Evolutionary Aspects of Diet: The Omega-6/Omega-3 Ratio and the Brain

Several sources of information suggest that human beings evolved on a diet that had a ratio of omega-6 to omega-3 fatty acids (FA) of about 1/1; whereas today, Western diets have a ratio of 10/1 to 20–25/1, indicating that Western diets are deficient in omega-3 FA compared with the diet on which humans evolved and their genetic patterns were established. Omega-6 and omega-3 FA are not interconvertible in the human body and are important components of practically all cell membranes. Studies with nonhuman primates and human newborns indicate that docosahexaenoic acid (DHA) is essential for the normal functional development of the brain and retina, particularly in premature infants. DHA accounts for 40% of the membrane phospholipid FA in the brain. Both eicosapentaenoic acid (EPA) and DHA have an effect on membrane receptor function and even neurotransmitter generation and metabolism. There is growing evidence that EPA and DHA could play a role in hostility and violence in addition to the beneficial effects in substance abuse disorders and alcoholism. The balance of omega-6 and omega-3 FA is important for homeostasis and normal development throughout the life cycle.

[1]  D. Mischoulon,et al.  Docosahexanoic acid and omega-3 fatty acids in depression. , 2000, The Psychiatric clinics of North America.

[2]  A. Simopoulos.  Evolutionary Aspects of Diet , 2001 .

[3]  Charles N. Serhan,et al.  Resolving inflammation: dual anti-inflammatory and pro-resolution lipid mediators , 2008, Nature Reviews Immunology.

[4]  R. Ryback.  Bioelectrical modulators and the cell membrane in psychiatric medicine. , 2001, Psychopharmacology bulletin.

[5]  Thomas Illig,et al.  FADS genotypes and desaturase activity estimated by the ratio of arachidonic acid to linoleic acid are associated with inflammation and coronary artery disease. , 2008, The American journal of clinical nutrition.

[6]  E. Berry,et al.  Effects of an Indo-Mediterranean diet on the omega-6/omega-3 ratio in patients at high risk of coronary artery disease: the Indian paradox. , 2003, World review of nutrition and dietetics.

[7]  S. Innis.  Essential fatty acids in growth and development. , 1991, Progress in lipid research.

[8]  A. Simopoulos.  New products from the agri-food industry: The return of n-3 fatty acids into the food supply , 2007, Lipids.

[9]  H. Saito,et al.  Dietary Docosahexaenoic Acid Increases Cerebral Acetylcholine Levels and Improves Passive Avoidance Performance in Stroke-Prone Spontaneously Hypertensive Rats , 1997, Pharmacology Biochemistry and Behavior.

[10]  H. Okuyama,et al.  Synaptic Vesicle Ultrastructural Changes in the Rat Hippocampus Induced by a Combination of α‐Linolenate Deficiency and a Learning Task , 1997, Journal of neurochemistry.

[11]  A. Simopoulos.  Genetic variation and dietary response: Nutrigenetics/nutrigenomics , 2002 .

[12]  S. Colagiuri,et al.  Evolutionary aspects of diet and insulin resistance. , 1999, World review of nutrition and dietetics.

[13]  Psychology. The theory? Diet causes violence. The lab? Prison. , 2009, Science.

[14]  T. Utsumi,et al.  Mechanisms of enhanced apoptosis in HL-60 cells by UV-irradiated n-3 and n-6 polyunsaturated fatty acids. , 2003, Free radical biology & medicine.

[15]  P. Elwood,et al.  EFFECTS OF CHANGES IN FAT, FISH, AND FIBRE INTAKES ON DEATH AND MYOCARDIAL REINFARCTION: DIET AND REINFARCTION TRIAL (DART) , 1989, The Lancet.

[16]  A. Simopoulos.  The role of fatty acids in gene expression: health implications. , 1996, Annals of nutrition & metabolism.

[17]  J. Kang.  Balance of omega-6/omega-3 essential fatty acids is important for health. The evidence from gene transfer studies. , 2005, World review of nutrition and dietetics.

[18]  Artemis P. Simopoulos,et al.  Nutrigenetics and nutrigenomics , 2004 .

[19]  K. Ehrlich,et al.  Role of Cyclooxygenase-1 and -2, Phospholipase C, and Protein Kinase C in Prostaglandin-Mediated Gastroprotection , 2003, Journal of Pharmacology and Experimental Therapeutics.

[20]  N. Bazan,et al.  Changing Fatty Acid Content of Growth Cone Lipids Prior to Synaptogenesis , 1992, Journal of neurochemistry.

[21]  T. Sanders.  Polyunsaturated fatty acids in the food chain in Europe. , 2000, The American journal of clinical nutrition.

[22]  D Kromhout,et al.  Dietary intake of fatty acids and fish in relation to cognitive performance at middle age , 2004, Neurology.

[23]  F. Corradeschi,et al.  Cognitive and physiological effects of Omega‐3 polyunsaturated fatty acid supplementation in healthy subjects , 2005, European journal of clinical investigation.

[24]  A. Simopoulos,et al.  Purslane: a terrestrial source of omega-3 fatty acids. , 1986, The New England journal of medicine.

[25]  Mary A Whooley,et al.  Association of marine omega-3 fatty acid levels with telomeric aging in patients with coronary heart disease. , 2010, JAMA.

[26]  H. Harizi,et al.  The impact of eicosanoids on the crosstalk between innate and adaptive immunity: the key roles of dendritic cells. , 2005, Tissue antigens.

[27]  R. Mensink,et al.  Trans fatty acids in human nutrition. , 1998 .

[28]  A. Simopoulos,et al.  Obesity : new directions in assessment and management , 1995 .

[29]  M. Crawford.  FATTY-ACID RATIOS IN FREE-LIVING AND DOMESTIC ANIMALS: Possible Implications for Atheroma , 1968 .

[30]  A. Caspi,et al.  Moderation of breastfeeding effects on the IQ by genetic variation in fatty acid metabolism , 2007, Proceedings of the National Academy of Sciences.

[31]  J. Schmidt,et al.  Arachidonic acid as a retrograde signal controlling growth and dynamics of retinotectal arbors , 2008, Developmental neurobiology.

[32]  A. Schene,et al.  Time after time: biological factors in the course of recurrent depression , 2013 .

[33]  Yuji Watanabe,et al.  [Trans fatty acids]. , 2006, Shokuhin eiseigaku zasshi. Journal of the Food Hygienic Society of Japan.

[34]  C. Stokes,et al.  Omega-3 Fatty Acids in the Treatment of Psychiatric Disorders , 2012, Drugs.

[35]  David T. Stark,et al.  Omega-3 fatty acid docosahexaenoic acid is the precursor of neuroprotectin D1 in the nervous system. , 2009, World review of nutrition and dietetics.

[36]  A. Simopoulos.  Omega-3 fatty acids and antioxidants in edible wild plants. , 2004, Biological research.

[37]  T. Starzl,et al.  Generation of cloned transgenic pigs rich in omega-3 fatty acids , 2006, Nature Biotechnology.

[38]  M. Sugano,et al.  Polyunsaturated fatty acids in the food chain in Japan. , 2000, The American journal of clinical nutrition.

[39]  K. O'dea,et al.  The analysis of polyunsaturated fatty acids in meat by capillary gas‐liquid chromatography , 1982 .

[40]  M. Lavialle,et al.  Polyunsaturated fatty acids in the central nervous system: evolution of concepts and nutritional implications throughout life. , 2004, Reproduction, nutrition, development.

[41]  H. Meltzer,et al.  Fatty acid composition in major depression: decreased omega 3 fractions in cholesteryl esters and increased C20: 4 omega 6/C20:5 omega 3 ratio in cholesteryl esters and phospholipids. , 1996, Journal of affective disorders.

[42]  H. Meltzer,et al.  Lower serum high‐density lipoprotein cholesterol (HDL‐C) in major depression and in depressed men with serious suicidal attempts: relationship with immune‐inflammatory markers , 1997, Acta psychiatrica Scandinavica.

[43]  A. Simopoulos,et al.  The Omega Diet: The Lifesaving Nutritional Program Based on the Diet of the Island of Crete , 1997 .

[44]  V. Ziboh,et al.  Effects of dietary supplementation with eicosapentaenoic acid or gamma-linolenic acid on neutrophil phospholipid fatty acid composition and activation responses , 1990, Inflammation.

[45]  P. Weber,et al.  Cardiovascular effects of n-3 fatty acids. , 1988, The New England journal of medicine.

[46]  J. Kang.  Fat-1 transgenic mice: a new model for omega-3 research. , 2007, Prostaglandins, leukotrienes, and essential fatty acids.

[47]  D. Garvey,et al.  Eicosanoids in inflammation: biosynthesis, pharmacology, and therapeutic frontiers. , 2007, Current topics in medicinal chemistry.

[48]  N. Raper,et al.  Omega-3 fatty acid content of the US food supply. , 1992, Journal of the American College of Nutrition.

[49]  H. Sewell,et al.  Cytochrome P-450 immunolocalization in human liver. , 1986, Lancet.

[50]  A. Hofman,et al.  Dietary fat intake and the risk of incident dementia in the Rotterdam study , 1997, Annals of neurology.

[51]  A. Simopoulos,et al.  n-3 fatty acids in eggs from range-fed Greek chickens. , 1989, The New England journal of medicine.

[52]  A. Simopoulos.  Omega-6/omega-3 essential fatty acids: biological effects. , 2009, World review of nutrition and dietetics.

[53]  S. Kallithraka,et al.  Nutritional composition of selected wild plants in the diet of Crete. , 2003, World review of nutrition and dietetics.

[54]  Albert J. Dijkstra,et al.  Trans fatty acids , 2008 .

[55]  A. Simopoulos,et al.  Egg yolk as a source of long-chain polyunsaturated fatty acids in infant feeding. , 1992, The American journal of clinical nutrition.

[56]  C. Godson,et al.  Lipoxins: endogenous regulators of inflammation. , 2004, American journal of physiology. Renal physiology.

[57]  P. Weber,et al.  A new era for science in nutrition. , 1987, The American journal of clinical nutrition.

[58]  Zhihong Chen,et al.  Adenoviral gene transfer of Caenorhabditis elegans n−3 fatty acid desaturase optimizes fatty acid composition in mammalian cells , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[59]  J. Hunter.  Omega-3 Fatty Acids from Vegetable Oils , 1989 .

[60]  A. Leaf.  Cardiovascular effects of fish oils. Beyond the platelet. , 1990, Circulation.

[61]  M. Linnoila,et al.  A replication study of violent and nonviolent subjects: cerebrospinal fluid metabolites of serotonin and dopamine are predicted by plasma essential fatty acids , 1998, Biological Psychiatry.

[62]  A. Simopoulos.  Omega-3 Fatty Acids in Inflammation and Autoimmune Diseases , 2002, Journal of the American College of Nutrition.

[63]  G. Burr,et al.  ON THE NATURE AND RÔLE OF THE FATTY ACIDS ESSENTIAL IN NUTRITION , 1930 .

[64]  G. Burdge.  Alpha-linolenic acid metabolism in men and women: nutritional and biological implications. , 2004, Current opinion in clinical nutrition and metabolic care.

[65]  S. Eaton,et al.  Dietary intake of long-chain polyunsaturated fatty acids during the paleolithic. , 1998, World review of nutrition and dietetics.

[66]  A. Simopoulos,et al.  The Importance of the Omega-6/Omega-3 Fatty Acid Ratio in Cardiovascular Disease and Other Chronic Diseases , 2008, Experimental biology and medicine.

[67]  Manabu T. Nakamura,et al.  Cloning, Expression, and Fatty Acid Regulation of the Human Δ-5 Desaturase* , 1999, The Journal of Biological Chemistry.

[68]  J. Kang,et al.  Transgenic mice: Fat-1 mice convert n-6 to n-3 fatty acids , 2004, Nature.

[69]  Manabu T. Nakamura,et al.  Cloning, Expression, and Nutritional Regulation of the Mammalian Δ-6 Desaturase* , 1999, The Journal of Biological Chemistry.

[70]  N. Bazan,et al.  Omega-3 fatty acids, the brain and retina. , 2008 .

[71]  P. Wainwright.  Dietary essential fatty acids and brain function: a developmental perspective on mechanisms , 2002, Proceedings of the Nutrition Society.

[72]  M. Haag,et al.  Essential Fatty Acids and the Brain , 2003, Canadian journal of psychiatry. Revue canadienne de psychiatrie.

[73]  A. Simopoulos.  Omega-3 fatty acids in health and disease and in growth and development. , 1991, The American journal of clinical nutrition.

[74]  F. Sacks,et al.  Trans-fatty-acid content of common foods. , 1993, The New England journal of medicine.

[75]  R. DuBois,et al.  Fishing for prostanoids: deciphering the developmental functions of cyclooxygenase-derived prostaglandins. , 2006, Developmental biology.

[76]  M. Freeman.  Omega-3 Fatty Acids in Psychiatry: A Review , 2000, Annals of clinical psychiatry : official journal of the American Academy of Clinical Psychiatrists.

[77]  T. Illig,et al.  Genetically determined variation in polyunsaturated fatty acid metabolism may result in different dietary requirements. , 2008, Nestle Nutrition workshop series. Paediatric programme.

[78]  J. Lönnqvist,et al.  Is low dietary intake of omega-3 fatty acids associated with depression? , 2004, The American journal of psychiatry.

[79]  H. P. Cho,et al.  Cloning, expression, and fatty acid regulation of the human delta-5 desaturase. , 1999, The Journal of biological chemistry.

[80]  S. Lemeshow,et al.  Depressive Symptoms, omega-6:omega-3 Fatty Acids, and Inflammation in Older Adults , 2007, Psychosomatic medicine.

[81]  S. Rapoport,et al.  Evidence for the Involvement of Docosahexaenoic Acid in Cholinergic Stimulated Signal Transduction at the Synapse , 1997, Neurochemical Research.

[82]  H. Meltzer,et al.  Fatty acid composition in major depression: decreased ω3 fractions in cholesteryl esters and increased C20:4ω6C20:5ω3 ratio in cholesteryl esters and phospholipids , 1996 .

[83]  R. Chandra.  Plants in human health and nutrition policy , 2003 .

[84]  Robert A. Lewis,et al.  CHAPTER 12 – EFFECTS OF OMEGA–3 FATTY ACIDS ON THE GENERATION OF PRODUCTS OF THE 5-LIPOXYGENASE PATHWAY1 , 1986 .

[85]  A. Simopoulos,et al.  Common purslane: a source of omega-3 fatty acids and antioxidants. , 1992, Journal of the American College of Nutrition.

[86]  M. Crawford,et al.  Linoleic acid and linolenic acid elongation products in muscle tissue of Sncerus caffer and other ruminant species. , 1969, The Biochemical journal.

[87]  T. Takeuchi,et al.  Influence of a dietary n-3 fatty acid deficiency on the cerebral catecholamine contents, EEG and learning ability in rat , 2002, Behavioural Brain Research.

[88]  P. Weber,et al.  CHAPTER 3 – DIETARY OMEGA–3 POLYUNSATURATED FATTY ACIDS AND EICOSANOID FORMATION IN MAN , 1986 .

[89]  David T George,et al.  Essential fatty acids predict metabolites of serotonin and dopamine in cerebrospinal fluid among healthy control subjects, and early- and late-onset alcoholics , 1998, Biological Psychiatry.

[90]  D. Horrobin,et al.  Depletion of Omega-3 Fatty Acid Levels in Red Blood Cell Membranes of Depressive Patients , 1998, Biological Psychiatry.

[91]  M. Fava,et al.  DOCOSAHEXANOIC ACID AND ω-3 FATTY ACIDS IN DEPRESSION , 2000 .

[92]  D Commenges,et al.  Cognitive process in preclinical phase of dementia. , 1998, Brain : a journal of neurology.

[93]  K. Sugioka,et al.  Chronic administration of docosahexaenoic acid improves reference memory-related learning ability in young rats , 1999, Neuroscience.

[94]  P. Nestel,et al.  Genetic variation and dietary response. , 1997 .

[95]  M. Konner,et al.  Stone Agers in the Fast Lane: Chronic Degenerative Diseases in Evolutionary Perspective , 1988 .

[96]  M. Branchey,et al.  Long-chain n-3 polyunsaturated fatty acids decrease feelings of anger in substance abusers , 2008, Psychiatry Research.

[97]  A. Stoll,et al.  Omega 3 Fatty Acids in Bipolar Disorder A Preliminary Double-blind, Placebo-Controlled Trial , 1999 .

[98]  A. Lusis,et al.  Nutrigenetic association of the 5-lipoxygenase gene with myocardial infarction. , 2008, The American journal of clinical nutrition.

[99]  J. Kang.  The importance of omega-6/omega-3 fatty acid ratio in cell function. The gene transfer of omega-3 fatty acid desaturase. , 2003, World review of nutrition and dietetics.

[100]  J. Witte,et al.  Dietary Omega-3 Fatty Acids, Cyclooxygenase-2 Genetic Variation, and Aggressive Prostate Cancer Risk , 2009, Clinical Cancer Research.

[101]  A. Simopoulos.  Overview of Evolutionary Aspects of ω3 Fatty Acids in the Diet , 1998 .

[102]  L. Palmer,et al.  Common genetic variants of the FADS1 FADS2 gene cluster and their reconstructed haplotypes are associated with the fatty acid composition in phospholipids. , 2006, Human molecular genetics.

[103]  J. Hibbeln,et al.  Dietary polyunsaturated fatty acids and depression: when cholesterol does not satisfy. , 1995, The American journal of clinical nutrition.

[104]  Yan Liu,et al.  Associations between diet, lifestyle factors, and telomere length in women. , 2010, The American journal of clinical nutrition.

[105]  Zhihong Chen,et al.  Effects of adenoviral gene transfer of C. elegans n-3 fatty acid desaturase on the lipid profile and growth of human breast cancer cells. , 2002, Anticancer research.

[106]  K. Vaddadi,et al.  A double-blind trial of essential fatty acid supplementation in patients with tardive dyskinesia , 1989, Psychiatry Research.

[107]  C. Schacky.  Prophylaxis of atherosclerosis with marine omega-3 fatty acids. A comprehensive strategy. , 1987 .

[108]  B. Puri,et al.  Eicosapentaenoic acid‐rich essential fatty acid supplementation in chronic fatigue syndrome associated with symptom remission and structural brain changes , 2004, International journal of clinical practice.

[109]  A. Heffernan.  THE FATTY ACID COMPOSITION OF HUMAN ADIPOSE TISSUE. , 1963, Clinical science.

[110]  C. Runyan,et al.  Age-related changes of n-3 and n-6 polyunsaturated fatty acids in the anterior cingulate cortex of individuals with major depressive disorder. , 2010, Prostaglandins, leukotrienes, and essential fatty acids.

[111]  A. Simopoulos,et al.  Purslane in human nutrition and its potential for world agriculture. , 1995, World review of nutrition and dietetics.

[112]  S. Innis,et al.  Genetic variants of the FADS1 FADS2 gene cluster are associated with altered (n-6) and (n-3) essential fatty acids in plasma and erythrocyte phospholipids in women during pregnancy and in breast milk during lactation. , 2008, The Journal of nutrition.

[113]  M. Katan,et al.  Lower ratio of n-3 to n-6 fatty acids in cultured than in wild fish. , 1990, The American journal of clinical nutrition.

[114]  A. Simopoulos.  Omega‐3 fatty acids in wild plants, nuts and seeds , 2002 .

[115]  A. Mendeloff.  Health Effects of ω3 Polyunsaturated Fatty Acids in Seafoods , 1991 .

[116]  A. Simopoulos.  Evolutionary aspects of omega-3 fatty acids in the food supply. , 1999, Prostaglandins, leukotrienes, and essential fatty acids.

[117]  A. Stoll,et al.  Omega-3 fatty acids in major depression. , 2001, World review of nutrition and dietetics.