For Those not Scientifically Inclined

This is a simplified summary of the last two posts.

Polyunsaturated fats in the diet are mostly omega-6 or omega-3. These get converted into a diverse and influential class of signaling molecules in the body called eicosanoids. On their way to becoming eicosanoids, they get elongated. These elongated versions can be measured in tissue, and the higher the proportion of elongated omega-6 in the total pool, the higher the risk of a heart attack.

Eicosanoids are either omega-6 or omega-3-derived. Omega-6 eicosanoids, in general, are very potent and participate in inflammatory processes and blood clotting. Omega-3 eicosanoids are less potent, less inflammatory, less clot-forming, and participate in long-term repair processes. This is a simplification, as there are exceptions, but in a broad sense seems to be true.

In the modern U.S. and most other affluent nations, we eat so much omega-6 (mostly in the form of liquid industrial vegetable oils), and so little omega-3, that we create a very inflammatory and pro-clotting environment, probably contributing to a number of chronic diseases including cardiovascular disease.

There are two ways to stay in balance: reduce omega-6, and increase omega-3. In my opinion, the former is more important than the latter, but only if you can reduce omega-6 to below 4% of calories. If you're above 4%, the only way to reduce your risk is to outcompete the omega-6 with additional omega-3. Keeping omega-6 below 4% and ensuring a modest but regular intake of omega-3, such as from wild-caught fish, will probably substantially reduce the risk of cardiovascular disease and other chronic illnesses.

Bottom line: ditch industrial vegetable oils such as corn, soybean, safflower and sunflower oil, and everything that contains them. This includes most processed foods, especially mayonnaise, grocery store salad dressings, and fried foods. We aren't meant to eat those foods and they derail our metabolism on a fundamental level. I also believe it's a good idea to have a regular source of omega-3, whether it comes from seafood, small doses of cod liver oil, or small doses of flax.

Eicosanoids and Ischemic Heart Disease, Part II

Here's where it gets more complicated and more interesting. The ratio of omega-6 to omega-3 matters, but so does the total amount of each. This is a graph from a 1992 paper by Dr. Lands:

Allow me to explain. These lines are based on values predicted by a formula developed by Dr. Lands that determines the proportion of omega-6 in tissue HUFA (highly unsaturated fatty acids; includes 20- to 22-carbon omega-6 and omega-3 fats), based on dietary intake of omega-6 and omega-3 fats. This formula seems to be quite accurate, and has been validated both in rodents and humans. As a tissue's arachidonic acid content increases, its EPA and DHA content decreases proportionally.

On the Y-axis (vertical), we have the proportion of omega-6 HUFA in tissue. On the X-axis (horizontal), we have the proportion of omega-6 in the diet as a percentage of energy. Each line represents the relationship between dietary omega-6 and tissue HUFA at a given level of dietary omega-3.

Let's start at the top. The first line is the predicted proportion of omega-6 HUFA in the tissue of a person eating virtually no omega-3. You can see that it maxes out around 4% of calories from omega-6, but it can actually be fairly low if omega-6 is kept very low. The next line down is what happens when your omega-3 intake is 0.1% of calories. You can see that the proportion of omega-6 HUFA is lower than the curve above it at all omega-6 intakes, but it still maxes out around 4% omega-6. As omega-3 intake increases, the proportion of omega-6 HUFA decreases at all levels of dietary omega-6 because it has to compete with omega-3 HUFA for space in the membrane.

In the U.S., we get a small proportion of our calories from omega-3. The horizontal line marks our average tissue HUFA composition, which is about 75% omega-6. We get more than 7% of our calories from omega-6. This means our tissue contains nearly the maximum proportion of omega-6 HUFA, creating a potently inflammatory and thrombotic environment! This is a very significant fact, because it explains three major observations:

1. The U.S has a very high rate of heart attack mortality.
2. Recent diet trials in which saturated fat was replaced with omega-6-rich vegetable oils didn't cause an increase in mortality, although some of the very first trials in the 1960s did.
3. Diet trials that increased omega-3 decreased mortality.

Observation number two is used by proponents of PUFA-rich vegetable oils, and it's a fair point. If omega-6 causes heart attacks, why hasn't that shown up in controlled trials? Here's the rebuttal. First of all, it did show up in two of the first controlled trials in the 1960s: Rose et al., and the unfortunately-named Anti-Coronary Club trial. In the first, replacing animal fat with corn oil caused a 4-fold increase in heart attack deaths and total mortality. In the second, replacing animal fat with polyunsaturated vegetable oil increased heart attack death rate, and total mortality more than doubled.

But the trend didn't continue into later trials. This makes perfect sense in light of the rising omega-6 intake over the course of the 20th century in the U.S. and other affluent nations. Once our omega-6 intake crossed the 4% threshold, more omega-6 had very little effect on the proportion of omega-6 HUFA in tissue. This may be why some of the very first PUFA diet trials caused increased mortality: there was a proportion of the population that was still getting less than 4% omega-6 in its regular diet at that time. By the 1980s, virtually everyone in the U.S. (and many other affluent nations) was eating more than 4% omega-6, and thus adding more did not significantly affect tissue HUFA or heart attack mortality.

If omega-3 intake is low, whether omega-6 intake is 5% or 10% doesn't matter much for heart disease. At that point, the only way to reduce tissue HUFA without cutting back on omega-6 consumption is to outcompete it with additional omega-3. That's what the Japanese do, and it's also what happened in several clinical trials including the DART trial.

This neatly explains why the French, Japanese and Kitavans have low rates of ischemic heart disease, despite the prevalence of smoking cigarettes in all three cultures. The French diet traditionally focuses on animal fats, eschews industrial vegetable oils, and includes seafood. They eat less omega-6 and more omega-3 than Americans. They have the lowest heart attack mortality rate of any affluent Western nation. The Japanese are known for their high intake of seafood. They also eat less omega-6 than Americans. They have the lowest heart attack death rate of any affluent nation. The traditional Kitavan diet contains very little omega-6 (probably less than 1% of calories), and a significant amount of omega-3 from seafood (about one teaspoon of fish fat per day). They have an undetectable incidence of heart attack and stroke.

In sum, this suggests that an effective way to avoid a heart attack is to reduce omega-6 consumption and ensure an adequate source of omega-3. The lower the omega-6, the less the omega-3 matters. This is a nice theory, but where's the direct evidence? In the next post, I'll discuss the controlled trial that proved this concept once and for all: the Lyon diet-heart trial.

Mengobati Panu Dengan Semut Hitam

Bahan-Bahan :- Semut Hitam (yang kecil) ............................... 10 ekor- Jahe ............................... 10 grCara Pembuatan :Jahe di parut. Kemudian parutan tersebut diremas dengan sebut hitam. Campurkan kedua bahan tersebut.Aturan Pakai :Oleskan ramuan tersebut pada kulit yang diserang panu.

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.

Eicosanoids, Fatty Liver and Insulin Resistance

I have to take a brief intermission from the heart disease series to write about a very important paper I just read in the journal Obesity, "COX-2-mediated Inflammation in Fat is Crucial for Obesity-linked Insulin Resistance and Fatty Liver". It's actually related to cardiovascular disease, although indirectly.

First, some background. Polyunsaturated fatty acids (PUFA) come mostly from omega-6 and omega-3 sources. Omega-6 and omega-3 are precursors to eicosanoids, a large and poorly understood class of signaling molecules that play a role in basically everything. Eicosanoids are either omega-6-derived or omega-3-derived. Omega-6 and omega-3 compete for the enzymes that convert PUFA into eicosanoids. Therefore, the ratio of omega-6 to omega-3 in tissues (related to the ratio in the diet) determines the ratio of omega-6-derived eicosanoids to omega-3-derived eicosanoids.

Omega-6 eicosanoids are very potent and play a central role in inflammation. They aren't "bad", in fact they're essential, but an excess of them is probably not good. Omega-3 eicosanoids are generally less potent, less inflammatory, and tend to participate in long-term repair processes. So in sum, the ratio of omega-6 to omega-3 in the diet will determine the potency and quality of eicosanoid signaling, which will determine an animal's susceptibility to inflammation-mediated disorders.

One of the key enzymes in the pathway from PUFA to eicosanoids (specifically, a subset of them called prostanoids) is cyclooxygenase (COX). COX-1 is expressed all the time and serves a "housekeeping" function, while COX-2 is induced by cellular stressors and contributes to the the formation of inflammatory eicosanoids. Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and ibuprofen inhibit COX enzymes, which is why they are effective against inflammatory problems like pain and fever. They are also used as a preventive measure against cardiovascular disease. Basically, they reduce the excessive inflammatory signaling promoted by a diet with a poor omega-6:3 balance. You wouldn't need to inhibit COX if it were producing the proper balance of eicosanoids to begin with.

Dr. Kuang-Chung Shih's group at the Department of Internal Medicine in Taipei placed rats on five different diets:

1. A control diet, eating normal low-fat rat chow.


2. A "high-fat diet", in which 45% of calories came from a combination of industrial lard and soybean oil, and 17% of calories came from sucrose*.


3. A "high-fat diet" (same as above), plus the COX-2 inhibitor celecoxib (Celebrex).


4. A "high-fat diet" (same as above), plus the COX-2 inhibitor mesulid.


5. An energy-restricted "high-fat diet".

The "high-fat diets", besides being high in sucrose (table sugar), also presumably had a poor omega-6:3 ratio, in the neighborhood of 10:1 or possibly higher. Weight and fat mass in rats and humans increases with increasing omega-6 in the diet, and also increases with a high 6:3 ratio. I wrote about that here. Rats eating the high-fat diets (groups 2- 4) gained weight as expected**.

Rats in group 2 not only gained weight, they also experienced increased fasting glucose, leptin, insulin, triglycerides, blood pressure and a massive decline in insulin sensitivity (seven-fold relative to group 1). Rats in groups 3 and 4 gained weight, but saw much less of a deterioration in insulin and leptin sensitivity, and blood pressure. Group 2 also developed fatty liver, which was attenuated in groups 3 and 4. If you're interested, group 5 (energy restricted high-fat) was similar to groups 3 and 4 on pretty much everything, including insulin sensitivity.

So there you have it folks: direct evidence that insulin resistance, leptin resistance, high blood pressure and fatty liver are mediated by excessive inflammatory eicosanoid signaling. I wrote about something similar before when I reviewed a paper showing that fish oil reverses many of the consequences of a high-vegetable oil, high-sugar diet in rats. I also reviewed two papers showing that in pigs and rats, a high omega-6:3 ratio promotes inflammation (mediated by COX-2) and lipid peroxidation in the heart. Are you going to quench the fire by taking drugs, or by reducing your intake of omega-6 and ensuring an adequate intake of omega-3?

*Of course, they didn't mention the sucrose in the methods section. I had to go digging around for the diet's composition. This is typical of papers on "high-fat diets". They load them up with sugar, and blame everything on the fat.

**Rats gain fat mass when fed a high-fat diet (even if it's not loaded with sugar). But humans don't necessarily gain weight on a high-fat diet (i.e. low-carb weight loss diet). What's the difference? Low-carbohydrate diet trials indicate that humans spontaneously reduce their caloric intake when eating low carbohydrate, high-fat food.

Tips Mencegah Uban Yang Tumbuh Sebelum Waktunya

Bahan-Bahan :- Hati ayam kampong ............................... 2 potong- Ragi kue ……………………………............................... 2 sendok teh- Kecap ………………………………............................... SecukupnyaCara Pembuatan :- Cuci bersih hati ayam kampong dalam air masak.- Setelah bersih, pangganglah di atas bara api hingga matang.- Setelah matang, taburi dengan ragi kue hingga merata.

The Coronary Heart Disease Epidemic: Possible Culprits Part II

In the last post, I reviewed some of the factors that I believe could have contributed to the epidemic of heart attacks that began in the 1920s and 1930s in the U.S. and U.K., and continues today. I ended on smoking, which appears to be a major player. But even smoking is clearly trumped by another factor or combination of factors, judging by the unusually low incidence of heart attacks in France, Japan and on Kitava.

One of the major changes in diet that I didn't mention in the last post was the rise of industrial liquid vegetable oils over the course of the 20th century. In the U.S. in 1900, the primary cooking fats were lard, beef tallow and butter. The following data only include cooking fats and spreads, because the USDA does not track the fats that naturally occur in milk and meat (source):

Animal fat is off the hook. This is the type of information that makes mainstream nutrition advice ring hollow. Let's see what happened to industrial vegetable oils in the early 1900s:

I do believe we're getting warmer. Now let's consider the composition of traditional American animal fats and industrial vegetable oils:
It's not hard to see that the two classes of fats (animal and industrial vegetable) are quite different. Animal fats are more saturated (blue). However, the biggest difference is that industrial vegetable oils contain a massive amount of omega-6 (yellow), far more than animal fats. If you accept that humans evolved eating primarily animal fats, which is well supported by the archaeological and anthropological literature, then you can begin to see the nature of the problem.

Omega-6 and omega-3 fats are polyunsaturated fatty acids that are precursors to a very important class of signaling molecules called eicosanoids, which have a hand in virtually every bodily process. Omega-6 and omega-3 fats compete with one another for the enzymes (desaturases and elongases) that convert them into eicosanoid precursors. Omega-6-derived eicosanoids and omega-3-derived eicosanoids have different functions. Therefore, the balance of omega-6 to omega-3 fats in the diet influences the function of the body on virtually every level. Omega-6 eicosanoids tend to be more inflammatory, although the eicosanoid system is extraordinarily complex and poorly understood.

What's better understood is the fact that our current omega-6 consumption is well outside of our ecological niche. In other words, we evolved in an environment that did not provide large amounts of omega-6 all year round. Industrial vegetable oils are a product of food processing techniques that have been widespread for about 100 years, not enough time for even the slightest genetic adaptation. Our current level of omega-6 intake, and our current balance between omega-6 and omega-3, are therefore unnatural.
The ideal ratio is probably very roughly 2:1 omega-6:omega-3. Leaf lard is 6.8, beef tallow is 2.4, good quality butter is 1.4, corn oil is 45, cottonseed oil is 260. It's clear that a large qualitative change in our fat consumption occurred over the course of the 20th century.

I believe this was a major factor in the rise of heart attacks from an obscure condition to the primary cause of death. I'll be reviewing the data that convinced me in the next few posts.

The Coronary Heart Disease Epidemic
The Coronary Heart Disease Epidemic: Possible Culprits Part I
The Omega Ratio
A Practical Approach to Omega Fats
Polyunsaturated Fat Intake: Effects on the Heart and Brain
Polyunsaturated Fat Intake: What About Humans?
Vegetable Oil and Homicide