632 lines
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632 lines
47 KiB
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<head>
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<title>
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Suitable Fats, Unsuitable Fats: Issues in Nutrition
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</title>
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</head>
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<body>
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<h1>
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Suitable Fats, Unsuitable Fats: Issues in Nutrition
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</h1>
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<p>
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For fifty years, the mass media have been making the public think about the fats in their diet, filling the
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culture with clich"s about bad saturated animal fats that raise cholesterol, or lately the trans-fats in
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margarine, and images of arteries clogged by bad fats. The public instruction about the fats we should eat
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resembles the owner's manual for a car, that tells you what kind of motor oil and fuel and coolant to use;
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they are telling us that they know how our body works, and that they know what it needs. But now, even after
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the human genome has supposedly been partly "decoded," the biological functions of the fats have hardly
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begun to be investigated.
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</p>
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<p>
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To understand the present issues regarding fats in nutrition and medicine it's helpful to look at the
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historical development of biochemical and physiological fat research in a variety of contexts, including
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agriculture and economics, as well as considering the effects of the changing ideas about cell structure,
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vitamins, hormones, immunology, brain development, evolution, and the growing understanding of the way
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physiology interacts with ecology. We need to recognize the complexity of the physiology of fats, to
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appreciate the complexity of the living organism.
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</p>
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<p>
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Financial considerations have driven fat research in very obvious ways. In 1883, Mark Twain described how
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commercial fraud was making use of new technology to substitute cheap fats and oils for butter and olive
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oil.. Hard fats such as tallow, which had been used for making soap and candles, began to be widely used as
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a substitute for butter in the 19th century. Around 1912, chemists found economical ways to solidify (for
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use as a butter substitute) the very cheap liquid oils, such as cottonseed oil, linseed oil, whale oil, and
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fish oils, which been used mostly as fuels or varnish. The seed oils were so cheap that meat packers quickly
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became major producers of hydrogenated cottonseed and soy oils, to extend their limited supply of lard or
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tallow for sale as shortening or margarine.
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</p>
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<p>
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Between 1912 and 1927 there were several studies that reported that animals could live on a fat-free diet,
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and that in fact they lived longer, and without the normal mortality from cancer. In the 1940s and 1950s,
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most textbooks that mentioned the idea that certain fats were essential nutrients described it as a
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controversial idea. But the oil industries used public relations effectively to sell the medical (heart
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protective) benefits of a diet containing increased amounts of linoleic and linolenic acids, which they
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called the essential fatty acids. They began citing a 1929 publication (by G. Burr and M. Burr) that claimed
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to demonstrate the essentiality of those fatty acids, while ignoring the publications that pointed in
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different directions.
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</p>
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<p>
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The cheapness of the seed oils led to their use in animal feeds, to promote growth. By the 1940s, the
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polyunsaturated oils, including fish oils, were known to cause deterioration of the brain, muscles, and
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gonads in a variety of animals, and this was found to be caused mainly by their destruction of vitamin E. A
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little later, the disease called steatitis or yellow fat disease was found to be produced in various animals
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that were fed too much fish or fish oil.
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</p>
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<p>
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The reason linseed oil and fish oil were used for making varnishes and paints was that they are "drying
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oils," reacting with oxygen to polymerize and harden. The physical and chemical propertiess of the oils are
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fairly well understood, and among the polyunsaturated fatty acids (PUFA) the omega -3 fatty acids react most
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easily with oxygen. Heat, light, and moisture increase their spontaneous interactions with oxygen, and
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besides polymerizing, these oils produce a variety of reactive particles, including acrolein, which combine
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with other substances, such as cellular proteins and DNA, with highly toxic effects. At low temperatures and
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low oxygen concentrations these oils are not highly reactive. Fats that harden at low temperatures (as
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saturated fats do) wouldn't be convenient for organisms that live in a cool environment, and so organisms
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regulate the type of fat they synthesize according to the temperature of their tissues. The fact that
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certain types of polyunsaturated fatty acids function nicely in fish, worms, and insects, doesn't mean that
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they are ideal fats for mammals.
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</p>
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<p>
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The fact that vitamin E prevented or cured some of the major diseases in farm animals caused by excessive
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PUFA, and that it could retard the development of rancidity in stored oils, led quickly to the persistent
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belief that lipid peroxidation is the only toxic effect of the vegetable oils. However, the oils were being
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seen to cause other problems, including accelerated aging and obesity, but those problems weren't of
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interest to farmers, who wanted to sell plump young animals as cheaply and quickly as possible. Even fresh
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oils have toxic effects, and the oxidative damage they do is often the consequence of these other toxic
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actions.
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</p>
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<p>
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Another cheap food additive, coconut oil, was found to increase feed consumption while slowing weight gain,
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so it wasn't popular in the meat industry. The highly unsaturated seed oils had the opposite effect, of
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producing a rapid fattening of the animal, while decreasing feed consumption, so by 1950 corn and soybeans
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were widely considered to be optimal feeds for maximizing profits in the production of meat animals. It was
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at this time that the industry found that it could market the liquid oils directly to consumers, as
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health-promoting foods, without bothering to turn them into solid shortening or margarine. Somehow, few
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physiologists continued to think about the implications of metabolic slowing, obesity, and the related
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degenerative diseases.
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</p>
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<p>
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As vitamin research advanced in the 1940s, Roger Williams' lab at the Clayton Foundation Biochemical
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Institute, University of Texas at Austin, recognized the "fat deficiency disease" of the Burrs as a
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deficiency of vitamin B6, and showed that when they produced the condition with a diet similar to the one
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the Burrs had used, they could cure it by administering vitamin B6. In the early 1930s George Burr had
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discovered that animals on a fat free diet had an extremely high rate of metabolism, but he didn't
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investigate the important ramifications of that observation, such as their increased need for vitamins and
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minerals, in accordance with their rate of metabolism. The PUFA slowed metabolism, and that effect was good
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for agriculture.
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</p>
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<p>
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The commercial pressure on fat research has created a new way of writing research reports, that several
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decades earlier wouldn't have been acceptable. For example, the effects of a specific fat on a few of the
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components of a complex process such as clotting are often described in the title, introduction, and
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conclusion of an article as if they were revealing a way to prevent heart disease. The effects of
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unsaturated fats on cells <em>
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in vitro</em> are often the opposite of their effects in living animals, but editors are allowing
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authors to claim that their <em>in vitro</em>
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results justify dietary or therapeutic use of the fats. Journals of medicine and nutrition are now preferred
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sites for commercial press releases, composed to superficially resemble scientific reports.
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</p>
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<p>
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The suppressive effects of unsaturated fats on mitochondrial energy production have been widely
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investigated, since it is that effect that makes animal fattening with PUFA so economical. Rather than
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interpreting that as a toxic effect, using the innate structure and function of the mitochondrion as a point
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of reference from which to evaluate dietary components, the consumption of "good" oils is being used as the
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reference point from which to evaluate the meaning of metabolism ("efficiency is good," "low oxygen
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consumption is good"). Building on the idea that the oils are health-promoters which increase metabolic
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efficiency, the never-viable "rate of aging" theory was resuscitated: The anti-respiratory effect of PUFA is
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used (illogically) to return to the idea that aging occurs in proportion to the amount of oxygen consumed,
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because animals which lack the supposedly essential nutrients ("defective animals") consume oxygen
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rapidly--burning calories rapidly, they are supposed to be like a candle that won't last as long if it burns
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intensely. The old theory is simply resuscitated to explain why the anti-respiratory action of PUFA might be
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beneficial, justifying further promotion of their use as food and drugs.
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</p>
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<p>
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Ordinarily, in biochemistry and physiology the inhibition of an enzyme is taken as a suggestion of toxicity,
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but when the point of reference is the idea of the goodness of PUFA, the <em>activity</em> of an intrinsic
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enzyme is taken to be evidence of harm, and its <em>inhibition</em> (by PUFA) is taken to be the proper,
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healthful situation. The enzyme that produces the Mead fatty acid is strongly inhibited by PUFA seed oils
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(less strongly by fish oils), and so the presence of the Mead acid in the tissues is taken as evidence that
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the animal is suffering damage resulting from the absence of PUFA. The Mead acid happens to have some
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valuable anti-inflammatory effects, and is associated with many biological advantages, but research in that
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direction is prevented by the lack of funding.
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</p>
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<p>
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By 1920, the polyunsaturated fatty acids were recognized to inhibit proteolytic enzymes. At that time, the
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production of unsaturated fat was considered to be a feature of certain pathogens, able to overcome the
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proteolytic-phagocytic functions of the immune system.
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</p>
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<p>
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Scattered studies have found that polyunsaturated fats inhibit the proteolytic enzymes involved in the
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digestion of food, in the removal of clots, in the formation of thyroid hormone, and many other essential
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physiological processes. But currently, the only implication being drawn from this broad class of effects of
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the PUFA is that some proteolytic enzymes are involved in disease processes, and consequently increased
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consumption of PUFA would be appropriate, because of their ability to suppress a conditionally harmful
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proteolytic enzyme. Since the organism consists mainly of proteins, there are complex innate systems for
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regulating the proteolytic enzymes, activating or inactivating them as needed, and such complexity isn't
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likely to depend on variable, unstable dietary factors. Exogenous substances that inhibit some proteases
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could create an unlimited variety of functional and anatomical irregularities.
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</p>
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<p>
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Some of the interesting enzymes affected specifically by polyunsaturated fatty acids are those involved in
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hormone production. While they inhibit the formation of progesterone and androgens, they activate the
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synthesis of estrogen, which in turn activates the release of more free polyunsaturated fatty acids from the
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tissues, in a positive feedback pattern.
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</p>
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<p>
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The inhibition of detoxification enzymes by PUFA (Tsoutsikos, et al., 2004) affects many processes, such as
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the elimination of estrogen, contributing to the positive feedback between estrogen and the oils. The
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meaning of this tends to be lost, because of the estrogen industry's effective campaigns.
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</p>
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<p>
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Another situation in which fatty acids participate in a positive feedback system is the stress reaction, in
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which the released fatty acids impair mitochondrial energy production, increasing the stress and leading to
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further release of fatty acids.
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</p>
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<p>
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One of the perennial theories of aging that has remained viable is the metaplasm/lipofuscin/age pigment
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theory, the idea that a toxic material accumulates in tissues over time. The age pigment contains proteins,
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cross-linked PUFA, and metals. The inhibition of proteolytic enzymes is involved in its accumulation, and
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the ratio of PUFA to saturated fatty acids is an important factor in its formation. Estrogen is one of the
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factors that can promote the formation of age pigment, probably partly because its lipolytic action
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increases the cells' exposure to free fatty acids. The lipofuscin contributes to inhibition of proteolysis,
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probably partly through increased production of free radicals and hydrogen peroxide.
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</p>
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<p>
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The proteolytic enzymes are an essential part of innate immunity, and the highly unsaturated fatty acid,
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EPA, which is the most immunosuppressive of the fats, strongly inhibits proteolysis in some cells. The
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natural killer (NK) cells and phagocytic cells are two types of cell that are suppressed by PUFA, and they
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are involved in many kinds of physiological events, not just the killing of tumor cells and virus infected
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cells.
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</p>
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<p>
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The immunosuppressive effects of PUFA are very general. Many metabolites that are known to have harmful
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effects on the immune system are increased by the PUFA (histamine [Masini, et al., 1990], serotonin,
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lactate, nitric oxide [Omura, et al., 2001]). These substances are also involved in tumor development.
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</p>
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<p>
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Besides inhibiting enzymes and being converted into prostaglandins, the polyunsaturated fatty acids have
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direct effects, as signals (or interference with signals) on many tissues. The belief that the PUFA are
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essential nutrients has influenced the way cellular excitability thresholds are being interpreted. Anxiety
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and panic may be interpreted as alertness, calmness may be interpreted as stupidity. Specifically, long-term
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potentiation (LTP) may contribute to seizures, senility, and excitotoxicity, as well as to learning, but
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many titles and conclusions equate increased LTP with "improved LTP," implying that it has biological value
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to the animal.
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</p>
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<p>
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The ability of nerve cells to become quiescent after excitation is essential to learning and perception.
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This ability is lost with aging, as the functional balance in the brain shifts away from GABA-ergic to
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glutamatergic nerves. The polyunsaturated fatty acids promote the excitatory nervous state. The combination
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of respiratory inhibition with excitation can produce excitotoxic cell death. If the doctrine of
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"essentiality of PUFA" hadn't been so influential, different interpretations of excitatory thresholds,
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energy metabolism, and even cell structure would have been allowed to develop more fully.
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</p>
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<p>
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The concentration of polyunsaturated fats in the brain has led many people to say that the "nutritionally
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essential fatty acids," especially the omega -3 fatty acids, are essential for brain development (for the
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formation of nerve cell membranes), and for the formation of synapses, and that increasing the amount of
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those fats in the diet would be desirable. The types of argument they use simply ignore the real
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evidence<strong>:</strong>
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Cells can multiply indefinitely in culture dishes without the essential fatty acids, insects can multiply
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for generations on diets without the unsaturated fats, forming normal synapses and brains, and mammals fed
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diets with extremely small amounts of the unsaturated fats grow with perfectly normal--possibly
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superior--brains.
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</p>
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<p>
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One of the fats in the omega -9 series, that the human body can synthesize, nervonic acid, is a major
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constituent of brain tissue, but its important functions in brain development have hardly been investigated.
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Unlike the unsaturated fatty acids oleic acid, linoleic acid, and eicosapentaenoic acid (EPA), nervonic acid
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isn't associated with the "coronary risk factors," and it has been suggested that it might be used in adults
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to prevent obesity-related diseases. (Oda, et al., 2005).
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</p>
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<p>
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One major area of research that has been neglected involves the role of fats in modifying the ways in which
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proteins and nucleic acids interact with water--arguably the most basic of all physiological processes.
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Unsaturated fats are more water soluble than saturated fats, and they are involved in many problems of
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permeability and edema.
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</p>
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<p>
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In aging and evolution, there are systematic changes in tissue water content that appear to correspond to
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changes in rate of metabolism, to the degree of unsaturation of cellular fats, and to thyroid function and
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temperature. Metabolic intensity and longevity can be modified by changing the degree of saturation of fats
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in the diet and tissues, but--despite almost a century of sporadic investigations--no one has yet worked out
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in detail the most appropriate way to do this. But it has become clear that the "uncoupled" mitochondrion,
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that "wastes oxygen and calories," is protective against free radicals, cancer, and aging. Thyroid hormone
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and the absence of PUFA are important factors in supporting the "wasteful" mitochondrion.
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</p>
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<p>
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Although the complex interactions of anatomy, energy, temperature, fat nutrition, tissue water content, and
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hormones haven't been systematically investigated, some of the principles regarding the biological
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suitability of specific fats are already being applied in the limited context of therapy.
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</p>
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<p>
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At present, the most important issue is to recognize the dangers presented by the intrusion of corporate
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power into science, especially as it relates to nutrition and medicine, and to consider the implications of
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the known effects of the PUFA on all of our biological systems.
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</p>
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<p>
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The food-derived polyunsaturated fatty acids play important roles in the development of all of the problems
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associated with aging--reduced immunity, insomnia, decreased learning ability, substitution of fat for
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muscle, susceptibility to tissue peroxidation and inflammation, growth of tumors, etc., and are probably
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involved in most other health problems, even in children. If research hadn't been guided by the economic
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interests of the seed oil industry, many of those problems would have been solved by now.
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</p>
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<p>
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The influence of the mass media on science can be seen in two issues that are currently well known.
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</p>
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<p>
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A popular test used for evaluating diabetes is the measurement of glycated hemoglobin, the attachment of a
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sugar-like fragment to the protein of hemoglobin. This is used to judge whether blood sugar is being
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controlled adequately. The glycation of proteins is widely believed to be a central process in aging, and is
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often used to argue that people should reduce their sugar consumption.
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</p>
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<p>
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Another well publicized problem supposedly involving the reaction between sugars and proteins has to do with
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the discovery of the carcinogen, acrylamide, in breads and french fries. The Whole Foods Market was sued in
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California for selling whole wheat bread without a warning that it contained a carcinogen.
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</p>
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<p>
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But the changes in proteins that occur in diabetes are mainly produced by the breakdown products of
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polyunsaturated fatty acids. Acrylamide is produced largely by the reaction of PUFA with proteins.
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</p>
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<p>
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Sugar, by reducing the level of free fatty acids in the body, actually tends to protect against these toxic
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effects of the PUFA. Diabetes, like cancer, has been known for a long time to be promoted by unsaturated
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oils in the diet, rather than by sugar. The seed oil industry has been more effective than the sugar
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industry in lobbying and advertising, and the effects can be seen in the assumptions that shape medical and
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biological research.
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</p>
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<p><h3>REFERENCES</h3></p>
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<p>
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Biochem Pharmacol. 1990 Mar 1;39(5):879-89. <strong>Histamine release from rat mast cells induced by
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metabolic activation of polyunsaturated fatty acids into free radicals.</strong> Masini E, Palmerani B,
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Gambassi F, Pistelli A, Giannella E, Occupati B, Ciuffi M, Sacchi TB, Mannaioni PF.
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</p>
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<p>
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Int Heart J. 2005 Nov;46(6):975-85. <strong>Relationships between serum unsaturated fatty acids and coronary
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risk factors: negative relations between nervonic acid and obesity-related risk factors.</strong> Oda E,
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Hatada K, Kimura J, Aizawa Y, Thanikachalam PV, Watanabe K. "The objective of the present study was to
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analyze the relationships between serum USFA and CRF [coronary risk factors]." "<strong><hr /></strong>"
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</p>
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<p>
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FEBS Lett. 2001 Jan 5;487(3):361-6. <strong>Eicosapentaenoic acid (EPA) induces Ca(2+)-independent
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activation and translocation of endothelial nitric oxide synthase and endothelium-dependent
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vasorelaxation.</strong> Omura M, Kobayashi S, Mizukami Y, Mogami K, Todoroki-Ikeda N, Miyake T,
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Matsuzaki M. "EPA stimulated NO production even in endothelial cells in situ loaded with a cytosolic Ca(2+)
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chelator . . . which abolished the [Ca(2+)]i elevations induced by ATP and EPA."
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</p>
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<p>
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Biochem Pharmacol. 2004 Jan 1;67(1):191-9. <strong>Evidence that unsaturated fatty acids are potent
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inhibitors of renal UDP-glucuronosyltransferases (UGT): kinetic studies using human kidney cortical
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microsomes and recombinant UGT1A9 and UGT2B7.</strong> Tsoutsikos P, Miners JO, Stapleton A, Thomas A,
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Sallustio BC, Knights KM.
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</p>
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<p>
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Lipids. 1997 Dec;32(12):1265-70. <strong>Dietary fatty acid profile affects endurance in rats.</strong> Ayre
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KJ, Hulbert AJ. "The diets comprised an essential fatty acid-deficient diet (containing mainly saturated
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fatty acids); a diet high in n-6 fatty acids, High n-6; and a diet enriched with n-3 fatty acids, High n-3.
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Submaximal endurance in rats fed the High n-3 diet was 44% less than in rats fed the High n-6 diet (P <
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0.02). All rats were then fed a standard commercial laboratory diet for a 6-wk recovery period, and their
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performances were reevaluated. Although endurance in all groups was lower then at 9 wk, it was again
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significantly 50% lower in the High n-3 group than the High n-6 group (P < 0.005). Although n-3 fats are
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considered beneficial for cardiovascular health, they appear to reduce endurance times, and their side
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effects need to be further investigated."
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</p>
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<p>
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Ann Biol Clin (Paris) 2000 Sep-Oct;58(5):595-600.<strong> [Studies on the genotoxic</strong>
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<strong>
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effects of crude liver oils from 3 species of Mediterranean sharks by means of in vitro micronucleus
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test using human lymphocytes]
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</strong>
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Bartfai E, Orsiere T, Duffaud F, Villani P, Pompili J, Botta A. "The results of this experimental study show
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that the crude liver oils of three species of sharks are genotoxic and confirm a high carcinogenic risk."
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</p>
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<p>
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Vaccine. 2002 Jan 31;20(9-10):1435-44. <strong>Long-term influence of lipid nutrition on the induction of
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CD8(+) responses to viral or bacterial antigens.</strong>
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Bassaganya-Riera J, Hontecillas R, Zimmerman DR, Wannemuehler MJ.
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</p>
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<p>
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J Nutr. 2001 Sep;131(9):2370-7.<strong>
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Dietary conjugated linoleic acid modulates phenotype and effector functions of porcine CD8(+)
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lymphocytes.</strong>
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Bassaganya-Riera J, Hontecillas R, Zimmerman DR, Wannemuehler MJ.
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</p>
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<p>
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J Anim Sci, 1984 Apr, 58:4, 971-8. <strong>Essential fatty acid status and characteristics associated with
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colostrum-deprived gnotobiotic and conventional lambs. Growth, organ development, cell membrane
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integrity and factors associated with lower bowel function.</strong> Bruckner G; Grunewald KK; Tucker
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RE; Mitchell GE Jr "The absence of dietary linoleic acid decreased liver and spleen weights and, in general,
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suppressed development of organs except the brain." "The results indicate that neonatal colostrum-deprived
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lambs have an EFA requirement, as evidenced by decreased growth and performance characteristics in the GN
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linoleic deficient vs GN supplemented group, and suggests that the required level is in excess of .32% of
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the total caloric intake as linoleic acid."
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</p>
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<p>
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Crit Care Med. 1996 Jul;24(7):1129-36. <strong>An increase in serum C18 unsaturated free fatty acids as a
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predictor of the development of acute respiratory distress syndrome.
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</strong>Bursten SL, Federighi DA, Parsons P, Harris WE, Abraham E, Moore EE Jr, Moore FA, Bianco JA, Singer
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JW, Repine JE.
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</p>
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<p>
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Free Radic Biol Med. 1999 Jul;27(1-2):51-9. <strong>Arachidonic acid interaction with the mitochondrial
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electron transport chain promotes reactive oxygen species generation.</strong> Cocco T, Di Paola M, Papa
|
|
S, Lorusso M. "It is shown that arachidonic acid causes an uncoupling effect under state 4 respiration of
|
|
intact mitochondria as well as a marked inhibition of uncoupled respiration. While, under our conditions,
|
|
the uncoupling effect is independent of the fatty acid species considered, the inhibition is stronger for
|
|
unsaturated acids. Experiments carried out with mitochondrial particles indicated that the arachidonic acid
|
|
dependent decrease of the respiratory activity is caused by a selective inhibition of Complex I and III. It
|
|
is also shown that arachidonic acid causes a remarkable increase of hydrogen peroxide production when added
|
|
to mitochondria respiring with either pyruvate+malate or succinate as substrate."
|
|
</p>
|
|
<p>
|
|
Antioxid Redox Signal. 2005 Jan-Feb;7(1-2):256-68. <strong>Lipid peroxidation in diabetes mellitus.</strong>
|
|
Davi G, Falco A, Patrono C.
|
|
</p>
|
|
<p>
|
|
Naunyn Schmiedebergs Arch Pharmacol. 2005 Mar;371(3):202-11. Epub 2005 Apr 15. <strong>Antiarrhythmic and
|
|
electrophysiological effects of long-chain omega-3 polyunsaturated fatty acids.
|
|
</strong>
|
|
Dhein S, Michaelis B, Mohr FW. "<strong>Atrioventricular conduction time was slowed only by DHA and
|
|
EPA."</strong> "Regarding antiarrhythmic activity we found that the <strong>threshold for elicitation of
|
|
a ventricular extrasystole was concentration-dependently enhanced by DHA and EPA, but not by ALA. DHA
|
|
dose-dependently reduced longitudinal propagation velocity V(L)</strong>
|
|
|
|
and to a lower extent transverse velocity V(T)."
|
|
</p>
|
|
<p>
|
|
J Biol Chem. 2002 Oct 18;277(42):39368-78. <strong>The mechanism of docosahexaenoic acid-induced
|
|
phospholipase D activation inhuman lymphocytes involves exclusion of the enzyme from lipid
|
|
rafts.</strong> Diaz O, Berquand A, Dubois M, Di Agostino S, Sette C, Bourgoin S, Lagarde M, Nemoz G,
|
|
Prigent AF. "Docosahexaenoic acid (DHA), an n-3 polyunsaturated fatty acid that inhibits T lymphocyte
|
|
activation, has been shown to stimulate phospholipase D (PLD) activity in stimulated human peripheral blood
|
|
mononuclear cells (PBMC)." "<strong>This PLD activation might be responsible for the immunosuppressive
|
|
effect of DHA because it is known to transmit antiproliferative signals in lymphoid cells."</strong>
|
|
</p>
|
|
<p>
|
|
Nutrition. 2003 Feb;19(2):144-9. <strong>
|
|
Diets rich in polyunsaturated fatty acids: effect on hepatic metabolism in rats.</strong> Gaiva MH,
|
|
Couto RC, Oyama LM, Couto GE, Silveira VL, Ribeiro EB, Nascimento CM. "Male Wistar rats, just weaned, were
|
|
fed ad libitum for 8 wk with one of the following diets: rat chow (C), rat chow containing 15% (w/w) soybean
|
|
oil (S), rat chow containing 15% (w/w) fish oil (F), and rat chow containing 15% soy bean and fish oil (SF;
|
|
5:1, w/w)." "Body weight gain was higher in F and SF than in C and S rats. Liver weight, lipid content, and
|
|
lipogenesis rate increased in F and SF rats, although adenosine triphosphate citrate lyase activity
|
|
decreased. Glycogen concentration decreased in S, F, and SF rats compared with C rats."
|
|
</p>
|
|
<p>
|
|
Br J Nutr. 2001 Sep;86(3):371-7. <strong>Polyunsaturated fatty acid-rich diets: effect on adipose tissue
|
|
metabolism in rats.</strong> Gaiva MH, Couto RC, Oyama LM, Couto GE, Silveira VL, Riberio EB, Nascimento
|
|
CM. "Wistar rats were fed ad libitum, for 8 weeks with one of the following diets: C, rat chow; S, rat chow
|
|
containing 15 % (w/w) soyabean oil; F, rat chow containing 15 % (w/w) fish oil; SF, rat chow containing 15 %
|
|
(w/w) soyabean and fish oil (5:1, w/w)." "Energy intake was reduced while carcass lipid content was
|
|
increased in the three fat-fed groups." "These results indicate that enrichment of the diet with
|
|
polyunsaturated fatty acids causes changes in adipose tissue metabolism that favour fat deposition.
|
|
Different metabolic pathways were preferentially affected by each type of fatty acid used."
|
|
</p>
|
|
<p>
|
|
Adv Exp Med Biol 266:3-15, 1989, <strong>"Lipofuscin and ceroid formation: the cellular recycling
|
|
system,"</strong> Harman, D.
|
|
</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. "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."
|
|
</p>
|
|
<p>
|
|
B. A. Houssay and C. Martinez, <strong>"Experimental diabetes and diet,"</strong>
|
|
Science 105, 548-549, 1947.
|
|
</p>
|
|
<p>
|
|
J Theor Biol. 2005 May 21;234(2):277-88. <strong>On the importance of fatty acid composition of membranes
|
|
for aging.</strong> Hulbert AJ.
|
|
</p>
|
|
|
|
<p>
|
|
Mech Ageing Dev. 2006 Apr 16; <strong>Extended longevity of wild-derived mice is associated with
|
|
peroxidation-resistant membranes.
|
|
</strong>
|
|
Hulbert AJ, Faulks SC, Harper JM, Miller RA, Buffenstein R. "Muscle and liver phospholipids from these
|
|
long-living mice lines have a reduced amount of the highly polyunsaturated omega-3 docosahexaenoic acid
|
|
compared to the DC mice, and consequently their membranes are less likely to peroxidative damage. The
|
|
relationship between maximum longevity and membrane peroxidation index is similar for these mice lines as
|
|
previously observed for mammals in general. It is suggested that peroxidation-resistant membranes may be an
|
|
important component of extended longevity."
|
|
</p>
|
|
<p>
|
|
Virchows Arch B Cell Pathol. 1975 Nov 21;19(3):239-54.<strong>
|
|
[Ultrastructure and morphogenesis of ceroid pigment. II. Late changes of lysosomes in Kupffer cells of
|
|
rat liver after phagocytosis of unsaturated lipids]
|
|
</strong>
|
|
Kajihara H, Totovic V, Gedigk P. "These lipids, which have been changed in their molecular structure, cannot
|
|
be hydrolized by lysosomal enzymes. They remain as an indigestible material, as a waste product in lysosomal
|
|
residual bodies. Both lipofuscin and ceroid are lysosomal structures containing oxidized and polymerized
|
|
lipids."
|
|
</p>
|
|
<p>
|
|
Reprod Nutr Dev. 1998 Jan-Feb;38(1):31-7. <strong>Effect of a high linoleic acid diet on delta 9-desaturase
|
|
activity, lipogenesis and lipid composition of pig subcutaneous adipose tissue.</strong> Kouba M, Mourot
|
|
J.
|
|
</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." "The data revealed characteristic patterns of age-related changes in ad libitum (AL) fed rats:
|
|
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." "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."
|
|
</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. "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."
|
|
"Considered together, these results suggest that DR maintains the integrity of the cardiac mitochondrial
|
|
membrane fluidity by minimizing membrane damage through modulation of membrane fatty acid profile."
|
|
</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>
|
|
Lipids 22(3), 133-6, 1987. <strong>Effects of parenteral nutrition with high doses of linoleate on the
|
|
developing human liver and brain,</strong> Martinez, M., and A. Ballabriga.
|
|
</p>
|
|
<p>
|
|
J Pharmacol Exp Ther. 1995 Jan;272(1):469-75. <strong>Acetic acid-induced colitis in normal and essential
|
|
fatty acid deficient rats.</strong> Mascolo N, Izzo AA, Autore G, Maiello FM, Di Carlo G, Capasso F.
|
|
</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>
|
|
J Nutrit 10:63(1935). <strong>The effect of retarded growth upon length of the life span and upon the
|
|
ultimate body size.</strong> McCay, CM., Crowell, MF., and Maynard, LA.
|
|
</p>
|
|
<p>
|
|
McCollum EV. 1957. <strong>A History of Nutrition.</strong> Boston: Houghton Mifflin. p 374.
|
|
</p>
|
|
|
|
<p>
|
|
J Biol Chem. 2003 Oct 24;278(43):42012-9. <strong>Pyridoxamine traps intermediates in lipid peroxidation
|
|
reactions in vivo: evidence on the role of lipids in chemical modification of protein and development of
|
|
diabetic complications.</strong>
|
|
Metz TO, Alderson NL, Chachich ME, Thorpe SR, Baynes JW.
|
|
</p>
|
|
<p>
|
|
FEBS Lett. 1998 Oct 16;437(1-2):24-8. <strong>Generation of protein carbonyls by glycoxidation and
|
|
lipoxidation reactions with autoxidation products of ascorbic acid and polyunsaturated fatty acids.
|
|
</strong>
|
|
Miyata T, Inagi R, Asahi K, Yamada Y, Horie K, Sakai H, Uchida K, Kurokawa K.
|
|
</p>
|
|
<p>
|
|
Naunyn Schmiedebergs Arch Pharmacol. 1996 Jul;354(2):109-19. <strong>Exposure to the n-3 polyunsaturated
|
|
fatty acid docosahexaenoic acid impairs alpha 1-adrenoceptor-mediated contractile responses and inositol
|
|
phosphate formation in rat cardiomyocytes.</strong> Reithmann C, Scheininger C, Bulgan T, Werdan K. "The
|
|
results presented show that <strong>chronic n-3 polyunsaturated fatty acid pretreatment of rat
|
|
cardiomyocytes leads to a marked impairment of alpha 1-adrenoceptor-induced positive inotropic effects
|
|
and induction of arrhythmias concomitant with a n-3 fatty acid-induced decrease in IP3 formation."
|
|
</strong>
|
|
</p>
|
|
|
|
<p>
|
|
Nutrition. 2000 Jan;16(1):11-4<strong>. Effects of eicosapentaenoic acid intake on plasma fibrinolytic and
|
|
coagulation activity by using physical load in the young.</strong> Sakamoto N, Nishiike T, Iguchi H,
|
|
Sakamoto K. "<strong>Thus, as determined by the load, a small amount of daily EPA intake clearly decreased
|
|
fibrinolytic activity and increased coagulation activity."</strong>
|
|
</p>
|
|
<p>
|
|
Diabetes. 2005 Aug;54(8):2314-9. <strong>Insulin resistance and type 2 diabetes in high-fat-fed mice are
|
|
linked to high glycotoxin intake.</strong> Sandu O, Song K, Cai W, Zheng F, Uribarri J, Vlassara H.
|
|
"These results demonstrate that the development of insulin resistance and type 2 diabetes during prolonged
|
|
high-fat feeding are linked to the excess AGEs/advanced lipoxidation end products inherent in fatty diets."
|
|
</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. "Dietary fat was fed to the rats as 10% of the total feed weight, starting two weeks before the
|
|
initiation. An increase in the n-3/n-6 ratio did not suppress the incidence or reduce the latency of mammary
|
|
tumor development. 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. <strong>As the n-3/n-6 ratios
|
|
were elevated, the total number and weight of tumors increased gradually."</strong> "These results
|
|
suggested that the increase in the n-3/n-6 ratio of dietary fat with the fixed PUFA-to-saturated fatty acid
|
|
ratio cannot suppress the mammary carcinogenesis but can promote development of tumors, despite reduced PGE2
|
|
concentration in the tumor."
|
|
</p>
|
|
|
|
<p>
|
|
J Cardiovasc Pharmacol. 2006 Mar;47(3):493-9. <strong>Mildronate, a novel fatty acid oxidation inhibitor and
|
|
antianginal agent, reduces myocardial infarct size without affecting hemodynamics.</strong> Sesti C,
|
|
Simkhovich BZ, Kalvinsh I, Kloner RA. "Mildronate is a fatty acid oxidation inhibitor approved as an
|
|
antianginal drug in parts of Europe."
|
|
</p>
|
|
<p>
|
|
J Nutr 2000 Dec;130(12):3028-33. <strong>Polyunsaturated (n-3) fatty acids susceptible to peroxidation are
|
|
increased in plasma and tissue lipids of rats fed docosahexaenoic acid-containing oils.</strong> Song
|
|
JH, Fujimoto K, Miyazawa T.. "Thus, high incorporation of (n-3) fatty acids (mainly DHA) into plasma and
|
|
tissue lipids due to DHA-containing oil ingestion may undesirably affect tissues by enhancing susceptibility
|
|
of membranes to lipid peroxidation and by disrupting the antioxidant system."
|
|
</p>
|
|
<p>
|
|
Diabetes Nutr Metab. 2002 Aug;15(4):205-14. <strong>Long-term effect of fish oil diet on basal and
|
|
stimulated plasma glucose and insulin levels in ob/ob mice.</strong>
|
|
|
|
Steerenberg PA, Beekhof PK, Feskens EJ, Lips CJ, Hoppener JW, Beems RB. "We have investigated, in comparison
|
|
to low and high fat diets, the effect of a fish oil diet on basal and stimulated plasma glucose and insulin
|
|
levels in male and female ob/ob mice." "Intercurrent deaths were found especially in the fish oil diet
|
|
group. Compared to the other diet groups, plasma insulin levels of the fish oil diet group were
|
|
significantly increased 3 months after the start of the diet and remained higher for another 3 months." "At
|
|
12 months, microscopy revealed an increased severity of hepatic brown pigment accumulation and
|
|
extramedullary haematopoiesis in the spleen of mice fed with fish oil." "Fish oil diet also increased
|
|
intercurrent mortality. However, a consistent course of death could not be established using morphological
|
|
parameters."
|
|
</p>
|
|
<p>
|
|
J Biol Chem. 2002 Feb 15;277(7):5692-7. <strong>Unsaturated fatty acids inhibit cholesterol efflux from
|
|
macrophages by increasing degradation of ATP-binding cassette transporter A1.</strong> Wang Y, Oram JF.
|
|
"These findings raise the possibility that an increased supply of unsaturated fatty acids in the artery wall
|
|
promotes atherogenesis by impairing the ABCA1 cholesterol secretory pathway in macrophages."
|
|
</p>
|
|
<p>
|
|
J Biol Chem. 2005 Oct 28;280(43):35896-903. Epub 2005 Aug 23. <strong>Unsaturated fatty acids phosphorylate
|
|
and destabilize ABCA1 through a phospholipase D2 pathway.</strong> Wang Y, Oram JF. "ATP-binding
|
|
cassette transporter ABCA1 mediates the transport of cholesterol and phospholipids from cells to HDL
|
|
apolipoproteins and thus modulates HDL levels and atherogenesis. Unsaturated fatty acids, which are elevated
|
|
in diabetes, impair the ABCA1 pathway in cultured cells by destabilizing ABCA1 protein." "Unsaturated but
|
|
not saturated fatty acids stimulated phospholipase D (PLD) activity, the PLD inhibitor 1-butanol prevented
|
|
the unsaturated fatty acid-induced reduction in ABCA1 levels, and the PLD2 activator mastoparan markedly
|
|
reduced ABCA1 protein levels, implicating a role for PLD2 in the ABCA1 destabilizing effects of fatty
|
|
acids." "These data provide evidence that intracellular unsaturated acyl-CoA derivatives destabilize ABCA1
|
|
by activating a PLD2 signaling pathway."
|
|
</p>
|
|
|
|
<p>
|
|
Isr J Med Sci. 1996 Nov;32(11):1134-43. <strong>Diet and disease--the Israeli paradox: possible dangers of a
|
|
high omega-6 polyunsaturated fatty acid diet.</strong> Yam D, Eliraz A, Berry EM. "Thus, rather than
|
|
being beneficial, high omega-6 PUFA diets may have some long-term side effects, within the cluster of
|
|
hyperinsulinemia, atherosclerosis and tumorigenesis."
|
|
</p>
|
|
|
|
© Ray Peat Ph.D. 2007. All Rights Reserved. www.RayPeat.com
|
|
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