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470 lines
48 KiB
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<head><title>Cholesterol, longevity, intelligence, and health.</title></head>
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<h1>
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Cholesterol, longevity, intelligence, and health.
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</h1>
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<strong>
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The biological meaning of cholesterol is just starting to be explored. Everything that doctors know about
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cholesterol is wrong. New information about cholesterol is clarifying important issues in physiology and
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pathology.
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</strong>
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Medical magazines and television stations like to propagate the idea that cholesterol is bad stuff, and as a
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result, that cliche is known to almost every American. Recent journal articles have promoted the idea that "the
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lower the serum cholesterol is, the better" it is for the health of the patient. The theory that heart disease
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is "caused by cholesterol" has gone through several stages, and most recently the use of the "statin" drugs has
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revived it in a radical way. One consistent theme for fifty years has been that people should eat more
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polyunsaturated fat and less saturated fat, to lower their cholesterol, and to avoid butter, cream, eggs, and
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"red meat," because they contain both saturated fat and cholesterol. Often, medical attention is focused on the
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fats in the atheroma, rather than on the whole disease process, including clotting factors, vascular spasms,
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heart rhythm, viscosity of the blood, deposition of calcium and iron in blood vessels, and the whole process of
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inflammation, including the reactions to absorbed bowel toxins. Almost 100 years ago, some experiments in Russia
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showed that feeding rabbits cholesterol caused them to develop atherosclerosis, but subsequent experiments
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showed that rabbits are unusual in responding that way to cholesterol, and that even rabbits don't develop
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atherosclerosis from cholesterol if they are given a supplement of thyroid (Friedland, 1933). By 1936, it was
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clear that hypercholesterolemia in humans and other animals was caused by hypothyroidism, and that
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hypothyroidism caused many diseases to develop, including cardiovascular disease and cancer. There was already
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more reason at that time to think that the increased cholesterol was a protective adaptation than to think that
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it was maladaptive. The strange idea that cholesterol causes atherosclerosis was revived in the 1950s when the
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vegetable oil industry learned that their polyunsaturated oils lowered serum cholesterol. (Many other toxins
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lower cholesterol, but that is never mentioned.) The industry began advertising their oils as "heart
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protective," and they enlisted some influential organizations to help in their advertising<strong>:</strong> The
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American Dietetic Association, the American Heart Association, the US Dept. of Agriculture and FDA, and the AMA.
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Besides the early rabbit research, which didn't make their case against cholesterol and might actually have had
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implications harmful to their argument (since Anitschkow had used vegetable oil as solvent for his cholesterol
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feedings), the oil industry helped to create and promote a large amount of fraudulent and unscientific work. The
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death rate from heart disease in the United States began increasing early in the twentieth century, and it
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reached its peak from about 1950 to 1975, and then began declining. During the decades in which the death rate
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was rising, consumption of animal fat was decreasing, and the use of vegetable oil was increasing. In the
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southern European countries that have been said to show that eating very little animal fat prevents heart
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disease, the trends after the second world war have been the opposite--they have been eating more animal fat
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without an increase in heart disease. The correspondence between heart disease and consumption of saturated fat
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and cholesterol is little more than advertising copy. If people were looking for the actual causes of heart
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disease, they would consider the factors that changed in the US during the time that heart disease mortality was
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increasing. Both increases in harmful factors, and decreases in protective factors would have to be considered.
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The consumption of manufactured foods, pollution of air and water, the use of lead in gasoline, cigarette
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smoking, increased medicalization and use of drugs, psychosocial and socioeconomic stress, and increased
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exposure to radiation--medical, military, and industrial--would be obvious things to consider, along with
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decreased intake of some protective nutrients, such as selenium, magnesium, and vitamins. But those harmful
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factors all had their defenders<strong>:</strong> Who defends socioeconomic stress? All of the social
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institutions that fail to alleviate it. In 1847, Rudolph Virchow was sent to Poland to study the health
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situation there, and when he returned, the highly regarded anatomist, physiologist and pathologist announced
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that the Poles wouldn't have a health problem if the government would stop oppressing them, and institute
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economic reforms to alleviate their poverty. The reforms weren't made, and Virchow lost his job. Other harmful
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factors, such as seed oils, degraded foods, and radiation, have specific, very well organized and powerful
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lobbies to defend them. Despite the growing knowledge about the dangers of polyunsaturated fats, many medical
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articles are still advocating the "official" heart protective diet (e.g., "<strong>... </strong>
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diets using nonhydrogenated unsaturated fats as the predominant form of dietary fat," Hu and Willet, 2002). Some
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dogs alertly look at the thing a person is pointing at, other dogs just sniff the pointing finger. The
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publicists who disregard the complete nutritional and ecological situation, to focus on cholesterol and fat in
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the diet, are like the finger sniffers. Recent articles in the medical and lipids journals are praising the 1950
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work of J. W. Gofman, and the 1914 rabbit studies of N. N. Anitschkow, as the research that revealed cholesterol
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to be the cause of heart disease. Anitschkow and his co-workers, however, understood that their experiment
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hadn't explained human heart disease, and John Gofman, about 50 years after publishing his work on the
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lipoproteins, has done some large studies that could be crucial in disproving the doctrine that has become
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almost a national religion. He has shown that mortality from both heart disease and cancer corresponds very
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closely to the population's exposure to medical services, and specifically to medical radiation. During the peak
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years of heart disease mortality, medical x-rays gave very large doses of radiation with each exposure, and the
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population was also exposed to radioactive fallout from atomic bomb testing (explosions from 1945 to 1963
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produced a peak of heavy fallout that persisted through the 'sixties and into the 'seventies). Around 1971,
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someone noticed that the commercial cholesterol being used in feeding experiments was oxidized, that is, it
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wasn't really cholesterol. Comparing carefully prepared, unoxidized cholesterol with the oxidized degraded
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material, it was found that dietary cholesterol wasn't necessarily atherogenic (Vine, et al., 1998). Dietitians
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often recommend eating poached salmon, rather than "red meat," to lower cholesterol. Experimenters have measured
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the toxic oxidized cholesterol in different foods prepared in a variety of ways. Steaming salmon produced
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several times as much oxidized cholesterol as frying it, because of the longer cooking time that allowed the
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polyunsaturated fatty acids to break down, producing toxins such as acrolein and free radicals that oxidize the
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cholesterol and other components of the fish. The toxic cholesterol content of the steamed salmon was much
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higher than that of beef cooked at a high temperature. When oxidized polyunsaturated oils, such as corn oil or
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linoleic acid, are added to food, they appear in the blood lipids, where they accelerate the formation of
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cholesterol deposits in arteries (Staprans, et al., 1994, 1996). Stress accelerates the oxidation of the
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polyunsaturated fatty acids in the body, so people who consume unsaturated vegetable oils and fish will have
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some oxidized cholesterol in their tissues. The constant turnover of cholesterol in the tissues tends to lower
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the proportion of the toxic oxidized degradation products of cholesterol, but in hypothyroidism, the use of
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cholesterol is slowed, allowing the toxic forms to accumulate. Many antioxidant nutrients act like a thyroid
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supplement did in the 1934 rabbit experiments, preventing atherosclerosis even when extra toxic cholesterol is
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given to the animals. People who eat seafood get much more selenium in their diet than people who eat nothing
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from the sea, and selenium is one of the extremely protective nutrients that prevent atherosclerosis in animal
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experiments with excess cholesterol. It is well established that several antioxidant nutrients are protective
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factors in heart disease. The medical establishment has expended a great amount of money and time in the last 60
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years fighting the use of vitamin E or selenium for treating or preventing heart disease, though many physicians
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now take vitamin E themselves. But people who study free radical chemistry recognize that polyunsaturated fats
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are highly susceptible to oxidation, and that saturated fats tend to slow their degradation, acting to some
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extent as antioxidants. Several experiments and observations have shown that cholesterol itself can protect
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against damaging oxidation of polyunsaturated fats, protecting DNA and other vital components of the cell. A
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consistent program to prevent the oxidation of cholesterol would have to include all of the vitamins and
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minerals that are involved in antioxidant defense, avoidance of nutrients that exacerbate the destructive
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oxidations, and an effort to normalize the hormones and other factors, such as carbon dioxide, that have
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protective effects against free radical oxidation. A low level of cholesterol might increase susceptibility to
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the oxidants. The steroids in general, especially those produced in large amounts, progesterone and DHEA, are
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important parts of the antioxidant defenses. Cholesterol, either that produced internally by the cell, or taken
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in from the blood stream, is the precursor for all the steroids in the body. Several of the major steroid
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hormones are antiinflammatory, and cholesterol itself is antiinflammatory. (Mikko, et al., 2002; Kreines, et
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al., 1990). Cholesterol also protects against radiation damage, and many forms of toxin (saponins, cobra venom,
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chloroform--W.G. MacCallum, <em>
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A Text-book of</em>
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<em>Pathology,</em> 1937, Saunders Co.; many more recent studies show that it protects blood cells against
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hemolysis--breakdown of red blood cells--caused by heat and other harmful agents; e.g., Dumas, et al., 2002,
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Velardi, et al., 1991). Cholesterol, vitamin E, progesterone, and vitamin D are considered to be "structural
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antioxidants," that prevent oxidation partly by stabilizing molecular structures. One of the basic functions of
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cholesterol seems to be the stabilization of mitochondria, preventing their destruction by stress. Serious
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stress lowers ATP, magnesium, and carbon dioxide. When ATP and intracellular magnesium are decreased,
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cholesterol synthesis increases. During stress, free fatty acids are released from the tissues, and circulating
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in the bloodstream they are highly susceptible to oxidation. They contribute to the formation of the age
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pigment, lipofuscin, which is an oxygen-wasting substance that's found in the atheroma plaques in the damaged
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blood vessels. Iron and calcium accumulation adds to the tissue damage. The hemolysis which is promoted by
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polyunsaturated fats and an imbalance of antioxidants and oxidants, releases iron and heme into the blood
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stream. The incidence of atherosclerosis is increased when the body iron stores are high (Kiechl, et al., 1997),
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probably because of its role in lipid peroxidation and lipofuscin formation. Especially when the lining of the
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blood vessel is too permeable, because of the influence of polyunsaturated fats, prostaglandins, estrogen, etc.,
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the heme and iron will enter the endothelial cells, where the iron will catalyze the formation of free radicals,
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and the heme will be broken down by the enzyme heme oxygenase, into biliverdin, iron, and carbon monoxide, which
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can contribute to the oxidative stress of the cells. Carbon monoxide makes the blood vessel lining more
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permeable, allowing fats and fibrinogen to enter the cells (Allen, et al., 1988). Although cholesterol is
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protective against oxidative and cytolytic damage, the chronic free radical exposure will oxidize it. During the
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low cholesterol turnover of hypothyroidism, the oxidized variants of cholesterol will accumulate, so cholesterol
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loses its protective functions. When the metabolic pathways of the steroid hormones were being worked out, an
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experimenter perfused an isolated ovary with blood. When the amount of cholesterol in the blood pumped into the
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ovary was increased, the amount of progesterone in the blood leaving the ovary increased proportionately. In the
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healthy organism, cholesterol is constantly being synthesized, and constantly converted into steroid hormones,
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and, in the liver, into the bile salts that are secreted to emulsify fats in the intestine. Thyroid hormone and
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vitamin A are used in the process of converting cholesterol into pregnenolone, the immediate precursor of
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progesterone and DHEA. Anything that interfered with these processes would be disastrous for the organism. The
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supply of cholesterol, thyroid and vitamin A must always be adequate for the production of steroid hormones and
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bile salts. When stress suppresses thyroid activity, increased cholesterol probably compensates to some extent
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by permitting more progesterone to be synthesized. In very young people, the metabolic rate is very high, and
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the rapid conversion of cholesterol into pregnenolone, DHEA, and progesterone usually keeps the level of
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cholesterol in the blood low. In the 1930s, a rise in the concentration of cholesterol was considered to be one
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of the most reliable ways to diagnose hypothyroidism (<em>1936 Yearbook of Neurology, Psychiatry, and
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Endocrinology,</em> E.L. Sevringhaus, editor, Chicago, p. 533). With aging, the metabolic rate declines, and
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the increase of cholesterol with aging is probably a spontaneous regulatory process, supporting the synthesis of
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the protective steroids, especially the neurosteroids in the brain and retina. Many people refer to the
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structural importance of cholesterol for "membranes," and often imply that the membranes are just at the surface
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of the cell (the plasma membrane). But in fact cholesterol is found in the nucleus in the chromosomes, bound to
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DNA and in the nuclear matrix that governs the activation of genes, and in the mitotic spindle, which regulates
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separation of the chromosomes during cell division<strong>:</strong> without sufficient cholesterol, cells
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divide irregularly, producing aneuploid daughter cells (i.e., they have an abnormal number of chromosomes).
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Aneuploidy is now coming to be recognized as an essential feature of cancer cells. A significant amount of
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cholesterol was recently discovered to bind to hemoglobin, suggesting that it will be found in association with
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many other types of protein, when it occurs to anyone to look for it. Osmotic regulation, which is closely
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involved in cell division and other functions, appears to require cholesterol synthesis. Around 1985, a big
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study in Hungary showed that lowering cholesterol with drugs caused a huge increase in the cancer death rate.
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Hundreds of publications appeared in the U.S. saying that wasn't possible, because low cholesterol is good, the
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lower the better. The extreme increase in cancer mortality in the Hungarian study was probably the result of the
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drug that was commonly used at that time to lower cholesterol, but the pattern of mortality in that study was
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approximately the same pattern seen in any group with very low cholesterol. In the last 20 years, there have
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been many studies showing that lowering cholesterol increases mortality, especially from cancer and suicide, and
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that people with naturally low cholesterol are more likely to die from cancer, suicide, trauma, and infections
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than people with normal or higher than average cholesterol. The increased mortality from accidents and suicide
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when cholesterol is lowered is reminiscent of the problems seen in progesterone deficiency, and it's very likely
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that a deficiency of the neurosteroids accounts for it. A deficiency of progesterone and other neurosteroids
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(the steroids synthesized by the nerves themselves) causes depression of mood and impaired learning ability,
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among other neurological changes. As was the case with cancer, the pharmaceutical industry continues to deny
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that their anticholesterol drugs cause suicide, depression, and dementia, but there is a large amount of
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evidence from human as well as animal studies showing that mood and intelligence are depressed by lowering
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cholesterol. Simply injecting cholesterol into animals can improve their learning ability. In the Framingham
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heart study of 1894 people extending over a period of about 20 years, people with cholesterol naturally in the
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"desirable" range, below 200 mg.%, scored lower on "verbal fluency, attention/concentration, abstract reasoning,
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and a composite score measuring multiple cognitive domains" than those with higher cholesterol (Elias, et al.,
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2005).
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<hr />
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The next step in studies of this sort should be to see how the combination of extra thyroid with adequate
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cholesterol influences longevity. The rising cholesterol that commonly occurs with aging is probably only
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partial compensation for declining thyroid function, and by optimizing all of the protective factors, radical
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changes in the aging process may be possible. In the roundworm C. elegans, which is now a very popular animal
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for testing aging theories, because its genes and cells have been thoroughly "mapped," it was recently found
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that adding a gene that simply allows it to synthesize cholesterol, rather than depending on food for its
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sterols, increased its life span by as much as 131% (Lee, et al., 2005). That would be like increasing the human
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lifespan to about 175 years. These worms are also more resistant than normal to radiation and heat stress. The
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cells of the thymus are extremely sensitive to radiation and other stressors, and their enrichment with
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cholesterol inhibits lipid peroxidation, DNA degradation, and death in response to radiation (Posokhov, et al.,
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1992). Many high altitude regions of the world have high levels of background radiation, from minerals as well
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as cosmic rays, so it has been dogmatically believed that mortality from cancer and heart disease would increase
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with altitude, but the reverse is true. Because oxygen at lower pressure displaces less carbon dioxide from the
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blood, the body is able to retain more carbon dioxide at high altitude. Carbon dioxide protects against free
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radicals, and also helps to deliver oxygen to tissues, to maintain efficient energy production, and to prevent
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cellular stress. One study found 18 times higher incidence of hypertension in low altitude populations than in
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high altitude people (Fiori, et al., 2000). For many years, these principles have been applied in treating
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atherosclerosis and other degenerative diseases, in high altitude health resorts. Even a short period of hypoxic
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treatment can improve the body's ability to eliminate atherogenic lipid peroxides, possibly by improving the
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stress-resistant functions of the liver (Meerson, et al., 1988; Aleshin, et al., 1993; Kitaev, et al., 1999). I
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think editors of medical journals generally see themselves as the purveyors of enlightenment, i.e., as the
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pushers of the stylish and prestigious doctrines. (Selectivity of evidence to serve the received doctrine is the
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commonest form of scientific dishonesty.) But because their mental framework is culturally narrow, they
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sometimes publish things which later could turn out to be embarrassing (if inconsistency could embarrass such
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types). The recent discovery that the size of the LDL particle is a predominant factor in the development of
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atherosclerosis is one of those things that the editors and medical professors should find embarrassing. Smaller
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lipoprotein particles have a greater surface area exposed to the oxidative factors in the serum, and so are more
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rapidly degraded into toxic substances. People with larger LDL particles are remarkably resistant to heart
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disease, and the drug companies are looking for a way to turn their lipoproteins into products. But the
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conditions that govern the size of the LDL particles are physically and chemically reasonable, and are causing
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confusion among the doctinaire. There have been several studies in India showing that consumption of butter and
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ghee is associated with a low incidence of heart disease; for example, according to one study, people in the
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north eat 19 times more fat (mostly butter and ghee) than in the south, yet the incidence of heart disease is
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seven times higher in the south. A study in Sweden found that the fatty acids in milk products are associated
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with larger LDL particles (Sjogren, et al., 2004). In a 35 day study, when butter (20% of the calories) was
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compared to various kinds of margarine (with more trans fatty acids) in a similar quantity, the LDL particles
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were bigger on the butter diet (Mauger, et al., 2003). But in a study of the habitual diet of 414 people, large
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LDL particles were found to be correlated with increased intake of protein, animal fat, and trans fatty acids
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(Kim and Campos, 2003). In a study of the effect of dietary cholesterol on the atherogenicity of the blood
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lipids, 52 people were given either an egg diet (with 640 mg. of extra cholesterol per day) or a placebo diet
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for 30 days. Those whose LDL increased the most on the high cholesterol diet had the largest LDL particle size
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(Herron, et al., 2004). They concluded that "these data indicate that the consumption of a high-cholesterol diet
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does not negatively influence the atherogenicity of the LDL particle." A similar study in Mexico found that
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"Intake of 2 eggs/d results in the maintenance of LDL:HDL and in the generation of a less atherogenic LDL in
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this population of Mexican children" (Ballesteros, et al., 2004). The estrogen industry tried to get into the
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heart disease business several times over the last half century, and they are still trying, but the issue of
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estrogen's harmful effects on LDL particle size is getting some attention. Estrogen clearly decreases the size
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of the LDL particles (Campos, et al., 1997). The LDL particles also get smaller at menopause, and in polycystic
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ovary syndrome, and in preeclamptic pregnancies, all of which involve a low ratio of progesterone to estrogen.
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But there are still journals publishing claims that estrogen will protect against heart disease, by reducing the
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atherogenic response in increasingly mysterious ways. Occasionally, people have argued not only that estrogen is
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the factor that protects women against heart attacks, but that androgens predispose men to heart disease. One of
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their arguments has been that androgens lower HDL, the "good" form of cholesterol. However, there are many
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studies that show that testosterone and DHEA (Arad, et al., 1989) are protective against atherosclerosis. The
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LDL particle size is increased by androgens, and postprandial triglyceridemia is decreased (Hislop, et al.,
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2001). The studies in the 1930s that showed the protective effects of thyroid hormone against atherosclerosis
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and heart disease have sometimes been interpreted to mean that the thyroid is protective <strong><em>because</em
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></strong>
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it lowers the cholesterol, but since cholesterol is protective, rather than harmful, something else explains the
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protective effect. Ever since the time of Virchow, who called atherosclerosis <strong><em>arteritis
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deformans,</em></strong>
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the inflammatory nature of the problem has been clear to those who aren't crazed by the anticholesterol cult. We
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are all subject to a variable degree of inflammatory stimulation from the endotoxin absorbed from the intestine,
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but a healthy liver normally prevents it from reaching the general circulation, and produces a variety of
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protective factors. The HDL lipoprotein is one of these, which protects against inflammation by binding
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bacterial endotoxins that have reached the bloodstream. (Things that increase absorption of endotoxin--exercise,
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estrogen, ethanol--cause HDL to rise.) Chylomicrons and VLDL also absorb, bind, and help to eliminate
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endotoxins. All sorts of stress and malnutrition increase the tendency of endotoxin to leak into the
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bloodstream. Thyroid hormone, by increasing the turnover of cholesterol and its conversion into the protective
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steroids, is a major factor in keeping the inflammatory processes under control. In hypothyroidism, the
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pituitary secretes more TSH to activate the thyroid gland, but TSH itself has a variety of pro-inflammatory
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actions. The C-reactive protein (CRP), which is recognized as a factor contributing to atherosclerosis, is
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increased in association with TSH. CRP activates mast cells, which are found in the atheroma plaques, to produce
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a variety of pro-inflammatory substances, including histamine. The belief that cells are controlled by a plasma
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membrane, and that cholesterol's main function is to participate in that membrane, has led to a culture that
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treats cholesterol physiology with little curiosity. A different perspective on the cell starts with a
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recognition of the lipophilic nature of the structural proteins (not "membrane proteins," but things like
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cytoskeleton-cytoplasmic ground substance, spindle, centrosome-centrioles, nuclear matrix, etc.), with which
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lipids interact. Modifying an extremely complex system, the living substance, cholesterol participates in
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complexity, and must be investigated with subtlety. I suspect that the physiological meaning of cholesterol has
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to do with movement, stability, differentiation, memory, and sensitivity of the parts of the cells, that is,
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with everything physiological. The functions of cholesterol parallel the functions of other sterols in plants
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and other types of organism. Its functions have been refined and extended with the development of other
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steroids, such as progesterone, as biological requirements have evolved, but cholesterol is still at the center
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of this system. To deliberately interfere with its synthesis, as contemporary medicine does, reveals a terrible
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arrogance. Many participants in the cholesterol-lowering cult believe that they have succeeded in hijacking our
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science culture, but when the patents on another generation of their drugs have expired, the cult could begin to
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fade away.
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<h3>REFERENCES</h3>
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Biochim Biophys Acta. 1996 Sep 13;1297(1):77-82. <strong>Effect of cholesterol on rhodopsin stability in disk
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membranes.</strong> Albert AD, Boesze-Battaglia K, Paw Z, Watts A, Epand RM. J Hepatol. 2003
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May;38(5):623-8. <strong>A possible role of cholesterol-sphingomyelin/phosphatidylcholine in nuclear matrix
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during rat liver regeneration.</strong> Albi E, Cataldi S, Rossi G, Magni MV. <strong>"In nuclear matrix,
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cholesterol and sphingomyelin are respectively five and three times higher than those present in chromatin;
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the amount of phosphatidylcholine, which it is enriched in saturated fatty acids, is lower, thus indicating
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a less fluid structure." "The nuclear matrix lipids are independent from chromatin lipids; the ratio
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cholesterol-sphingomyelin/phosphatidylcholine is higher and, as a consequence, nuclear matrix is less fluid
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in relation to DNA synthesis, suggesting a specific role of nuclear matrix as a structure involved in DNA
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duplication.</strong>" Gynecol Endocrinol. 1997 Aug;11(4):281-8. <strong>Impact of combined hormone
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replacement therapy on serum lipid metabolism: new aspects.</strong> Alexandersen P, Haarbo J, Christiansen
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C. J Vasc Surg. 1988 Jan;7(1):139-52<strong>. The effect of cigarette smoke, nicotine, and carbon monoxide on
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the permeability of the arterial wall.</strong>
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Allen DR, Browse NL, Rutt DL, Butler L, Fletcher C. Ziegler's Beitrage, 1913, lvi, 379; 1914, lvii, 201.
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Anitschkow, N.N. Arteriosclerosis. 1989 Mar-Apr;9(2):159-66. <strong>Dehydroepiandrosterone feeding prevents
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aortic fatty streak formation and cholesterol accumulation in cholesterol-fed rabbit.
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</strong>Arad Y, Badimon JJ, Badimon L, Hembree WC, Ginsberg HN. Fiziol Zh Im I M Sechenova. 1995
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Feb;81(2):47-52. <strong>[The unknown physiological role of carbon dioxide]</strong> Baev VI, Vasil'eva IV,
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L'vov SN, Shugalei IV. Am J Clin Nutr. 2004 Oct;80(4):855-61. <strong>Dietary cholesterol does not increase
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biomarkers for chronic disease in a pediatric population from northern Mexico.</strong> Ballesteros MN,
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Cabrera RM, Saucedo Mdel S, Fernandez ML. Atherosclerosis. 2002 Jun;162(2):425-32. <strong>Changes in LDL size
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and HDL concentration in normal and preeclamptic pregnancies.</strong> Belo L, Caslake M, Gaffney D,
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