938 lines
63 KiB
HTML
938 lines
63 KiB
HTML
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<head><title>Fats and degeneration</title></head>
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<body>
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<h1>
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Fats and degeneration
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</h1>
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<p>
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<hr />
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<hr />
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<hr />
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</p>
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<p>
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<strong>50 years ago, in the first phase of marketing the polyunsaturated fatty acids (PUFA), linoleic acid
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was "heart protective," and the saturated fats raised cholesterol and caused heart disease.</strong>
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</p>
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<p>
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<strong>In the second phase, the other "essential fatty acid," linolenic acid, was said to be even better
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than linoleic acid.</strong>
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</p>
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<p>
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<strong>In the third phase, the longer chain omega -3 (omega minus three, or n minus three) fatty acids, DHA
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and EPA, are said to be even better than linolenic acid.</strong>
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</p>
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<p>
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<strong>Along the way, the highly unsaturated arachidonic acid, which we and other animals make out of the
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linoleic acid in foods, was coming to be identified with the "harmful animal fats." But we just didn't
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hear much about how the amount of arachidonic acid in the tissues depended on the amount of linoleic
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acid in the diet.</strong>
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</p>
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<p>
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<strong>U.S. marketing dominates the world economy, including of course the communication media, so we
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shouldn't expect to hear much about the role of PUFA in causing cancer, diabetes, obesity, aging,
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thrombosis, arthritis and immunodeficiency, or to hear about the benefits of the saturated fats.
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</strong>
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</p>
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<p>
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<strong>The saturated fats include the "tropical fats," because they are synthesized in very warm organisms,
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and are very stable at those temperatures. Their stability offers some protection against the unstable
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PUFA.
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</strong>
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</p>
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<p>
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<strong>Several of the degenerative conditions produced by the "essential fatty acids" can be reversed by
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use of saturated fats, varying in length from the short chains of coconut oil to the very long chains of
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waxes.</strong>
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</p>
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<p>
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<hr />
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<hr />
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<hr />
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</p>
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<p>
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When a person uses a drug, there is generally an awareness that the benefit has to be weighed against the
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side effects. But if something is treated as a "nutrient," especially an "essential nutrient," there is an
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implication that it won't produce undesirable side effects.
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</p>
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<p>
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Over the last thirty years I have asked several prominent oil researchers what the evidence is that there is
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such a thing as an "essential fatty acid." One professor cited a single publication about a solitary sick
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person who recovered from some sickness after being given some unsaturated fat. (If he had known of any
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better evidence, wouldn't he have mentioned it?) The others (if they answered at all) cited "Burr and Burr,
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1929." The surprising thing about that answer is that these people can consider any nutritional research
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from 1929 to be definitive. It's very much like quoting a 1929 opinion of a physicist regarding the
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procedure for making a hydrogen bomb. What was known about nutrition in 1929? Most of the B vitamins weren't
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even suspected, and it had been only two or three years since "vitamin B" had been subdivided into two
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factors, the "antineuritic factor," B<sub>1</sub>, and the "growth factor," B<sub>2</sub>. Burr had no way
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of really understanding what deficiencies or toxicities were present in his experimental diet.
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</p>
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<p>
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A few years after the first experiments, Burr put one of his "essential fatty acid deficient" rats under a
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bell jar to measure its metabolic rate, and found that the deficient animals were metabolizing 50% faster
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than rats that were given linoleic and linolenic acids as part of their diet. That was an important
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observation, but Burr didn't understand its implications. Later, many experiments showed that the
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polyunsaturated fats slowed metabolism by profoundly interfering with the function of the thyroid hormone
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and the cellular respiratory apparatus. Without the toxic fats, respiratory energy metabolism was very
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intense, and a diet that was nutritionally sufficient for a sluggish animal wouldn't necessarily be adequate
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for the vigorous animals.
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</p>
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<p>
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Several publications between 1936 and 1944 made it very clear that Burr's basic animal diet was deficient in
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various nutrients, especially vitamin B<sub>6</sub>. <strong>
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The disease that appeared in Burr's animals could be cured by fat free B-vitamin preparations, or by
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purified vitamin B6 when it became available.</strong>
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<strong>
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A zinc deficiency produces similar symptoms,
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</strong>
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and at the time Burr did his experiments, there was no information on the effects of fats on mineral
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absorption. If a diet is barely adequate in the essential minerals, increasing the metabolic rate, or
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decreasing intestinal absorption of minerals, will produce mineral deficiencies and metabolic problems.
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</p>
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<p>
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Although "Burr's disease" clearly turned out to be a B-vitamin deficiency, probably combined with a mineral
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deficiency, it continues to be cited as the basis justifying the multibillion dollar industry that has grown
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up around the "essential" oils.
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</p>
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<p>
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Two years before Burr's experiment, German researchers found that a fat-free diet prevented almost all
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spontaneous cancers in rats. Later work showed that the polyunsaturated fats both initiate and promote
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cancer. With that knowledge, the people who kept claiming that "linoleic, linolenic, and maybe arachidonic
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acid are the essential fatty acids," should have devoted some effort to finding out how much of that
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"essential nutrient" was enough, so that people could minimize their consumption of the carcinogenic stuff.
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</p>
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<p>
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Between the first and second world wars, cod liver oil was recommended as a vitamin supplement, at first as
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a source of vitamin A, and later as a source of vitamins A and D. But in the late 1940s, experimenters used
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it as the main fat in dogs' diet, and found that they all died from cancer, while the dogs on a standard
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diet had only a 5% cancer mortality. That sort of information, and the availability of synthetic vitamins,
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led to the decreased use of cod liver oil.
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</p>
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<p>
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But around that time, the seed oil industry was in crisis because the use of those oils in paints and
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plastics was being displaced by new compounds made from petroleum. The industry needed new markets, and
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discovered ways to convince the public that seed oils were better than animal fats. They were called the
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"heart protective oils," though human studies soon showed the same results that the animal studies had,
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namely, that they were toxic to the heart and increased the incidence of cancer.
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</p>
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<p>
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The "lipid hypothesis" of heart disease argued that cholesterol in the blood caused atherosclerosis, and
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that the polyunsaturated oils lowered the amount of cholesterol in the blood. Leaving behind the concept of
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nutritional essentiality, this allowed the industry (and their academic supporters, such as Frederick Stare
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at Harvard) to begin promoting the oils as having drug-like therapeutic properties. Larger amounts of
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polyunsaturated fat were supposed to be more protective by lowering the cholesterol, and were to be
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substituted for the saturated fats, which supposedly raised cholesterol and increased heart disease,
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producing atherosclerotic plaques in the blood vessels and increasing the formation of blood clots.
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</p>
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<p>
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Since all ordinary foods contain significant amounts of the polyunsaturated fats, there was no reason to
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think that, even if they were essential nutrients, people were likely to become deficient in them. So the
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idea of treating the seed oils as drug-like substances, to be taken in large amounts, appealed to the food
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oil industry.
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</p>
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<p>
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Prostaglandins, which are produced in the body by oxidizing the polyunsaturated fatty acids, provided an
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opportunity for the drug industry to get involved in a new market, and<strong>
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the prostaglandins offered a new way of arguing for the nutritional essentiality of linoleic and related
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acids: A whole system of "hormones" is made from these molecules.</strong> Since some of the
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prostaglandins suppress immunity, cause inflammation and promote cancer growth, some people have divided
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them into the "good prostaglandins" and the "bad prostaglandins."
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</p>
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<p>
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PGI2, or prostacyclin, is considered to be a good prostaglandin, because it causes vasodilatation, and so
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drug companies have made their own synthetic equivalents: Epoprostenol, iloprost, taprostene, ciprostene,
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UT-15, beraprost, and cicaprost. Some of these are being investigated for possible use in killing cancer.
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</p>
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<p>
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But many very useful drugs that already existed, including cortisol and aspirin, were found to achieve some
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of their most important effects by inhibiting the formation of the prostaglandins. It was the body's load of
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polyunsaturated fats which made it very susceptible to inflammation, stress, trauma, infection, radiation,
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hormone imbalance, and other fundamental problems, and drugs like aspirin and cortisone, which limit the
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activation of the stored "essential fatty acids," gain their remarkable range of beneficial effects partly
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by the restraint they impose on those stored toxins.
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</p>
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<p>
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Increasingly, the liberation of arachidonic acid from tissues during stress is seen as a central factor in
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all forms of stress, either acute (as in burns or exercise) or chronic (as in diabetes or aging). And, as
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the fat stores become more toxic, it seems that they more readily liberate the free fatty acids. (For
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example, see Iritani, et al., 1984)
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</p>
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<p>
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During this same period, a few experimenters were finding that animals which were fed a diet lacking the
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"essential" fatty acids had some remarkable properties<strong>:</strong> They consumed oxygen and calories
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at a very high rate, their mitochondria were unusually tough and stable, their tissues could be transplanted
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into other animals without provoking immunological rejection, and they were very hard to kill by trauma and
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a wide variety of toxins that easily provoke lethal shock in animals on the usual diet. As the Germans had
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seen in 1927, they had a low susceptibility to cancer, and new studies were showing that they weren't
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susceptible to various fibrotic conditions, including alcoholic liver cirrhosis.
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</p>
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<p>
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In 1967 a major nutrition publication, <em>Present Knowledge in Nutrition,</em>
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published Hartroft and Porta's observation that the "age pigment," lipofuscin, was formed in proportion to
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the amount of polyunsaturated fat and oxidants in the diet. The new interest in organ transplantation led to
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the discovery that the polyunsaturated fats prolonged graft survival, by suppressing the immune system.
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Immunosuppression was considered to have a role in the carcinogenicity of the "essential" fatty acids.
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</p>
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<p>
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Around the same time, there were studies that showed that unsaturated fats retarded brain development and
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produced obesity.
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</p>
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<p>
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Substances very much like the prostaglandins, called isoprostanes and neuroprostanes, are formed
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spontaneously from highly unsaturated fatty acids, and are useful as indicators of the rate of lipid
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peroxidation in the body. Most of the products of lipid peroxidation are toxic, as a result of their
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reactions with proteins, DNA, and the mitochondria. The age-related glycation products that are usually
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blamed on sugar, are largely the result of peroxidation of the polyunsaturated fatty acids.
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</p>
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<p>
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Through the 1970s, this sort of information about the harmful effects of the PUFA was being slowly
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assimilated by the culture, though many dietitians still spoke of "the essential fatty acids, vitamin F." By
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1980, it looked as though responsible researchers would see the promotion of cancer, heart disease,
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mitochondrial damage, hypothyroidism and immunosuppression caused by the polyunsaturated fats as their most
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important feature, and would see that there had never been a basis for believing that they were essential
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nutrients.
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</p>
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<p>
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But then, without acknowledging that there had been a problem with the doctrine of essentiality, fat
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researchers just started changing the subject, shifting the public discourse to safer, more profitable
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topics. The fats that had been called essential, but that had so many toxic effects, were no longer
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emphasized, and the failed idea of "essentiality" was shifted to different categories of polyunsaturated
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fats.
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</p>
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<p>
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The addition of the long chain highly unsaturated fats to baby food formulas was recently approved, on the
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basis of their supposed "essentiality for brain development." One of the newer arguments for the
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essentiality of the PUFA is that "they are needed for making cell membranes." But human cells can grow and
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divide in artificial culture solutions which contain none of the polyunsaturated fats, and no one has
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claimed that they are growing "without membranes."
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</p>
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<p>
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The long chain fats found in fish and some algae don't interfere with animal enzymes as strongly as the seed
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oils do, and so by comparison, they aren't so harmful. They are also so unstable that relatively little of
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them is stored in the tissues. (And when they are used as food additives, it's necessary to use antioxidants
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to keep them from becoming smelly and acutely toxic.)
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</p>
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<p>
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When meat is grilled at a high temperature, the normally spaced double bonds in PUFA migrate towards each
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other, becoming more stable, so that linoleic acid is turned into "conjugated linoleic acid." This analog of
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the "essential" linoleic acid competes against the linoleic acid in tissues, and protects against cancer,
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atherosclerosis, inflammation and other effects of the normal PUFA. Presumably, anything which interferes
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with the essential fatty acids is protective, when the organism contains dangerous amounts of PUFA. Even the
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trans-isomers of the unsaturated fatty acids (found in butterfat, and convertible into conjugated linoleic
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acid) can be protective against cancer.
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</p>
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<p>
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In the 1980s the oil promoters were becoming more sophisticated, and were publishing many experiments in
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which the fish oils were compared with corn oil, or safflower, or soy oil, and in many of those experiments,
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the animals' health was better when they didn't eat the very toxic seed oils, that contained the "essential
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fatty acids," linoleic and linoleic acids.
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</p>
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<p>
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Besides comparing the fish oils to the stronger toxins, another trick is to take advantage of the same
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immunosuppressive property that had seemed troublesome, and to emphasize their ability to temporarily
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alleviate some autoimmune or allergic diseases. X-rays were once used that way, to treat arthritis and
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ringworm, for example.
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</p>
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<p>
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And, knowing that cancer cells have the ability to consume large amounts of fatty acids, they would test
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these fats in tissue culture dishes, and demonstrate that they were poisonous, cytotoxic, to the fast
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growing cancer cells. Although they caused cancer in animals, if they could be shown to kill cancer cells in
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a dish, they could be sold as anticancer drugs/nutrients, with the special mystique of being "essential
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fatty acids." Strangely, their ability to kill cancer cells under some circumstances and to suppress some
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immunological reactions is being promoted in close association with the doctrine that these fats are
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nutritionally essential.
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</p>
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<p>
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Arachidonic acid is made from linoleic acid, and so those two oils were considered as roughly equivalent in
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their ability to meet our nutritional needs, but a large part of current research is devoted to showing the
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details of how fish oils protect against arachidonic acid. The "balance" between the omega -3 and the omega
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-6 fatty acids is increasingly being presented as a defense against the toxic omega -6 fats. But the
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accumulation of unsaturated fats with aging makes any defense increasingly difficult, and the extreme
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instability of the highly unsaturated omega -3 fats creates additional problems.
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</p>
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<p>
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PUFA and x-rays have many biological effects in common. They are immunosuppressive, but they produce their
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own inflammatory reactions, starting with increased permeability of capillaries, disturbed coagulation and
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proteolysis, and producing fibrosis and tumefaction or tissue atrophy. This isn't just a coincidence, since
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ionizing radiation attacks the highly unstable polyunsaturated molecules, simply accelerating processes that
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ordinarily happen more slowly as a result of stress and aging.
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</p>
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<p>
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Prolonged stress eventually tends to be a self-sustaining process, impairing the efficient respiratory
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production of energy, converting muscle tissue to amino acids, suppressing the thyroid, and activating
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further mobilization of fatty acids. Fatty acids are mobilized from within the structure of cells by
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phospholipases, and from fat tissues by other lipases.
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</p>
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<p>
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The highly unsaturated fatty acids, as well as the ordinary "essential fatty acids," act directly to
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increase capillary permeability, even without conversion into prostaglandins, and they interfere in many
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ways with the clotting and clot removal systems. The effects of PUFA taken in a meal probably disturb the
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clotting system more than the same quantity of saturated fat, contrary to many of the older publications.
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The PUFA are widely believed to prevent clotting, but when cod liver oil is given to "EFA deficient"
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animals, it activates the formation of clots (Hornstra, et al., 1989). An opposite effect is seen when a
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long chain fatty acid synergizes with aspirin, to restrain clotting (Molina, et al., 2003).
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</p>
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<p>
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Fibrosis is a generalized consequence of the abnormal capillary permeability produced by things that disrupt
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the clotting system. Estrogen, with its known contribution to the formation of blood clots and edema and
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fibrosis and tumors, achieves part of its effect by maintaining a chronically high level of free fatty
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acids, preferentially liberating arachidonic acid, rather than saturated fatty acids.
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</p>
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<p>
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Butter, beef fat, and lamb fat are the only mostly saturated fats produced on a large scale in the U.S., and
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the cheapness/profitability of the seed oils made it easy to displace them. But, in the face of the immense
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amount of propagandistic "health" claims that have been made against the saturated fats, it's instructive to
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look at some of their actual effects, especially on the clotting system, and the related fibrotic reactions.
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</p>
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<p>
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The saturated fatty acids are very unreactive chemically. Coconut oil, despite containing about 1% of the
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unstable PUFA, can be left in a bucket at room temperature for a year or more without showing any evidence
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of deterioration, suggesting that the predominance of saturated fat acts as an antioxidant for the
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unsaturated molecules. In the body, the saturated fats seem to act the same way, preventing or even
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reversing many of the conditions caused by oxidation of fats.
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</p>
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<p>
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The stress-induced liberation of arachidonic acid causes blood vessels to leak, and this allows fibrin to
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escape from the blood stream, into the basement membrane and beyond into the extracellular matrix, where it
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produces fibrosis. (Cancer, autoimmune diseases, and heart disease involve the same inflammatory,
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thrombotic, fibrotic processes as the nominal fibroses.) Scleroderma, liver cirrhosis, fibrosis of the
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lungs, heart, and other organs, and all the diseases in which fibrous tissue becomes dense and progressively
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contracts, involve similar processes, and the treatments which are successful are those that stop the
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inflammation produced by the oxidation of the polyunsaturated fatty acids.
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</p>
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<p>
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Retroperitoneal fibrosis is now known to be produced by estrogen, and is treated by antiestrogenic and
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antiserotonergic drugs, but as early as 1940 Alejandro Lipschutz demonstrated that chronic exposure to very
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low doses of estrogen produced fibromas in essentially every part of the body. Earlier, Loeb had studied the
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action of large doses of estrogen, which produced fibrosis of the uterus, as if it had accelerated aging.
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Following Lipschutz' work, in which he demonstrated the "antifibromatogenic" actions of pregnenolone and
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progesterone, several Argentine researchers showed that progesterone prevented and cured abdominal adhesions
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and other fibrotic conditions, including retroperitoneal fibrosis.
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</p>
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<p>
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Since estrogen produces both leakiness of the capillaries and excessive formation of fibrin, its effects
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will be seen first in the organs where it concentrates, but eventually anywhere capillaries leak fibrin.
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Estrogen activates the phospholipase which liberates arachidonic acid, and progesterone inhibits that
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phospholipase.
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</p>
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<p>
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As the fat tissues become more burdened with arachidonic acid, they release it more easily in response to
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moderately lipolytic stress signals. This could explain the increased levels of free fatty acids and lipid
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peroxidation that occur with aging. In animals that are "deficient" in the polyunsaturated fatty acids,
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adrenalin doesn't have the lipolytic effect that it does in animals on the standard diet. With aging, there
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is not only a tendency to have chronically higher free fatty acids in the blood, but for those fatty acids
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to be more unsaturated. The phospholipids of mitochondria and microsomes become more unsaturated with aging
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(Laganiere and Yu, 1993, Lee, et al., 1999). In the human retina there is a similar accumulation of PUFA
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with aging (Nourooz-Zadeh and Pereira, 1999), which implies that the aged retina will be more easily damaged
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by light.
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</p>
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<p>
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Several studies suggest that a high degree of unsaturation in the fats is fundamentally related to the aging
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process, since long lived species have a lower degree of unsaturation in their fats. Caloric restriction
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decreases the age-related accumulation of the fatty acids with 4 and 5 double bonds.
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</p>
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<p>
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Although publicity has emphasized the anti-inflammatory effects of fish oil, experiments show that it is
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extremely effective in producing alcohol-related liver cirrhosis. Breakdown products of polyunsaturated fats
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(isoprostanes and 4-HNE) are found in the blood of people with alcoholic liver disease (Aleynik, et al.,
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1998). In the absence of polyunsaturated fats, alcohol doesn't produce cirrhosis. Saturated fats allow the
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fibrosis to regress<strong>:</strong>
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</p>
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<p>
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<strong>"A diet enriched in saturated fatty acids effectively reverses alcohol-induced necrosis,
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inflammation, and fibrosis despite continued alcohol consumption. The therapeutic effects of saturated
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fatty acids may be explained, at least in part, by reduced endotoxemia and lipid peroxidation...."
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(Nanji, et al., 1995, 2001)</strong>
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</p>
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<p>
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In these studies, the animals were switched from fish oil to either palm oil or medium chain triglycerides
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(a major fraction of coconut oil). In other studies, Knittel, et al. (1995), show that fibrinogen, in "a
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clotting-like process," is involved in the development of liver fibrosis, and that this appears to provide a
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basis for the growth of additional extracellular matrix.
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</p>
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<p>
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Brown, et al. (1989), discussed this developmental process (leaky capillaries, fibrosis) in relation to
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wound healing, lung disease, and tumor growth.
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</p>
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<p>
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The relatively few studies of fish oil and linoleic acid that compare them with palmitic acid or coconut oil
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have produced some very important results. For example, pigs exposed to endotoxin developed severe lung
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problems (resembling "shock lung") when they had been on a diet with either fish oil or Intralipid (which is
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mostly linoleic acid, used for intravenous feeding in hospitals), but not after palmitic acid (Wolfe, et
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al., 2002).
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</p>
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<p>
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Eating low-fat seafood (sole, whitefish, turbot, scallops, oysters, lobster, shrimp, squid, etc.) once in a
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while can provide useful trace minerals, without much risk. However, fish from some parts of the ocean
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contain industrial contaminants in the fat, and large fish such as tuna, swordfish, Chilean sea bass and
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halibut contain toxic amounts of mercury in the muscles. Chilean sea bass (Patagonian toothfish) is very
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high in fat, too.
|
|
</p>
|
|
<p>
|
|
About ten years ago I met a young man with a degenerative brain disease, and was interested in the fact that
|
|
he (working on a fishing boat) had been eating almost a pound of salmon per day for several years. There is
|
|
now enough information regarding the neurotoxic effects of fish oil to justify avoidance of the fatty fish.
|
|
</p>
|
|
<p>
|
|
Some of the current advertising is promoting fish oil to prevent cancer, so it's important to remember that
|
|
there are many studies showing that it increases cancer.
|
|
</p>
|
|
<p>
|
|
The developmental and physiological significance of the type of fatty acid in the diet has been established
|
|
for a long time, but cultural stereotypes and commercial interests are threatened by it, so it can't be
|
|
discussed publicly.
|
|
</p>
|
|
|
|
<p>REFERENCES</p>
|
|
<p>
|
|
Alcohol Clin Exp Res 1998 Feb;22(1):192-6.<strong>
|
|
Increased circulating products of lipid peroxidation in patients with alcoholic liver disease.</strong>
|
|
Aleynik SI, Leo MA, Aleynik MK, Lieber CS
|
|
</p>
|
|
<p>
|
|
Ann N Y Acad Sci. 1976;275:28-46. <strong>Metabolic influences in experimental thrombosis.</strong>
|
|
Antoniades HN, Westmoreland N.
|
|
</p>
|
|
|
|
<p>
|
|
Nutr Cancer. 2001;41(1-2):91-7.<strong>
|
|
Vaccenic acid feeding increases tissue levels of conjugated linoleic acid and suppresses development of
|
|
premalignant lesions in rat mammary gland.</strong> Banni S, Angioni E, Murru E, Carta G, Melis MP,
|
|
Bauman D, Dong Y, Ip C.
|
|
</p>
|
|
<p>
|
|
Obstet Gynecol. 1987 Sep;70(3 Pt 2):502-4. <strong>The treatment of retroperitoneal fibromatosis with
|
|
medroxyprogesterone acetate.</strong> Barnhill D, Hoskins W, Burke T, Weiser E, Heller P, Park R. Wide
|
|
excision is the recommended primary therapy for retroperitoneal fibromatosis. Radiation therapy and a
|
|
variety of medications have been used to treat patients with recurrent tumors, but the response to these
|
|
agents has not been uniform. The patient presented was successfully treated with medroxyprogesterone acetate
|
|
for recurrent retroperitoneal fibromatosis that was refractory to multiple operative resections and
|
|
radiation therapy.
|
|
</p>
|
|
<p>
|
|
Medicina (B Aires). 1978 Mar-Apr;38(2):215-6. <strong>[Fibromatosis, relaxin and progesterone]</strong> [in
|
|
Spanish] Barousse AP. [Letter]
|
|
</p>
|
|
|
|
<p>
|
|
Medicina (B Aires). 1985;45(2):159-63.<strong>
|
|
Progesterone as therapy for retroperitoneal fibrosis.</strong> Bilder CR, Barousse AP, Mazure PA.
|
|
</p>
|
|
<p>
|
|
Adv Exp Med Biol. 1976;75:497-503. <strong>Effect of ionizing radiation on liver microcirculation and
|
|
oxygenation.</strong> Bicher HI, Dalrymple GV, Ashbrook D, Smith R, Harris D.
|
|
</p>
|
|
<p>
|
|
Lipids. 1981 May;16(5):323-7. <strong>Iodination of docosahexaenoic acid by lactoperoxidase and thyroid
|
|
gland in vitro: formation of an lodolactone.</strong>
|
|
Boeynaems JM, Watson JT, Oates JA, Hubbard WC. "In the presence of iodide, hydrogen peroxide and
|
|
lactoperoxidase, docosahexaenoic acid (22:6 omega 3) was converted into iodinated compounds."
|
|
</p>
|
|
<p>
|
|
Am Rev Respir Dis 1989 Oct;140(4):1104-7.<strong>
|
|
Leaky vessels, fibrin deposition, and fibrosis: a sequence of events common to solid tumors and to many
|
|
other types of disease.</strong> Brown LF, Dvorak AM, Dvorak HF
|
|
</p>
|
|
<p>
|
|
Medicina (B Aires). 1979 Sep-Oct;39(5):652-4.<strong>
|
|
[Effect of progesterone in the treatment of a patient with idiopathic retroperitoneal fibrosis]</strong>
|
|
[in Spanish] Casadei DH, Najun Zarazaga C, Leanza HJ, Schiappapietra JH.
|
|
</p>
|
|
<p>
|
|
Biochem Mol Biol Int 1993 Jan;29(1):175-83.<strong>
|
|
Influence of antioxidant vitamins on fatty acid inhibition of lymphocyte proliferation.</strong> Calder
|
|
PC, Newsholme EA. "Vitamin E (10 microM) increased human lymphocyte proliferation by 35%. However, vitamin E
|
|
did not prevent the inhibitory effects of fatty acids upon lymphocyte proliferation. It is concluded that
|
|
inhibition of lymphocyte proliferation by fatty acids is not caused by their conversion to peroxidised
|
|
products."
|
|
</p>
|
|
|
|
<p>
|
|
Clin Sci (Lond). 1992 Jun;82(6):695-700.<strong>
|
|
Polyunsaturated fatty acids suppress human peripheral blood lymphocyte proliferation and interleukin-2
|
|
production.</strong> Calder PC, Newsholme EA.
|
|
</p>
|
|
<p>
|
|
J Neurochem 1980 Oct;35(4):1004-7. <strong>
|
|
Transient formation of superoxide radicals in polyunsaturated fatty acid-induced brain swelling.</strong
|
|
> Chan PH, Fishman RA
|
|
</p>
|
|
<p>
|
|
Int J Cancer 2001 Mar 15;91(6):894-9. <strong>Tumor invasiveness and liver metastasis of colon cancer cells
|
|
correlated with cyclooxygenase-2 (COX-2) expression and inhibited by a COX-2-selective inhibitor,
|
|
etodolac.</strong> Chen WS, Wei SJ, Liu JM, Hsiao M, Kou-Lin J, Yang WK.
|
|
</p>
|
|
|
|
<p>
|
|
Free Radic Biol Med. 1999 Jul;27(1-2):51-9. <strong>Arachidonic acid interaction with the mitochondrial
|
|
electron transport chain promotes reactive oxygen species generation.</strong> Cocco T, Di Paola M, Papa
|
|
S, Lorusso M.
|
|
</p>
|
|
<p>
|
|
Clin Exp Metastasis 1997 Jul;15(4):410-7. <strong>Influence of lipid diets on the number of metastases and
|
|
ganglioside content of H59 variant tumors.</strong> Coulombe J, Pelletier G, Tremblay P, Mercier G, Oth
|
|
D.
|
|
</p>
|
|
<p>
|
|
BJU Int. 2003 Jun;91(9):830-8. <strong>Fibrin as an inducer of fibrosis in the tunica albuginea of the rat:
|
|
a new animal model of Peyronie's disease.</strong>
|
|
|
|
Davila HH, Ferrini MG, Rajfer J, Gonzalez-Cadavid NF.
|
|
</p>
|
|
<p>
|
|
Carcinogenesis 1994 Jul;15(7):1399-404. <strong>Peroxidation of linoleic, arachidonic and oleic acid in
|
|
relation to the induction of oxidative DNA damage and cytogenetic effects.</strong> de Kok TM, ten
|
|
Vaarwerk F, Zwingman I, van Maanen JM, Kleinjans JC.
|
|
</p>
|
|
<p>
|
|
Biochem Biophys Res Commun. 2000 Oct 14;277(1):128-33. <strong>Arachidonic acid causes cytochrome c release
|
|
from heart mitochondria.</strong> Di Paola M, Cocco T, Lorusso M.
|
|
</p>
|
|
|
|
<p>
|
|
J Physiol. 1998 Mar 1;507 ( Pt 2):541-7. <strong>Arachidonic acid increases cerebral microvascular
|
|
permeability by free radicals in single pial microvessels of the anaesthetized rat.
|
|
</strong>
|
|
Easton AS, Fraser PA.
|
|
</p>
|
|
<p>
|
|
Am J Physiol. 1992 May;262(5 Pt 1):E637-43. ATP depletion stimulates calcium-dependent protein breakdown in
|
|
chick skeletal Muscle. Fagan JM, Wajnberg EF, Culbert L, Waxman L.
|
|
</p>
|
|
<p></p>
|
|
<p>
|
|
Cancer Res 1998 Aug 1;58(15):3312-9. <strong>Dietary omega-3 polyunsaturated fatty acids promote colon
|
|
carcinoma metastasis in rat liver.</strong> Griffini P, Fehres O, Klieverik L, Vogels IM, Tigchelaar W,
|
|
Smorenburg SM, Van Noorden CJ.
|
|
</p>
|
|
|
|
<p>
|
|
J Indian Med Assoc 1997 Mar;95(3):67-9, 83.<strong>
|
|
Association of dietary ghee intake with coronary heart disease and risk factor prevalence in rural
|
|
males.
|
|
</strong>
|
|
Gupta R, Prakash H
|
|
</p>
|
|
<p>
|
|
Transplantation 1995 Sep 27;60(6):570-7. <strong>The effect of dietary polyunsaturated fatty acids (PUFA) on
|
|
acute rejection and cardiac allograft blood flow in rats.</strong> Haw MP, Linnebjerg H, Chavali SR,
|
|
Forse RA. "The immunosuppressive effect of dietary PUFA warrants further investigation, and their use as a
|
|
possible adjunctive treatment in organ transplantation should be considered."
|
|
</p>
|
|
<p>
|
|
Dtsch Med Wochenschr. 2003 Jun 20;128(25-26):1395-8. <strong>[Rare cause of chronic abdominal pain:
|
|
retractile mesenteritis]</strong> [in German] Hermann F, Speich R, Schneemann M. "Retractile
|
|
mesenteritis is a rare cause of chronic abdominal pain with variable symptoms. Its aetiology is unknown. In
|
|
case of bowel ischemia a surgical approach is preferred, milder forms may be treated with immunosuppressive
|
|
agents as well as oral progesterone. Progesterone has exhibited positive effects on fatty tissue with
|
|
successful treatment in desmoid tumors and retroperitoneal fibrosis. Here in we could demonstrate its safe
|
|
and efficient use in a patient with retractile mesenteritis."
|
|
</p>
|
|
|
|
<p>
|
|
Mech Ageing Dev 2001 Apr 15;122(4):427-43. <strong>Effect of the degree of fatty acid unsaturation of rat
|
|
heart mitochondria on their rates of H2O2 production and lipid and protein oxidative damage.</strong>
|
|
Herrero A, Portero-Otin M, Bellmunt MJ, Pamplona R, Barja G. "Previous comparative studies have shown that
|
|
long-lived animals have lower fatty acid double bond content in their mitochondrial membranes than
|
|
short-lived ones. In order to ascertain whether this trait protects mitochondria by decreasing lipid and
|
|
protein oxidation and oxygen radical generation, the double bond content of rat heart mitochondrial
|
|
membranes was manipulated by chronic feeding with semi-purified AIN-93G diets rich in highly unsaturated
|
|
(UNSAT) or saturated (SAT) oils. UNSAT rat heart mitochondria had significantly higher double bond content
|
|
and lipid peroxidation than SAT mitochondria. They also showed increased levels of the markers of protein
|
|
oxidative damage malondialdehyde-lysine, protein carbonyls, and N(e)-(carboxymethyl)lysine adducts." "These
|
|
results demonstrate that increasing the degree of fatty acid unsaturation of heart mitochondria increases
|
|
oxidative damage to their lipids and proteins, and can also increase their rates of mitochondrial oxygen
|
|
radical generation in situations in which the degree of reduction of Complex III is higher than normal.
|
|
These observations strengthen the notion that the relatively low double bond content of the membranes of
|
|
long-lived animals could have evolved to protect them from oxidative damage."
|
|
</p>
|
|
<p>
|
|
Biochem J. 1994 May 15;300 ( Pt 1):251-5. <strong>Regulation of fibrinolysis by non-esterified fatty
|
|
acids.</strong> Higazi AA, Aziza R, Samara AA, Mayer M. "<strong>Examination of the fatty acid
|
|
specificity showed that a minimal chain length of 16 carbon atoms and the presence of at least one
|
|
double bond, preferably in a cis configuration, were required for inhibition of the fibrinolytic
|
|
activity of plasmin."
|
|
</strong>
|
|
</p>
|
|
<p>
|
|
Science. 1976 Feb 27;191(4229):861-2. <strong>Nicotinic acid reduction of plasma volume loss after thermal
|
|
trauma.</strong> Hilton JG, Wells CH. Intravenous administration of nicotinic acid to the anesthetized
|
|
dog prior to thermal trauma reduced plasma loss at 10 minutes after burn from 7 milliliters per kilogram to
|
|
less than 2 millimeters per kilogram. During the next 50 minutes plasma loss was the same in treated and
|
|
untreated animals. An additional dose of nicotinic acid 30 minutes after burn prevented this further loss.
|
|
</p>
|
|
|
|
<p>
|
|
Z Gesamte Inn Med. 1976 Oct 15;31(20):838-43. <strong>[Age-dependence of catecholamine effects in man. IV.
|
|
Effects of specific inhibitors on the lipolytic action of alpha and beta adrenergics]</strong> [in
|
|
German] Hoffmann H.
|
|
</p>
|
|
<p>
|
|
Neurochem Res. 2000 Feb;25(2):269-76. <strong>Cortical impact injury in rats promotes a rapid and sustained
|
|
increase in polyunsaturated free fatty acids and diacylglycerols.</strong> Homayoun P, Parkins NE,
|
|
Soblosky J, Carey ME, Rodriguez de Turco EB, Bazan NG.<strong> </strong>"At day one, free 22:6 and 22:6-DAGs
|
|
showed the greatest increase (590% and 230%, respectively). These results suggest that TBI elicits the
|
|
hydrolysis of phospholipids enriched in excitable membranes, targeting early on 20:4-phospholipids (by 30
|
|
min post- trauma) and followed 24 hours later by<strong>
|
|
preferential hydrolysis of DHA-phospholipids. These lipid metabolic changes may contribute to the
|
|
initiation and maturation of neuronal and fiber track degeneration observed following cortical impact
|
|
injury."</strong>
|
|
</p>
|
|
<p>
|
|
Thromb Res. 1989 Jan 1;53(1):45-53. <strong>Normalization by dietary cod-liver oil of reduced thrombogenesis
|
|
in essential fatty acid deficient rats.</strong>
|
|
Hornstra G, Haddeman E, Don JA.
|
|
</p>
|
|
<p>
|
|
Radiographics. 2003 Nov-Dec;23(6):1561-7. <strong>CT Findings in Sclerosing Mesenteritis (Panniculitis):
|
|
Spectrum of Disease.</strong> Horton KM, Lawler LP, Fishman EK.
|
|
</p>
|
|
<p>
|
|
Nutr Cancer. 1985;7(4):199-209. <strong>Isomeric fatty acids and tumorigenesis: a commentary on recent
|
|
work.</strong> Hunter JE, Ip C, Hollenbach EJ. "Neither epidemiological nor experimental studies
|
|
published to date have demonstrated any valid association between trans fatty acid ingestion and
|
|
tumorigenesis. A recent study showed that under controlled conditions, a fat with a high content of trans
|
|
fatty acids did not promote the development of mammary tumors induced in rats by
|
|
7,12-dimethylbenz[a]anthracene to any greater extent than did a comparable fat with a high content of cis
|
|
fatty acids. In addition, in this<strong>
|
|
study a high trans fat was less tumor promoting than was a blend of fats that simulated the dietary fat
|
|
composition of the United States and had a lower level of trans fatty acids.</strong>"
|
|
</p>
|
|
|
|
<p>
|
|
Medicina (B Aires). 1978 Mar-Apr;38(2):215. <strong>[Progesterone and retroperitoneal fibrosis]</strong> [in
|
|
Spanish] Introzzi A.[Letter]
|
|
</p>
|
|
<p>
|
|
Cancer Res. 1985 May;45(5):1997-2001. <strong>Requirement of essential fatty acid for mammary tumorigenesis
|
|
in the rat.</strong> Ip C, Carter CA, Ip MM. "<strong>Mammary tumorigenesis was very sensitive to
|
|
linoleate intake and increased proportionately in the range of 0.5 to 4.4% of dietary
|
|
linoleate."</strong>
|
|
</p>
|
|
<p>
|
|
Biochim Biophys Acta. 1984 Nov 6;802(1):17-23.<strong>
|
|
Activation of bovine platelets induced by long-chain unsaturated fatty acids at just below their lytic
|
|
concentrations, and its mechanism.</strong> Kitagawa S, Endo J, Kametani F.
|
|
</p>
|
|
|
|
<p>
|
|
Clin Exp Metastasis 2000;18(5):371-7. <strong>Promotion of colon cancer metastases in rat liver by fish oil
|
|
diet is not due to reduced stroma formation.</strong>
|
|
Klieveri L, Fehres O, Griffini P, Van Noorden CJ, Frederiks WM. <strong>
|
|
"Recently, it was demonstrated that dietary omega-3 polyunsaturated fatty acids (PUFAs) induce 10-fold
|
|
more metastases in number and 1000-fold in volume in an animal model of colon cancer metastasis in rat
|
|
liver."</strong>
|
|
</p>
|
|
<p>
|
|
Folia Haematol Int Mag Klin Morphol Blutforsch. 1977;104(1):1-10. <strong>[Review: hemorrhagic diathesis
|
|
resulting from acute exposure to ionizing Radiation]</strong>
|
|
[Article in German] Krantz S, Lober M. The symptoms of the acute radiopathy are chiefly characterized by a
|
|
severe blood coagulation disorder. The main results and problems of research work on this haemorrhagic
|
|
diathesis are shortly reviewed.
|
|
</p>
|
|
<p>
|
|
Prostaglandins. 1978 Apr;15(4):557-64. <strong>Prostaglandin I2 as a potentiator of acute inflammation in
|
|
rats.</strong> Komoriya K, Ohmori H, Azuma A, Kurozumi S, Hashimoto Y, Nicolaou KC, Barnette WE, Magolda
|
|
RL.
|
|
</p>
|
|
<p>
|
|
Gerontology 1993;39(1):7-18. <strong>Modulation of membrane phospholipid fatty acid composition by age and
|
|
food restriction.</strong> Laganiere S, Yu BP. H.M. "Phospholipids from liver mitochondrial and
|
|
microsomal membrane preparations were analyzed to further assess the effects of age and lifelong calorie
|
|
restriction on membrane lipid composition." <strong>"The data revealed characteristic patterns of
|
|
age-related changes in ad libitum (AL) fed rats:</strong>
|
|
<strong>
|
|
membrane levels of long-chain polyunsaturated fatty acids, 22:4 and 22:5, increased progressively, while
|
|
membrane linoleic acid (18:2) decreased steadily with age. Levels of 18:2 fell by approximately 40%, and
|
|
22:5 content almost doubled making the peroxidizability index increase with age.</strong>" "<strong>We
|
|
concluded that the membrane-stabilizing action of long-term calorie restriction relates to the selective
|
|
modification of membrane long-chain polyunsaturated fatty acids during aging.</strong>"
|
|
</p>
|
|
<p>
|
|
Medicina (B Aires). 1978 Mar-Apr;38(2):123-32. <strong>[Effective treatment of several types of fibromatosis
|
|
with progesterone. Fibrous mediastinitis, desmoid tumors, paraneoplastic fibrosis]</strong> [in Spanish]
|
|
Lanari A, Molinas FC, Castro Rios M, Paz RA.
|
|
</p>
|
|
|
|
<p>
|
|
Medicina (B Aires). 1979 Nov-Dec;39(6):826-35. <strong>[Progesterone in fibromatosis and
|
|
atherosclerosis]</strong> [in Spanish] Lanari A.
|
|
</p>
|
|
<p>
|
|
Free Radic Biol Med 1999 Feb;26(3-4):260-5. <strong>Modulation of cardiac mitochondrial membrane fluidity by
|
|
age and calorie intake.</strong> Lee J, Yu BP, Herlihy JT. <strong>"The fatty acid composition of the
|
|
mitochondrial membranes of the two ad lib fed groups differed: the long-chain polyunsaturated 22:4 fatty
|
|
acid was higher in the older group, although linoleic acid (18:2) was lower. DR eliminated the
|
|
differences."</strong> "Considered together, these results suggest that DR <strong>maintains the
|
|
integrity of the cardiac mitochondrial membrane fluidity by minimizing membrane damage through
|
|
modulation of membrane fatty acid profile."</strong>
|
|
</p>
|
|
<p>
|
|
Lipids 2001 Jun;36(6):589-93. <strong>
|
|
Effect of dietary restriction on age-related increase of liver susceptibility to peroxidation in
|
|
rats.</strong> Leon TI, Lim BO, Yu BP, Lim Y, Jeon EJ, Park DK.
|
|
</p>
|
|
<p>
|
|
Acta Chir Scand. 1976;142(1):20-5. <strong>Induction of endogenous fibrinolysis inhibition in the dog.
|
|
Effect of intravascular coagulation and release of free fatty acids.</strong> Lindquist O, Bagge L,
|
|
Saldeen T. "In all groups subjected to infusion of thrombin an increase in plasma free fatty acids (FFA) was
|
|
observed. The role of this increase for the development <strong>
|
|
of fibrinolysis inhibition was tested by infusion of norepinephrine alone and in combination with
|
|
nicotinic acid. Norepinephrine caused an increase of FFA after 2 hours and in urokinase inhibitor
|
|
activity after 24-48 hours.</strong> Both of these were diminished by high doses of nicotinic acid,
|
|
indicating that the release of FFA rather than intravascular coagulation might be the principal mechanism
|
|
underlying the occurrence of fibrinolysis inhibition following trauma."
|
|
</p>
|
|
|
|
<p>
|
|
Proc Natl Acad Sci U S A 1990 Nov;87(22):8845-9. <strong>Incorporation of marine lipids into mitochondrial
|
|
membranes increases susceptibility to damage by calcium and reactive oxygen species: evidence for
|
|
enhanced activation of phospholipase A2 in mitochondria enriched with n-3 fatty acids.</strong>
|
|
Malis CD, Weber PC, Leaf A, Bonventre JV.
|
|
</p>
|
|
<p>
|
|
Prostaglandins Leukot Essent Fatty Acids 1994 Jul;51(1):33-40.<strong>
|
|
Suppression of human T-cell growth in vitro by cis-unsaturated fatty acids: relationship to free
|
|
radicals and lipid peroxidation.</strong> Madhavi N, Das UN, Prabha PS, Kumar GS, Koratkar R, Sagar PS.
|
|
</p>
|
|
<p>
|
|
Clin Exp Metastasis 1998 Jul;16(5):407-14.<strong>
|
|
Diminution of the development of experimental metastases produced by murine metastatic lines in
|
|
essential fatty acid-deficient host mice.</strong> Mannini A, Calorini L, Mugnai G, Ruggieri S.
|
|
</p>
|
|
<p>
|
|
Biochem Pharmacol. 1990 Mar 1;39(5):879-89. <strong>Histamine release from rat mast cells induced by
|
|
metabolic activation of polyunsaturated fatty acids into free radicals.</strong> Masini E, Palmerani B,
|
|
Gambassi F, Pistelli A, Giannella E, Occupati B, Ciuffi M, Sacchi TB, Mannaioni PF.
|
|
</p>
|
|
<p>
|
|
Journal of Lipid Research, Vol. 44, 271-279, February 2003. <strong>Arachidonic acid and prostacyclin
|
|
signaling promote adipose tissue development : a human health concern?</strong>
|
|
F. Massiera, P. Saint-Marc, J. Seydoux , T. Murata , T. Kobayashi , S. Narumiya , P. Guesnet, Ez-Zoubir
|
|
Amri, R. Negrel and G. Ailhaud1.
|
|
</p>
|
|
<p>
|
|
Infection. 1994 Mar-Apr;22(2):106-12. <strong>Influence of dietary (n-3)-polyunsaturated fatty acids on
|
|
leukotriene B4 and prostaglandin E2 synthesis and course of experimental tuberculosis in guinea
|
|
pigs.</strong> Mayatepek E, Paul K, Leichsenring M, Pfisterer M, Wagner D, Domann M, Sonntag HG, Bremer
|
|
HJ.
|
|
</p>
|
|
|
|
<p>
|
|
Biochim Biophys Acta 1994 Sep 15;1214(2):209-20. <strong>Reinvestigation of lipid peroxidation of linolenic
|
|
acid.</strong> Mlakar A, Spiteller G. "Thus, a great number of previously unknown lipid peroxidation
|
|
products was detected. It is assumed that these compounds also occur--at least as intermediates--in lipid
|
|
peroxidation processes in mammalian tissue."
|
|
</p>
|
|
<p>
|
|
Prostaglandins Leukot Essent Fatty Acids. 2003 May;68(5):305-10. <strong>Synergistic effect of D-003 and
|
|
aspirin on experimental thrombosis models.</strong> Molina V, Arruzazabala ML, Carbajal D, Mas R.
|
|
</p>
|
|
<p>
|
|
Chem Res Toxicol. 2001 Apr;14(4):431-7. <strong>Defining mechanisms of toxicity for linoleic acid
|
|
monoepoxides and diols in Sf-21 cells.</strong> Moran JH, Mon T, Hendrickson TL, Mitchell LA, Grant DF.
|
|
</p>
|
|
|
|
<p>
|
|
J Biochem (Tokyo). 1977 Aug;82(2):529-33. <strong>Effects of free fatty acids on fibrinolytic
|
|
activity.</strong> Muraoka T, Okuda H. A novel method for the estimation of fibrinolytic activity is
|
|
proposed. In this method, a fibrin clot suspension is used as a substrate (fibrin is known to be a
|
|
physiological substrate of plasmin). The fibrin clot suspension was prepared by homogenization of human
|
|
fibrin clots. With this method, we found that free fatty<strong>
|
|
acids inhibited the plasmin activity, and long-chain, unsaturated free fatty acids had a particularly
|
|
strong inhibitory action on plasmin. As regards the mechanism of the inhibitory action, free fatty acids
|
|
may not inhibit complex formation between plasmin and fibirin, but may make it impossible for plasmin to
|
|
act on fibrin due to deformation of the surface of the fibrin clot.</strong>
|
|
</p>
|
|
<p>
|
|
Alcohol Clin Exp Res. 1986 Jun;10(3):271-3. <strong>Dietary factors and alcoholic cirrhosis.</strong> Nanji
|
|
AA, French SW.
|
|
</p>
|
|
<p>
|
|
Gastroenterology. 1995 Aug;109(2):547-54. <strong>Dietary saturated fatty acids: a novel treatment for
|
|
alcoholic liver disease.
|
|
</strong>
|
|
|
|
Nanji AA, Sadrzadeh SM, Yang EK, Fogt F, Meydani M, Dannenberg AJ.
|
|
</p>
|
|
<p>
|
|
J Pharmacol Exp Ther. 1996 Jun;277(3):1694-700. <strong>Medium chain triglycerides and vitamin E reduce the
|
|
severity of established experimental alcoholic liver disease.</strong> Nanji AA, Yang EK, Fogt F,
|
|
Sadrzadeh SM, Dannenberg AJ.
|
|
</p>
|
|
<p>
|
|
Hepatology. 1997 Dec;26(6):1538-45.<strong>
|
|
Dietary saturated fatty acids down-regulate cyclooxygenase-2 and tumor necrosis factor alfa and reverse
|
|
fibrosis in alcohol-induced liver disease in the rat.</strong> Nanji AA, Zakim D, Rahemtulla A, Daly T,
|
|
Miao L, Zhao S, Khwaja S, Tahan SR, Dannenberg AJ.
|
|
</p>
|
|
|
|
<p>
|
|
J Pharmacol Exp Ther. 2001 Nov;299(2):638-44. <strong>
|
|
Dietary saturated fatty acids reverse inflammatory and fibrotic changes in rat liver despite continued
|
|
ethanol administration.</strong> Nanji AA, Jokelainen K, Tipoe GL, Rahemtulla A, Dannenberg AJ.
|
|
</p>
|
|
<p>
|
|
Gastroenterology 1995 Apr;108(4):1124-35.<strong>
|
|
Accumulation and cellular localization of fibrinogen/fibrin during short-term and long-term rat liver
|
|
injury.</strong>
|
|
Neubauer K, Knittel T, Armbrust T, Ramadori G "<strong>Fibrinogen/fibrin deposition in damaged livers was
|
|
studied by immunohistology."
|
|
</strong>
|
|
"Immunohistology showed striking amounts of fibrinogen and fibrin deposits in pericentral necrotic areas
|
|
(short-term damage) and within fibrotic septa (long-term damage)." "The results show fibrinogen/fibrin
|
|
deposition during short-term liver injury and liver fibrogenesis, which may suggest the involvement of a
|
|
"clotting-like process" in short-term liver damage and liver fibrosis. The data might indicate that
|
|
fibrin/fibronectin constitute a "provisional matrix," which affects the attraction and proliferation of
|
|
inflammatory and matrix-producing cells."
|
|
</p>
|
|
<p>
|
|
Ophthalmic Res. 1999;31(4):273-9. <strong>Age-related accumulation of free polyunsaturated fatty acids in
|
|
human retina.</strong> Nourooz-Zadeh J, Pereira P.
|
|
</p>
|
|
<p>
|
|
Chem Res Toxicol. 2002 Mar;15(3):367-72. <strong>Formation of cyclic deoxyguanosine adducts from omega-3 and
|
|
omega-6 polyunsaturated fatty acids under oxidative conditions.</strong> Pan J, Chung FL.
|
|
</p>
|
|
<p>
|
|
Radiobiologiia. 1985 Nov-Dec;25(6):763-7. <strong>[Mechanism of circulatory disorders in animals irradiated
|
|
at high doses]</strong> [in Russian] Pozharisskaia TD, Vasil'eva TP, Sokolova EN, Alekseeva II. Some
|
|
data are reported on pathoanatomical changes, a status of the microcirculatory channel and the coagulogram
|
|
of animals affected by high doses of ionizing radiation. <strong>The signs of disseminated intravascular
|
|
blood coagulation have been revealed.</strong>
|
|
</p>
|
|
<p>
|
|
J Biol Chem. 1998 May 29;273(22):13605-12. <strong>Formation of isoprostane-like compounds (neuroprostanes)
|
|
in vivo from docosahexaenoic acid.</strong> Roberts LJ 2nd, Montine TJ, Markesbery WR, Tapper AR, Hardy
|
|
P, Chemtob S, Dettbarn WD, Morrow JD.
|
|
</p>
|
|
<p>
|
|
Nutr Cancer 1995;24(1):33-45.<strong>
|
|
Effects of linoleic acid and gamma-linolenic acid on the growth and metastasis of a human breast cancer
|
|
cell line in nude mice and on its growth and invasive capacity in vitro.</strong> Rose DP, Connolly JM,
|
|
Liu XH
|
|
</p>
|
|
<p>
|
|
Arch Toxicol. 1997;71(9):563-74.<strong>
|
|
Impaired cellular immune response in rats exposed perinatally to Baltic Sea herring oil or
|
|
2,3,7,8-TCDD.</strong>
|
|
|
|
Ross PS, de Swart RL, van der Vliet H, Willemsen L, de Klerk A, van Amerongen G, Groen J, Brouwer A,
|
|
Schipholt I, Morse DC, van Loveren H, Osterhaus AD, Vos JG.
|
|
</p>
|
|
<p>
|
|
Nutr Cancer 1998;30(2):137-43. <strong>
|
|
Effects of dietary n-3-to-n-6 polyunsaturated fatty acid ratio on mammary carcinogenesis in rats.
|
|
</strong>Sasaki T, Kobayashi Y, Shimizu J, Wada M, In'nami S, Kanke Y, Takita T. "An increase in the n-3/n-6
|
|
ratio did not suppress the incidence or reduce the latency of mammary tumor development. <strong>
|
|
The number and weight of mammary tumors per tumor-bearing rat tended to be large in the group with an
|
|
n-3/n-6 ratio of 7.84 compared with those in the other groups. As the n-3/n-6 ratios were elevated, the
|
|
total number and weight of tumors increased gradually.</strong>"
|
|
</p>
|
|
<p>
|
|
J. Biol. Chem. 1940 132: 539-551.<strong> Essential fatty acids, vitamin B</strong>
|
|
<sub><strong>6</strong></sub>
|
|
<strong>, and other factors in the cure of rat acrodynia</strong>. H. Schneider, H. Steenbock, and Blanche
|
|
R. Platz
|
|
</p>
|
|
|
|
<p>
|
|
Science. 1988 May 20;240(4855):1032-3. <strong>Essential fatty acid depletion of renal allografts and
|
|
prevention of rejection.</strong> Schreiner GF, Flye W, Brunt E, Korber K, Lefkowith JB.
|
|
</p>
|
|
<p>
|
|
Physiol Bohemoslov. 1990;39(2):125-34.<strong>
|
|
Proportion of individual fatty acids in the non-esterified (free) fatty acid (FFA) fraction in the serum
|
|
of laboratory rats of different ages.</strong> Smidova L, Base J, Mourek J, Cechova I.
|
|
</p>
|
|
<p>
|
|
Placenta. 2003 Nov;24(10):965-73. <strong>Augmented PLA(2)Activity in Pre-eclamptic Decidual Tissue-A Key
|
|
Player in the Pathophysiology of 'Acute Atherosis' in Pre-eclampsia?</strong> Staff AC, Ranheim T,
|
|
Halvorsen B.
|
|
</p>
|
|
<p>
|
|
Acta Neurochir Suppl (Wien) 1994;60:20-3<strong>. Mechanisms of glial swelling by arachidonic acid.</strong>
|
|
Staub F, Winkler A, Peters J, Kempski O, Baethmann A.
|
|
</p>
|
|
<p>
|
|
Arch Biochem Biophys. 1991 Aug 15;289(1):33-8. <strong>A possible mechanism of mitochondrial dysfunction
|
|
during cerebral ischemia: inhibition of mitochondrial respiration activity by arachidonic acid.
|
|
</strong>
|
|
Takeuchi Y, Morii H, Tamura M, Hayaishi O, Watanabe Y.
|
|
</p>
|
|
<p>
|
|
J Drug Target. 2003 Jan;11(1):45-52.<strong>
|
|
Modulation of tumor-selective vascular blood flow and extravasation by the stable prostaglandin 12
|
|
analogue beraprost sodium.</strong> Tanaka S, Akaike T, Wu J, Fang J, Sawa T, Ogawa M, Beppu T, Maeda H.
|
|
</p>
|
|
<p>
|
|
Am J Clin Nutr. 2003 May;77(5):1125-32. <strong>Effect of individual dietary fatty acids on postprandial
|
|
activation of blood coagulation factor VII and fibrinolysis in healthy young men.</strong> Tholstrup T,
|
|
Miller GJ, Bysted A, Sandstrom B.
|
|
</p>
|
|
<p>
|
|
Biochem Soc Trans. 2003 Oct;31(Pt 5):1075-9. <strong>Regression of pre-established atherosclerosis in the
|
|
apoE-/- mouse by conjugated linoleic acid.</strong>
|
|
|
|
Toomey S, Roche H, Fitzgerald D, Belton O.
|
|
</p>
|
|
<p>
|
|
Int J Biochem Cell Biol. 2003 May;35(5):749-55. <strong>Increased muscle proteasome activities in rats fed a
|
|
polyunsaturated fatty acid supplemented diet.</strong> Vigouroux S, Farout L, Clavel S, Briand Y, Briand
|
|
M. "Changes in the proteasome system, a dominant actor in protein degradation in eukaryotic cells, have been
|
|
documented in a large number of physiological and pathological conditions." "With the polyunsaturated fatty
|
|
acid enriched diet, the chymotrypsin-like and peptidylglutamylpeptide hydrolase activities increased by 45%
|
|
in soleus and extensor digitorum longus (EDL), and by 90% in the gastrocnemius medialis (GM) muscle.
|
|
Trypsin-like activity of the proteasome increased by 250% in soleus, EDL and GM." "Proteasome activities and
|
|
level were less stimulated with a monounsaturated fatty acid supplemented diet." "Unsaturated fatty acids
|
|
are particularly prone to free radical attack. Thus, we suggest that alterations in muscle proteasome may
|
|
result from monounsaturated and polyunsaturated fatty acid-induced peroxidation, in order to eliminate
|
|
damaged proteins."
|
|
</p>
|
|
<p>
|
|
J Am Coll Nutr. 2000 Aug;19(4):478S-486S. <strong>Conjugated linoleic acid and bone biology.</strong>
|
|
Watkins BA, Seifert MF. "Recent investigations with<strong> </strong>growing rats given butter fat and
|
|
supplements of CLA demonstrated an increased rate of bone formation and reduced ex vivo bone PGE2
|
|
production, respectively."
|
|
</p>
|
|
|
|
<p>
|
|
Ups J Med Sci. 1979;84(3):195-201. <strong>Effect of nicotinic acid on the posttraumatic increase in free
|
|
fatty acids and fibrinolysis inhibition activity in the rat.</strong> Wegener T, Bagge L, Saldeen T.
|
|
Nicotinic acid effectively inhibited the posttraumatic increase in both free fatty acids (FFA) and
|
|
fibrinolysis inhibition activity (FIA) in the blood in rats, indicating that FFA might be involved in the
|
|
posttraumatic increase of FIA. The FIA in the liver was greater than that in other organs studied and was
|
|
increased in the posttraumatic phase. The possible role of the liver in the posttraumatic increase of FIA is
|
|
discussed.
|
|
</p>
|
|
<p>
|
|
Am J Physiol Regul Integr Comp Physiol. 2001 Mar;280(3):R908-12. <strong>CLA reduces antigen-induced
|
|
histamine and PGE(2) release from sensitized guinea pig tracheae.</strong> Whigham LD, Cook EB, Stahl
|
|
JL, Saban R, Bjorling DE, Pariza MW, Cook ME.
|
|
</p>
|
|
<p>
|
|
Toxicol Appl Pharmacol 1993 May;120(1):72-9.<strong>
|
|
Essential fatty acid deficiency in cultured human keratinocytes attenuates toxicity due to lipid
|
|
peroxidation.</strong>
|
|
|
|
Wey HE, Pyron L, Woolery M.
|
|
</p>
|
|
<p>
|
|
Nutrition. 2002 Jul-Aug;18(7-8):647-53. <strong>Dietary fat composition alters pulmonary function in
|
|
pigs.</strong> Wolfe RR, Martini WZ, Irtun O, Hawkins HK, Barrow RE. © Ray Peat Ph.D. 2009. All Rights
|
|
Reserved. www.RayPeat.com
|
|
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|
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