Evolutionary aspects of diet, the omega-6/omega-3 ratio and genetic variation: nutritional implications for chronic diseases

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Abstract

Anthropological and epidemiological studies and studies at the molecular level indicate 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 to 16.7/1. A high omega-6/omega-3 ratio, as is found in today's Western diets, promotes the pathogenesis of many diseases, including cardiovascular disease, cancer, osteoporosis, and inflammatory and autoimmune diseases, whereas increased levels of omega-3 polyunsaturated fatty acids (PUFA) (a lower omega-6/omega-3 ratio), exert suppressive effects. Increased dietary intake of linoleic acid (LA) leads to oxidation of low-density lipoprotein (LDL), platelet aggregation, and interferes with the incorporation of EFA in cell membrane phospholipids. Both omega-6 and omega-3 fatty acids influence gene expression. Omega-3 fatty acids have anti-inflammatory effects, suppress interleukin 1β (IL-1β), tumor necrosis factor-α (TNFα) and interleukin-6 (IL-6), whereas omega-6 fatty acids do not. Because inflammation is at the base of many chronic diseases, 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). Carotid intima media thickness (IMT) taken as a marker of the atherosclerotic burden is significantly increased, by 80%, in the variant group compared to carriers with the common allele, suggesting increased 5-LO promoter activity associated with the (variant) allele. Dietary arachidonic acid (AA) and LA increase the risk for cardiovascular disease in those with the variants, whereas dietary intake of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) decrease the risk. A lower ratio of omega-6/omega-3 fatty acids is needed for the prevention and management of chronic diseases. Because of genetic variation, the optimal omega-6/omega-3 fatty acid ratio would vary with the disease under consideration.

Introduction

A number of anthropological, nutritional and genetic studies indicate that human's overall diet, including energy intake and energy expenditure, has changed over the past 10,000 years with major changes occurring during the past 150 years in the type and amount of fat and in vitamins C and E intake [1], [2], [3], [4], [5], [6], [7], [8].

Food technology and agribusiness provided the economic stimulus that dominated the changes in the food supply. From per capita quantities of foods available for consumption in the US national food supply in 1985, the amount of eicosapentaenoic acid (EPA) is reported to be about 50 mg per capita per day and the amount of docosahexaenoic acid (DHA) is 80 mg per capita per day. The two main sources are fish and poultry [9]. It has been estimated that the present Western diet is “deficient” in omega-3 fatty acids with a ratio of omega-6 to omega-3 of 15/1 to 16.7/1, instead of 1/1 as is the case with wild animals and presumably human beings [1], [2], [3], [4], [5], [6], [7]. An absolute and relative change of omega-6/omega-3 in the food supply of Western societies has occurred over the last 100 years. A balance existed between omega-6 and omega-3 for millions of years during the long evolutionary history of the genus Homo, and genetic changes occurred partly in response to these dietary influences. During evolution, omega-3 fatty acids were found in all foods consumed: meat, wild plants, eggs, fish, nuts and berries. Recent studies by Cordain [8] on wild animals confirm the original observations of Crawford [10]. However, rapid dietary changes over short periods of time as have occurred over the past 100–150 years is a totally new phenomenon in human evolution [11], [12], [13], [14], [15].

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 [1], [2], [3], [4], [5], [6], [7]. 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.

Section snippets

Biological effects and the omega-6/omega-3 ratio

Mammalian cells cannot convert omega-6 to omega-3 fatty acids because they lack the converting enzyme, omega-3 desaturase. Linoleic acid (LA) and α-linolenic acid (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

Omega-3 fatty acids and gene expression

Previous studies have shown that fatty acids released from membrane phospholipids by cellular phospholipases, or made available to the cell from the diet or other aspects of the extracellular environment, are important cell signaling molecules. They can act as second messengers or substitute for the classical second messengers of the inositide phospholipid and the cyclic AMP signal transduction pathways. They can also act as modulator molecules mediating responses of the cell to extracellular

Diet–gene interactions: genetic variation and omega-6 and omega-3 fatty acid intake in the risk for cardiovascular disease

As discussed above, leukotrienes are inflammatory mediators generated from AA by the enzyme 5-lipoxygenase (5-LO). Since atherosclerosis involves arterial inflammation, Dwyer et al. hypothesized that a polymorphism in the 5-LO gene promoter could relate to atherosclerosis in humans, and that this effect could interact with the dietary intake of competing 5-LO substrates [46]. The study consisted of 470 healthy middle-aged women and men from the Los Angeles Atherosclerosis study, randomly

Conclusion

  • Evidence from studies on the evolutionary aspects of diet, modern day hunter-gatherers, and traditional diets indicate that 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.

  • Many of the chronic conditions—cardiovascular disease, diabetes, cancer, obesity, autoimmune diseases, rheumatoid arthritis, asthma and depression—are associated with increased production of thromboxane A2 (TXA2), leukotriene B4 (LTB

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