Dossier: Polyunsaturated fatty acids in biology and diseases
The importance of the ratio of omega-6/omega-3 essential fatty acids

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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 ∼ 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 low 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, that are being exported to the rest of the world.

Introduction

The interaction of genetics and environment, nature, and nurture is the foundation for all health and disease. In the last two decades, using the techniques of molecular biology, it has been shown that genetic factors determine susceptibility to disease and environmental factors determine which genetically susceptible individuals will be affected 〚81〛, 〚82〛, 〚84〛, 〚87〛. Nutrition is an environmental factor of major importance. Whereas major changes have taken place in our diet over the past 10,000 years since the beginning of the Agricultural Revolution, our genes have not changed. The spontaneous mutation rate for nuclear DNA is estimated at 0.5% per million years. Therefore, over the past 10,000 years, there has been time for very little change in our genes, perhaps 0.005%. In fact, our genes today are very similar to the genes of our ancestors during the Paleolithic period 40,000 years ago, at which time our genetic profile was established 〚21〛. Genetically speaking, humans today live in a nutritional environment that differs from that for which our genetic constitution was selected. Studies on the evolutionary aspects of diet indicate that major changes have taken place in our diet, particularly in the type and amount of essential fatty acids (EFA) and in the antioxidant content of foods 〚21〛, 〚64〛, 〚75〛, 〚76〛, 〚77〛 (Table 1, Fig. 1). Using the tools of molecular biology and genetics, research is defining the mechanisms by which genes influence nutrient absorption, metabolism and excretion, taste perception, and degree of satiation, and the mechanisms by which nutrients influence gene expression.

Whereas evolutionary maladaptation leads to reproductive restriction (or differential fertility), the rapid changes in our diet, particularly the last 100 years, are potent promoters of chronic diseases such as atherosclerosis, essential hypertension, obesity, diabetes, and many cancers. In addition to diet, sedentary lifestyles and exposure to noxious substances interact with genetically controlled biochemical processes leading to chronic disease. This paper reviews the scientific evidence for a balanced intake of omega-6 and omega-3 EFA, focusing on the evolutionary aspects of diet, the biological and metabolic functions, and the health implications. Appendix A is a portion of the summary of the workshop on the essentiality of and recommended dietary intakes (RDIs) for Omega-6 and Omega-3 Fatty Acids, held at the National Institutes of Health (NIH) in Bethesda, Maryland, USA, April 7–9, 1999, which provides recommendations for adequate intakes (AI) of EFA for adults and infants 〚83〛.

Section snippets

Evolutionary aspects of diet with emphasis on omega-6 and omega-3 EFA

The foods that were commonly available to pre-agricultural humans (lean meat, fish, green leafy vegetables, fruits, nuts, berries and honey) were the foods that shaped modern humans’ genetic nutritional requirements. Cereal grains as a staple food are a relatively recent addition to the human diet and represent a dramatic departure from those foods to which we are genetically programmed and adapted 〚13〛, 〚67〛, 〚78〛. Cereals did not become a part of our food supply but only very recently,

Large-scale production of vegetable oils

The increased consumption of omega-6 fatty acids in the last 100 years is due to the development of technology at the turn of the century that marked the beginning of the modern vegetable oil industry, and to modern agriculture with the emphasis on grain feeds for domestic livestock (grains are rich in omega-6 fatty acids) 〚36〛. The invention of the continuous screw press, named Expeller® by V.D. Anderson, and the steam-vacuum deodorization process by D. Wesson made possible the industrial

Biological effects and metabolic functions of omega-6 and omega-3 fatty acids

Mammalian cells cannot convert omega-6 to omega-3 fatty acids because they lack the converting enzyme, omega-3 desaturase. LA and ALA and their long-chain derivatives are important components of animal and plant cell membranes. These two classes of EFA are not interconvertible, are metabolically and functionally distinct, and often have important opposing physiological functions. The balance of EFA is important for good health and normal development. When humans ingest fish or fish oil, the EPA

Clinical intervention studies and the omega-6/omega-3 EFA balance

The Lyon Heart Study was a dietary intervention study in which a modified diet of Crete (the experimental diet) was compared with the prudent diet or Step I American Heart Association Diet (the control diet) 〚19〛, 〚20〛, 〚56〛. The experimental diet provided a ratio of LA to ALA of 4/1. This ratio was achieved by substituting olive oil and canola (oil) margarine for corn oil. Since olive oil is low in LA whereas corn oil is high, 8% and 61%, respectively, the ALA incorporation into cell membranes

Conclusions

In conclusion:

  • Human beings evolved on a diet in which the ratio of omega-6/omega-3 EFA was about 1, whereas in the Western diets, the ratio is 15/1 to 16.7/1. Such evidence comes from studies on the evolutionary aspects of diet, modern day hunter-gatherers, and traditional diets. Agribusiness and modern agriculture have led to decreases in omega-3 fatty acids and increases in omega-6 fatty acids. Such practices have led to excessive amounts of omega-6 fatty acids, upsetting the balance that was

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