Research
Publications by Dr. Artemis Simopoulos
Exp Biol Med (Maywood). 2008 Jun;233(6):674-88. doi: 10.3181/0711-MR-311. Epub 2008 Apr 11.
The importance of the omega-6/omega-3 fatty acid ratio in cardiovascular disease and other chronic diseases
Simopoulos, A. P.
The Center for Genetics, Nutrition and Health, 2001 S Street, NW, Suite 530, Washington, DC 20009, USA. cgnh@bellatlantic.net
Abstract
Several sources of information suggest that human beings evolved on a diet with a ratio of omega-6 to omega-3 essential fatty acids (EFA) of approximately 1 whereas in Western diets the ratio is 15/1-16.7/1. Western diets are deficient in omega-3 fatty acids, and have excessive amounts of omega-6 fatty acids compared with the diet on which human beings evolved and their genetic patterns were established. Excessive amounts of omega-6 polyunsaturated fatty acids (PUFA) and a very high omega-6/omega-3 ratio, as is found in today's Western diets, promote the pathogenesis of many diseases, including cardiovascular disease, cancer, and inflammatory and autoimmune diseases, whereas increased levels of omega-3 PUFA (a lower omega-6/omega-3 ratio), exert suppressive effects. In the secondary prevention of cardiovascular disease, a ratio of 4/1 was associated with a 70% decrease in total mortality. A ratio of 2.5/1 reduced rectal cell proliferation in patients with colorectal cancer, whereas a ratio of 4/1 with the same amount of omega-3 PUFA had no effect. The lower omega-6/omega-3 ratio in women with breast cancer was associated with decreased risk. A ratio of 2-3/1 suppressed inflammation in patients with rheumatoid arthritis, and a ratio of 5/1 had a beneficial effect on patients with asthma, whereas a ratio of 10/1 had adverse consequences. These studies indicate that the optimal ratio may vary with the disease under consideration. This is consistent with the fact that chronic diseases are multigenic and multifactorial. Therefore, it is quite possible that the therapeutic dose of omega-3 fatty acids will depend on the degree of severity of disease resulting from the genetic predisposition. A lower ratio of omega-6/omega-3 fatty acids is more desirable in reducing the risk of many of the chronic diseases of high prevalence in Western societies, as well as in the developing countries.
Prostaglandins Leukot Essent Fatty Acids. 1999 May-Jun;60(5-6):421-9.
Evolutionary aspects of omega-3 fatty acids in the food supply.
Simopoulos, A. P.
The Center for Genetics, Nutrition and Health, Washington, DC 20009, USA. Lcgnh@bellatlantic.net
Abstract
Information from archaeological findings and studies from modern day hunter-gatherers suggest that the Paleolithic diet is the diet we evolved on and for which our genetic profile was programmed. The Paleolithic diet is characterized by lower fat and lower saturated fat intake than Western diets; a balanced intake of omega-6 and omega-3 essential fatty acids; small amounts of trans fatty acids, contributing less than 2% of dietary energy; more green leafy vegetables and fruits providing higher levels of vitamin E and vitamin C and other antioxidants than today's diet and higher amounts of calcium and potassium but lower sodium intake. Studies on the traditional Greek diet (diet of Crete) indicate an omega-6/omega-3 ratio of about 1/1. The importance of a balanced ratio of omega-6:omega-3, a lower saturated fatty acid and lower total fat intake (30-33%), along with higher intakes of fruits and vegetables leading to increases in vitamin E and C, was tested in the Lyon Heart study. The Lyon study, based on a modified diet of Crete, confirmed the importance of omega-3 fatty acids from marine and terrestrial sources, and vitamin E and vitamin C, in the secondary prevention of coronary heart disease, and cancer mortality.
Asia Pac J Clin Nutr. 2008;17 Suppl 1:131-4.
The omega-6/omega-3 fatty acid ratio, genetic variation, and cardiovascular disease.
Simopoulos, A. P.
The Center for Genetics, Nutrition and Health, 2001 S Street, NW, Suite 530, Washington, DC 20009 USA. cgnh@bellatlantic.net
Abstract
A high omega-6/omega-3 ratio, as is found in today's Western diets, promotes the pathogenesis of many chronic diseases, including cardiovascular disease. Increased dietary intake of linoleic acid (LA) leads to oxidation of low-density lipoprotein (LDL), platelet aggregation, and interferes with the incorporation of essential fatty acids (EFA) in cell membrane phopholipids. Both omega-6 and omega-3 fatty acids influence gene expression. Omega-3 fatty acids have strong anti-inflammatory effects, suppress interleukin 1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF alpha) and interleukin-6 (IL-6), whereas omega-6 fatty acids tend to be pro-inflammatory. Because inflammation is at the base of many chronic diseases, including coronary heart disease, dietary intake of omega-3 fatty acids plays an important role in the manifestation of disease, particularly in persons with genetic variation, as for example in individuals with genetic variants at the 5-lipoxygenase (5-LO). Increased dietary arachidonic acid (AA) significantly enhances the apparent atherogenic effect of genotype, whereas increased dietary intake of omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) blunts this effect. The diet-gene interaction further suggests that dietary omega-6 fatty acids promote, whereas marine omega-3 fatty acids EPA and DHA inhibit leukotriene-mediated inflammation that leads to atherosclerosis in this subpopulation.
Am J Clin Nutr. 1999; 70: 560s-569s
Essential fatty acids in health and chronic disease
Simopoulos, A. P.
The Center for Genetics, Nutrition and Health, 2001 S Street, NW, Suite 530, Washington, DC 20009 USA. cgnh@bellatlantic.net
Abstract
Human beings evolved consuming a diet that contained about equal amounts of n-3 and n-6 essential fatty acids. Over the past 100–150 y there has been an enormous increase in the consumption of n-6 fatty acids due to the increased intake of vegetable oils from corn, sunflower seeds, safflower seeds, cottonseed, and soybeans. Today, in Western diets, the ratio of n-6 to n-3 fatty acids ranges from <20–30:1 instead of the traditional range of 1–2:1. Studies indicate that a high intake of n-6 fatty acids shifts the physiologic state to one that is prothrombotic and proaggregatory, characterized by increases in blood viscosity, vasospasm, and vasoconstriction and decreases in bleeding time. n-3 fatty acids, however, have antiinflammatory, antithrombotic, antiarrhythmic, hypolipidemic, and vasodilatory properties. These beneficial effects of n-3 fatty acids have been shown in the secondary prevention of coronary heart disease, hypertension, type 2 diabetes, and, in some patients with renal disease, rheumatoid arthritis, ulcerative colitis, Crohn disease, and chronic obstructive pulmonary disease. Most of the studies were carried out with fish oils [eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)]. However, a-linolenic acid , found in green leafy vegetables, flaxseed, rapeseed, and walnuts, desaturates and elongates in the human body to EPA and DHA and by itself may have beneficial effects in health and in the control of chronic diseases.
Poult Sci. 2000 Jul;79(7):961-70.
Human requirement for N-3 polyunsaturated fatty acids.
Simopoulos, A. P.
The Center for Genetics Nutrition and Health, Washington, DC 20009, USA. cgnh@bellatlantic.net
Abstract
The diet of our ancestors was less dense in calories, being higher in fiber, rich in fruits, vegetables, lean meat, and fish. As a result, the diet was lower in total fat and saturated fat, but contained equal amounts of n-6 and n-3 essential fatty acids. Linoleic acid (LA) is the major n-6 fatty acid, and alpha-linolenic acid (ALA) is the major n-3 fatty acid. In the body, LA is metabolized to arachidonic acid (AA), and ALA is metabolized to eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). The ratio of n-6 to n-3 essential fatty acids was 1 to 2:1 with higher levels of the longer-chain polyunsaturated fatty acids (PUFA), such as EPA, DHA, and AA, than today's diet. Today this ratio is about 10 to 1:20 to 25 to 1, indicating that Western diets are deficient in n-3 fatty acids compared with the diet on which humans evolved and their genetic patterns were established. The n-3 and n-6 EPA are not interconvertible in the human body and are important components of practically all cell membranes. The N-6 and n-3 fatty acids influence eicosanoid metabolism, gene expression, and intercellular cell-to-cell communication. The PUFA composition of cell membranes is, to a great extent, dependent on dietary intake. Therefore, appropriate amounts of dietary n-6 and n-3 fatty acids need to be considered in making dietary recommendations. These two classes of PUFA should be distinguished because they are metabolically and functionally distinct and have opposing physiological functions; their balance is important for homeostasis and normal development. Studies with nonhuman primates and human newborns indicate that DHA is essential for the normal functional development of the retina and brain, particularly in premature infants. A balanced n-6/n-3 ratio in the diet is essential for normal growth and development and should lead to decreases in cardiovascular disease and other chronic diseases and improve mental health. Although a recommended dietary allowance for essential fatty acids does not exist, an adequate intake (AI) has been estimated for n-6 and n-3 essential fatty acids by an international scientific working group. For Western societies, it will be necessary to decrease the intake of n-6 fatty acids and increase the intake of n-3 fatty acids. The food industry is already taking steps to return n-3 essential fatty acids to the food supply by enriching various foods with n-3 fatty acids. To obtain the recommended AI, it will be necessary to consider the issues involved in enriching the food supply with n-3 PUFA in terms of dosage, safety, and sources of n-3 fatty acids.
Mol Neurobiol. 2011 Oct;44(2):203-15.
Evolutionary aspects of diet: the omega-6/omega-3 ratio and the brain.
Simopoulos, A. P.
The Center for Genetics Nutrition and Health, Washington, DC 20009, USA. cgnh@bellatlantic.net
Abstract
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.
