–119 Synechocystis sp., 118–119, 120 Systemic lupus erythematosus (SLE), omega-3 diet supplementation effect on, 314 Systesis dasyneurae Mani, 37 609 T Taonia atomaria, 114 Tau protein, 236 T-cell inhibitors, for rheumatoid arthritis, 145, 147 Telomeres, and life span, Terrestrial plants, 106–108, 107f Tetrastichus sp., 37 Thalassiosira pseudonana, 116, 117, 119 Thraustochytrium, 101, 112–113 TNF-α inhibitors, for rheumatoid arthritis, 145 Total cholesterol, 70 Trachydiscus minutes, 111 Triacylglycerol (TAG) formation of, 209 synthesis, 209–210, 210f metabolic flux of, 210 during seed development, 210–211 synthesis from DAG, 209–210 Triglycerides (TG), 68 clearance, 69 effects on metabolic syndrome, 197–198 rich lipoproteins, effects on metabolic syndrome, 197–198 U Ulva, 104, 106, 114 Ulva lacuta, 115 Ulva linza, 114 Umbellularia californica (U californica), 118 Undaria, 105 Undaria pinnatifida (U pinnatifida), 114, 115 Unrefined cold pressed oils, cardiac protective effects of, 405 Utera system, 32 V Vascular cell adhesion molecule-1 (VCAM-1), 141 Vascular disease, alpha-linolenic acid and, 406 Vascular plaque, omega-3 fats and, 400 Vegans, 477–478 Vegetarianism, 4–5 Vegetarians, 477–478 Very low-density lipoproteins (VLDL), 69 Vesicles, 332–339, 335–338f Vicia hirsute, 36 Vitamins B group, 507 D, 52, 522 E, 59, 370 K, and minerals in linseed, 176t Volcanic, 322–332 W Warburg effect, Weed management, for linseed, 36 Wilt disease development, 38 management, 38–39 610 X Xenograft models, 160, 162, 164–165 effects of dietary PUFA, 167 Y Yarrowia lipolytica, 120 Index Yeast, LPCAT gene, 215–216 Z Zinc, 33, 53t, 252, 503 Zinc sulphate (ZnSO4), 33, 330 Zinc sulphide, 326 ... Kanchana 37 Role of Omega- 3 Fatty Acids in Cardiovascular Disorders 5 13 Soumia Peter and Jubbin Jagan Jacob 38 Beneficial Effect of Long-Chain Omega- 3 Fatty Acids in Psoriasis 531 ... desaturases have higher affinity to omega- 3 than omega- 6 fatty acids Therefore, even at five times less level of omega- 3 fatty PUFA’s can be equally converted Omega- 3 fatty acids are one of the most sought... incorporating omega- 3 fatty acid in milk and its utility for human health v vi The major problem today is the severe imbalance of the two essential fatty acids namely omega- 3 and omega- 6 fatty acids Omega- 3