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THE DETOX REVOLUTION
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Phase I and II Reactions
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Oxidations, reductions, and acetylations are the Phase I enzymatic reactions necessary to decrease the toxic effect of chemicals, to make them more water soluble, and in some cases to facilitate subsequent conjugation reactions and excretion. Here is an example of Phase I and Phase II reactions followed by excretion:
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PHASE I REACTIONS PHASE II REACTIONS
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toxins carcinogens steroid hormones sterols
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conjugation with either glucuronide, sulfate, or glutathione
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Perhaps by now you are beginning to feel a bit of the awe I have for this marvelously elegant protective system of the body. But at this stage of the discussion, awe gives way to drama, because through an apparent perversity of nature, an enzyme called -glucuronidase acts to reverse the work of glucuronidation, thereby reintroducing toxins including steroid hormones such as estrogens and androgens back into the body. It has been suggested that -glucuronidase, which is found in many tissues throughout the body, is intended to work as a salvage enzyme, recycling important compounds made within the body for further work. But something obviously went wrong because when it is applied to toxins, cancer-causing agents, and steroid hormones, it appears that rather than serving the body well, -glucuronidase does damage. What we know about -glucuronidase is that it exists in all of us in different concentrations. High levels of this enzyme in the body have been associated with an increased risk for cancer development, whereas low levels indicate a decreased risk. Elevated levels have been observed in people following exposure to tobacco smoke, industrial chemicals, and other cancer-causing agents such as polycyclic aromatic hydrocarbons and nitrosamines. I have already mentioned my interest in the compound D-glucarate, which is found naturally in fruits and vegetables. Here s why it s so important: D-glucarate has been found to be a potent inhibitor of -glucuronidase. People who eat a diet high in fruits and
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D E T O X I F I C AT I O N : T H E K E Y T O W E L L N E S S
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Sources of Toxins Controlled by the Xenobiotic Detoxification System
Exposure to certain substances found in our own bodies as well as substances in our environment can have destructive effects on health. Xenobiotic detoxification helps to eliminate toxic compounds from many sources.
IN THE ENVIRONMENT WITHIN THE BODY
cigarette smoke tobacco products certain drugs combustion by-products charcoal-cooked meats overcooked meats herbicides and pesticides organic solvents toxins in food
androgens estrogens other steroids bile acids other cellular chemicals
vegetables and who supplement with D-glucarate often have low levels of -glucuronidase. This is because an active constituent of D-glucarate actually and very effectively halts the reversing affect of -glucuronidase on the glucuronidation and preserves its good work in eliminating toxins from the body.
D- GLUCARATE I S A P OTENT D ETOXIFICATION AGENT
Significant levels of the beneficial compound D-glucarate are found in cruciferous vegetables including cabbage, broccoli, brussels sprouts, watercress, alfalfa, and bean sprouts. Apples, grapefruits, cherries, and apricots also contain high levels of D-glucarate.
In this inhibiting role, D-glucarate has been found to have a protective effect against cancers of the breast, prostate, lung, colon, bladder, and skin. It has been observed in research studies of the detoxification
THE DETOX REVOLUTION
process to safely regulate bile acids and steroid hormones to levels that are not likely to progress to cancer. In other scientific studies, D-glucarate has been shown to inhibit the growth of cancer cells. Not surprisingly then, high levels of D-glucarate in the blood are associated with a decreased risk of cancer and low levels with increased risk. D-glucarate has also been shown to lower triglycerides, total cholesterol, LDL, and vLDL (the so-called bad cholesterols), while not affecting HDL (the so-called good cholesterol). And in studies of both humans and animals, no toxicity has been associated with the consumption of D-glucarate. The significant role D-glucarate and other phytochemicals appear to play in the xenobiotic detoxification will be discussed throughout this book.
The Antioxidant Detoxification System
Antioxidant detoxification involves deactivating or destroying what are known as oxygen reactive species, the most significant category of which is free radicals. At the risk of oversimplification, free radicals can be thought of as very unstable electric charges sparks that if not properly controlled can set up extremely serious toxic conditions within the body. Free radicals can be generated by environmental factors such as exposure to cigarette smoke and other pollutants or created from internal reactions such as mitochondrial respiration (the use of oxygen to generate energy), by-products of chemical metabolism, inflammation from strenuous exercise or physical work, and the intake of too many calories. Excessive free radicals rob electrons from normal, healthy tissue creating potentially serious damage at the cellular level. Even more profound, we have recently realized that unchecked free radicals can modify DNA structure, possibly leading to mutations and altered gene programming that can initiate the cancer process. Parkinson s disease, cataracts, artherosclerosis, sperm abnormalities, emphysema, sickle cell anemia, abnormal aging, and stroke are all significantly linked to excessive free radicals in the body. Fortunately, free radicals can be destroyed by these elements: specific antioxidant enzymatic reactions antioxidants, which are found in a wide variety of foods and are even produced by the body itself certain phytochemicals with antioxidant properties, including flavonoids, sulfur-containing compounds such as those in onions, terpenoids from herbs and spices, and certain vitamins and minerals
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