Eicosanoids and Ischemic Heart Disease

Dr. William Lands, one of the pioneers of the eicosanoid field, compiled this graph. It may be the single most important clue we have about the relationship between diet and ischemic heart disease (heart attacks).

To explain it fully, we have to take a few steps back. Dietary polyunsaturated fatty acids (PUFA) are primarily omega-6 and omega-3. This is a chemical designation that refers to the position of a double bond along the fatty acid's carbon chain. Omega-6 fats are found abundantly in industrial vegetable oils (corn, soybean, sunflower, cottonseed, etc.) and certain nuts, and in lesser amounts in meats, dairy and grains. Omega-3 fats are found abundantly in seafood and a few seeds such as flax and walnuts, and in smaller amounts in meats, green vegetables and dairy.

The body uses a multi-step process to convert omega-3 and omega-6 fats into eicosanoids, which are a diverse and potent class of signaling molecules. The first step is to convert PUFA into highly unsaturated fatty acids, or HUFA. These include arachidonic acid (AA), an omega-6 HUFA, eicosapentaenoic acid (EPA), an omega-3 HUFA, and several others in the 20- to 22-carbon length range.

HUFA are stored in cell membranes and they are the direct precursors of eicosanoids. When the cell needs eicosanoids, it liberates HUFA from the membrane and converts it. The proportion of omega-6 to omega-3 HUFA in the membrane is proportional to the long-term proportion of omega-6 and omega-3 in the diet. Enzymes do not discriminate between omega-6 and omega-3 HUFA when they create eicosanoids. Therefore, the proportion of omega-6- to omega-3-derived eicosanoids is proportional to dietary intake.

Omega-6 eicosanoids are potently inflammatory and thrombotic (promote blood clotting, such as thromboxane A2), while omega-3 eicosanoids are less inflammatory, less thrombotic and participate in long-term repair processes.

Many of the studies that have looked at the relationship between HUFA and heart attacks used blood plasma (serum lipids). Dr. Lands has pointed out that plasma HUFA do not accurately reflect dietary omega-6/3 balance, and they don't correlate well with heart attack risk. What does correlate strikingly well with both dietary intake and heart attack risk is the proportion of omega-6 HUFA in tissue, which reflects the amount contained in cell membranes. That's what we're looking at in the graph above: the proportion of omega-6 HUFA in the total tissue HUFA pool, vs. coronary heart disease death rate.

You can see that the correlation is striking, both between populations and within them. Greenland Inuit have the lowest proportion of omega-6 HUFA, due to a low intake of omega-6 and an exceptionally high intake of seafood. They also have an extraordinarily low risk of heart attack death. The red dots are from the Multiple Risk Factor Intervention Trial (MRFIT), which I'll be covering in a bit more detail in a later post. They're important because they confirm that the trend holds true within a population, and not just between populations.

In the next post, I'll be delving into this concept in more detail, and explaining why it's not just the ratio that matters, but also the total intake of omega-6. I'll also be providing more evidence to support the theory.