Ischemic Heart Attacks: Disease of Civilization

Or, more precisely, disease of industrial civilization.

The scientific literature contains examples of cultures that don't suffer from the chronic non-communicable diseases that are so common in modern societies. Much of what I've read indicates that heart attacks are practically unique to cultures that have adopted industrial foodways and a modern lifestyle, being infrequent or entirely absent in those that have not.

I recently came across an incredible paper from 1964 in the American Journal of Cardiology, titled "Geographic Pathology of Myocardial Infarction", by lead author Dr. Kyu Taik Lee (Am. J. Cardiol. 13:30. 1964). This was published during a period of intense research into the cardiovascular health of non-industrial cultures, including Dr. George V. Mann's famous study of the Masai.

The first thing Lee and his colleagues did was collect autopsy statistics from San Francisco and Los Angeles hospitals. They analyzed the data by race, including categories for Caucasian-Americans (white), Japanese-Americans, Chinese-Americans, and Filipino-Americans. All races had a similar incidence of autopsy-proven myocardial infarction (MI = heart attack), including both silent (healed) and fatal MI. For comparison, they included a table with autopsy data from hospitals in Tokyo, South Japan and North Japan. I'm including the data from Tokyo in the graph because it's also an urban environment, but the finding was the same in all three regions. Here's what they found, by age group: The Japanese had a very low rate of MI compared to both Caucasian-Americans and Japanese-Americans. The rate of MI in Caucasian-Americans and Japanese-Americans did not differ significantly. Thus, location but not race determined the susceptibility to MI.

Next, the investigators collected autopsy data from hospitals in New Orleans, again divided by race. This time they exained Caucasian-Americans and African-Americans. Both groups had a very high rate of MI, as expected, although the African-Americans had a lower rate than Caucasian-Americans. They also collected data from autopsies in Nigeria and Uganda for comparison. Here are the data for men: And for women: Again, location but not race largely determined the incidence of MI. MI was extremely rare in the African autopsies. Here's what they had to say:

There was only 1 case of healed myocardial infarction among over 4,000 adult autopsies in the Uganda series, and only 2 cases of healed myocardial infarction among over 500 adult autopsies in the Nigerian series. In the New Orleans Negro series the occurrence rate was far greater in every sex and age group than in either one of the Negro series in East and West Africa.

Over 4,500 autopsies and not a single fatal MI. If this isn't worth studying, what is? These data should be part of first-year training in medicine and health programs.

To satisfy the skeptics, Lee and colleagues imported hundreds of hearts from consecutive autopsies in Albany (USA), Africa, Korea and Japan. They had an American pathologist analyze them side-by side to eliminate any diagnostic bias. Here's what they found:

In the African Negro series no infarct was found in any age group [out of 244 hearts, 39 over 60 years old]. In the Korean series there were only 2 cases of myocardial infarction [out of 106 hearts] and they were both women... In the Japanese series there were 8 cases of myocardial infarction in 259 hearts. All were men...

In the American sample, nearly 40% of the hearts of men and women over 60 showed signs of MI. The findings of the American pathologist confirmed the international autopsy data, showing that diagnostic bias did not contribute to the results significantly. They also took measurements of the thickness of the coronary artery wall, an index of atherosclerosis. They found that the Americans had the most atherosclerosis, but all cultures had some degree of it and there was overlap in the amount of atherosclerosis between samples. This led the investigators to state:

Myocardial infarction and coronary thrombosis are almost nonexistent in Uganda and Nigeria, and the amount of coronary arteriosclerosis is significantly less in Africans than in whites. However, in the two groups there was some overlapping in the degree of arteriosclerosis. No Africans had infarcts, but some had the same or a greater degree of coronary arteriosclerosis as a few whites who had myocardial infarctions. One explanation for this may be that some difference in clotting or clot-lysis mechanisms is present in the two groups. In a previous study, we showed that the incidence of thromboembolic phenomena in the pulmonary circulation [blood clots in the lungs] was low in East Africans as compared with Americans.

Now, the authors' conclusions:

These data strongly suggest that among the Orientals the environmental factor is playing a major role in the etiology of myocardial infarction and coronary thrombosis. If the genetic factor is an important one, those Orientals who moved to this country many years ago or who were born in this country should still maintain their low occurrence rate of myocardial infarction at least to some extent, and one would not expect to see similar occurrence rates of myocardial infarction in Orientals and whites as old as 50 to 59 years... As with the Orientals, this suggests that for Negroes in the United States environmental factors are more important than genetic factors in the etiology of myocardial infarction.

Africans in Africa and Japanese in Japan = low incidence of MI. Africans, Japanese and Caucasians in the US = high and similar incidence of MI. Genes only influence a person's susceptibility to MI when they live in an environment that promotes MI. Otherwise, genes are basically irrelevant.

What do the traditional diets and lifestyles of Japan and Africa have in common? Not much. Even within Nigeria, the diet varies from heavily starch-based (root vegetables, soaked/fermented non-gluten grains, beans, plantains) to mostly reliant on high-fat dairy and meat. In fact, I believe it's the wrong question to ask. A better question is "what do we eat/do in the US that traditional Japanese, Koreans, Chinese, Polynesians, Melanesians and Africans don't"? For starters, none of them rely on industrial vegetable oils, sugar and wheat to nearly the same extent as modern America. Their food is generally prepared at home using wholesome ingredients and traditional methods.

They probably get more exercise than Americans, even if it's only walking in Tokyo or domestic tasks for women in parts of Africa. Traditional Africans surely get more sunlight and thus more vitamin D. I can't imagine life is less stressful in Tokyo than in San Francisco or Los Angeles.

I really like this study, and I think these graphs should be disseminated as much as possible. I've prepared high-resolution versions in JPEG, Powerpoint and PDF formats. E-mail me (click on my profile for the link) if you would like a copy. Let me know which format(s) you want.

Cleave and Yudkin on Fats

Drs. T. L. Cleave (1906-1983) and John Yudkin (1910-1995) were two diet-health researchers who believed that refined carbohydrate-- and particularly refined sugar-- are behind many modern health problems. They made their case in the scientific journals, as well as in books aimed at the general public. They were also witheringly dismissive of the idea that animal fats could be behind the coronary heart disease epidemic of the 20th century. I'm going to post a few quotes of theirs that I'm particularly fond of, relating to this. I'll start off with a few oldies but goodies from T. L. Cleave's The Saccharine Disease, page 100:

Those who incriminate animal fats in raising the blood lipids and causing coronary disease would have us stop eating the fats that we have been eating from immemorial time, such as the fat found in meat and in the butter and cream derived from milk, and eat instead a whole lot of new oils, mainly expressed from vegetable seeds, many of which oils are alien to us.

From pages 100-101:

The keeping of flocks of sheep, herds of cattle, and other domestic animals, in order to provide a continuity of meat and milk, started with neolithic man many thousands of years before the Christian era... To these fats we are therefore well adapted, quite apart from man, as a hunter, being well acquainted with the fat of animals in evolutionary times far more remote than the neolithic ones.

From page 101:

Contrast with these ancient fats the new oils, mainly expressed from vegetable seeds. Not only are many of these seeds not a natural food for man (e.g., cotton seed and sunflower seed-- and incidentally the sunflower does not even come from the Old World, as we do in the British isles, but from the New), but also the oils expressed from many of them never existed in any quantity before the invention of the modern hydraulic press or the new solvent procedures, and consequently were scarcely eaten in this country before the introduction of margarine, circa 1916, during the First World War. Evolutionarily these oils make us not so much men as the equivalent of a flock of greenfinches, and the evolutionary incongruity is heightened by the fact that the coronary explosion amongst us, as will be seen later, came in since the introduction of just these oils at the period stated, though in margarine they are often saturated by a stream of hydrogen.

Now for a little John Yudkin. From "Dietary Factors in Arteriosclerosis: Sucrose" (Lipids 13(5):370. 1978):

In principle, it is very doubtful that one can in any way profoundly modify the diet of any species, including Homo sapiens, without introducing some hazard. The consumption of large quantities of PUFA [polyunsaturated fat] has been made possible only by the very recent development of sophisticated techniques of cultivating oilseeds, and extracting and refining vegetable oils. Before such techniques were available, these oils made only a small contribution to our diets, as they still do in the poorer countries. We cannot ignore the evidence that the large amounts widely recommended nowadays as a preventive of CHD can produce undesirable effects, such as increasing the risk of gallstones and possibly of carcinomatous changes in the skin. On the other hand, the reduction of the high amounts of sugar that we now consume is not known to be accompanied by any hazard.

Drs. T. L. Cleave and John Yudkin: making sense since 1936.

The Diet-Heart Hypothesis: Oxidized LDL, Part II

In the last post, I presented the evidence that oxidized LDL (oxLDL) is a dominant factor in the arterial disease known as atherosclerosis, although probably not the only factor. In this post, I'll describe some of the major contributors to oxLDL.

Polyunsaturated Fats Increase LDL Oxidation

The serum concentration of oxLDL is strongly influcenced by diet. One dietary determinant of oxLDL is dietary polyunsaturated fat (PUFA). PUFA are inherently susceptible to oxidative damage, compared to monounsaturated and saturated fats. The predominant PUFA in the modern diet is linoleic acid, found excessively in industrial seed oils like corn oil, sunflower oil, safflower oil, cottonseed oil and soy oil. LDL is naturally rich in linoleic acid, even in cultures such as the Kitavans who have a very low dietary intake of it. However, LDL content of linoleic acid does correlate with dietary intake, and the Kitavans have a comparatively small amount of linoleic acid in their LDL, relative to industrial cultures.

There have been a number of media reports in the last few years proclaiming that monounsaturated fat reduces LDL oxidation compared to saturated and polyunsaturated fat. This is rather implausible on the surface, so let's take a closer look. There are two ways to measure oxLDL:

1. Measure it directly from the blood
   
2. Take normal LDL from the blood, expose it to copper in a test tube, and see how fast it oxidizes

The first reflects actual oxLDL in the blood, whereas the second reflects "susceptibility to oxidation" and has a dubious relationship with actual oxidized LDL in the bloodstream. This results in statements like the following (ref):

LDL resistance to copper-induced oxidation, expressed as lag time, was highest during the MUFA-rich diet (55.1�7.3 minutes) and lowest during the PUFA(n-3)� (45.3�7 minutes) and SFA- (45.3�6.4 minutes) rich diets.

This was published in a paper by P. Mata and colleagues in 1996. They fed 42 volunteers one of four different diets for 5 weeks each: one rich in saturated fat, one rich in monounsaturated fat, one rich in linoleic acid PUFA, and one rich in linoleic acid plus omega-3 PUFA. They emphasized the finding quoted above, as did the media. But there's an embarrassing piece of data buried in the paper that the authors, and the media, ignored (thanks to Chris Masterjohn for pointing this out). Here's what they saw when they looked directly at LDL oxidation in their volunteers:

Oops! LDL oxidation in the two PUFA groups was increased by more than 31%. The difference between the leftmost two groups and the rightmost two was statistically significant. As one would expect, oxidized LDL is proportional to the amount of PUFA in LDL, which is proportional to dietary PUFA. This somehow got left out of the abstract and media reports. The same investigators published a similar report a year later.

In another diet trial, participants were placed on one of two diets for 5 weeks: a low-fat, high PUFA diet low in vegetables; or a low-fat, high PUFA diet high in vegetables. The authors were forthright about their findings, so I'll let them summarize:

The median plasma OxLDL-EO6 increased by 27% (P less than 0.01) in response to the low-fat, low-vegetable diet and 19% (P less than 0.01) in response to the low-fat, high-vegetable diet. Also, the Lp(a) concentration was increased by 7% (P less than 0.01) and 9% (P=0.01), respectively.

This is the diet mainstream cardiologists have been prescribing to heart attack patients for 40 years. The trials I mentioned above are the only three I'm aware of in which fat quality was manipulated and oxLDL was directly measured (the first two were based on subsets of the same data). They all suggest that replacing saturated fat with PUFA increases oxLDL.

I suspect that the effect has less to do with the decrease in saturated fat and more to do with the increase in PUFA, although there's no way to know for sure. In the Lyon Diet-Heart trial, which I believe was the most successful diet trial of all time, linoleic acid was reduced to 3.6% of calories, but saturated fat was also reduced. Another reason is that there are numerous low-fat, low PUFA, high-carbohydrate cultures that have low levels of atherosclerosis and heart attacks. The Kitavans, for example, don't seem to have heart attacks or strokes (although no autopsies have been done so we don't know how much atherosclerosis they have).

They get 69% of their calories from high-glycemic starchy tubers, and their 21% fat comes mostly from coconut so it's highly saturated. Their blood lipids are low in omega-6 linoleic acid and very saturated. But there's a little surprise in the data: their lipids are full of palmitic acid (saturated), despite the fact that their diet contains very little of it. The reason is that their livers are turning all that carbohydrate into saturated fat, which is what happens when you eat more carbohydrate than you can burn immediately or store as glycogen. The moral of the story is that you don't need to eat saturated fat to have saturated LDL: a high-carbohydrate diet can accomplish the same thing, especially if it has a high glycemic index.

Fat-Soluble Antioxidants Decrease LDL Oxidation

LDL carries fat-soluble antioxidants, predominantly vitamin E and coenzyme Q10 (CoQ10). One form of vitamin E, alpha-tocopherol, slows atherosclerosis in most animal models but has shown equivocal results in human trials. There is even the suggestion that it may increase LDL oxidation under some circumstances. I don't recommend supplementing with vitamin E. However, the first line of antioxidant defense in LDL is provided by CoQ10. CoQ10 unequivocally reduces LDL oxidation in human subjects, and potently reduces atherosclerosis in animal models.

CoQ10 has a special relationship with cardiovascular health. Levels are reduced in individuals with cardiovascular disease and high oxLDL. Whether this is cause or effect, it's difficult to say. However, supplementing with CoQ10 has been repeatedly shown to be effective for high blood pressure and congestive heart failure. There has been one controlled trial of CoQ10 (120 mg/day) supplementation for the prevention of heart attacks, which reduced cardiac events including deaths by 45%, compared to a group receiving B vitamins. The CoQ10 group showed a large reduction in plasma lipid oxidation. This is a promising result and the experiment should be repeated.

CoQ10 is not an essential nutrient, although food does contribute a small portion of our total CoQ10 use. The large majority of CoQ10 is synthesized by the body itself, and this is dependent on a number of essential nutrients, including vitamin B2, B3, B5, B6, B12, vitamin C and folic acid. Thus, the body's synthesis of CoQ10 is dependent on overall nutritional status. Sub-clinical deficiency of any of these vitamins can hypothetically contribute to reduced CoQ10 production and thus oxLDL. This is potentially a big problem since modern Americans get more than half their calories from nutrient-poor refined foods. Liver is the single best source of many of these vitamins, and also holds the title of Most Nutritious Food on the Planet. It's also rich in CoQ10.

CoQ10 synthesis declines with age and is reduced in people with disorders involving oxidative stress, like cardiovascular disease. It's also greatly reduced by the cholesterol-lowering drugs statins. I'm not generally in favor of supplements, but CoQ10 seems to have a lot of promise and nothing but positive side effects that I'm aware of. CoQ10 deficiency may be a common theme in a number of modern disorders.

Excess Blood Sugar and Fructose Increase LDL Oxidation

Both type I and type II diabetes are associated with higher levels of oxLDL, therefore, prolonged high blood glucose may contribute to LDL oxidation due to glycosylation of the LDL protein ApoB. Fructose consumption increases oxLDL relative to glucose. Fructose is a very powerful glycosylating agent (binds non-specifically to other molecules, causing damage). Although it isn't present at high levels in the general circulation, it does interact with blood lipids in the hepatic portal vein as it moves from the digestive tract to the liver to be turned into fat (palmitic acid). Peter at Hyperlipid has written extensively about the role of glycosylation in LDL oxidation.

The Diet-Heart Hypothesis: The Verdict

The diet-heart hypothesis, the idea that dietary saturated fat and cholesterol raise blood cholesterol and thus increase heart attack risk, is a half-century embarrassment to the international scientific community. It requires willful ignorance of the fact that saturated fat does not increase total cholesterol or LDL in humans, in the long term. It requires a simplistic view of blood lipids that ignores the potentially harmful effects of replacing animal fats with carbohydrate or industrial seed oils. Worst of all, it requires selective citation of the literature on diet modification trials.

I have to conclude that if dietary saturated fat and cholesterol play any role whatsoever in cardiovascular disease, it's a minor one that's trumped by other factors. Industrial seed oils and sugar are likely to play an important role in cardiovascular disease.

The Diet-Heart Hypothesis: Oxidized LDL, Part I

In my reading about lipoprotein particles (LDL, HDL, etc.) and how they associate with cardiac risk, I've come across three LDL-related markers that associate with risk: LDL cholesterol, LDL particle number, and LDL size/density. Is this a coincidence, or is there a reason for it?

The first marker, LDL cholesterol, is probably nothing more than a crude approximation of particle number. But LDL particle number and size/density are related to something else, that probably actually causes atherosclerosis rather than simply being associated with it: oxidized LDL (oxLDL).

oxLDL is formed when the lipids in LDL particles react with oxygen and break down. This happens specifically to the unsaturated fats in LDL, because saturated fats, by their chemical nature, are very resistant to oxidative damage. Polyunsaturated fats are much more susceptible to oxidative damage than saturated or monounsaturated fats. Linoleic acid (the omega-6 fatty acid found abundantly in industrial seed oils) is the main polyunsaturated fatty acid in LDL.

LDL is packaged with antioxidants in the liver, primarily vitamin E and coenzyme Q10 (CoQ10), to prevent its oxidation*. However, the more time it spends in the blood, the more likely it is to exhaust its antioxidant store and become oxidized. Also, the smaller the LDL particle, the more likely it is to become trapped in the vessel wall and become oxidized there.

Oxidized LDL Correlates Tightly with Cardiac Risk

oxLDL has turned out to be a very sensitive marker of cardiac risk, surpassing traditional markers like LDL, HDL, and triglycerides in most studies to date. Since the discovery of sensitive assays that detect oxidized LDL drawn directly from patient blood, a number of studies have been published supporting its ability to detect atherosclerosis (plaque buildup in the arteries), heart attack risk and even the metabolic syndrome.

Holovet and colleagues published a study comparing the ability of oxLDL and a traditional risk factor assessment to detect coronary artery disease. The traditional method is called the Global Risk Factor Assessment Score (GRAS), and includes age, total cholesterol, HDL, blood pressure, diabetes and smoking status. It's similar to the commonly used Framingham risk score (which, interestingly enough, doesn't include LDL).

GRAS was able to correctly differentiate a healthy person from a person with coronary artery disease 49% of the time, while oxLDL was correct 82% of the time. Thus, oxLDL by itself was far more accurate than a whole battery of traditional cholesterol and cardiac markers. Coronary patients had more than twice the level of circulating oxLDL than the healthy comparison group.

In a large prospective study by Meisinger and colleagues, participants with high oxLDL had a 4.25 higher risk of heart attack than patients with lower oxLDL. oxLDL blew away all other blood lipid markers by nearly a factor of two. From the abstract:

Plasma oxLDL was the strongest predictor of CHD events compared with a conventional lipoprotein profile and other traditional risk factors for CHD.

Oxidized LDL Makes Sense

It's time to cross the threshold from markers of heart attack risk to causes of atherosclerosis. Regular, non-oxidized LDL has few properties that would make it a suspect in atherosclerosis. It's just a little particle carrying cholesterol and fats from the liver to other organs. As soon as it oxidizes, however, it becomes pro-inflammatory, immunogenic, damaging to the vessel wall, and most importantly, capable of transforming immune cells called macrophages into foam cells, a major constituent of arterial plaque.

Researchers have been interested in the plaque-generating properties of oxLDL for over three decades, and quite a bit of data have accumulated. They've identified cellular receptors that allow macrophages to ingest oxLDL (CD36 and SR-A). These receptors are specific for oxLDL and do not recognize normal LDL to a significant degree. Mice whose macrophages lack either of these two receptors have the same amount of circulating LDL as normal mice, yet have 60 to 70 percent less atherosclerosis when fed a plaque-forming diet (1, 2). Shorter-term studies have not always been consistent however, suggesting that there are alternative mechanisms. I'll expand on this more later.

Another line of evidence comes from the ability of LDL-borne antioxidants to prevent atherosclerosis in animal models. The powerful synthetic antioxidant probucol greatly reduces atherosclerosis in a number of animal models. It also reduces the extremely high cholesterol rodents and herbivorous animals get when they eat a high-cholesterol "atherogenic diet", but several studies have concluded that the majority of probucol's effect is due to its antioxidant ability rather than its ability to reduce cholesterol (ref).

Vitamin E and CoQ10 are two other LDL-borne antioxidants that can reduce atherosclerosis in animal models, particularly in combination with one another. Vitamin E alone is not as effective, and in some studies totally ineffective, which is one possible explanation for the equivocal results of vitamin E cardiovascular trials in humans. The most effective combination of antioxidants is probably the one provided by a nutrient-dense diet.

In Summary

Multiple lines of evidence suggest that oxidized LDL plays a dominant role in atherosclerosis. Not only is it associated with cardiovascular risk, there's also a large body of evidence suggesting it actually directly contributes to it. In the next post, I'll describe how you can modify your level of oxidized LDL using diet.

* People often think of colorful fruits and vegetables when they think of antioxidants, but vitamin E and CoQ10 are found in both plant and animal foods. Fruits and vegetables are generally not good sources of these fat-soluble antioxidants. Good sources include organ meats, nuts, pastured butter, avocados and red palm oil. The body also manufactures CoQ10 itself.

The Diet-Heart Hypothesis: Subdividing Lipoproteins

Two posts ago, we made the rounds of the commonly measured blood lipids (total cholesterol, LDL, HDL, triglycerides) and how they associate with cardiac risk. It's important to keep in mind that many things associate with cardiac risk, not just blood lipids. For example, men with low serum vitamin D are at a 2.4-fold greater risk of heart attack than men with higher D levels. That alone is roughly equivalent to the predictive power of the blood lipids you get measured at the doctor's office. Coronary calcium scans (a measure of blood vessel calcification) also associate with cardiac risk better than the most commonly measured blood lipids.

Lipoproteins Can be Subdivided into Several Subcategories

In the continual search for better measures of cardiac risk, researchers in the 1980s decided to break down lipoprotein particles into sub-categories. One of these researchers is Dr. Ronald M. Krauss. Krauss published extensively on the association between lipoprotein size and cardiac risk, eventually concluding (source):

The plasma lipoprotein profile accompanying a preponderance of small, dense LDL particles (specifically LDL-III) is associated with up to a threefold increase in the susceptibility of developing [coronary artery disease]. This has been demonstrated in case-control studies of myocardial infarction and angiographically documented coronary disease.

Krauss found that small, dense LDL (sdLDL) doesn't travel alone: it typically comes along with low HDL and high triglycerides*. He called this combination of factors "lipoprotein pattern B"; its opposite is "lipoprotein pattern A": large, buoyant LDL, high HDL and low triglycerides. Incidentally, low HDL and high triglycerides are hallmarks of the metabolic syndrome, the quintessential modern metabolic disorder.

Krauss and his colleagues went on to hypothesize that sdLDL promotes atherosclerosis because of its ability to penetrate the artery wall more easily than large LDL. He and others subsequently showed that sdLDL are also more prone to oxidation than large LDL (1, 2).

Diet Affects LDL Subcategories

The next step in Krauss's research was to see how diet affects lipoprotein patterns. In 1994, he published a study comparing the effects of a low-fat (24%), high-carbohydrate (56%) diet to a "high-fat" (46%), "low-carbohydrate" (34%) diet on lipoprotein patterns. The high-fat diet also happened to be high in saturated fat-- 18% of calories. He found that (quote source):

Out of the 87 men with pattern A on the high-fat diet, 36 converted to pattern B on the low-fat diet... Taken together, these results indicate that in the majority of men, the reduction in LDL cholesterol seen on a low-fat, high-carbohydrate diet is mainly because of a shift from larger, more cholesterol-enriched LDL to smaller, cholesterol-depleted LDL [sdLDL].

In other words, in the majority of people, high-carbohydrate diets lower LDL cholesterol not by decreasing LDL particle count (which might be good), but by decreasing LDL size and increasing sdLDL (probably not good). This has been shown repeatedly, including with a 10% fat diet and in children. However, in people who already exhibit pattern B, reducing fat does reduce LDL particle number. Keep in mind that the majority of carbohydrate in modern America comes from wheat and sugar.

Krauss then specifically explored the effect of saturated fat on LDL size (free full text). He re-analyzed the data from the study above, and found that:

In summary, the present study showed that changes in dietary saturated fat are associated with changes in LDL subclasses in healthy men. An increase in saturated fat, and in particular, myristic acid [as well as palmitic acid], was associated with increases in larger LDL particles (and decreases in smaller LDL particles). LDL particle diameter and peak flotation rate [density] were also positively associated with saturated fat, indicating shifts in LDL-particle distribution toward larger, cholesterol-enriched LDL.

Participants who ate the most saturated fat had the largest LDL, and vice versa. Kudos to Dr. Krauss for publishing these provocative data. It's not an isolated finding. He noted in 1994 that:

Cross-sectional population analyses have suggested an association between reduced LDL particle size and relatively reduced dietary animal-fat intake, and increased consumption of carbohydrates.

Diet Affects HDL Subcategories

Krauss also tested the effect of his dietary intervention on HDL. Several studies have found that the largest HDL particles, HDL2b, associate most strongly with HDL's protective effects (more HDL2b = fewer heart attacks). Compared to the diet high in total fat and saturated fat, the low-fat diet decreased HDL2b significantly. A separate study found that the effect persists at one year. Berglund et al. independently confirmed the finding using the low-fat American Heart Association diet in men and women of diverse racial backgrounds. Here's what they had to say about it:

The results indicate that dietary changes suggested to be prudent for a large segment of the population will primarily affect [i.e., reduce] the concentrations of the most prominent antiatherogenic [anti-heart attack] HDL subpopulation.

Saturated and omega-3 fats selectively increase large HDL. Dr. B. G. of Animal Pharm has written about this a number of times.

Wrapping it Up

Contrary to the simplistic idea that saturated fat increases LDL and thus cardiac risk, total fat and saturated fat have a complex influence on blood lipids, the net effect of which is unclear, but is associated with a lower risk of heart attacks. These blood lipid changes persist for at least one year, so they may represent a long-term effect. It's important to remember that the primary sources of carbohydrate in the modern Western diet are wheat and sugar. Are the blood lipid patterns that associate with heart attack risk in Western countries partially acting as markers of wheat and sugar intake?

* This is why you may read that small, dense LDL is not an "independent predictor" of heart attack risk. Since it travels along with a particular pattern of HDL and triglycerides, in most studies it does not give information on cardiac risk beyond what you can get by measuring other lipoproteins.

Menopause : Symptoms and Treatment of Menopause

Menopause


Menopause is the transitional change in a woman's life when menstruation ceases. It is a natural occurrence, which marks the end of the reproductive years, just as the first menstrual period during puberty marked the start.

As women approach menopause the production of hormones by the ovaries starts to slow down. As this process accelerates, hormone levels fluctuate more and

Image by David Jackmanson via Flickr

often a woman notices changes in her menstrual cycle. The hormone levels will fall to a level where menstruation (periods) will cease altogether and the menopause is reached.


Symptoms of menopause

* hot flushes and cold sweating
* palpitations
* tingling, or itching sensations
* vertigo
* aches and pains in muscles and bones
* forgetfulness
* headaches
* irritability
* insomnia
* depression
* lack of self-esteem
* reduced sex drive
* tiredness
* urinary frequency
* vaginal dryness.

There are many aspects of your lifestyle and diet that you can alter to help improve the symptoms that can be associated with menopause. These include following a diet that will help to balance the hormones.

* eating plenty of fresh fruit and vegetables
* eating whole grains like brown rice and oats
* eating organic foods
* eating phytoestrogens, including, beans such as lentils, chickpeas and soy products,
* eating oily foods - fish, nuts, seeds and oils
* reducing your intake of saturated fat from dairy products and meat
* drinking plenty of pure filtered water
* increase your intake of fiber
* avoid additives, preservatives and chemicals, such as artificial sweeteners
* avoid or reduce your intake of caffeinated beverages
* reduce alcohol
* avoid sugar on its own and hidden in foods
* regular exercise, at least 30-45 minutes most days of the week
* a good multivitamin and mineral supplement designed for women like Complete Balance for Menopause AM/PM Formula. It reduces night sweats and assists in getting a good night's rest.

MRFIT Mortality

The Multiple Risk Factor Intervention trial was a very large controlled diet trial conducted in the 1980s. It involved an initial phase in which investigators screened over 350,000 men age 35-57 for cardiovascular risk factors including total blood cholesterol. 12,866 participants with major cardiovascular risk factors were selected for the diet intervention trial, while the rest were followed for six years. I discussed the intervention trial here.

During the six years of the observational arm of MRFIT, investigators kept track of deaths in the patients they had screened. They compared the occurrence of deaths from multiple causes to the blood cholesterol values they had measured at the beginning of the study. Here's a graph of the results (source):


Click on the graph for a larger image. Coronary heart disease does indeed rise with increasing total cholesterol in American men of this age group. But total mortality is nearly as high at low cholesterol levels as at high cholesterol levels. What accounts for the increase in mortality at low cholesterol levels, if not coronary heart disease? Stroke is part of the explanation. It was twice as prevalent in the lowest-cholesterol group as it was in other participants. But that hardly explains the large increase in mortality.

Possible explanations from other studies include higher cancer rates and higher rates of accidents and suicide. But the study didn't provide those statistics so I'm only guessing.

The MRFIT study cannot be replicated, because it was conducted at a time when fewer people were taking cholesterol-lowering drugs. In 2009, a 50-year old whose doctor discovers he has high cholesterol will likely be prescribed a statin, after which he will probably no longer have high cholesterol. This will confound studies examining the association between blood cholesterol and disease outcomes.

Thanks to The Great Cholesterol Con by Anthony Colpo for the MRFIT reference.