621 lines
44 KiB
HTML
621 lines
44 KiB
HTML
<html>
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<head><title>Caffeine: A vitamin-like nutrient, or adaptogen</title></head>
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<body>
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<h1>
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Caffeine: A vitamin-like nutrient, or adaptogen
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</h1>
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<p>
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<strong>
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Questions about tea and coffee, cancer and other degenerative diseases, and the hormones.</strong>
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</p>
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<p></p>
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<p>
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There is a popular health-culture that circulates mistaken ideas about nutrition, and coffee drinking has
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been a perennial target of this culture. It is commonly said that coffee is a drug, not a food, and that its
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drug action is harmful, and that this harm is not compensated by any nutritional benefit. Most physicians
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subscribe to most of these "common sense" ideas about coffee, and form an authoritative barrier against the
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assimilation of scientific information about coffee.
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</p>
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<p>
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I think it would be good to reconsider coffee"s place in the diet and in health care.
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</p>
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<p>
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<strong>Coffee drinkers have a lower incidence of thyroid disease, including cancer,
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thannon-drinkers.</strong>
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</p>
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<p>
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<strong>Caffeine protects the liver from alcohol and acetaminophen (Tylenol) and other toxins, and coffee
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drinkers are less likely than people who don"t use coffee to have elevated serum enzymes and other
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indications of liver damage.</strong>
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</p>
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<p>
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<strong>Caffeine protects against cancer caused by radiation, chemical carcinogens, viruses, and
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estrogens.</strong>
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</p>
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<p>
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<strong>Caffeine synergizes with progesterone, and increases its concentration in blood and tissues.</strong
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>
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</p>
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<p>
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<strong>Cystic breast disease is not caused by caffeine, in fact caffeine"s effects are likely to be
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protective; a variety of studies show that coffee, tea, and caffeine are protective against breast
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cancer.</strong>
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</p>
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<p>
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<strong>Coffee provides very significant quantities of magnesium, as well as other nutrients including
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vitamin B1.</strong>
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</p>
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<p><strong>Caffeine "improves efficiency of fuel use" and performance: JC Wagner 1989.</strong></p>
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<p><strong>Coffee drinkers have a low incidence of suicide.</strong></p>
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<p><strong>Caffeine supports serotonin uptake in nerves, and inhibits blood platelet aggregation.</strong></p>
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<p>
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<strong>Coffee drinkers have been found to have lower cadmium in tissues; coffee making removes heavy metals
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from water.</strong>
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</p>
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<p><strong>Coffee inhibits iron absorption if taken with meals, helping to prevent iron overload.</strong></p>
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<p>
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<strong>Caffeine, like niacin, inhibits apoptosis, protecting against stress-induced cell death, without
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interfering with normal cell turnover.</strong>
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</p>
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<p><strong>Caffeine can prevent nerve cell death.</strong></p>
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<p><strong>Coffee (or caffeine) prevents Parkinson"s Disease (Ross, et al., 2000).</strong></p>
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<p>
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<strong>The prenatal growth retardation that can be caused by feeding large amounts of caffeine is prevented
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by supplementing the diet with sugar.</strong>
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</p>
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<p>
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<strong>Caffeine stops production of free radicals by inhibiting xanthine oxidase, an important factor in
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tissue stress.
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</strong>
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</p>
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<p>
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<strong>Caffeine lowers serum potassium following exercise; stabilizes platelets, reducing thromboxane
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production.</strong>
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</p>
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<p>
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One definition of a vitamin is that it is an organic chemical found in foods, the lack of which <strong><em
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>causes</em></strong> a specific <strong><em>disease,</em></strong>
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or group of diseases. A variety of substances that have been proposed to be vitamins haven"t been recognized
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as being essential, and some substances that aren"t essential are sometimes called vitamins. Sometimes these
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issues haven"t had enough scientific investigation, but often nonscientific forces regulate nutritional
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ideas.
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</p>
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<p>
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The definition of "a disease" isn"t as clear as text-book writers have implied, and "causality" in biology
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is always more complex than we like to believe.
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</p>
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<p>
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Nutrition is one of the most important sciences, and should certainly be as prestigious and well financed as
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astrophysics and nuclear physics, but while people say "it doesn"t take a brain surgeon to figure that out,"
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no one says "it doesn"t take a nutritionist to understand that." Partly, that"s because medicine treated
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scientific nutrition as an illegitimate step-child, and refused throughout the 20th century to recognize
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that it is a central part of scientific health care. In the 1970s, physicians and dietitians were still
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ridiculing the idea that vitamin E could prevent or cure diseases of the circulatory system, and babies as
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well as older people were given "total intravenous nutrition" which lacked nutrients that are essential to
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life, growth, immunity, and healing. Medicine and science are powerfully institutionalized, but no
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institution or profession has existed for the purpose of encouraging people to act reasonably.
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</p>
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<p>
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In this environment, most people have felt that subtleties of definition, logic and evidence weren"t
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important for nutrition, and a great amount of energy has gone into deciding whether there were "four food
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groups" or "seven food groups" or a "nutritional pyramid." The motives behind governmental and
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quasi-governmental nutrition policies usually represent something besides a simple scientific concern for
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good health, as when health care institutions say that Mexican babies should begin eating beans when they
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reach the age of six months, or that non-whites don"t need milk after they are weaned. In a culture that
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discourages prolonged breast feeding, the effects of these doctrines can be serious.
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</p>
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<p>
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After a century of scientific nutrition, public nutritional policies are doing approximately as much harm as
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good, and they are getting worse faster than they are getting better..
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</p>
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<p>
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In this culture, what we desperately need is a recognition of the complexity of life, and of the
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political-ecological situation we find ourselves in. Any thinking which isn"t "system thinking" should be
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treated with caution, and most contemporary thinking about health neglects to consider relevant parts of the
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problem-system. "Official" recommendations about salt, cholesterol, iron, unsaturated and saturated fats,
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and soybeans have generally been inappropriate, unscientific, and strongly motivated by business interests
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rather than by biological knowledge.
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</p>
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<p>
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Definitions have rarely distinguished clearly between nutrients and drugs, and new commercial motives are
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helping to further blur the distinctions.
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</p>
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<p>
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<strong>Essential nutrients, defensive (detoxifying, antistress) nutrients, hormone-modulating nutrients,
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self-actualization nutrients, growth regulating nutrients, structure modifiers, life extension agents,
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transgenerationally active (imprinting)</strong>
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<strong>nutrients--</strong>the line between nutrients and biological modifiers often depends on the
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situation. Vitamins D and A clearly have hormone-like properties, and vitamin E"s effects, and those of many
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terpenoids and steroids and bioflavonoids found in foods, include hormone-like actions as well as
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antioxidant and pro-oxidant functions. The concept of "adaptogen" can include things that act like both
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drugs and nutrients.
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</p>
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<p>
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Some studies have suggested that trace amounts of nutrients could be passed on for a few generations, but
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the evidence now indicates that these transgenerational effects are caused by phenomena such as
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"imprinting." But the hereditary effects of nutrients are so complex that their recognition would force
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nutrition to be recognized as one of the most complex sciences, interwoven with the complexities of growth
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and development.
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</p>
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<p>
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The idea that poor nutrition stunts growth has led to the idea that good nutrition can be defined in terms
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of the rate of growth and the size ultimately reached. In medicine, it is common to refer to an obese
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specimen as "well nourished," as if quantity of food and quantity of tissue were necessarily good things.
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But poisons can stimulate growth ("hormesis"), and food restriction can extend longevity. <strong>We still
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have to determine basic things such as the optimal rate of growth, and the optimal size.</strong>
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</p>
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<p>
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Nutrition textbooks flatly describe caffeine as a drug, not a nutrient, as if it were obvious that nutrients
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can"t be drugs. Any of the essential nutrients, if used in isolation, can be used as a drug, for a specific
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effect on the organism that it wouldn"t normally have when eaten as a component of ordinary food. And
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natural foods contain thousands of chemicals, other than the essential nutrients. Many of these are called
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nonessential nutrients, but their importance is being recognized increasingly. The truth is that we aren"t
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sure what they "aren"t essential" for. Until we have more definite knowledge about the organism I don"t
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think we should categorize things so absolutely as drugs or nutrients.
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</p>
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<p>
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The bad effects ascribed to coffee usually involve administering large doses in a short period of time.
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While caffeine is commonly said to raise blood pressure, this effect is slight, and may not occur during the
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normal use of coffee. Experimenters typically ignore essential factors. Drinking plain water can cause an
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extreme rise in blood pressure, especially in old people, and eating a meal (containing carbohydrate) lowers
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blood pressure. The increased metabolic rate caffeine produces increases the cellular consumption of
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glucose, so experiments that study the effects of coffee taken on an empty stomach are measuring the effects
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of increased temperature and metabolic rate, combined with increased adrenaline (resulting from the decrease
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of glucose), and so confuse the issue of caffeine"s intrinsic effects.
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</p>
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<p>
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In one study (Krasil"nikov, 1975), the drugs were introduced directly into the carotid artery to study the
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effects on the blood vessels in the brain. Caffeine increased the blood volume in the brain, while
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decreasing the resistance of the vessels, and this effect is what would be expected from its stimulation of
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brain metabolism and the consequent increase in carbon dioxide, which dilates blood vessels.
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</p>
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<p>
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In the whole body, increased carbon dioxide also decreases vascular resistance, and this allows circulation
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to increase, while the heart"s work is decreased, relative to the amount of blood pumped. But when the whole
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body"s metabolism is increased, adequate nutrition is crucial.
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</p>
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<p>
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In animal experiments that have been used to argue that pregnant women shouldn"t drink coffee, large doses
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of caffeine given to pregnant animals retarded the growth of the fetuses. But simply giving more sucrose
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prevented the growth retardation. Since caffeine tends to correct some of the metabolic problems that could
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interfere with pregnancy, it is possible that rationally constructed experiments could show benefits to the
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fetus from the mother"s use of coffee, for example by lowering bilirubin and serotonin, preventing
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hypoglycemia, increasing uterine perfusion and progesterone synthesis, synergizing with thyroid and cortisol
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to promote lung maturation, and providing additional nutrients.
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</p>
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<p>
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One of the most popular misconceptions about caffeine is that it causes fibrocystic breast disease. Several
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groups demonstrated pretty clearly that it doesn"t, but there was no reason that they should have had to
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bother, except for an amazingly incompetent, but highly publicized, series of articles--classics of their
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kind--by J. P. Minton, of Ohio State University. Minton neglected to notice that the healthy breast contains
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a high percentage of fat, and that the inflamed and diseased breast has an increased proportion of glandular
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material Fat cells have a low level of cyclic AMP, a regulatory substance that is associated with normal
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cellular differentiation and function, and is involved in mediating caffeine"s ability to inhibit cancer
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cell multiplication. Minton argued that cAMP increases progressively with the degree of breast disease, up
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to cancer, and that cAMP is increased by caffeine. A variety of substances other than caffeine that inhibit
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the growth of cancer cells (as well as normal breast cells) act by <em>increasing</em> the amount of cyclic
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AMP, while estrogen lowers the amount of cAMP and increases cell growth. Minton"s argument should have been
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to use more caffeine, in proportion to the degree of breast disease, if he were arguing logically from his
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evidence. Caffeine"s effect on the breast resembles that of progesterone, opposing estrogen"s effects.
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</p>
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<p>
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Many studies over the last 30 years have shown caffeine to be highly protective against all kinds of
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carcinogenesis, including estrogen"s carcinogenic effects on the breast. Caffeine is now being used along
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with some of the standard cancer treatments, to improve their effects or to reduce their side effects. There
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are substances in the coffee berry besides caffeine that protect against mutations and cancer, and that have
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shown strong therapeutic effects against cancer. Although many plant substances are protective against
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mutations and cancer, I don"t know of any that is as free of side effects as coffee.
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</p>
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<p>
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To talk about caffeine, it"s necessary to talk about uric acid. <strong>
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Uric acid, synthesized in the body, is both a stimulant and a very important antioxidant, and its
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structure is very similar to that of caffeine.
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</strong>
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A deficiency of uric acid is a serious problem. Caffeine and uric acid are in the group of chemicals called
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purines.
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</p>
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<p>
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Purines (along with pyrimidines) are components of the nucleic acids, DNA and RNA, but they have many other
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functions. In general, substances related to purines are stimulants, and substances related to pyrimidines
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are sedatives.
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</p>
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<p>
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When the basic purine structure is oxidized, it becomes in turn hypoxanthine, xanthine, and uric acid, by
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the addition of oxygen atoms. When methyl groups (CH<sub>3</sub>) are added to nitrogens in the purine ring,
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the molecule becomes less water soluble. Xanthine (an intermediate in purine metabolism) has two oxygen
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atoms, and when three methyl groups are added, it becomes trimethyl xanthine, or caffeine. With two methyl
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groups, it is theophylline, which is named for its presence in tea. We have enzyme systems which can add and
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subtract methyl groups<strong>;</strong> for example, when babies are given theophylline, they can convert
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it into caffeine.
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</p>
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<p>
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We have enzymes that can modify all of the methyl groups and oxygen atoms of caffeine and the other purine
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derivatives. Caffeine is usually excreted in a modified form, for example as a methylated uric acid.
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</p>
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<p>
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One of the ways in which uric acid functions as an "antioxidant" is by modifying the activity of the enzyme
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xanthine oxidase, which in stress can become a dangerous source of free radicals. Caffeine also restrains
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this enzyme. There are several other ways in which uric acid and caffeine (and a variety of intermediate
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xanthines) protect against oxidative damage. Coffee drinkers, for example, have been found to have lower
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levels of cadmium in their kidneys than people who don"t use coffee, and coffee is known to inhibit the
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absorption of iron by the intestine, helping to prevent iron overload.
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</p>
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<p>
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Toxins and stressors often kill cells, for example in the brain, liver, and immune system, by causing the
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cells to expend energy faster than it can be replaced. There is an enzyme system that repairs genetic
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damage, called "PARP." The activation of this enzyme is a major energy drain, and substances that inhibit it
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can prevent the death of the cell. Niacin and caffeine can inhibit this enzyme sufficiently to prevent this
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characteristic kind of cell death, without preventing the normal cellular turnover<strong>;</strong> that
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is, they don"t produce tumors by preventing the death of cells that aren"t needed.
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</p>
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<p>
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The purines are important in a great variety of regulatory processes, and caffeine fits into this complex
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system in other ways that are often protective against stress. For example, it has been proposed that tea
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can protect against circulatory disease by preventing abnormal clotting, and the mechanism seems to be that
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caffeine (or theophylline) tends to restrain stress-induced platelet aggregaton.
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</p>
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<p>
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When platelets clump, they release various factors that contribute to the development of a clot. Serotonin
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is one of these, and is released by other kinds of cell, including mast cells and basophils and nerve cells.
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Serotonin produces vascular spasms and increased blood pressure, blood vessel leakiness and inflammation,
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and the release of many other stress mediators. Caffeine, besides inhibiting the platelet aggregation, also
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tends to inhibit the release of serotonin, or to promote its uptake and binding.
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</p>
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<p>
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J. W. Davis, et al., 1996, found that high uric acid levels seem to protect against the development of
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Parkinson"s disease. They ascribed this effect to uric acid"s antioxidant function. Coffee drinking, which
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<em>lowers</em> uric acid levels, nevertheless appeared to be much more strongly protective against
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Parkinson"s disease than uric acid.
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</p>
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<p>
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Possibly more important than coffee"s ability to protect the health is the way it does it. The studies that
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have tried to gather evidence to show that coffee is harmful, and found the opposite, have provided insight
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into several diseases. For example, coffee"s effects on serotonin are very similar to carbon dioxide"s, and
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the thyroid hormone"s. Noticing that coffee drinking is associated with a low incidence of Parkinson"s
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disease could focus attention on the ways that thyroid and carbon dioxide and serotonin, estrogen, mast
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cells, histamine and blood clotting interact to produce nerve cell death.
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</p>
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<p>
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Thinking about how caffeine can be beneficial across such a broad spectrum of problems can give us a
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perspective on the similarities of their underlying physiology and biochemistry, expanding the implications
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of stress, biological energy, and adaptability.
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</p>
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<p>
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The observation that coffee drinkers have a low incidence of suicide, for example, might be physiologically
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related to the large increase in suicide rate among people who use the newer antidepressants called
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"serotonin reuptake inhibitors." Serotonin excess causes several of the features of depression, such as
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learned helplessness and reduced metabolic rate, while coffee stimulates the <em>uptake</em> (inactivation
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or storage) of serotonin, increases metabolic energy, and tends to improve mood. In animal studies, it
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reverses the state of helplessness or despair, often more effectively than so-called antidepressants.
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</p>
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<p>
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The research on caffeine"s effects on blood pressure, and on the use of fuel by the more actively
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metabolizing cells, hasn"t clarified its effects on respiration and nutrition, but some of these experiments
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confirm things that coffee drinkers usually learn for themselves.
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</p>
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<p>
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Often, a woman who thinks that she has symptoms of hypoglycemia says that drinking even the smallest amount
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of coffee makes her anxious and shaky. Sometimes, I have suggested that they try drinking about two ounces
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of coffee with cream or milk along with a meal. It"s common for them to find that this reduces their
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symptoms of hypoglycemia, and allows them to be symptom-free between meals. Although we don"t know exactly
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why caffeine improves an athlete"s endurance, I think the same processes are involved when coffee increases
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a person"s "endurance" in ordinary activities.
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</p>
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<p>
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Caffeine has remarkable parallels to thyroid and progesterone, and the use of coffee or tea can help to
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maintain their production, or compensate for their deficiency. Women spontaneously drink more coffee
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premenstrually, and since caffeine is known to increase the concentration of progesterone in the blood and
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in the brain, this is obviously a spontaneous and rational form of self-medication, though medical editors
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like to see things causally reversed, and blame the coffee drinking for the symptoms it is actually
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alleviating. Some women have noticed that the effect of a progesterone supplement is stronger when they take
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it with coffee. This is similar to the synergy between thyroid and progesterone, which is probably involved,
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since caffeine tends to <em>locally</em> activate thyroid secretion by a variety of mechanisms, increasing
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cyclic AMP and decreasing serotonin in thyroid cells, for example, and also by lowering the systemic stress
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mediators.
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</p>
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<p>
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Medical editors like to publish articles that reinforce important prejudices, even if, scientifically, they
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are trash. The momentum of a bad idea can probably be measured by the tons of glossy paper that have gone
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into its development. Just for the sake of the environment, it would be nice if editors would try to think
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in terms of evidence and biological mechanisms, rather than stereotypes.
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</p>
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<p>
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<strong><h3>REFERENCES</h3></strong>
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</p>
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<p>
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Fiziol Zh SSSR Im I M Sechenova 1975 Oct;61(10):1531-8. <strong>[Changes in the resistance and capacity of
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the cerebral vascular bed under the influence of vasoactive substances].</strong> [Article in Russian]
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Krasil'nikov, V.G. Effects of intracarotid injections of vasoactive agents on cerebrovascular resistance
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(CVR) and cerebral blood volume (CBV) were studied in hemodynamically isolated brain of cats. Perfusion
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pressure shifts at a constant blood volume perfusion reflected CVR changes, and changes of venous outflow -
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CBV alterations. Administration of adrenaline, serotonin, and angiotensine was followed mainly by an
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increase of CVR and a decrease of CBV. The <strong>CVR</strong>
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<strong>
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could be reduced by isopropilnoradrenaline, acetylcholine, histamine, and caffeine.</strong>
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<strong>CBV was decreased after isopropilnoradrenaline, acetycholine, histamine injections and increased by
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caffeine.
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</strong>The possible role of the active changes of cerebral capacitance vessels in the transcapillary fluid
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exchange is discussed. Capacitance vessels active responses are supposed to entail wrong results when using
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certain techniques for measurement of cerebral blood flow and metabolism.
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</p>
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<p>
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Proc Soc Exp Biol Med 1999 Apr;220(4):244-8. <strong>The prevention of lung cancer induced by a
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tobacco-specific carcinogen in rodents by green and black Tea.</strong> Chung FL "The oxidation products
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found in black tea, thearubigins and theaflavins, also possess antioxidant activity, suggesting that black
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tea may also inhibit NNK-induced lung tumorigenesis. Indeed, bioassays in A/J mice have shown that black tea
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given as drinking water retarded the development of lung cancer caused by NNK." "We conducted a 2-year
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lifetime bioassay in F344 rats to determine <strong>whether black tea and caffeine are protective against
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lung tumorigenesis induced by NNK. Our studies in both mice and rats have generated important new data
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that support green and black tea and</strong>
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<strong>
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caffeine as potential preventive agents against lung cancer, suggesting that a closer examination of the
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roles of tea and caffeine on lung cancer</strong>
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in smokers may be warranted."
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</p>
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<p>
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Pharmacol Biochem Behav 2000 May;66(1):39-45. <strong>Caffeine-induced increases in the brain and plasma
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concentrations of neuroactive steroids in the rat.</strong> Concas A, Porcu P, Sogliano C, Serra M,
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Purdy RH, Biggio G. "A single intraperitoneal injection of caffeine induced dose- and time-dependent
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increases in the concentrations of pregnenolone, progesterone, and 3alpha-hydroxy-5alpha-pregnan-20-one
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(allopregnanolone) in the cerebral cortex." "Caffeine also increased the plasma<strong>
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concentrations of pregnenolone and progesterone with a dose-response relation similar to that observed
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in the brain . . ."
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</strong>
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"Moreover, the brain and plasma concentrations of pregnenolone, progesterone, and allopregnanolone were not
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affected by caffeine in adrenalectomized-orchiectomized rats."
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</p>
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<p>
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Cancer Res 1998 Sep 15;58(18):4096-101. <strong>Inhibition of</strong>
|
|
<strong>lung carcinogenesis by black tea in Fischer rats treated with a tobacco-specific carcinogen:
|
|
caffeine as an important constituent.</strong> Chung FL, Wang M, Rivenson A, Iatropoulos MJ, Reinhardt
|
|
JC, Pittman B, Ho CT, Amin SG. "The NNK-treated group, given 2% black tea, showed a significant reduction of
|
|
the <strong>total lung tumor (adenomas, adenocarcinomas, and adenosquamous carcinomas) incidence from 47% to
|
|
19%, whereas the group given 1% and 0.5% black tea showed no change. The 2% tea also reduced liver tumor
|
|
incidence</strong> induced by NNK from 34% in the group given only deionized water to 12%." <strong>"The
|
|
most unexpected finding was the remarkable reduction of the lung tumor incidence, from 47% to 10%, in
|
|
the group treated with 680 ppm caffeine, a concentration equivalent to that found in the 2% tea. This
|
|
incidence is comparable to background</strong> levels seen in the control group. This study demonstrated
|
|
for the first time in a 2-year lifetime bioassay that black tea protects against lung tumorigenesis in F344
|
|
rats, <strong>and this effect appears to be attributed, to a significant extent, to caffeine as an active
|
|
ingredient of tea."</strong>
|
|
</p>
|
|
|
|
<p>
|
|
Cancer Lett 1991 Mar;56(3):245-50.<strong>
|
|
Inhibition by caffeine of ovarian hormone-induced mammary gland tumorigenesis in female GR mice.</strong
|
|
> VanderPloeg LC, Welsch CW. "Hormone treatment induced mammary tumors in 95-100% of the mice. Caffeine
|
|
treatment significantly (P less than 0.05) reduced the mean number of mammary tumors per mouse and
|
|
significantly (P less than 0.05) increased the mean latency period of mammary tumor appearance."
|
|
</p>
|
|
<p>
|
|
Breast Cancer Res Treat 1991 Nov;19(3):269-75.<strong>
|
|
Caffeine inhibits development of benign mammary gland tumors in carcinogen-treated female Sprague-Dawley
|
|
rats.</strong> Wolfrom DM, Rao AR, Welsch CW.
|
|
</p>
|
|
<p>
|
|
Cancer 1985 Oct 15;56(8):1977-81.<strong>
|
|
The inhibitory effect of caffeine on hormone-induced rat breast cancer.</strong> Petrek JA, Sandberg WA,
|
|
Cole MN, Silberman MS, Collins DC. "The current investigation examines the effect of two caffeine doses in
|
|
ACI rats with and without diethylstilbestrol (DES). Without DES, cancer did not develop in any of the rats
|
|
receiving either of the two caffeine dosages. With DES, increasing caffeine dosage lengthened the time to
|
|
first cancer, decreased the number of rats that developed cancers, and decreased the number of cancers
|
|
overall." "In conclusion, chronic caffeine ingestion inhibits rat breast cancer, neither by interfering with
|
|
the high prolactin levels--a necessary step in murine tumor development--nor by causing hypocaloric intake."
|
|
</p>
|
|
|
|
<p>
|
|
Nutr Cancer 1998;30(1):21-4.<strong>
|
|
Association of coffee, green tea, and caffeine intakes with serum concentrations of estradiol and sex
|
|
hormone-binding globulin in premenopausal Japanese women.</strong> Nagata C, Kabuto M, Shimizu H.
|
|
"Although the <strong>effect of caffeine cannot be distinguished from effects of coffee and green tea,
|
|
consumption of caffeine-containing beverages appeared to favorably alter hormone levels associated with
|
|
the risk of developing breast cancer."</strong>
|
|
</p>
|
|
<p>
|
|
J Environ Pathol Toxicol Oncol 1992; 11(3):177-89.<strong>
|
|
Caffeine, theophylline, theobromine, and developmental growth of the mouse mammary gland.</strong>
|
|
VanderPloeg LC, Wolfrom DM, Rao AR, Braselton WE, Welsch CW. <strong>"These data demonstrate that certain
|
|
methylxanthines (e.g., caffeine and theophylline) but not others (e.g., theobromine) can significantly
|
|
enhance mammotrophic hormone-induced mammary lobulo-alveolar differentiation
|
|
</strong>
|
|
|
|
in female Balb/c mice, an effect that appears not to be manifested via a direct action of the
|
|
methylxanthines on the mammary gland."
|
|
</p>
|
|
<p>
|
|
J Environ Pathol Toxicol Oncol 1994;13(2):81-8.<strong>
|
|
Enhancement by caffeine of mammary gland lobulo-alveolar development in mice: a function of increased
|
|
corticosterone.</strong> Welsch CW, VanderPloeg LC. Previously we have reported that the stimulatory
|
|
effect of caffeine on<strong>
|
|
lobulo-alveolar development
|
|
</strong>in the mammary glands of female Balb/c mice is not due to a direct action of the drug on the
|
|
mammary gland but appears to be due to a caffeine-induced alteration of a yet to be defined systemic
|
|
physiological process (VanderPloeg et al., J Environ Pathol Toxicol Oncol 11:177-189, 1992). "In the present
|
|
study, we administered caffeine (via the drinking water, 500 mg/L) to ovariectomized, estrogen- and
|
|
progesterone-treated Balb/c mice. After 30 days of caffeine treatment, a significant (p < 0.001)
|
|
enhancement of lobulo-alveolar development in the mammary glands of the hormone-treated mice, compared with
|
|
hormone treated control mice, was observed."
|
|
</p>
|
|
<p>
|
|
Am J Clin Nutr 1997 Jun;65(6):1826-30. <strong>Dietary caffeine intake and bone status of postmenopausal
|
|
women.</strong> Lloyd T, Rollings N, Eggli DF, Kieselhorst K, Chinchilli VM.
|
|
</p>
|
|
|
|
<p>
|
|
Eur J Epidemiol 1993 May;9(3):293-7. <strong>Unexpected effects of coffee consumption on liver
|
|
enzymes.</strong> Casiglia E, Spolaore P, Ginocchio G, Ambrosio GB. Istituto di Medicina Clinica,
|
|
Universita di Padova, Italy. The effects of regular daily coffee consumption on liver enzymes were studied
|
|
in a large number of subjects from the general population. In coffee drinkers, liver enzymes (gamma-glutamyl
|
|
transferase, alanine-amino transferase, and alkaline phosphatase) and serum bilirubin were lower than in
|
|
non-coffee-drinking subjects or in those consuming less than 3 cups daily. The hypothesis proposed is that
|
|
liver enzymes are a target for caffeine contained in coffee.
|
|
</p>
|
|
<p>
|
|
Anticancer Res 1996 Jan-Feb;16(1):151-3<strong>
|
|
Suppression by coffee cherry of the growth of spontaneous mammary tumours in SHN mice.</strong> Nagasawa
|
|
H, Yasuda M, Sakamoto S, Inatomi H Experimental Animal Research Laboratory, Meiji University, Kanagawa,
|
|
Japan. We previously found that coffee cherry (CC), residue after removal of coffee beans, significantly
|
|
suppressed the development of spontaneous mammary tumours of mice. In this paper, the effects of CC on the
|
|
growth of the palpable size of this type of tumour was examined. Free access as drinking<strong>
|
|
water of 0.5% solution of the hot water extract of CC for 10 days resulted in a marked inhibition of the
|
|
tumour growth: The percent changes of tumour sizes were 53.8 +/- 11.7% and 13.8 +/- 10.9% in the
|
|
</strong>
|
|
control and the experimental groups, respectively. Associated with this, thymidylate synthetase activity in
|
|
the mammary tumours was significantly lower in the experimental group than in the control. Normal and
|
|
preneoplastic mammary gland growth, body weight change and weights and structures of endocrine organs were
|
|
only slightly affected by the treatment. The findings indicate that CC is promising as an antitumour agent.
|
|
</p>
|
|
<p>
|
|
Yakugaku Zasshi 1997 Jul;117(7):448-54. <strong>[Effect of tea extracts, catechin and caffeine against
|
|
type-I allergic reaction].</strong> [Article in Japanese] Shiozaki T, Sugiyama K, Nakazato K, Takeo
|
|
T.<strong>
|
|
"Caffeine also showed a inhibitory effect on the PCA reaction. These results indicate that tea could
|
|
provide a significant protection against the type-I allergic reaction. These findings also suggest that
|
|
tea catechins and caffeine play an important role in having an inhibitory effect on the type-I allergic
|
|
reaction."
|
|
</strong>
|
|
</p>
|
|
|
|
<p>
|
|
Acta Chir Scand 1989 Jun-Jul;155(6-7):317-20. <strong>Does coffee consumption protect against thyroid
|
|
disease?</strong> Linos A, Linos DA, Vgotza N, Souvatzoglou A, Koutras DA
|
|
</p>
|
|
<p>
|
|
Br J Nutr 1999 Aug;82(2):125-30.<strong>
|
|
Inverse association between coffee drinking and serum uric acid concentrations in middle-aged Japanese
|
|
males.</strong> Kiyohara C, Kono S, Honjo S, Todoroki I, Sakurai Y, Nishiwaki M, Hamada H, Nishikawa H,
|
|
Koga H, Ogawa S, Nakagawa K
|
|
</p>
|
|
<p>
|
|
Cancer Res 1997 Jul 1;57(13):2623-9. <strong>Effects of tea, decaffeinated tea, and caffeine on UVB
|
|
light-induced complete carcinogenesis in SKH-1 mice: demonstration of caffeine as a biologically
|
|
important constituent of tea</strong>. Huang MT, Xie JG, Wang ZY, Ho CT, Lou YR, Wang CX, Hard GC,
|
|
Conney A.H.
|
|
</p>
|
|
|
|
<p>
|
|
Mutat Res 1981 Jun;89(2):161-77. <strong>Non-mutagenicity of urine from coffee drinkers compared with that
|
|
from cigarette smokers.</strong> Aeschbacher HU, Chappuis C.
|
|
</p>
|
|
<p>
|
|
Biol Neonate 1981;40(3-4):196-8. <strong>The effects of maternal carbohydrate (sucrose) supplementation on
|
|
the growth of offspring of pregnancies with habitual caffeine consumption.</strong> Dunlop M, Court JM,
|
|
Larkins RG. "When maternal caffeine (10 mg/kg/day) was consumed together with supplementary sucrose (7
|
|
g/kg/day) the expected offspring growth reduction attributed to caffeine did not occur."
|
|
</p>
|
|
<p>
|
|
Biochim Biophys Acta 1992 Dec 15;1175(1):114-22. <strong>Caffeine promotes survival of cultured sympathetic
|
|
neurons deprived of nerve growth factor through a cAMP-dependent mechanism.</strong> Tanaka S, Koike T.
|
|
</p>
|
|
|
|
<p>
|
|
JAMA 2000 May 24-31;283(20):2674-9. <strong>Association of coffee and caffeine intake with the risk of
|
|
Parkinson disease.</strong> Ross GW, Abbott RD, Petrovitch H, Morens DM, Grandinetti A, Tung KH, Tanner
|
|
CM, Masaki KH, Blanchette PL, Curb JD, Popper JS, White LR.
|
|
</p>
|
|
<p>
|
|
Farmakol Toksikol 1983 Sep-Oct;46(5):107-11 <strong>[Use of the swimming test for demonstrating
|
|
antidepressive activity of drugs during single and repeated administration].</strong> [Article in
|
|
Russian] Rusakov DIu, Val'dman AV. <strong>
|
|
"The use of the "swimming test" made it possible to identify the activity of tricyclic (desipramine,
|
|
chlorimipramine, amitryptyline) and atypical antidepressants (befuralin, zimelidine, trazodon), that of
|
|
pyrazidol (type A MAO inhibitor) and of a number</strong> of new compounds--derivatives of benzofuran
|
|
and morpholine upon single and chronic administration. To define the method specificity, use was made of the
|
|
neuroleptic haloperidol, the tranquilizer diazepam, and of nembutal, which did not exhibit any activity in
|
|
the test in question.<strong>
|
|
Psychostimulants (amphetamine, caffeine) dramatically increased the time of active swimming. The effect
|
|
lasted throughout all the 30 minutes of testing, which is not characteristic for
|
|
antidepressants."</strong>
|
|
</p>
|
|
<p>
|
|
Gen Pharmacol 1996 Jan;27(1):167-70 <strong>The influence of antagonists of poly(ADP-ribose) metabolism on
|
|
acetaminophen hepatotoxicity.</strong> Kroger H, Ehrlich W, Klewer M, Gratz R, Dietrich A, Miesel R.
|
|
</p>
|
|
<p>
|
|
Ann Clin Lab Sci 1977 Jan-Feb;7(1):68-72. <strong>Effects of drugs on platelet function.</strong> Morse EE.
|
|
</p>
|
|
<p>
|
|
Thromb Haemost 1982 Apr 30;47(2):90-5. <strong>Effect of cAMP phosphodiesterase inhibitors on ADP-induced
|
|
shape change, cAMP and nucleoside diphosphokinase activity of rabbit platelets.
|
|
</strong>
|
|
|
|
Lam SC, Guccione MA, Packham MA, Mustard JF.
|
|
</p>
|
|
<p>
|
|
Carcinogenesis 1998 Aug;19(8):1369-75.<strong>
|
|
The coffee-specific diterpenes cafestol and kahweol protect against aflatoxin B1-induced genotoxicity
|
|
through a dual mechanism.</strong> Cavin C, Holzhauser D, Constable A, Huggett AC, Schilter B.
|
|
</p>
|
|
<p>
|
|
Am J Epidemiol 1994 Apr 1;139(7):723-7.<strong>
|
|
Coffee and serum gamma-glutamyltransferase: a study of self-defense officials in Japan.</strong>
|
|
Kono S, Shinchi K, Imanishi K, Todoroki I, Hatsuse K.
|
|
</p>
|
|
<p>
|
|
Carcinogenesis 1996 Nov;17(11):2377-84<strong>
|
|
Placental glutathione S-transferase (GST-P) induction as a potential mechanism for the anti-carcinogenic
|
|
effect of the coffee-specific components cafestol and kahweol</strong>. Schilter B, Perrin I, Cavin C,
|
|
Huggett AC
|
|
</p>
|
|
|
|
<p>
|
|
J Nutr 1999 Jul;129(7):1361-7.<strong>
|
|
Teas and other beverages suppress D-galactosamine-induced liver injury in rats.</strong> Sugiyama K, He
|
|
P, Wada S, Saeki S
|
|
</p>
|
|
<p>
|
|
Nutr Cancer 1999;33(2):146-53.<strong>
|
|
Effects of oral administration of tea,</strong>
|
|
<strong>decaffeinated tea, and caffeine on the formation and growth of tumors in high-risk SKH-1 mice
|
|
previously treated</strong> with ultraviolet B light. Lou YR, Lu YP, Xie JG, Huang MT, Conney AH.
|
|
</p>
|
|
<p>
|
|
Ind Health 2000 Jan;38(1):99-102. <strong>Effects of coffee consumption against the development of liver
|
|
dysfunction: a 4-year follow-up study of middle-aged Japanese male office workers.
|
|
</strong>Nakanishi N, Nakamura K, Suzuki K, Tatara K.
|
|
</p>
|
|
|
|
<p>
|
|
Ind Health 2000 Jan;38(1):99-102. <strong>Effects of coffee consumption against the development of liver
|
|
dysfunction: a 4-year follow-up study of middle-aged Japanese male office workers.
|
|
</strong>Nakanishi N, Nakamura K, Suzuki K, Tatara K. .
|
|
</p>
|
|
<p>
|
|
Biochim Biophys Acta 1992 Dec 15; 1175(1):114-22. <strong>Caffeine promotes survival of cultured sympathetic
|
|
neurons deprived of nerve growth factor through a cAMP-dependent mechanism.</strong> Tanaka S, Koike T.
|
|
</p>
|
|
<p>
|
|
Int J Epidemiol 1998 Jun;27(3):438-43. <strong>Coffee consumption and decreased serum
|
|
gamma-glutamyltransferase and aminotransferase activities among male alcohol drinkers.</strong> Tanaka
|
|
K, Tokunaga S, Kono S, Tokudome S, Akamatsu T, Moriyama T, Zakouji H. <strong>
|
|
". . . recent epidemiological studies have suggested unexpected, possibly beneficial effects of coffee
|
|
against the occurrence of alcoholic liver cirrhosis</strong> and upon serum liver enzyme levels."
|
|
"Increased coffee consumption was strongly and independently associated with decreased GGT activity among
|
|
males (P trend < 0.0001); the inverse association between coffee and serum GGT was more evident among
|
|
heavier alcohol consumers (P < 0.0001), and was absent among non-alcohol drinkers." "Similar inverse
|
|
associations with coffee and interactions between coffee and alcohol intake were observed for serum
|
|
aspartate aminotransferase and alanine aminotransferase. Intake of green tea, another popular source of
|
|
caffeine in Japan, did not materially influence the liver enzyme levels. CONCLUSIONS: Our results suggest
|
|
that coffee may inhibit the induction of GGT in the liver by alcohol consumption, and may possibly protect
|
|
against liver cell damage due to alcohol."
|
|
</p>
|
|
<p>
|
|
Am J Hosp Pharm 1989 Oct;46(10):2059-67. <strong>Abuse of drugs used to enhance athletic performance.
|
|
</strong>Wagner JC.
|
|
</p>
|
|
<p>
|
|
© Ray Peat 2006. All Rights Reserved. www.RayPeat.com
|
|
</p>
|
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|
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