1153 lines
87 KiB
HTML
1153 lines
87 KiB
HTML
<html>
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<head><title>Glycemia, starch, and sugar in context</title></head>
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<body>
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<h1>
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Glycemia, starch, and sugar in context
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</h1>
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<p>
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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><em>Monosaccharide -- a simple sugar; examples, glucose,</em></strong>
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<em> </em>
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<strong><em>fructose, ribose, galactose (galactose is also called cerebrose, brain sugar).</em></strong>
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</p>
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<p>
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<strong><em>Disaccharide -- two monosaccharides bound together; examples, sucrose, lactose, maltose.</em
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></strong>
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</p>
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<p>
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<strong><em>Oligosaccharide -- a short chain of monosaccharides, including disaccharides and slightly longer
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chains.</em></strong>
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</p>
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<p><strong><em>Polysaccharide -- example, starch, cellulose, glycogen.</em></strong></p>
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<p><strong><em>Glycation -- the attachment of a sugar to a protein.</em></strong></p>
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<p>
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<strong><em>Lipolysis - the liberation of free fatty acids from triglycerides, the neutral form in which
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fats are stored, bound to glycerine.</em></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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</p>
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<p>
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In the 1920s, "diabetes" was thought to be a disease of insulin deficiency. Eventually, measurements of
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insulin showed that "diabetics" often had normal amounts of insulin, or above-normal amounts. There are now
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"two kinds of diabetes," with suggestions that "the disease" will soon be further subdivided.
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</p>
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<p>
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The degenerative diseases that are associated with hyperglycemia and commonly called diabetes, are only
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indirectly related to insulin, and as an approach to understanding or treating diabetes, the "glycemic
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index" of foods is useless. Physiologically, it has no constructive use, and very little meaning.
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</p>
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<p>
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Insulin is important in the regulation of blood sugar, but its importance has been exaggerated because of
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the diabetes/insulin industry. Insulin itself has been found to account for only about 8% of the
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"insulin-like activity" of the blood, with potassium being probably the largest factor. There probably isn't
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any process in the body that doesn't potentially affect blood sugar.
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</p>
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<p>
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Glucagon, cortisol, adrenalin, growth hormone and thyroid tend to increase the blood sugar, but it is common
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to interpret hyperglycemia as "diabetes," without measuring any of these factors. Even when "insulin
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dependent diabetes" is diagnosed, it isn't customary to measure the insulin to see whether it is actually
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deficient, before writing a prescription for insulin. People resign themselves to a lifetime of insulin
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injections, without knowing why their blood sugar is high.
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</p>
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<p>
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Insulin release is also stimulated by amino acids such as leucine, and insulin stimulates cells to absorb
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amino acids and to synthesize proteins. Since insulin lowers blood sugar as it disposes of amino acids,
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eating a large amount of protein without carbohydrate can cause a sharp decrease in blood sugar. This leads
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to the release of adrenalin and cortisol, which raise the blood sugar. Adrenalin causes fatty acids to be
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drawn into the blood from fat stores, especially if the liver's glycogen stores are depleted, and cortisol
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causes tissue protein to be broken down into amino acids, some of which are used in place of carbohydrate.
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Unsaturated fatty acids, adrenaline, and cortisol cause insulin resistance.
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</p>
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<p>
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<hr />
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<hr />
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</p>
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<p>
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"Professional opinion" can be propagated about 10,000 times faster than research can evaluate it, or, as C.
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H. Spurgeon said, "A lie travels round the world while Truth is putting on her boots."
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</p>
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<p>
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In the 1970s, dietitians began talking about the value of including "complex carbohydrates" in the diet.
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Many dietitians (all but one of the Registered Dietitians that I knew of) claimed that starches were more
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slowly absorbed than sugars, and so should be less disruptive to the blood sugar and insulin levels. People
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were told to eat whole grains and legumes, and to avoid fruit juices.
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</p>
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<p>
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These recommendations, and their supporting ideology, are still rampant in the culture of the United States,
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fostered by the U.S. Department of Agriculture and the American Dietetic Association and the American
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Diabetes Association and innumerable university departments of home economics, dietetics, or nutrition.
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</p>
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<p>
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Judging by present and past statements of the American Dietetic Association, I think some kind of
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institutional brain defect might account for their recommendations. Although the dietetic association now
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feebly acknowledges that sugars don't raise the blood sugar more quickly than starches do, they can't get
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away from their absurd old recommendations, which were never scientifically justified<strong>:</strong> "Eat
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more starches, such as bread, cereal, and starchy vegetables--6 servings a day or more. Start the day with
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cold (dry) cereal with nonfat/skim milk or a bagel with one teaspoon of jelly/jam. Put starch center
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stage--pasta with tomato sauce, baked potato with chili, rice and stir-fried beef and vegetables. Add cooked
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black beans, corn, or garbanzo beans (chickpeas) to salads or casseroles."
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</p>
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<p>
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The Dietetic Association's association with General Mills, the breakfast cereal empire, (and Kellog,
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Nabisco, and many other food industry giants) might have something to do with their starchy opinions.
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Starch-grain embolisms can cause brain damage, but major money can also make people say stupid things.
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</p>
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<p>
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In an old experiment, a rat was tube-fed ten grams of corn-starch paste, and then anesthetized. Ten minutes
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after the massive tube feeding, the professor told the students to find how far the starch had moved along
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the alimentary canal. No trace of the white paste could be found, demonstrating the speed with which starch
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can be digested and absorbed. The very rapid rise of blood sugar stimulates massive release of insulin, and
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rapidly converts much of the carbohydrate into fat.
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</p>
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<p>
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It was this sort of experiment that led to the concept of "glycemic index," that ranks foods according to
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their ability to raise the blood sugar. David Jenkins, in 1981, knew enough about the old studies of starch
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digestion to realize that the dietitians had created a dangerous cult around the "complex carbohydrates,"
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and he did a series of measurements that showed that starch is more "glycemic" than sucrose. But he simply
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used the amount of increase in blood glucose during the first two hours after ingesting the food sample,
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compared to that following ingestion of pure glucose, for the comparison, neglecting the physiologically
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complex facts, all of the processes involved in causing a certain amount of glucose to be present in the
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blood during a certain time. (Even the taste of sweetness, without swallowing anything, can stimulate the
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release of glucagon, which raises blood sugar.)
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</p>
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<p>
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More important than the physiological vacuity of a simple glycemic measurement was the ideology within which
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the whole issue developed, namely, the idea that diabetes (conceived as chronic hyperglycemia) is caused by
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eating too much sugar, i.e., chronic hyperglycemia the illness is caused by the recurrent hyperglycemia of
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sugar gluttony. The experiments of Bernardo Houssay (1947 Nobel laureate) in the 1940s, in which sugar and
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coconut oil protected against diabetes, followed by Randle's demonstration of the antagonism between fats
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and glucose assimilation, and the growing recognition that polyunsaturated fatty acids cause insulin
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resistance and damage the pancreas, have made it clear that the dietetic obsession with sugar in relation to
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diabetes has been a dangerous diversion that has retarded the understanding of degenerative metabolic
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diseases.
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</p>
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<p>
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Starting with the insulin industry, a culture of diabetes and sugar has been fabulized and expanded and
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modified as new commercial industries found ways to profit from it. Seed oils, fish oils, breakfast cereals,
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soybean products, and other things that were never eaten by any animal in millions of years of evolution
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have become commonplace as "foods," even as "health foods."
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</p>
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<p>
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Although many things condition the rate at which blood sugar rises after eating carbohydrates, and affect
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the way in which blood glucose is metabolized, making the idea of a "glycemic index" highly misleading, it
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is true that blood sugar and insulin responses to different foods have some meaningful effects on physiology
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and health.
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</p>
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<p>
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Starch and glucose efficiently stimulate insulin secretion, and that accelerates the disposition of glucose,
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activating its conversion to glycogen and fat, as well as its oxidation. <strong>Fructose inhibits the
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stimulation of insulin by glucose, so this means that eating ordinary sugar, sucrose (a disaccharide,
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consisting of glucose and fructose), in place of starch, will reduce the tendency to store fat.</strong>
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Eating "complex carbohydrates," rather than sugars, is a reasonable way to promote obesity. Eating starch,
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by increasing insulin and lowering the blood sugar, stimulates the appetite, causing a person to eat more,
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so the effect on fat production becomes much larger than when equal amounts of sugar and starch are eaten.
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The obesity itself then becomes an additional physiological factor; the fat cells create something analogous
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to an inflammatory state. There isn't anything wrong with a high carbohydrate diet, and even a high starch
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diet isn't necessarily incompatible with good health, but when better foods are available they should be
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used instead of starches. For example, fruits have many advantages over grains, besides the difference
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between sugar and starch. Bread and pasta consumption are strongly associated with the occurrence of
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diabetes, fruit consumption has a strong inverse association.
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</p>
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<p>
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Although pure fructose and sucrose produce less glycemia than glucose and starch do, the different effects
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of fruits and grains on the health can't be reduced to their effects on blood sugar.
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</p>
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<p>
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Orange juice and sucrose have a lower glycemic index than starch or whole wheat or white bread, but it is
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common for dietitians to argue against the use of orange juice, because its index is the same as that of
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Coca Cola. But, if the glycemic index is very important, to be rational they would have to argue that Coke
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or orange juice should be substituted for white bread.
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</p>
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<p>
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After decades of "education" to promote eating starchy foods, obesity is a bigger problem than ever, and
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more people are dying of diabetes than previously. The age-specific incidence of most cancers is increasing,
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too, and there is evidence that starch, such as pasta, contributes to breast cancer, and possibly other
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types of cancer.
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</p>
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<p>
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The epidemiology would appear to suggest that complex carbohydrates cause diabetes, heart disease, and
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cancer. If the glycemic index is viewed in terms of the theory that hyperglycemia, by way of
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"glucotoxicity," causes the destruction of proteins by glycation, which is seen in diabetes and old age,
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that might seem simple and obvious.
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</p>
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<a name="0.1_table04"></a>
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<a name="0.1_table03"></a>
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<a name="0.1_table02"></a>
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<a name="0.1_table01"></a>
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<p>
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But there are many reasons to question that theory.
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</p>
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<p>
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Oxidation of sugar is metabolically efficient in many ways, including sparing oxygen consumption. It
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produces more carbon dioxide than oxidizing fat does, and carbon dioxide has many protective functions,
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including increasing Krebs cycle activity and inhibiting toxic damage to proteins. The glycation of proteins
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occurs under stress, when less carbon dioxide is being produced, and the proteins are normally protected by
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carbon dioxide.
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</p>
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<p>
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When sugar (or starch) is turned into fat, the fats will be either saturated, or in the series derived from
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omega -9 monounsaturated fatty acids. When sugar isn't available in the diet, stored glycogen will provide
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some glucose (usually for a few hours, up to a day), but as that is depleted, protein will be metabolized to
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provide sugar. If protein is eaten without carbohydrate, it will stimulate insulin secretion, lowering blood
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sugar and activating the stress response, leading to the secretion of adrenalin, cortisol, growth hormone,
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prolactin, and other hormones. The adrenalin will mobilize glycogen from the liver, and (along with other
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hormones) will mobilize fatty acids, mainly from fat cells. Cortisol will activate the conversion of protein
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to amino acids, and then to fat and sugar, for use as energy. (If the diet doesn't contain enough protein to
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maintain the essential organs, especially the heart, lungs, and brain, they are supplied with protein from
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the skeletal muscles. Because of the amino acid composition of the muscle proteins, their destruction
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stimulates the formation of additional cortisol, to accelerate the movement of amino acids from the less
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important tissues to the essential ones.)
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</p>
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<p>
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The diabetic condition is similar in many ways to stress, inflammation, and aging, for example in the
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chronic elevation of free fatty acids, and in various mediators of inflammation, such as tumor necrosis
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factor (TNF).
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</p>
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<p>
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Rather than the sustained hyperglycemia which is measured for determining the glycemic index, I think the
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"diabetogenic" or "carcinogenic" action of starch has to do with the stress reaction that follows the
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intense stimulation of insulin release. This is most easily seen after a large amount of protein is eaten.
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Insulin is secreted in response to the amino acids, and besides stimulating cells to take up the amino acids
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and convert them into protein, the insulin also lowers the blood sugar. This decrease in blood sugar
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stimulates the formation of many hormones, including cortisol, and under the influence of cortisol both
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sugar and fat are produced by the breakdown of proteins, including those already forming the tissues of the
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body. At the same time, adrenalin and several other hormones are causing free fatty acids to appear in the
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blood.
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</p>
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<p>
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Since the work of Cushing and Houssay, it has been understood that blood sugar is controlled by antagonistic
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hormones<strong>:</strong> Remove the pituitary along with the pancreas, and the lack of insulin doesn't
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cause hyperglycemia. If something increases cortisol a little, the body can maintain normal blood sugar by
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secreting more insulin, but that tends to increase cortisol production. A certain degree of glycemia is
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produced by a particular balance between opposing hormones.
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</p>
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<p>
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Tryptophan, from dietary protein or from the catabolism of muscles, is turned into serotonin which activates
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the pituitary stress hormones, increasing cortisol, and intensifying catabolism, which releases more
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tryptophan. It suppresses thyroid function, which leads to an increased need for the stress hormones.
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Serotonin impairs glucose oxidation, and contributes to many of the problems associated with diabetes.
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</p>
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<p>
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"Diabetes" is often the diagnosis, when excess cortisol is the problem. The hormones have traditionally not
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been measured before diagnosing diabetes and prescribing insulin or other chemical to lower the blood sugar.
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Some of the worst effects of "diabetes," including retinal damage, are caused or exacerbated by insulin
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itself.
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</p>
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<p>
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Antiserotonin drugs can sometimes alleviate stress and normalize blood sugar. Simply eating sucrose was
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recently discovered to restrain the stress hormone system ("A new perspective on glucocorticoid
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feedback<strong>:</strong> relation to stress, carbohydrate feeding and feeling better," J Neuroendocrinol
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13(9), 2001, KD Laugero).
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</p>
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<p>
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The free fatty acids released by the stress hormones serve as supplemental fuel, and increase the
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consumption of oxygen and the production of heat. (This increased oxygen demand is a problem for the heart
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when it is forced to oxidize fatty acids. [A. Grynberg, 2001]) But if the stored fats happen to be
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polyunsaturated, they damage the blood vessels and the mitochondria, suppress thyroid function, and cause
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"glycation" of proteins. They also damage the pancreas, and impair insulin secretion.
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</p>
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<p>
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A repeated small stress, or overstimulation of insulin secretion, gradually tends to become amplified by the
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effects of tryptophan and the polyunsaturated fatty acids, with these fats increasing the formation of
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serotonin, and serotonin increasing the liberation of the fats.
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</p>
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<p>
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The name, "glycation," indicates the addition of sugar groups to proteins, such as occurs in diabetes and
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old age, but when tested in a controlled experiment, <strong>lipid peroxidation of polyunsaturated fatty
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acids produces the protein damage about 23 times faster than the simple sugars do</strong>
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(Fu, et al., 1996). And the oxidation of fats rather than glucose means that the proteins won't have as much
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protective carbon dioxide combined with their reactive nitrogen atoms, so the real difference in the
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organism is likely to be greater than that seen by Fu, et al.
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</p>
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<p>
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These products of lipid peroxidation, HNE, MDA, acrolein, glyoxal, and other highly reactive aldehydes,
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damage the mitochondria, reducing the ability to oxidize sugar, and to produce energy and protective carbon
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dioxide.
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</p>
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<p>
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<strong>Fish oil, which is extremely unstable in the presence of oxygen and metals such as iron, produces
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some of these dangerous products very rapidly.</strong>
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The polyunsaturated "essential fatty acids" and their products, arachidonic acid and many of the
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prostaglandin-like materials, also produce them.
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</p>
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<p>
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When glucose can't be oxidized, for any reason, there is a stress reaction, that mobiles free fatty acids.
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Drugs that oppose the hormones (such as adrenalin or growth hormone) that liberate free fatty acids have
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been used to treat diabetes, because lowering free fatty acids can restore glucose oxidation.
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</p>
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<p>
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Brief exposures to polyunsaturated fatty acids can damage the insulin-secreting cells of the pancreas, and
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the mitochondria in which oxidative energy production takes place. Prolonged exposure causes progressive
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damage. Acutely, the free polyunsaturated fatty acids cause capillary permeability to increase, and this can
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be detected at the beginning of "insulin resistance" or "diabetes." After chronic exposure, the leakiness
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increases and albumin occurs in the urine, as proteins leak out of the blood vessels. The retina and brain
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and other organs are damaged by the leaking capillaries.
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</p>
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<p>
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The blood vessels and other tissues are also damaged by the chronically increased cortisol, and at least in
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some tissues (the immune system is most sensitive to the interaction) the polyunsaturated fats increase the
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ability of cortisol to kill the cells.
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</p>
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<p>
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When cells are stressed, they are likely to waste glucose in two ways, turning some of it into lactic acid,
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and turning some into fatty acids, even while fats are being oxidized, in place of the sugar that is
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available. Growth hormone and adrenalin, the stress-induced hormones, stimulate the oxidation of fatty
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acids, as well as their liberation from storage, so the correction of energy metabolism requires the
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minimization of the stress hormones, and of the free fatty acids. Prolactin, ACTH, and estrogen also cause
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the shift of metabolism toward the fatty acids.
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</p>
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<p>
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Sugar and thyroid hormone (T3, triiodothyronine) correct many parts of the problem. The conversion of T4
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into the active T3 requires glucose, and in diabetes, cells are deprived of glucose. Logically, all
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diabetics would be functionally hypothyroid. Providing T3 and sugar tends to shift energy metabolism away
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from the oxidation of fats, back to the oxidation of sugar.
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</p>
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<p>
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Niacinamide, used in moderate doses, can safely help to restrain the excessive production of free fatty
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acids, and also helps to limit the wasteful conversion of glucose into fat. There is evidence that diabetics
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are chronically deficient in niacin. Excess fatty acids in the blood probably divert tryptophan from niacin
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synthesis into serotonin synthesis.
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</p>
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<p>
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Sodium, which is lost in hypothyroidism and diabetes, increases cellular energy. Diuretics, that cause loss
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of sodium, can cause apparent diabetes, with increased glucose and fats in the blood. <strong>Thyroid,
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sodium, and glucose work very closely together to maintain cellular energy and stability.</strong>
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</p>
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<p>
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In Houssay's experiments, sugar, protein, and coconut oil protected mice against developing diabetes. The
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saturated fats of coconut oil are similar to those we synthesize ourselves from sugar. Saturated fats, and
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the polyunsaturated fats synthesized by plants, have very different effects on many important physiological
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processes. In every case I know about, the vegetable polyunsaturated fats have harmful effects on our
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physiology.
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</p>
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<p>
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For example, they bind to the "receptor" proteins for cortisol, progesterone, and estrogen, and to all of
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the major proteins related to thyroid function, and to the vesicles that take up nerve transmitter
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substances, such as glutamic acid.
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</p>
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<p>
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They allow glutamic acid to injure and kill cells through excessive stimulation; this process is similar to
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the nerve damage done by cobra venom, and other toxins.
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</p>
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<p>
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Excess cortisol makes nerve cells more sensitive to excitotoxicity, but the cells are protected if they are
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provided with an unusually large amount of glucose.
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</p>
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<p>
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The cells of the thymus gland are very sensitive to damage by stress or cortisol, but they too can be
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rescued by giving them enough extra glucose to compensate for the cortisol. Polyunsaturated fatty acids have
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the opposite effect, sensitizing the thymus cells to cortisol. This partly accounts for the
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immunosuppressive effects of the polyunsaturated fats. (AIDS patients have increased cortisol and
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polyunsaturated fatty acids in their blood.[E.A. Nunez, 1988.])
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</p>
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<p>
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Unsaturated fatty acids activate the stress hormones, sugar restrains them.
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</p>
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<p>
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Simply making animals "deficient" in the unsaturated vegetable oils (which allows them to synthesize their
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own series of animal polyunsaturated fats, which are very stable), protects them against "autoimmune"
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diabetes, and against a variety of other "immunological" challenges. The "essential fatty acid" deficiency
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increases the oxidation of glucose, as it increases the metabolic rate generally.
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</p>
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<p>
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Saturated fats improve the insulin-secreting response to glucose.
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</p>
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<p>
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The protective effects of sugar, and the harmful effects of excessive fat metabolism, are now being widely
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recognized, in every field of physiology. The unsaturated vegetable fats, linoleic and linolenic acid and
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their derivatives, such as arachidonic acid and the long chain fish oils, have excitatory, stress promoting
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effects, that shift metabolism away from the oxidation of glucose, and finally destroy the respiratory
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metabolism altogether. Since cell injury and death generally involve an imbalance between excitation and the
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ability to produce energy, it is significant that the oxidation of unsaturated fatty acids seems to consume
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energy, lowering cellular ATP (Clejan, et al, 1986).
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</p>
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<p>
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The bulk of the age-related tissue damage classified as "glycation end-products" (or "advanced glycation
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end-products," AGE) is produced by decomposition of the polyunsaturated fats, rather than by sugars, and
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this would be minimized by the protective oxidation of glucose to carbon dioxide.
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</p>
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<p>
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Protein of the right kind, in the right amount, is essential for reducing stress. Gelatin, with its
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antiinflammatory amino acid balance, helps to regulate fat metabolism.
|
|
</p>
|
|
<p>
|
|
Aspirin's antiinflammatory actions are generally important when the polyunsaturated fats are producing
|
|
inflammatory and degenerative changes, and aspirin prevents many of the problems associated with diabetes,
|
|
reducing vascular leakiness. It improves mitochondrial respiration (De Cristobal, et al., 2002) and helps to
|
|
regulate blood sugar and lipids (Yuan, et al., 2001). Aspirin's broad range of beneficial effects is
|
|
probably analogous to vitamin E's, being proportional to protection against the broad range of toxic effects
|
|
of the polyunsaturated "essential" fatty acids.
|
|
</p>
|
|
<p>
|
|
<strong><h3>REFERENCES</h3></strong>
|
|
</p>
|
|
<p>
|
|
<strong>Diabetes Care 1993 Sep;16(9):1301-5. Metabolic effects of dietary sucrose in type II diabetic
|
|
subjects. Bantle JP, Swanson JE, Thomas W, Laine DC "CONCLUSIONS--A high sucrose diet did not adversely
|
|
affect glycemia or lipemia in type II diabetic subjects."</strong>
|
|
</p>
|
|
<p>
|
|
Am J Physiol 1997 Nov;273(5 Pt 1):C1732-8. <strong>Glycolysis inhibition by palmitate in renal cells
|
|
cultured in a two-chamber system.</strong> Bolon C, Gauthier C, Simonnet H ""palmitate promoted a
|
|
long-term decrease in lactate production and sustained excellent cellular growth. After 4 days of contact,
|
|
decreased glycolysis was maintained even in the absence of carnitine"."
|
|
</p>
|
|
<p>
|
|
Diabetes 1989 Oct;38(10):1314-9. <strong>Effects of fish oil supplementation on glucose and lipid metabolism
|
|
in NIDDM.</strong> Borkman M, Chisholm DJ, Furler SM, Storlien LH, Kraegen EW, Simons LA, Chesterman CN.
|
|
Garvan "<strong>In summary, dietary fish oil supplementation adversely affected glycemic control in NIDDM
|
|
subjects without producing significant beneficial effects on plasma lipids. The effect of safflower oil
|
|
supplementation was not significantly different from fish oil,
|
|
</strong>suggesting that the negative effects on glucose metabolism may be related to the extra energy or
|
|
fat intake." Randomized Controlled Trial
|
|
</p>
|
|
|
|
<p>
|
|
Ann Clin Lab Sci 1988 Jul-Aug;18(4):337-43. <strong>Effects of peroxidized polyunsaturated fatty acids on
|
|
mitochondrial function and structure: pathogenetic implications for Reye's syndrome.</strong> Brown RE,
|
|
Bhuvaneswaran C, Brewster M. "<strong>Linoleic acid, a polyunsaturated fatty acid, is a constituent of
|
|
margosa oil which has been implicated as a cause of Reye's syndrome (RS) in infants. Increased
|
|
concentrations of polyunsaturated fatty acids have been found in sera from patients with RS." Isolated
|
|
rat liver mitochondria exposed to the</strong> peroxidized (but not unperoxidized) methyl esters of
|
|
linoleic (C18:2) or linolenic (C18:3) acids showed decreases in state 3 and uncoupled respiratory rates and
|
|
in respiratory control and ADP/O ratios. In addition, they caused mitochondrial swelling as demonstrated
|
|
spectrophotometrically. Between the two, the peroxidized methyl ester of linolenic acid was more toxic and
|
|
was capable of inducing high amplitude swelling ultrastructurally similar to that seen in the hepatocytes of
|
|
RS victims. The ability of rat liver mitochondria to oxidize glutamate was inversely related to the peroxide
|
|
concentration in the medium."
|
|
</p>
|
|
<p>
|
|
J Neurochem 1982 Feb;38(2):525-31.<strong>
|
|
Phospholipid degradation and cellular edema induced by free radicals in brain cortical slices.
|
|
</strong>
|
|
Chan PH, Yurko M, Fishman RA. "<strong>These data suggest that lipases are activated by free radicals and
|
|
lipid peroxides in the pathogenesis of cellular swelling."</strong>
|
|
</p>
|
|
|
|
<p>
|
|
J Neurochem 1988 Apr;50(4):1185-93. <strong>Induction of intracellular superoxide radical formation by
|
|
arachidonic acid and by polyunsaturated fatty acids in primary astrocytic cultures.</strong> Chan PH,
|
|
Chen SF, Yu AC. "Other PUFAs, including linoleic acid, linolenic acid, and docosahexaenoic acid, were also
|
|
effective in stimulating NBF formation in astrocytes, whereas saturated palmitic acid and monounsaturated
|
|
oleic acid were ineffective. Similar effects of these PUFAs were observed in malondialdehyde formation in
|
|
cells and lactic acid accumulation in incubation medium. These data indicate that both membrane integrity
|
|
and cellular metabolism were perturbed by arachidonic acid and by other PUFAs."
|
|
</p>
|
|
<p>
|
|
Can J Biochem 1978 Feb;56(2):111-6. <strong>Uncoupling activity of endogenous free fatty acids in rat liver
|
|
mitochondria.</strong> Chan SH, Higgins E Jr.
|
|
</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. "The polyunsaturated fatty acids linoleic acid (18:2), linolenic acid (18:3),
|
|
arachidonic acid (20:4), and docosahexaenoic acid (22:6) caused brain swelling concomitant with increases in
|
|
superoxide and membrane lipid<strong>
|
|
peroxidation. Palmitic acid (16:0) and oleic acid (18:1) had no such effect."</strong> "These in vitro
|
|
data support the hypothesis that both superoxide radicals and lipid peroxidation are involved in the
|
|
mechanism of polyunsaturated fatty acid-induced brain edema."
|
|
</p>
|
|
|
|
<p>
|
|
Arch Biochem Biophys 1986 May 1;246(2):820-8. <strong>Effect of growth hormone on fatty acid oxidation:
|
|
growth hormone increases the activity of 2,4-dienoyl-CoA reductase in mitochondria.
|
|
</strong>Clejan S, Schulz H. "<strong>Rates of respiration supported by polyunsaturated fatty
|
|
acylcarnitines, in contrast to rates observed with palmitoylcarnitine or oleoylcarnitine, were slightly
|
|
lower in hypophysectomized rats than in normal rats, but were higher in hypophysectomized rats treated
|
|
with growth hormone. The effects were most pronounced with docosahexaenoylcarnitine, the substrate with
|
|
the highest degree of unsaturation.</strong>
|
|
Since uncoupling of mitochondria with 2,4-dinitrophenol resulted in lower rates of
|
|
docosahexaenoylcarnitine-supported respiration, while substitution of ATP for ADP yielded higher rates, it
|
|
appears that <strong>
|
|
energy is required for the effective oxidation of polyunsaturated</strong>
|
|
fatty acids. Growth hormone treatment of hypophysectomized rats caused a threefold increase in t`he activity
|
|
of 2,4-dienoyl-CoA reductase or 4-enoyl-CoA reductase (EC 1.3.1.34) in mitochondria, but not in
|
|
peroxisomes." "Rates of acetoacetate formation from linolenoylcarnitine, but not from palmitoylcarnitine,
|
|
were stimulated by glutamate in mitochondria from hypophysectomized rats and hypophysectomized rats treated
|
|
with growth hormone. All data together <strong>lead to the conclusion that the mitochondrial oxidation of
|
|
highly polyunsaturated fatty acids is limited by the availability of NADPH
|
|
</strong>and the activity of 2,4-dienoyl-CoA reductase which is induced by growth hormone treatment."
|
|
</p>
|
|
<p>
|
|
V. Coiro, et al., "Low-dose ovine corticotropin-releasing hormone stimulation test in diabetes mellitus with
|
|
or without neuropathy," Metabolism--Clinical and Experimental 44(4), 538-542, 1995.<strong>
|
|
"...basal and CRH-induced cortisol levels were significantly higher in diabetics than in normal
|
|
controls." "...even uncomplicated diabetes mellitus is associated with adrenal hyperfunction."</strong>
|
|
</p>
|
|
<p>
|
|
Stroke 2002 Jan;33(1):261-7. <strong>
|
|
Inhibition of glutamate release via recovery of ATP levels accounts for a neuroprotective effect of
|
|
aspirin in rat cortical neurons exposed to oxygen-glucose deprivation.</strong> De Cristobal J, Cardenas
|
|
A, Lizasoain I, Leza JC, Fernandez-Tome P, Lorenzo P, Moro MA. "Aspirin is preventive against stroke not
|
|
only because of its antithrombotic properties but also by other direct effects." "Aspirin inhibited
|
|
OGD-induced neuronal damage at concentrations lower (0.3 mmol/L) than those reported to act via inhibition
|
|
of the transcription factor nuclear factor-kappaB (which are >1 mmol/L), an effect that <strong
|
|
>correlated with the inhibition caused by aspirin on glutamate release.</strong> This effect was shared by
|
|
sodium salicylate but not by indomethacin, thus excluding the involvement of cyclooxygenase. A
|
|
pharmacological dissection of the components involved indicated that aspirin selectively inhibits the
|
|
increase in extracellular glutamate concentration that results from reversal of the glutamate transporter, a
|
|
component of release that is due to ATP depletion. Moreover, aspirin-afforded neuroprotection occurred in
|
|
parallel with a lesser decrease in ATP levels after OGD. <strong>Aspirin elevated ATP levels not only in
|
|
intact cortical neurons but also in isolated brain mitochondria, an effect concomitant with an increase
|
|
in NADH-dependent respiration by brain submitochondrial particles."</strong> "Taken together, our
|
|
present findings show a novel mechanism for the neuroprotective effects of aspirin, which takes place at
|
|
concentrations in the antithrombotic-analgesic range, useful in the management of patients with high risk of
|
|
ischemic events."
|
|
</p>
|
|
|
|
<p>
|
|
Diabetes 2002 Jun;51(6):1825-33. <strong>The composition of dietary fat directly influences
|
|
glucose-stimulated insulin secretion in rats.</strong> Dobbins RL, Szczepaniak LS, Myhill J, Tamura Y,
|
|
Uchino H, Giacca A, McGarry JD. <strong>"Insulin responses during hyperglycemic clamps were augmented by
|
|
saturated but not unsaturated fat (580 +/- 25, 325 +/- 30, and 380 +/- 50 pmol x l(-1) x min(-1) in
|
|
Lard, Soy, and Low-Fat groups, respectively).</strong>" <strong>
|
|
"These data indicate that prolonged exposure to saturated fat enhances GSIS (but this does not entirely
|
|
compensate for insulin resistance), whereas unsaturated fat, given in the diet or by infusion, impairs
|
|
GSIS."</strong>
|
|
</p>
|
|
<p>
|
|
C. Douillet and M. Ciavatti, <strong>"Effect of vitamin E treatment on tissue fatty acids and cholesterol
|
|
content in experimental diabetes,"</strong>
|
|
J. Nutr. Biochem. 6(6), 319-326, 1995. <strong>
|
|
"Diabetes induced a decrease of monounsaturated fatty acids and particularly palmitoleic acid in all
|
|
studied tissues: liver, aorta, plasma." "C18:3 n-6 and C20:4 n-6 were increased by diabetes."</strong>
|
|
</p>
|
|
|
|
<p>
|
|
Diabetologia 1992 Feb;35(2):165-72. <strong>Long-term effects of linoleic-acid-enriched diet on albuminuria
|
|
and lipid levels in type 1 (insulin-dependent) diabetic patients with elevated urinary albumin
|
|
excretion.</strong> Dullaart RP, Beusekamp BJ, Meijer S, Hoogenberg K, van Doormaal JJ, Sluiter WJ. "We
|
|
conducted a 2-year prospective randomised study to investigate the effects of a linoleic-acid-enriched diet
|
|
on albuminuria and lipid levels in Type 1 (insulin-dependent) diabetic patients with elevated urinary
|
|
albumin excretion (overnight urinary albumin excretion rate between 10 and 200 micrograms/min)." "Clinical
|
|
characteristics,<strong> </strong>
|
|
albuminuria, blood pressure, glomerular filtration rate, metabolic control and dietary composition were
|
|
similar in the two groups at baseline. In the high linoleic acid diet group, linoleic intake rose from 7 +/-
|
|
4 to 11 +/- 2 energy % and polyunsaturated:saturated fatty acids ratio rose from 0.60 +/- 0.28 to 0.96 +/-
|
|
0.16 (p less than 0.001 compared to usual diet group). The median increase albuminuria was 58% (95%
|
|
confidence interval, 13 to 109) during the first year (p less than 0.02) and 55% (95% confidence interval,
|
|
11 to 127) (p less than 0.01) during the second year."
|
|
</p>
|
|
<p>
|
|
J Biol Chem 1996 Apr 26;271(17):9982-6. <strong>The advanced glycation end product,
|
|
Nepsilon-(carboxymethyl)lysine, is a product of both lipid peroxidation and glycoxidation
|
|
reactions.</strong>
|
|
Fu MX, Requena JR, Jenkins AJ, Lyons TJ, Baynes JW, Thorpe SR. Nepsilon-(Carboxymethyl)lysine (CML) is an
|
|
advanced glycation end product formed on protein by combined nonenzymatic glycation and oxidation
|
|
(glycoxidation) reactions. We now report that CML is also formed during metal-catalyzed oxidation of
|
|
polyunsaturated fatty acids in the presence of protein. During copper-catalyzed oxidation in vitro, the CML
|
|
content of low density lipoprotein increased in concert with conjugated dienes but was independent of the
|
|
presence<strong>
|
|
of the Amadori compound, fructoselysine, on the protein. CML was also formed in a time-dependent manner
|
|
in RNase incubated under aerobic conditions in phosphate buffer containing arachidonate or linoleate;
|
|
only trace amounts of CML were formed from oleate. After 6 days of incubation the yield of CML in RNase
|
|
from arachidonate was approximately 0.7 mmol/mol lysine compared with only 0.03 mmol/mol lysine for
|
|
protein incubated under the same conditions with glucose.</strong> Glyoxal, a known precursor of CML,
|
|
was also formed during incubation of Rnase with arachidonate. These results suggest that lipid peroxidation,
|
|
as well as glycoxidation, may be an important source of CML in tissue proteins in vivo and that CML may be a
|
|
general marker of oxidative stress and long term damage to protein in aging, atherosclerosis, and diabetes.
|
|
</p>
|
|
|
|
<p>
|
|
J Nutr 2000 Oct;130(10):2503-7. <strong>A high carbohydrate versus a high monounsaturated fatty acid diet
|
|
lowers the atherogenic potential of big VLDL particles in patients with type 1 diabetes.</strong>
|
|
Georgopoulos A, Bantle JP, Noutsou M, Hoover HA. "A high (25%) monounsaturated fatty acid (Mono) diet and a
|
|
high (61%) carbohydrate (CHO) diet were provided for 4 wk in a randomized crossover design to 19
|
|
normolipidemic, nonobese patients with type 1 diabetes. The two diets were matched for protein,
|
|
polyunsaturated/saturated fatty acids, cholesterol and fiber content." "We conclude that a high CHO diet
|
|
might be preferable to a high Mono diet, on the basis of the premise that more big VLDL particles could
|
|
increase the atherosclerotic risk in patients with diabetes."
|
|
</p>
|
|
<p>
|
|
J. Girard, "Role of free fatty acids in insulin resistance of subjects with non-insulin-dependent diabetes,"
|
|
Diabetes Metab. 21(2), 79-88, 1995. <strong>"Studies performed in the rat suggest that impaired
|
|
glucose-induced insulin secretion could also be related to chronic exposure of pancreatic beta cells to
|
|
elevated plasma free fatty acid levels."</strong>
|
|
</p>
|
|
<p>
|
|
Ann Intern Med 1988 May;108(5):663-8. <strong>Adverse metabolic effect of omega-3 fatty acids in
|
|
non-insulin-dependent diabetes mellitus.
|
|
</strong>
|
|
<hr />
|
|
<strong><hr /></strong> but unchanged glucose disposal rates. Caution should be used when recommending
|
|
omega-3 fatty acids in type II diabetic persons."
|
|
</p>
|
|
<p>
|
|
A. Golay, et al., "Effect of lipid oxidation on the regulation of glucose utilization in obese patients,"
|
|
Acta Diabetologica 32(1), 44-48, 1995. <strong>[Free fatty acids strongly and quickly depress the ability to
|
|
oxidize or store glucose.]</strong>
|
|
</p>
|
|
<p>
|
|
Biol Neonate 1985;47(6):343-9. <strong>Increased maternal-fetal transport of fat in diabetes assessed by
|
|
polyunsaturated fatty acid content in fetal lipids.</strong>
|
|
Goldstein R, Levy E, Shafrir E. The distribution of fatty acids was determined by gas-liquid chromatography
|
|
in total lipid and triglyceride fraction of extracts of several tissues of streptozotocin-diabetic rats and
|
|
their fetuses on day 20 of pregnancy. In maternal rats, diabetes did not significantly affect fatty acid
|
|
distribution apart from small changes in the relative content of linoleate in adipose tissue and liver. In
|
|
the placenta, the fetal carcass and the fetal liver the<strong>
|
|
triglyceride content increased approximately 2-fold as a result of maternal diabetes, in association
|
|
with the elevation in triglycerides and free fatty</strong>
|
|
|
|
acids in the maternal circulation. A pronounced increase in the relative content<strong>
|
|
of linoleate was recorded in the total lipid and triglyceride extracts of placenta (35 and 59%), fetal
|
|
carcass (56 and 66%) and fetal liver (100 and 205%). Small increases in arachidonate proportion were
|
|
also seen in some fetal tissues. The large increase in fetal hepatic linoleate indicates that
|
|
this</strong> tissue is an important uptake target of maternal lipids transported in excess into the
|
|
fetus. The results confirm the previous observations on increased transplacental fat passage in diabetes by
|
|
demonstrating that the increment in the essential fatty acid, linoleate, parallels the diabetes-induced
|
|
triglyceride accumulation in the fetoplacental unit.
|
|
</p>
|
|
<p>
|
|
A. Gomes, et al., "Anti-hyperglycemic effect of black tea (Camellia sinensis) in rat," J. of
|
|
Ethnopharmacology 45(3), 223-226, 1995. <strong>
|
|
It "was found to possess both preventive and curative effects on experimentally produced diabetes in
|
|
rats."</strong>
|
|
</p>
|
|
<p>
|
|
J Endocrinol 2002 Apr;173(1):73-80. <strong>Acute effects of fatty acids on insulin secretion from rat and
|
|
human islets of Langerhans.</strong> Gravena C, Mathias PC, Ashcroft SJ. "Long-chain fatty<strong>
|
|
acids (palmitate and stearate) were more effective than medium-chain (octanoate). Saturated fatty acids
|
|
(palmitate, stearate) were more effective than unsaturated (palmitoleate, linoleate, elaidate)."</strong
|
|
>
|
|
</p>
|
|
|
|
<p>
|
|
Diabetes Metab 2001 Nov;27(5 Pt 2):S12-9. <strong>[Modifications in myocardial energy metabolism in diabetic
|
|
patients]]</strong> [Article in French] Grynberg A. "<strong>Because FA is the main heart fuel (although
|
|
the most expensive one in oxygen, and prompt to induce deleterious effects), this process is based on a
|
|
balanced fatty acid (FA) metabolism.</strong> Several pathological situations are associated with an
|
|
accumulation of FA or derivatives, or with an excessive b-oxidation. The diabetic cardiomyocyte is
|
|
characterised by an over consumption of FA. The control of the FA/glucose balance clearly appears as a new
|
|
strategy for cytoprotection, particularly in diabetes and requires a reduced FA contribution to ATP
|
|
production. Cardiac myocytes can control FA mitochondrial entry, but display weak ability to control FA
|
|
uptake, thus the fate of non beta-oxidized FA appear as a new impairment for the cell." "Sudden death,
|
|
hypercatecholaminemia, diabetes and heart failure have been associated with an altered PUFA content in
|
|
cardiac membranes."
|
|
</p>
|
|
<p>
|
|
Diabetologia 1996 Mar;39(3):251-5. <strong>Acceleration of experimental diabetic retinopathy in the rat by
|
|
omega-3 fatty Acids.</strong> Hammes HP, Weiss A, Fuhrer D, Kramer HJ, Papavassilis C, Grimminger F.
|
|
Omega-3 fatty acids exert several important biological effects on factors that may predispose to diabetic
|
|
retinopathy. Potential pathogenetic mechanisms include platelet dysfunction, altered eicosanoid production,
|
|
increased blood viscosity in association with impaired cell deformability and pathologic
|
|
leucocyte/endothelium interaction. Therefore, we tested whether a 6-month administration of fish oil (750 mg
|
|
Maxepa, 5 times per week), containing 14% eicosapentaenoic acid (EPA) and 10% docosahexaenic acid, could
|
|
inhibit the development of experimental retinopathy of the streptozotocin-diabetic rat. The efficiency of
|
|
fish oil supplementation was evaluated by measuring EPA concentrations in total, plasma and membrane fatty
|
|
acids and by measuring the generation of lipid mediators (leukotrienes and thromboxanes). Retinal digest
|
|
preparations were quantitatively analysed for pericyte loss, and the formation of acellular capillaries.
|
|
Omega-3 fatty acid administration to diabetic rats resulted in a twofold increase of EPA 20:5 in total fatty
|
|
acids, and a reduction of the thromboxane ratio from 600 (untreated diabetic rats) to 50 (treated diabetic
|
|
rats). Despite these biochemical changes, diabetes-associated pericyte loss remained unaffected and the
|
|
formation of acellular, occluded capillaries was increased by 75% in the fish oil treated diabetic group
|
|
(115.1 +/- 26.8; untreated diabetic 65.2 +/- 15.0 acellular capillary segments/mm2 of retinal area). We
|
|
conclude from this study that dietary fish oil supplementation may be harmful for the diabetic
|
|
microvasculature in the retina.
|
|
</p>
|
|
<p>
|
|
Y. Hattori, et al., "Phorbol esters elicit Ca++-dependent delayed contractions in diabetic rat aorta," Eur.
|
|
J. Pharmacol. 279(1), 51-58, 1995. <strong>[Diabetic tissue is more responsive to activation of protein
|
|
kinase C by phorbol esters.]</strong>
|
|
</p>
|
|
|
|
<p>
|
|
Nutr Metab 1975;18(1):41-8. <strong>Adipose tissue metabolism in essential fatty acid deficienty. Effects of
|
|
prostaglandin e1, epinephrine, and ACTH.</strong>
|
|
Hazinski TA, Barr M, Hertelendy F. In an effort to better define some of the metabolic changes that
|
|
accompany essential fatty acid deficiency (EFAD), we studied glucose metabolism in adipose tissue of EFAD
|
|
and normal mice under basal conditions and in the presence of prostaglandin E1 (PGE1), epinephrine, and
|
|
ACTH1-18. Isolated fat cells were incubated in Krebs-Ringer bicarbonate medium containing glucose 1(-14C) or
|
|
6(-14C), and the incorporation of radioactive carbon into CO2, total fat, fatty acids, and
|
|
glyceride-glycerol was determined. <strong>It was found that EFAD increased glucose uptake over controls
|
|
which could be attributed to increased oxidation to CO2 and fatty acid synthesis. The contribution of
|
|
the pentose cycle to glucose oxidation was 50-80% higher in EFAD adipocytes as compared to controls.
|
|
ACTH1-18</strong> (0.1 mug/ml) suppressed this by 18 and 30% in the control and EFAD groups,
|
|
respectively, while epinephrine decreased pentose cycle activity by 83 and 55% in the two groups,
|
|
respectively. PGE1 alone had no significant effect, but in combination with epinephrine it abolished the
|
|
inhibitory action of the catecholamine in both groups."
|
|
</p>
|
|
<p>
|
|
J Neurosci Res 1989 Oct;24(2):247-50. <strong>Brain mitochondrial swelling induced by arachidonic acid and
|
|
other long chain free fatty acids.</strong> Hillered L, Chan PH. "<strong>Polyunsaturated fatty acids
|
|
(PUFAs), arachidonic acid in particular, are well known, potent inducers of edema in the brain, while
|
|
monounsaturated and saturated long chain fatty acids do not possess this quality."</strong>
|
|
"<strong>ATP-MgCl2 both prevented and reversed this swelling, while binding of the 20:4 by the addition of
|
|
bovine serum albumin could only prevent but not reverse the swelling." "Moreover, reversal of the
|
|
swelling occurred without recovery of respiratory function."
|
|
</strong>
|
|
</p>
|
|
|
|
<p>
|
|
J Neurosci Res 1988 Aug;20(4):451-6. <strong>
|
|
Role of arachidonic acid and other free fatty acids in mitochondrial dysfunction in brain ischemia.
|
|
</strong>
|
|
Hillered L, Chan PH.
|
|
</p>
|
|
<p>
|
|
B. A. Houssay and C. Martinez, <strong>"Experimental diabetes and diet,"</strong>
|
|
Science 105, 548-549, 1947. <strong>[Mortality was zero on the high coconut oil diet, 100% on the high lard
|
|
diet. It was 90% on the low protein diet, and 33% on the high protein diet. With a combination of
|
|
coconut oil and lard, 20%.]</strong>
|
|
</p>
|
|
<p>
|
|
B. A. Houssay, et al., <strong>"Accion de la administracion prolongada de glucosa sobre la diabetes de la
|
|
rata,"</strong> Rev. Soc. argent. de biol. 23, 288-293, 1947.
|
|
</p>
|
|
|
|
<p>
|
|
S. Ikemoto, et al., <strong>"High fat diet-induced hyperglycemia: Prevention by low level expression of a
|
|
glucose transporter (GLUT4) minigene in transgenic mice,"</strong> Proc. Nat. Acad. Sci. USA 92(8),
|
|
3096-3099, 1995. <strong>
|
|
"...mice fed a high-fat (safflower oil) diet develop defective glycemic control, hyperglycemia, and
|
|
obesity."</strong>
|
|
</p>
|
|
<p>
|
|
M. Inaba, et al., <strong>"Influence of high glucose on 1,25-dihydroxyvitamin D-3-induced effect on human
|
|
osteoblast-like MG-63 cells,"</strong> J. Bone Miner. Res. 10(7), 1050-1056, 1995.
|
|
</p>
|
|
<p>
|
|
J. S. Jensen, et al., <strong>"Microalbuminuria reflects a generalized transvascular albumin leakiness in
|
|
clinically healthy subjects,"</strong>
|
|
|
|
Clin. Sci. 88(6), 629-633, 1995.
|
|
</p>
|
|
<p>
|
|
J Am Geriatr Soc 1984 May;32(5):375-9.<strong>
|
|
Low triiodothyronine and raised reverse triiodothyronine levels in patients over fifty years of age who
|
|
have type II diabetes mellitus: influence of metabolic control, not age.</strong> Kabadi UM,
|
|
Premachandra BN. "Several studies have demonstrated that the uncontrolled diabetic state in both type I as
|
|
well as type II diabetes mellitus is characterized by altered thyroid hormone metabolism, which results in
|
|
the<strong>
|
|
lowering of serum triiodothyronine (T3) levels and a reciprocal elevation of T3 (rT3) levels."
|
|
</strong>
|
|
"Serum T3 levels declined and rT3 levels rose in the diabetic patients with worsening of the metabolic
|
|
control."
|
|
</p>
|
|
<p>
|
|
Metabolism 1989 Mar;38(3):278-81. <strong>The effect of fatty acids on the vulnerability of lymphocytes to
|
|
cortisol.</strong> Klein A, Bruser B, Malkin A. "We have shown previously that cortisol-sensitive
|
|
lymphocytes (thymocytes) have a much lower capacity than cortisol-resistant cells to catabolize cortisol and
|
|
that <strong>linoleic acid inhibits the catabolism of cortisol by lymphocytes and modulates the sensitivity
|
|
of lymphocytes to cortisol.</strong>" "Measuring the effect of fatty acids on cortisol catabolism by
|
|
lymphocytes indicated that <strong>the polyunsaturated fatty acids, linoleate, arachidonate, and
|
|
eicosapentaenoic, inhibit cortisol catabolism by lymphocytes." "Examining the effect of fatty acids on
|
|
the vulnerability of lymphocytes to cortisol, we noted that saturated fatty acids had no significant
|
|
effect, whereas the aforementioned polyunsaturated fatty acids make lymphocytes more sensitive to
|
|
cortisol."</strong>
|
|
</p>
|
|
|
|
<p>
|
|
Jpn J Pharmacol 1978 Apr;28(2):277-87. <strong>Relationship between cerebral energy failure and free fatty
|
|
acid accumulation following prolonged brain ischemia.</strong>
|
|
Kuwashima J, Nakamura K, Fujitani B, Kadokawa T, Yoshida K, Shimizu M. "Mitochondria isolated from the
|
|
ischemic brain showed an impairment of oxidative phosphorylation. The ischemic<strong>
|
|
brain was also characterized by remarkable accumulation of free fatty acids known to have properties as
|
|
an uncoupling factor." "These results indicate that cerebral energy failure in the ischemic brain is
|
|
related to the accumulation of free fatty acids, which are derived from endogenous brain
|
|
lipids."</strong>
|
|
</p>
|
|
<p>
|
|
Probl Endokrinol (Mosk) 1992 Nov-Dec; 38(6):53-4. <strong>[Effect of protein content in rat diet on
|
|
water-soluble vitamin metabolism in streptozotocin-induced diabetes]
|
|
</strong>[Article in Russian] Kodentsova VM, Sadykova RE, Dreval' AV, Vrzhesinskaia OA, Sokol'nikov AA,
|
|
Beketova NA. Water-soluble group B vitamins metabolism was studied over the course of streptozotocin-induced
|
|
diabetes mellitus in rats fed semisynthetic isocaloric diets containing 18 and 50% of protein. A
|
|
high-protein diet in diabetes mellitus does not influence riboflavin metabolism disordered in this disease
|
|
but reduced 4-pyridoxyl acid excretion to the level characteristic of healthy animals. The observed trend to
|
|
an increase of liver nicotinamide coenzymes levels and of 1-methylnicotinamide urinary excretion reflects
|
|
increased niacin synthesis from<strong>
|
|
the diet protein tryptophan, for niacin level is reduced in diabetes.</strong>
|
|
</p>
|
|
<p>
|
|
M. Kusunoki, et al., <strong>"Amelioration of high fat feeding-induced insulin resistance in skeletal muscle
|
|
with the antiglucocorticoid RU486,"
|
|
</strong>
|
|
|
|
Diabetes 44(6), 718-720, 1995. <strong>"These results suggest that glucocorticoids play, in a
|
|
tissue-specific manner, a role in the maintenance and/or production of insulin resistance produced by
|
|
high-fat feeding."</strong>
|
|
</p>
|
|
<p>
|
|
J Neuroendocrinol 2001 Sep;13(9):827-35. <strong>A new perspective on glucocorticoid feedback: relation to
|
|
stress, carbohydrate feeding and feeling better.
|
|
</strong>Laugero KD. "In this review, I discuss findings that have led us to view glucocorticoid feedback in
|
|
the HPA axis in a new light. Much of what has precipitated this view comes from a very surprising finding in
|
|
our laboratory; sucrose ingestion normalizes feeding, energy balance and central corticotropin releasing
|
|
factor expression in adrenalectomized (ADX) rats." "Taken together, recent findings of the well-known
|
|
importance of glucocorticoids to feeding and energy balance, and the modulatory actions of carbohydrate
|
|
ingestion on both basal and stress-induced activity in the HPA axis, strongly suggest that many metabolic
|
|
(e.g. obesity) and psychological (e.g. depression) pathologies, which often present together and have been
|
|
associated with stress and HPA dysregulation, might, in part, be understood in light of our new view of
|
|
glucocorticoid feedback."
|
|
</p>
|
|
<p>
|
|
Endocrinology 2001 Jul;142(7):2796-804. <strong>Sucrose ingestion normalizes central expression of
|
|
corticotropin-releasing-factor messenger ribonucleic acid and energy balance in adrenalectomized rats: a
|
|
glucocorticoid-metabolic-brain axis?</strong>
|
|
Laugero KD, Bell ME, Bhatnagar S, Soriano L, Dallman MF. "Both CRF and norepinephrine (NE) inhibit food
|
|
intake and stimulate ACTH secretion and sympathetic outflow. CRF also increases anxiety; NE increases
|
|
attention and cortical arousal. Adrenalectomy (ADX) changes CRF and NE activity in brain, increases ACTH
|
|
secretion and sympathetic outflow and reduces food intake and weight gain; all of these effects are
|
|
corrected by administration of adrenal steroids. Unexpectedly, we recently found that ADX rats drinking
|
|
sucrose, but not saccharin, also have normal caloric intake, metabolism, and ACTH." <strong>"Voluntary
|
|
ingestion of sucrose restores CRF and dopamine-beta-hydroxylase messenger RNA expression in brain, food
|
|
intake, and caloric efficiency and fat deposition, circulating triglyceride, leptin, and insulin to
|
|
normal."</strong>
|
|
</p>
|
|
<p>
|
|
A. Lazarow, "Protection against alloxan diabetes," Anat. Rec. 97, 353, 1947.
|
|
</p>
|
|
|
|
<p>
|
|
A. Lazarow, "Protective effect of glutathione and cysteine against alloxan diabetes in the rat," Proc. Soc.
|
|
Exp. Biol. & Med. 61, 441-447, 1946. <strong>[While certain doses of cysteine, glutathione, and
|
|
thioglycolic acid completely prevented alloxan diabetes, it was interesting that all of the rats
|
|
receiving ascorbic acid became diabetic. To me, this argues for the free radical cause of diabetes,
|
|
rather than just the sulfhydryl oxidation. Lazarow suggested that succinic dehydrogenase, and various
|
|
other sulfhydryl enzymes, including those involved in fatty acid oxidation, might be involved.]</strong>
|
|
</p>
|
|
<p>
|
|
Minerva Endocrinol 1990 Oct-Dec;15(4):273-7. <strong>
|
|
[Postprandial thermogenesis and obesity: effects of glucose and fructose].</strong>
|
|
[Article in Italian] Macor C, De Palo C, Vettor R, Sicolo N, De Palo E, Federspil G. "Energy expenditure was
|
|
calculated both in basal conditions and during the test (resting metabolic rate: RMR) using indirect
|
|
calorimetry expressed per kg of lean weight, as assessed using bioimpedance measurement techniques. Blood
|
|
samples were collected to assay glycemia and insulinemia. Results show that increased RMR induced by glucose
|
|
was significantly reduced in the group of obese subjects compared to controls. <strong>In the same group of
|
|
obese subjects, RMR was found to be significantly higher following fructose in comparison to the glucose
|
|
response but did not differ from that in controls.</strong> Data confirm the existence of reduced
|
|
thermogenesis in obese subjects induced by glucose. The fact that this phenomenon was not recorded in the
|
|
same subjects following the fructose tolerance test, whose metabolism is insulin-independent, supports the
|
|
hypothesis that reduced glucose-induced thermogenesis in obese subjects may depend on insulin resistance."
|
|
</p>
|
|
|
|
<p>
|
|
Diabetes Care 2000 Oct;23(10):1472-7. <strong>Dietary unsaturated fatty acids in type 2 diabetes: higher
|
|
levels of postprandial lipoprotein on a linoleic acid-rich sunflower oil diet compared with an oleic
|
|
acid-rich olive oil diet.</strong> Madigan C, Ryan M, Owens D, Collins P, Tomkin GH.
|
|
</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. "Mitochondrial site 1 (NADH coenzyme Q reductase) activity was
|
|
reduced to 45 and 85% of control values in fish-oil- and beef-tallow-fed groups, respectively. <strong
|
|
>Exposure to Ca2+ and reactive oxygen species enhance the release of polyunsaturated fatty acids enriched at
|
|
the sn-2 position of phospholipids from mitochondria of fish-oil-fed rats when compared with similarly
|
|
treated mitochondria of beef-tallow-fed rats."</strong> "<strong>Phospholipase A2 activity and
|
|
mitochondrial damage are enhanced when mitochondrial membranes are enriched with n-3 fatty
|
|
acids."</strong>
|
|
</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. "In vitro incubation of
|
|
proteins with ascorbic acid accelerated the production of protein carbonyls as well as CML and pentosidine,
|
|
and incubation with arachidonate accelerated the production of protein carbonyls as well as CML, MDA, and
|
|
HNE. By contrast, incubation of proteins with glucose resulted in the production of CML and pentosidine, but
|
|
not protein carbonyls." <strong>"The present study suggests that ascorbate and polyunsaturated fatty acids,
|
|
but not glucose, represent potential sources of protein carbonyls, and that both the glycoxidation and
|
|
lipoxidation reactions contribute to protein carbonyl formation in aging and various diseases."</strong>
|
|
</p>
|
|
<p>
|
|
Chem Phys Lipids 1996 Jan 25;79(1):47-53. <strong>Previously unknown aldehydic lipid peroxidation compounds
|
|
of arachidonic acid.
|
|
</strong>
|
|
Mlakar A, Spiteller G. Lehrstuhl fr Organische Chemie I, "Arachidonic acid was oxidized by iron ascorbate."
|
|
"<strong>The main aldehydic lipid peroxidation product was found to be the well-known 4-hydroxy-2-nonenal
|
|
(HNE), but 2-hydroxy heptanal (HH) -- a previously unknown lipid peroxidation product of arachidonic
|
|
acid -- was detected to be nearly equally abundant. Malondialdehyde (MDA), glyoxal and
|
|
2-hydroxy-4-decenal (HDE) were detected to be produced in up to 100 times lower amounts compared to
|
|
HNE.". . . .</strong> "Since this and analogous hydroxy acids (LOHs) are the main biological
|
|
degradation<strong>
|
|
products of hydroperoxides of unsaturated acids (LOOHs) their further peroxidation seems to be a main
|
|
source of toxic aldehydes."</strong>
|
|
</p>
|
|
<p>
|
|
J Clin Endocrinol Metab 2000 Dec;85(12):4515-9. <strong>Acute fructose administration decreases the glycemic
|
|
response to an oral glucose tolerance test in normal adults.</strong> Moore MC, Cherrington AD, Mann SL,
|
|
Davis SN. "In animal models, a small (catalytic) dose of fructose administered with glucose decreases the
|
|
glycemic response to the glucose load." "<strong>In conclusion, low dose fructose improves the glycemic
|
|
response to an oral glucose load in normal adults without significantly enhancing the insulin or
|
|
triglyceride response. Fructose appears most effective in those normal individuals who have the poorest
|
|
glucose tolerance."</strong>
|
|
</p>
|
|
|
|
<p>
|
|
Tumour Biol 1988;9(5):225-32. <strong>Modulation of cell-mediated immune response by steroids and free fatty
|
|
acids in AIDS patients: a critical survey.</strong>
|
|
Nunez EA. "The overall data presented in this review show that cortisol and free fatty acids, <strong>in
|
|
particular long-chain polyunsaturated fatty acids, each have immunoinhibitory properties</strong> on
|
|
lymphoblastic transformation of certain T lymphocytes. This effect is enhanced when the two factors are
|
|
associated. These data could explain in part the immunosuppression observed in acquired immunodeficiency
|
|
syndrome (AIDS) patients <strong>where enhanced concentrations of cortisol and polyunsaturated fatty acids
|
|
have been observed</strong>." "These new weapons could be the administration of diets or treatments
|
|
(liposomes) modifying the lipid profile of circulating cells and/or viruses and the utilization of hormonal
|
|
therapy in AIDS and in some types of cancer which often present a biologic picture similar to that of AIDS."
|
|
</p>
|
|
<p>
|
|
Diabetes Care 1984 Sep-Oct;7(5):465-70. <strong>Effect of protein ingestion on the glucose and insulin
|
|
response to a standardized oral glucose load.</strong>
|
|
Nuttall FQ, Mooradian AD, Gannon MC, Billington C, Krezowski P. "The plasma glucose area above the baseline
|
|
following a glucose meal was reduced 34% when protein was given with the glucose." "The insulin area
|
|
following glucose was only modestly greater than with a protein meal (97 +/- 35, 83 +/- 19 microU X h/ml,
|
|
respectively)." "When various amounts of protein were given with 50 g glucose, the insulin area response was
|
|
essentially first order. Subsequently, subjects were given 50 g glucose or 50 g glucose with 50 g protein as
|
|
two meals 4 h apart in random sequence. The insulin areas were not significantly different for each meal but
|
|
were higher when protein + glucose was given. After the second glucose meal the plasma glucose area was 33%
|
|
less than after the first meal. Following the second glucose + protein meal the plasma glucose area was
|
|
markedly reduced, being only 7% as large as after the first meal. <strong>These data indicate that protein
|
|
given with glucose will increase insulin secretion and reduce the plasma glucose rise in at least some
|
|
type II diabetic persons."</strong> Randomized Controlled Trial
|
|
</p>
|
|
|
|
<p>
|
|
Biochem J 1985 Sep 1;230(2):329-37. <strong>Inhibitory effects of some long-chain unsaturated fatty acids on
|
|
mitochondrial beta-oxidation. Effects of streptozotocin-induced diabetes on mitochondrial beta-oxidation
|
|
of polyunsaturated fatty acids.</strong> Osmundsen H, Bjornstad K.<strong>
|
|
"Evidence showing that some unsaturated fatty acids, and in particular docosahexaenoic acid, can be
|
|
powerful inhibitors of mitochondrial beta-oxidation is presented. This inhibitory property is, however,
|
|
also observed with the cis- and trans-isomers of the C18:1(16) acid. Hence it is probably the position
|
|
of the double bond(s), and not the degree of unsaturation, which confers the inhibitory property. It is
|
|
suggested that the inhibitory effect is caused by accumulation of 2,4-di- or 2,4,7-tri-enoyl-CoA esters
|
|
in the mitochondrial matrix."
|
|
</strong>
|
|
</p>
|
|
<p>
|
|
Free Radic Biol Med 1999 Oct;27(7-8):901-10. <strong>Thyroid status modulates glycoxidative and lipoxidative
|
|
modification of tissue Proteins.
|
|
</strong>
|
|
Pamplona R, Portero-Otin M, Ruiz C, Bellmunt MJ, Requena JR, Thorpe SR, Baynes JW, Romero M, Lopez-Torres M,
|
|
Barja G. Steady state protein modification by carbonyl compounds is related to the rate of carbonyl adduct
|
|
formation and the half-life of the protein. <strong>Thyroid hormones are physiologic modulators of both
|
|
tissue oxidative stress and protein degradation.</strong>
|
|
<strong>The levels of the glycation product </strong>
|
|
N(epsilon)-fructoselysine (FL) and those of the <strong>oxidation products, </strong>
|
|
|
|
N(epsilon)-(carboxymethyl)lysine (CML) and<strong> malondialdehyde-lysine</strong>
|
|
(MDA-lys), identified by GC/MS in liver proteins, <strong>decreased significantly in hyperthyroid
|
|
rats,</strong> as well as (less acutely) in hypothyroid animals. Immunoblotting of liver proteins for
|
|
advanced glycation end-products (AGE) is in agreement with the results obtained by GC/MS. Cytosolic
|
|
proteolytic activity against carboxymethylated foreign proteins measured in vitro was significantly
|
|
increased in hypo- and hyperthyroidism. Oxidative damage to DNA, estimated as
|
|
8-oxo-7,8-dihydro-2'-deoxyguanosine (8oxodG), did not show significant differences between groups. The
|
|
results suggests that the steady state levels of these markers depend on the levels of thyroid hormones,
|
|
presumably through their<strong>
|
|
combined effects on the rates of protein degradation and oxidative stress,</strong> whereas DNA is more
|
|
protected from oxidative damage.
|
|
</p>
|
|
<p>
|
|
Metabolism 1999 Mar;48(3):406-9. <strong>The blood vessel, linchpin of diabetic lesions.</strong>
|
|
|
|
Plante GE, Alfred J, Chakir M. "The morbidity and mortality associated with diabetes mellitus are
|
|
essentially related to the vascular lesions that develop over time in this condition. Both the
|
|
macrocirculation and microcirculation are involved, and as a consequence, vital organs such as the brain,
|
|
retina, heart, and kidney and the limbs become damaged." "Changes in the structure of conduit arteries,
|
|
partly responsible for the alteration in compliance characteristics, could well be related to the way these
|
|
arteries are fed by the vasa vasorum system." "Preliminary results indicate that the size of terminal
|
|
arterioles of the vasa vasorum (increased diameter) and the capillary permeability to albumin (markedly
|
|
enhanced) in this specialized network are profoundly affected in the thoracic aorta obtained from diabetic
|
|
animals. Albumin extravasation into the interstitial fluid compartment of the aorta is likely to lead to
|
|
structural and physicochemical changes: in fact, removal of interstitial macromolecules via lymphatic
|
|
drainage is poor in the blood vessel wall of large arteries."
|
|
</p>
|
|
<p>
|
|
Metabolism 2001 Dec;50(12):1472-8. <strong>
|
|
Serum phospholipid fatty acid composition and insulin action in type 2 diabetic patients.
|
|
</strong>Pelikanova T, Kazdova L, Chvojkova S, Base J. <strong>"Increased contents of highly unsaturated n-6
|
|
family FA (P <.01), arachidonic acid in particular . . . were found in all groups of diabetics
|
|
compared with HS [healthy subjects],</strong> while lower levels of linoleic acid were seen in DMN (P
|
|
<.001) and DMH (P <.05). The contents of saturated FA and monounsaturated FA were comparable in HS,
|
|
DMN, and DMD."
|
|
</p>
|
|
<p>
|
|
J Clin Invest 2002 Mar;109(6):805-15. <strong>Acute intensive insulin therapy exacerbates diabetic
|
|
blood-retinal barrier breakdown via hypoxia-inducible factor-1alpha and VEGF.</strong> Poulaki V, Qin W,
|
|
Joussen AM, Hurlbut P, Wiegand SJ, Rudge J, Yancopoulos GD, Adamis AP. "Here we demonstrate that acute
|
|
intensive insulin therapy markedly increases VEGF mRNA and protein levels in the retinae of diabetic rats."
|
|
"Blood-retinal barrier breakdown is markedly increased with acute intensive insulin therapy. . . ." "<strong
|
|
>To our knowledge, these data are the first to identify a specific mechanism for the transient worsening of
|
|
diabetic retinopathy, specifically blood-retinal barrier breakdown, that follows the institution of
|
|
intensive insulin therapy."</strong>
|
|
</p>
|
|
|
|
<p>
|
|
Acta Endocrinol (Copenh) 1992 Apr;126(4):378-80. <strong>Lipid peroxidation in early experimental diabetes
|
|
in rats: effects of diabetes and insulin.</strong>
|
|
Rungby J, Flyvbjerg A, Andersen HB, Nyborg K. "In the kidney, lipid<strong>
|
|
peroxidation was increased after one week of diabetes; insulin treatment reduced the level of lipid
|
|
peroxidation to levels lower than seen in controls. In the liver, diabetes caused an increased lipid
|
|
peroxidation, which could be reversed by insulin; no additional effect of insulin was found. In heart
|
|
and pancreas no effects of diabetes or insulin were demonstrated. The present paper provides</strong>
|
|
evidence that lipid peroxidation is increased in the early stages of<strong>
|
|
experimental diabetes and is reversible by insulin treatment. Hyperinsulinaemia may, in itself,
|
|
counteract lipid peroxidation in kidney."</strong>
|
|
</p>
|
|
<p>
|
|
Br J Nutr 1997 Sep;78(3):459-67. <strong>Influence of dietary protein and fat on serum lipids and metabolism
|
|
of essential fatty acids in rats.</strong> Ratnayake WM, Sarwar G, Laffey P. A "In general, the
|
|
concentrations of serum triacylglycerols and<strong>
|
|
total cholesterol and liver phospholipid levels of arachidonic acid (AA) and docosahexaenoic acid (DHA)
|
|
were higher in rats fed on casein diets compared with those fed on the gelatin diets. These effects were
|
|
more pronounced in rats fed</strong> on the high-casein (300 g/kg)-high-fat (150 g/kg) diet. <strong
|
|
>Gelatin was hypocholesterolaemic and also suppressed the liver phospholipid levels of AA and DHA (reported
|
|
for the first time).</strong> The difference in the amino acid composition between casein and gelatin
|
|
may be responsible for the observed effects. Casein contains higher levels of glutamic acid, methionine,
|
|
phenylalanine and tyrosine, while gelatin contains higher levels of arginine, glycine and hydroxyproline."
|
|
</p>
|
|
|
|
<p>
|
|
Br Med J 1979 Jun 30;1(6180):1753-6. <strong>Improved glucose control in maturity-onset diabetes treated
|
|
with high-carbohydrate-modified fat diet.</strong> Simpson RW, Mann JI, Eaton J, Moore RA, Carter R,
|
|
Hockaday TD. "Fourteen patients with established maturity-onset diabetes were treated as outpatients with a
|
|
high-carbohydrate-(about 60% of total daily energy requirements)-modified fat diet (ratio of polyunsaturated
|
|
fatty acids to other fatty acids greater than or equal to 1:1) for six weeks." <strong>"The findings suggest
|
|
that it is no longer justifiable to prescribe a low-carbohydrate diet for maturity-onset
|
|
diabetes."</strong>
|
|
</p>
|
|
<p>
|
|
Postgrad Med J 1981 Aug;57(670):511-5. <strong>Severe hypertriglyceridaemia responding to insulin and
|
|
nicotinic acid therapy.</strong> Smith SR. "Treatment with insulin and restriction of dietary
|
|
carbohydrate led to a 50% reduction in the triglyceride concentration, and the addition of nicotinic acid in
|
|
modest doses led ultimately to a complete normalization of the patient's lipid values. A close
|
|
correlation<strong>
|
|
was noted between the falling triglyceride concentration and the rising serum sodium concentration
|
|
during the course of successful therapy. Overall, it is felt likely that this patient's severe and
|
|
reversible hypertriglyceridaemia was on the basis of excessively rapid lipolysis
|
|
</strong>leading to high concentrations of very low density lipoprotein production."
|
|
</p>
|
|
<p>
|
|
Am J Clin Nutr 1993 Nov;58(5 Suppl):766S-770S. <strong>Fructose and dietary thermogenesis.</strong> Tappy L,
|
|
Jequier E. "<strong>Fructose ingestion induces a greater thermogenesis than does glucose. This can be
|
|
explained by the hydrolysis of 3.5-4.5 mol ATP/mol fructose stored as glycogen, vs 2.5 mol ATP/mol
|
|
glucose stored. Therefore the large thermogenesis of fructose corresponds essentially to an increase in
|
|
obligatory thermogenesis.</strong> Obese individuals and obese patients with non-insulin-dependent
|
|
diabetes mellitus commonly have a decrease in glucose-induced thermogenesis. <strong>These individuals in
|
|
contrast display a normal thermogenesis after ingestion of fructose.</strong>
|
|
|
|
This may be explained by the fact that the initial hepatic fructose metabolism is independent of insulin."
|
|
</p>
|
|
<p>
|
|
Diabetes 2002 Jun;51(6):1772-8. <strong>
|
|
Inhibition of interleukin-1beta-induced COX-2 and EP3 gene expression by sodium salicylate enhances
|
|
pancreatic islet beta-cell function.</strong>
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|
Tran PO, Gleason CE, Robertson RP.
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</p>
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<p>
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Proc Natl Acad Sci U S A 1998 Apr 28;95(9):4882-7. <strong>Protein-bound acrolein: potential markers for
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|
oxidative stress.</strong>
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<hr />
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|
<strong>
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|
Here we show that this notorious aldehyde is not just a pollutant, but also a lipid peroxidation product
|
|
that could be ubiquitously generated in biological systems. Upon incubation with BSA, acrolein was
|
|
rapidly incorporated into the protein and generated the protein-linked carbonyl derivative, a putative
|
|
marker of oxidatively modified proteins under oxidative stress." "</strong>Immunohistochemical analysis
|
|
of atherosclerotic lesions from a human aorta demonstrated that antigenic materials recognized by mAb5F6
|
|
indeed constituted the lesions, in which intense positivity was associated primarily with macrophage-derived
|
|
foam cells and the thickening neointima of arterial walls. <strong>The observations that (i) oxidative
|
|
modification of low-density lipoprotein with Cu2+ generated the acrolein-low-density lipoprotein adducts
|
|
and (ii) the iron-catalyzed oxidation of arachidonate in the presence of protein</strong>
|
|
|
|
resulted in the formation of antigenic materials suggested that<strong>
|
|
polyunsaturated fatty acids are sources of acrolein that cause the production of protein-bound acrolein.
|
|
These data suggest that the protein-bound acrolein represents potential markers of oxidative stress and
|
|
long-term damage to protein in aging, atherosclerosis, and diabetes."</strong>
|
|
</p>
|
|
<p>
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|
J Intern Med 1990 Aug;228(2):165-71. <strong>Dietary supplementation with n-3 fatty acids may impair glucose
|
|
homeostasis in patients with non-insulin-dependent diabetes mellitus.</strong> Vessby B, Boberg M. "The
|
|
blood glucose concentration<strong>
|
|
tended to increase during MaxEPA treatment, and to decrease during the placebo period, the changes under
|
|
the two regimes being significantly different (P less than 0.01). In addition, the rate constant for
|
|
glucose disappearance (k value) for the intravenous insulin-tolerance test, which reflected the
|
|
peripheral insulin sensitivity, tended to decrease during MaxEPA treatment and increase</strong> during
|
|
administration of the placebo, there being a significant difference (P less than 0.03) between the changes
|
|
during the two treatments. The reason for the observed changes in blood glucose concentration and peripheral
|
|
insulin sensitivity is still unclear."
|
|
</p>
|
|
<p>
|
|
Diabet Med 1992 Mar;9(2):126-33. <strong>Polyunsaturated fatty acids may impair blood glucose control in
|
|
type 2 diabetic Patients.</strong> Vessby B, Karlstrom B, Boberg M, Lithell H, Berne C. "<strong><hr
|
|
/></strong>
|
|
</p>
|
|
|
|
<p>
|
|
Drugs 1999;58 Suppl 1:31-9; discussion 75-82. <strong>The antihyperglycaemic effect of metformin:
|
|
therapeutic and cellular mechanisms.</strong> Wiernsperger NF, Bailey CJ "Other effects involved in the
|
|
blood<strong>
|
|
glucose-lowering effect of metformin include an insulin-independent suppression of fatty acid oxidation
|
|
and a reduction in hypertriglyceridaemia. These effects reduce the energy supply for gluconeogenesis and
|
|
serve to balance the glucose-fatty acid (Randle) cycle."
|
|
</strong>
|
|
</p>
|
|
<p>
|
|
J Biol Chem 2001 Mar 30;276(13):9800-7. <strong>Polyunsaturated fatty acids suppress hepatic sterol
|
|
regulatory element-binding protein-1 expression by accelerating transcript decay.
|
|
</strong>Xu J, Teran-Garcia M, Park JH, Nakamura MT, Clarke SD. "Our initial studies<strong>
|
|
indicated that the induction of SREBP-1 expression by insulin and glucose was blocked by PUFA. Nuclear
|
|
run-on assays suggested PUFA reduced SREBP-1 mRNA by</strong> post-transcriptional mechanisms." "<strong
|
|
>Although the mechanism by which PUFA accelerate SREBP-1 mRNA decay</strong> remains to be determined,
|
|
cloning and sequencing of the 3'-untranslated region for the rat SREBP-1 transcript revealed the presence of
|
|
an A-U-rich region that is characteristic of a destablizing element."
|
|
</p>
|
|
|
|
<p>
|
|
Recent Adv Stud Cardiac Struct Metab 1976 May 26-29;12:271-7. <strong>Arrhythmogenic effects of acute free
|
|
fatty acid mobilization on ischemic heart.</strong>
|
|
Yamazaki N, Suzuki Y, Kamikawa T, Ogawa K, Mizutani K, Kakizawa N, Yamamoto M.
|
|
</p>
|
|
<p>
|
|
Science 1978 Jul 28;201(4353):358-60. <strong>Brain edema: induction in cortical slices by polyunsaturated
|
|
fatty acids.
|
|
</strong>
|
|
Chan PH, Fishman RA The presence of polyunsaturated and saturated fatty acids in leukocytic membranes
|
|
prompted study of their possible role in the induction of brain edema. Polyunsaturated fatty acids including
|
|
sodium arachidonate, sodium linoleate, sodium linolenate, and docasahexaenoic acids induced edma in slices
|
|
of rat brain cortex. <strong>This cellular edema was specific, since neither saturated fatty acids nor a
|
|
fatty acid containing a single double bond had such effect.</strong>
|
|
</p>
|
|
<p>
|
|
J Neurochem 1986 Oct;47(4):1181-9. <strong>Effects of arachidonic acid on glutamate and gamma-aminobutyric
|
|
acid uptake in primary cultures of rat cerebral cortical astrocytes and neurons.</strong> Yu AC, Chan
|
|
PH, Fishman RA. "Arachidonic acid inhibited glutamate uptake in both astrocytes and neurons. The inhibitory
|
|
effect was observed within 10 min of incubation with arachidonic acid and reached approximately 80% within
|
|
120 min in both types of culture. The arachidonic acid effect was not only time-dependent, but also
|
|
dose-related. Arachidonic acid, at concentrations of 0.015 and 0.03 mumol/mg protein, significantly
|
|
inhibited glutamate uptake in neurons, whereas 20 times higher concentrations were required for astrocytes.
|
|
The effects of arachidonic acid were not as deleterious on GABA uptake as on glutamate uptake in both
|
|
astrocytes and neurons." "<strong>Other polyunsaturated fatty acids, such as docosahexaenoic acid, affected
|
|
amino acid uptake in a manner similar to arachidonic acid in both astrocytes and neurons. However,
|
|
saturated fatty acids, such as palmitic acid, exerted no such effect."
|
|
</strong>
|
|
</p>
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|
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© Ray Peat Ph.D. 2009. All Rights Reserved. www.RayPeat.com
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