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    <head><title>Cholesterol, longevity, intelligence, and health.</title></head>
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        <h1>
            Cholesterol, longevity, intelligence, and health.
        </h1>

        <strong>
            The biological meaning of cholesterol is just starting to be explored. Everything that doctors know about
            cholesterol is wrong. New information about cholesterol is clarifying important issues in physiology and
            pathology.
        </strong>

        Medical magazines and television stations like to propagate the idea that cholesterol is bad stuff, and as a
        result, that cliche is known to almost every American. Recent journal articles have promoted the idea that "the
        lower the serum cholesterol is, the better" it is for the health of the patient. The theory that heart disease
        is "caused by cholesterol" has gone through several stages, and most recently the use of the "statin" drugs has
        revived it in a radical way. One consistent theme for fifty years has been that people should eat more
        polyunsaturated fat and less saturated fat, to lower their cholesterol, and to avoid butter, cream, eggs, and
        "red meat," because they contain both saturated fat and cholesterol. Often, medical attention is focused on the
        fats in the atheroma, rather than on the whole disease process, including clotting factors, vascular spasms,
        heart rhythm, viscosity of the blood, deposition of calcium and iron in blood vessels, and the whole process of
        inflammation, including the reactions to absorbed bowel toxins. Almost 100 years ago, some experiments in Russia
        showed that feeding rabbits cholesterol caused them to develop atherosclerosis, but subsequent experiments
        showed that rabbits are unusual in responding that way to cholesterol, and that even rabbits don't develop
        atherosclerosis from cholesterol if they are given a supplement of thyroid (Friedland, 1933). By 1936, it was
        clear that hypercholesterolemia in humans and other animals was caused by hypothyroidism, and that
        hypothyroidism caused many diseases to develop, including cardiovascular disease and cancer. There was already
        more reason at that time to think that the increased cholesterol was a protective adaptation than to think that
        it was maladaptive. The strange idea that cholesterol causes atherosclerosis was revived in the 1950s when the
        vegetable oil industry learned that their polyunsaturated oils lowered serum cholesterol. (Many other toxins
        lower cholesterol, but that is never mentioned.) The industry began advertising their oils as "heart
        protective," and they enlisted some influential organizations to help in their advertising<strong>:</strong> The
        American Dietetic Association, the American Heart Association, the US Dept. of Agriculture and FDA, and the AMA.
        Besides the early rabbit research, which didn't make their case against cholesterol and might actually have had
        implications harmful to their argument (since Anitschkow had used vegetable oil as solvent for his cholesterol
        feedings), the oil industry helped to create and promote a large amount of fraudulent and unscientific work. The
        death rate from heart disease in the United States began increasing early in the twentieth century, and it
        reached its peak from about 1950 to 1975, and then began declining. During the decades in which the death rate
        was rising, consumption of animal fat was decreasing, and the use of vegetable oil was increasing. In the
        southern European countries that have been said to show that eating very little animal fat prevents heart
        disease, the trends after the second world war have been the opposite--they have been eating more animal fat
        without an increase in heart disease. The correspondence between heart disease and consumption of saturated fat
        and cholesterol is little more than advertising copy. If people were looking for the actual causes of heart
        disease, they would consider the factors that changed in the US during the time that heart disease mortality was
        increasing. Both increases in harmful factors, and decreases in protective factors would have to be considered.
        The consumption of manufactured foods, pollution of air and water, the use of lead in gasoline, cigarette
        smoking, increased medicalization and use of drugs, psychosocial and socioeconomic stress, and increased
        exposure to radiation--medical, military, and industrial--would be obvious things to consider, along with
        decreased intake of some protective nutrients, such as selenium, magnesium, and vitamins. But those harmful
        factors all had their defenders<strong>:</strong> Who defends socioeconomic stress? All of the social
        institutions that fail to alleviate it. In 1847, Rudolph Virchow was sent to Poland to study the health
        situation there, and when he returned, the highly regarded anatomist, physiologist and pathologist announced
        that the Poles wouldn't have a health problem if the government would stop oppressing them, and institute
        economic reforms to alleviate their poverty. The reforms weren't made, and Virchow lost his job. Other harmful
        factors, such as seed oils, degraded foods, and radiation, have specific, very well organized and powerful
        lobbies to defend them. Despite the growing knowledge about the dangers of polyunsaturated fats, many medical
        articles are still advocating the "official" heart protective diet (e.g., "<strong>... </strong>
        diets using nonhydrogenated unsaturated fats as the predominant form of dietary fat," Hu and Willet, 2002). Some
        dogs alertly look at the thing a person is pointing at, other dogs just sniff the pointing finger. The
        publicists who disregard the complete nutritional and ecological situation, to focus on cholesterol and fat in
        the diet, are like the finger sniffers. Recent articles in the medical and lipids journals are praising the 1950
        work of J. W. Gofman, and the 1914 rabbit studies of N. N. Anitschkow, as the research that revealed cholesterol
        to be the cause of heart disease. Anitschkow and his co-workers, however, understood that their experiment
        hadn't explained human heart disease, and John Gofman, about 50 years after publishing his work on the
        lipoproteins, has done some large studies that could be crucial in disproving the doctrine that has become
        almost a national religion. He has shown that mortality from both heart disease and cancer corresponds very
        closely to the population's exposure to medical services, and specifically to medical radiation. During the peak
        years of heart disease mortality, medical x-rays gave very large doses of radiation with each exposure, and the
        population was also exposed to radioactive fallout from atomic bomb testing (explosions from 1945 to 1963
        produced a peak of heavy fallout that persisted through the 'sixties and into the 'seventies). Around 1971,
        someone noticed that the commercial cholesterol being used in feeding experiments was oxidized, that is, it
        wasn't really cholesterol. Comparing carefully prepared, unoxidized cholesterol with the oxidized degraded
        material, it was found that dietary cholesterol wasn't necessarily atherogenic (Vine, et al., 1998). Dietitians
        often recommend eating poached salmon, rather than "red meat," to lower cholesterol. Experimenters have measured
        the toxic oxidized cholesterol in different foods prepared in a variety of ways. Steaming salmon produced
        several times as much oxidized cholesterol as frying it, because of the longer cooking time that allowed the
        polyunsaturated fatty acids to break down, producing toxins such as acrolein and free radicals that oxidize the
        cholesterol and other components of the fish. The toxic cholesterol content of the steamed salmon was much
        higher than that of beef cooked at a high temperature. When oxidized polyunsaturated oils, such as corn oil or
        linoleic acid, are added to food, they appear in the blood lipids, where they accelerate the formation of
        cholesterol deposits in arteries (Staprans, et al., 1994, 1996). Stress accelerates the oxidation of the
        polyunsaturated fatty acids in the body, so people who consume unsaturated vegetable oils and fish will have
        some oxidized cholesterol in their tissues. The constant turnover of cholesterol in the tissues tends to lower
        the proportion of the toxic oxidized degradation products of cholesterol, but in hypothyroidism, the use of
        cholesterol is slowed, allowing the toxic forms to accumulate. Many antioxidant nutrients act like a thyroid
        supplement did in the 1934 rabbit experiments, preventing atherosclerosis even when extra toxic cholesterol is
        given to the animals. People who eat seafood get much more selenium in their diet than people who eat nothing
        from the sea, and selenium is one of the extremely protective nutrients that prevent atherosclerosis in animal
        experiments with excess cholesterol. It is well established that several antioxidant nutrients are protective
        factors in heart disease. The medical establishment has expended a great amount of money and time in the last 60
        years fighting the use of vitamin E or selenium for treating or preventing heart disease, though many physicians
        now take vitamin E themselves. But people who study free radical chemistry recognize that polyunsaturated fats
        are highly susceptible to oxidation, and that saturated fats tend to slow their degradation, acting to some
        extent as antioxidants. Several experiments and observations have shown that cholesterol itself can protect
        against damaging oxidation of polyunsaturated fats, protecting DNA and other vital components of the cell. A
        consistent program to prevent the oxidation of cholesterol would have to include all of the vitamins and
        minerals that are involved in antioxidant defense, avoidance of nutrients that exacerbate the destructive
        oxidations, and an effort to normalize the hormones and other factors, such as carbon dioxide, that have
        protective effects against free radical oxidation. A low level of cholesterol might increase susceptibility to
        the oxidants. The steroids in general, especially those produced in large amounts, progesterone and DHEA, are
        important parts of the antioxidant defenses. Cholesterol, either that produced internally by the cell, or taken
        in from the blood stream, is the precursor for all the steroids in the body. Several of the major steroid
        hormones are antiinflammatory, and cholesterol itself is antiinflammatory. (Mikko, et al., 2002; Kreines, et
        al., 1990). Cholesterol also protects against radiation damage, and many forms of toxin (saponins, cobra venom,
        chloroform--W.G. MacCallum, <em>
            A Text-book of</em>
        <em>Pathology,</em> 1937, Saunders Co.; many more recent studies show that it protects blood cells against
        hemolysis--breakdown of red blood cells--caused by heat and other harmful agents; e.g., Dumas, et al., 2002,
        Velardi, et al., 1991). Cholesterol, vitamin E, progesterone, and vitamin D are considered to be "structural
        antioxidants," that prevent oxidation partly by stabilizing molecular structures. One of the basic functions of
        cholesterol seems to be the stabilization of mitochondria, preventing their destruction by stress. Serious
        stress lowers ATP, magnesium, and carbon dioxide. When ATP and intracellular magnesium are decreased,
        cholesterol synthesis increases. During stress, free fatty acids are released from the tissues, and circulating
        in the bloodstream they are highly susceptible to oxidation. They contribute to the formation of the age
        pigment, lipofuscin, which is an oxygen-wasting substance that's found in the atheroma plaques in the damaged
        blood vessels. Iron and calcium accumulation adds to the tissue damage. The hemolysis which is promoted by
        polyunsaturated fats and an imbalance of antioxidants and oxidants, releases iron and heme into the blood
        stream. The incidence of atherosclerosis is increased when the body iron stores are high (Kiechl, et al., 1997),
        probably because of its role in lipid peroxidation and lipofuscin formation. Especially when the lining of the
        blood vessel is too permeable, because of the influence of polyunsaturated fats, prostaglandins, estrogen, etc.,
        the heme and iron will enter the endothelial cells, where the iron will catalyze the formation of free radicals,
        and the heme will be broken down by the enzyme heme oxygenase, into biliverdin, iron, and carbon monoxide, which
        can contribute to the oxidative stress of the cells. Carbon monoxide makes the blood vessel lining more
        permeable, allowing fats and fibrinogen to enter the cells (Allen, et al., 1988). Although cholesterol is
        protective against oxidative and cytolytic damage, the chronic free radical exposure will oxidize it. During the
        low cholesterol turnover of hypothyroidism, the oxidized variants of cholesterol will accumulate, so cholesterol
        loses its protective functions. When the metabolic pathways of the steroid hormones were being worked out, an
        experimenter perfused an isolated ovary with blood. When the amount of cholesterol in the blood pumped into the
        ovary was increased, the amount of progesterone in the blood leaving the ovary increased proportionately. In the
        healthy organism, cholesterol is constantly being synthesized, and constantly converted into steroid hormones,
        and, in the liver, into the bile salts that are secreted to emulsify fats in the intestine. Thyroid hormone and
        vitamin A are used in the process of converting cholesterol into pregnenolone, the immediate precursor of
        progesterone and DHEA. Anything that interfered with these processes would be disastrous for the organism. The
        supply of cholesterol, thyroid and vitamin A must always be adequate for the production of steroid hormones and
        bile salts. When stress suppresses thyroid activity, increased cholesterol probably compensates to some extent
        by permitting more progesterone to be synthesized. In very young people, the metabolic rate is very high, and
        the rapid conversion of cholesterol into pregnenolone, DHEA, and progesterone usually keeps the level of
        cholesterol in the blood low. In the 1930s, a rise in the concentration of cholesterol was considered to be one
        of the most reliable ways to diagnose hypothyroidism (<em>1936 Yearbook of Neurology, Psychiatry, and
            Endocrinology,</em> E.L. Sevringhaus, editor, Chicago, p. 533). With aging, the metabolic rate declines, and
        the increase of cholesterol with aging is probably a spontaneous regulatory process, supporting the synthesis of
        the protective steroids, especially the neurosteroids in the brain and retina. Many people refer to the
        structural importance of cholesterol for "membranes," and often imply that the membranes are just at the surface
        of the cell (the plasma membrane). But in fact cholesterol is found in the nucleus in the chromosomes, bound to
        DNA and in the nuclear matrix that governs the activation of genes, and in the mitotic spindle, which regulates
        separation of the chromosomes during cell division<strong>:</strong> without sufficient cholesterol, cells
        divide irregularly, producing aneuploid daughter cells (i.e., they have an abnormal number of chromosomes).
        Aneuploidy is now coming to be recognized as an essential feature of cancer cells. A significant amount of
        cholesterol was recently discovered to bind to hemoglobin, suggesting that it will be found in association with
        many other types of protein, when it occurs to anyone to look for it. Osmotic regulation, which is closely
        involved in cell division and other functions, appears to require cholesterol synthesis. Around 1985, a big
        study in Hungary showed that lowering cholesterol with drugs caused a huge increase in the cancer death rate.
        Hundreds of publications appeared in the U.S. saying that wasn't possible, because low cholesterol is good, the
        lower the better. The extreme increase in cancer mortality in the Hungarian study was probably the result of the
        drug that was commonly used at that time to lower cholesterol, but the pattern of mortality in that study was
        approximately the same pattern seen in any group with very low cholesterol. In the last 20 years, there have
        been many studies showing that lowering cholesterol increases mortality, especially from cancer and suicide, and
        that people with naturally low cholesterol are more likely to die from cancer, suicide, trauma, and infections
        than people with normal or higher than average cholesterol. The increased mortality from accidents and suicide
        when cholesterol is lowered is reminiscent of the problems seen in progesterone deficiency, and it's very likely
        that a deficiency of the neurosteroids accounts for it. A deficiency of progesterone and other neurosteroids
        (the steroids synthesized by the nerves themselves) causes depression of mood and impaired learning ability,
        among other neurological changes. As was the case with cancer, the pharmaceutical industry continues to deny
        that their anticholesterol drugs cause suicide, depression, and dementia, but there is a large amount of
        evidence from human as well as animal studies showing that mood and intelligence are depressed by lowering
        cholesterol. Simply injecting cholesterol into animals can improve their learning ability. In the Framingham
        heart study of 1894 people extending over a period of about 20 years, people with cholesterol naturally in the
        "desirable" range, below 200 mg.%, scored lower on "verbal fluency, attention/concentration, abstract reasoning,
        and a composite score measuring multiple cognitive domains" than those with higher cholesterol (Elias, et al.,
        2005).
        <hr />

        The next step in studies of this sort should be to see how the combination of extra thyroid with adequate
        cholesterol influences longevity. The rising cholesterol that commonly occurs with aging is probably only
        partial compensation for declining thyroid function, and by optimizing all of the protective factors, radical
        changes in the aging process may be possible. In the roundworm C. elegans, which is now a very popular animal
        for testing aging theories, because its genes and cells have been thoroughly "mapped," it was recently found
        that adding a gene that simply allows it to synthesize cholesterol, rather than depending on food for its
        sterols, increased its life span by as much as 131% (Lee, et al., 2005). That would be like increasing the human
        lifespan to about 175 years. These worms are also more resistant than normal to radiation and heat stress. The
        cells of the thymus are extremely sensitive to radiation and other stressors, and their enrichment with
        cholesterol inhibits lipid peroxidation, DNA degradation, and death in response to radiation (Posokhov, et al.,
        1992). Many high altitude regions of the world have high levels of background radiation, from minerals as well
        as cosmic rays, so it has been dogmatically believed that mortality from cancer and heart disease would increase
        with altitude, but the reverse is true. Because oxygen at lower pressure displaces less carbon dioxide from the
        blood, the body is able to retain more carbon dioxide at high altitude. Carbon dioxide protects against free
        radicals, and also helps to deliver oxygen to tissues, to maintain efficient energy production, and to prevent
        cellular stress. One study found 18 times higher incidence of hypertension in low altitude populations than in
        high altitude people (Fiori, et al., 2000). For many years, these principles have been applied in treating
        atherosclerosis and other degenerative diseases, in high altitude health resorts. Even a short period of hypoxic
        treatment can improve the body's ability to eliminate atherogenic lipid peroxides, possibly by improving the
        stress-resistant functions of the liver (Meerson, et al., 1988; Aleshin, et al., 1993; Kitaev, et al., 1999). I
        think editors of medical journals generally see themselves as the purveyors of enlightenment, i.e., as the
        pushers of the stylish and prestigious doctrines. (Selectivity of evidence to serve the received doctrine is the
        commonest form of scientific dishonesty.) But because their mental framework is culturally narrow, they
        sometimes publish things which later could turn out to be embarrassing (if inconsistency could embarrass such
        types). The recent discovery that the size of the LDL particle is a predominant factor in the development of
        atherosclerosis is one of those things that the editors and medical professors should find embarrassing. Smaller
        lipoprotein particles have a greater surface area exposed to the oxidative factors in the serum, and so are more
        rapidly degraded into toxic substances. People with larger LDL particles are remarkably resistant to heart
        disease, and the drug companies are looking for a way to turn their lipoproteins into products. But the
        conditions that govern the size of the LDL particles are physically and chemically reasonable, and are causing
        confusion among the doctinaire. There have been several studies in India showing that consumption of butter and
        ghee is associated with a low incidence of heart disease; for example, according to one study, people in the
        north eat 19 times more fat (mostly butter and ghee) than in the south, yet the incidence of heart disease is
        seven times higher in the south. A study in Sweden found that the fatty acids in milk products are associated
        with larger LDL particles (Sjogren, et al., 2004). In a 35 day study, when butter (20% of the calories) was
        compared to various kinds of margarine (with more trans fatty acids) in a similar quantity, the LDL particles
        were bigger on the butter diet (Mauger, et al., 2003). But in a study of the habitual diet of 414 people, large
        LDL particles were found to be correlated with increased intake of protein, animal fat, and trans fatty acids
        (Kim and Campos, 2003). In a study of the effect of dietary cholesterol on the atherogenicity of the blood
        lipids, 52 people were given either an egg diet (with 640 mg. of extra cholesterol per day) or a placebo diet
        for 30 days. Those whose LDL increased the most on the high cholesterol diet had the largest LDL particle size
        (Herron, et al., 2004). They concluded that "these data indicate that the consumption of a high-cholesterol diet
        does not negatively influence the atherogenicity of the LDL particle." A similar study in Mexico found that
        "Intake of 2 eggs/d results in the maintenance of LDL:HDL and in the generation of a less atherogenic LDL in
        this population of Mexican children" (Ballesteros, et al., 2004). The estrogen industry tried to get into the
        heart disease business several times over the last half century, and they are still trying, but the issue of
        estrogen's harmful effects on LDL particle size is getting some attention. Estrogen clearly decreases the size
        of the LDL particles (Campos, et al., 1997). The LDL particles also get smaller at menopause, and in polycystic
        ovary syndrome, and in preeclamptic pregnancies, all of which involve a low ratio of progesterone to estrogen.
        But there are still journals publishing claims that estrogen will protect against heart disease, by reducing the
        atherogenic response in increasingly mysterious ways. Occasionally, people have argued not only that estrogen is
        the factor that protects women against heart attacks, but that androgens predispose men to heart disease. One of
        their arguments has been that androgens lower HDL, the "good" form of cholesterol. However, there are many
        studies that show that testosterone and DHEA (Arad, et al., 1989) are protective against atherosclerosis. The
        LDL particle size is increased by androgens, and postprandial triglyceridemia is decreased (Hislop, et al.,
        2001). The studies in the 1930s that showed the protective effects of thyroid hormone against atherosclerosis
        and heart disease have sometimes been interpreted to mean that the thyroid is protective <strong><em>because</em
            ></strong>
        it lowers the cholesterol, but since cholesterol is protective, rather than harmful, something else explains the
        protective effect. Ever since the time of Virchow, who called atherosclerosis <strong><em>arteritis
                deformans,</em></strong>
        the inflammatory nature of the problem has been clear to those who aren't crazed by the anticholesterol cult. We
        are all subject to a variable degree of inflammatory stimulation from the endotoxin absorbed from the intestine,
        but a healthy liver normally prevents it from reaching the general circulation, and produces a variety of
        protective factors. The HDL lipoprotein is one of these, which protects against inflammation by binding
        bacterial endotoxins that have reached the bloodstream. (Things that increase absorption of endotoxin--exercise,
        estrogen, ethanol--cause HDL to rise.) Chylomicrons and VLDL also absorb, bind, and help to eliminate
        endotoxins. All sorts of stress and malnutrition increase the tendency of endotoxin to leak into the
        bloodstream. Thyroid hormone, by increasing the turnover of cholesterol and its conversion into the protective
        steroids, is a major factor in keeping the inflammatory processes under control. In hypothyroidism, the
        pituitary secretes more TSH to activate the thyroid gland, but TSH itself has a variety of pro-inflammatory
        actions. The C-reactive protein (CRP), which is recognized as a factor contributing to atherosclerosis, is
        increased in association with TSH. CRP activates mast cells, which are found in the atheroma plaques, to produce
        a variety of pro-inflammatory substances, including histamine. The belief that cells are controlled by a plasma
        membrane, and that cholesterol's main function is to participate in that membrane, has led to a culture that
        treats cholesterol physiology with little curiosity. A different perspective on the cell starts with a
        recognition of the lipophilic nature of the structural proteins (not "membrane proteins," but things like
        cytoskeleton-cytoplasmic ground substance, spindle, centrosome-centrioles, nuclear matrix, etc.), with which
        lipids interact. Modifying an extremely complex system, the living substance, cholesterol participates in
        complexity, and must be investigated with subtlety. I suspect that the physiological meaning of cholesterol has
        to do with movement, stability, differentiation, memory, and sensitivity of the parts of the cells, that is,
        with everything physiological. The functions of cholesterol parallel the functions of other sterols in plants
        and other types of organism. Its functions have been refined and extended with the development of other
        steroids, such as progesterone, as biological requirements have evolved, but cholesterol is still at the center
        of this system. To deliberately interfere with its synthesis, as contemporary medicine does, reveals a terrible
        arrogance. Many participants in the cholesterol-lowering cult believe that they have succeeded in hijacking our
        science culture, but when the patents on another generation of their drugs have expired, the cult could begin to
        fade away.

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