Phase I Detoxification
In this phase, a group of 50 to 100 specialized enzymes alter toxins to prepare them for phase II. The molecular structure of the toxin is changed in a way that readies it to be changed further during the next step of the detoxification process. We like to think of phase I as the activation step. Phase I has three basic ways to neutralize toxic chemicals:
It can change the chemical structure of a toxic molecule so that it can be dissolved in water.
It can break a toxic chemical into two or more less toxic or harmless chemicals.
It can change a toxic molecule into a different type of molecule so that other enzymes can detoxify it more easily.
Activated toxins-toxins that have been through phase I liver detoxification-are sometimes more toxic than the original compound, so it is very important that they be moved into phase II. In some instances, a substance that does not cause cancer becomes carcinogenic after activation, and is then neutralized in phase II. This is true of some hormones that must undergo detoxification to be eliminated from the body. Thus, if phase I is accelerated or phase II is slowed down, activated toxins build up and can damage the liver or pass out of the liver into the general circulation. If phase I is slowed down, the liver becomes unable to keep up with detoxification demands. You can think of this as a stream that cascades over two waterfalls, with a cold, clear pond between them. When the water flows steadily, the pond remains clear and clean. If the second waterfall is clogged, the pond becomes stagnant until it overflows, carrying debris into the stream below it. If the first waterfall becomes clogged, the flow backs up and stagnates above it as the pond below dries up.
Alcohol, tobacco smoke, and some medications (for example, the steroid drug prednisone) have the effect of speeding up phase I detoxification. So do the toxins found in charcoal-broiled meats. Many environmental toxins, including chemicals in car exhaust, paint, nail polish, and pesticides, also rev up phase I, potentially causing an accumulation of activated toxins in the body.
The key here is to maintain balance between the two parts of the detoxification system. The best ways to do that are to avoid toxic substances whenever possible and to supply your body with all of the nutrients it needs to run smoothly through both phases. As long as phase II can keep up with phase I, some acceleration may be more helpful than harmful. Some highly nutritious foods speed up phase I. The cruciferous vegetables-broccoli, brussels sprouts, cabbage, cauliflower, and their relatives-have this effect.
The most popular drug treatments for postpartum depression, including fluoxetine (Prozac) and other drugs in its class, slow down phase I detoxification. So do the benzodiazepine tranquilizers, such as alprazolam (Xanax), diazepam (Valium), and lorazepam (Ativan); many antibiotics; antihistamines given for allergies; and stomach-acid blockers such as cimetidine (Tagamet) and ranitidine (Zantac). When drugs inhibit phase I detoxification, other toxins (including other drugs) can build up to harmful levels because of the liver’s decreased ability to get rid of them.
Phase I can also be inhibited by nutritious foods. Grapefruit juice contains a substance that inhibits phase I enzymes so strongly that it can cause drug overdoses. The enzymes are slowed so much that they cannot detoxify drugs fast enough, and the levels of the drug in the bloodstream climb too high. Capsaicin, the compound that makes hot peppers hot, also slows down phase I.
The common spice turmeric, found most commonly in curry powder, slows down phase I while egging on phase II, an effect that can help to move toxins more quickly through the two phases. This may explain turmeric’s powerful anticancer properties.
Certain nutrients act as coenzymes to the phase I detoxifying enzymes. Vitamins B2, B3, B6, and B12 plus folic acid, bioflavonoids, branched-chain amino acids, and phospholipids are needed to keep phase I going smoothly. If some of these nutrients sound unfamiliar to you, don’t worry. You will learn everything you need to know about them later on. Our goal here is to show you how nutrients keep your body systems working smoothly. We will get to specifics about those nutrients-and ways to tell whether you need more of them-later in the book.
The more detoxifying work phase I has to do, the more free radicals it produces. Liver tissues can end up being damaged by these free radicals if there aren’t enough antioxidants available to handle them. Vitamin C, beta-carotene, vitamin E, coenzyme Q10 and the minerals copper, manganese, selenium, and zinc are all needed to prevent free-radical overload in the liver. Substances known as thiol compounds , which are found in garlic, onions, and the cruciferous vegetables, add to the liver’s antioxidant power. Bioflavonoids and anthocyanidins are other nutrients that help to quench free radical fires.
Phase II Detoxification
During phase II detoxification, activated substances from phase I-other wise known as intermediates -are altered further. Seven different major biochemical reactions occur in this phase, known as glutathione conjugation, amino acid conjugation, methylation, sulfation, acetylation, glucuronidation, and sulfoxidation. Each of these reactions works on specific types of intermediates and needs specific nutrients in order to proceed to successful completion. Basically, these reactions work by adding a molecule to the intermediate from phase I, making it less toxic and soluble in water. Then the final product can be flushed out of the body in either the urine or the bile, another product of the liver. Bile leaves the body as part of solid waste.
The nutrients required for phase II fall into two categories. The first are the amino acids, which donate molecules that are attached to phase I intermediates. These include the sulfur donors, among which are the amino acids methionine, taurine, cysteine, and N-acetylcysteine. Other, non-sulfur-containing amino acids are also required: glycine, taurine, glutamine, ornithine, and arginine. The antioxidant amino acid glutathione is also required for phase II detoxification.
Following is a brief summary of the individual phase II processes, the types of toxins they are used to eliminate, and the nutrients required for them to be carried out properly:
Acetylation is a phase II liver detoxification pathway that attaches acetyl co-A to toxins to make them far less harmful and easy to excrete. This process requires vitamin B pantothenic acid, and vitamin C to function properly.
Amino acid conjugation helps the body to rid itself of many toxic chemicals, called xenobiotics, from the environment. The amino acids glycine, taurine, glutamine, arginine, and ornithine must be available for this liver detoxification pathway to function properly. Amino acids are available in protein-rich foods if they are eaten in adequate amounts.
Glucuronidation helps to detoxify many prescription drugs and, to some extent, the reproductive and adrenal hormones. Glucuronidation requires magnesium and vitamin B.
Glutathione conjugation helps to detoxify and eliminate poisons in the liver, lungs, intestines, and kidneys. Glutathione is one of the most important antioxidants and anti carcinogens in the body. Its synthesis requires adequate amounts of the amino acids cysteine, glutamic acid, and glycine. Nutrients that help to raise glutathione levels include vitamin C, alpha-lipoic acid, whey protein, and the amino acids glutamine and methionine.
Methylation helps to detoxify many of the steroid hormones, including estrogen. The methylation pathway begins with the amino acid methionine, and needs vitamin B folic acid, choline, and vitamin B to function properly. Methylation eventually yields usable sulfate with the help of the trace mineral molybdenum.
Sulfation is the main liver detoxification pathway that neutralizes the stress hormone cortisol, as well as many environmental toxins, food additives, microbial products, and some commonly prescribed drugs. Usable sulfur is needed for sulfation to run unimpeded. Sources of sulfur include the sulfur-bearing amino acids methionine and cysteine, and the nutritional product methylsulfonylmethane (MSM).
Sulfoxidation transforms toxic sulfite molecules into sulfate with the assistance of the mineral molybdenum. This is the last part of the methylation process (see above). Sulfites are compounds that are added to some foods to preserve freshness. For example, they are often found in wine, dried fruit, dehydrated foods, seasonings, and salad dressings. Many restaurants use them on salad bar foods. Ironically, sulfites, which can be highly allergenic and can interfere with breathing in those who are sensitive to them, are also added to some asthma medications.
A diet low in protein-all too common in women who are trying to lose weight with a low-fat diet-can dramatically slow phase II detoxification. Aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs), including ibuprofen (found in Advil, Nuprin, and other products), also slow phase II detoxification.
Does even the smallest bit of caffeine keep you wide awake at night? You could have sluggish phase I detox. Can you guzzle two cups of coffee in the afternoon and sleep just fine? Your phase I enzymes might be over active. Does garlic make you sick? Does your urine have a strong smell after you eat asparagus? Did you suffer from toxemia during your pregnancy? Any of these symptoms may indicate problems with phase II. Specially targeted nutrients can do wonders for your liver’s detoxifying ability.
The Six Phase Table
The six-phase table is a field matrix reflecting medical experience based on careful observation and empirical learning. It is a phase-by-phase arrangement of disorders with no direct relationship between them. No causal pathogenetic link between disorders can be inferred.
The structure of the table makes it suitable for developing a prediction system giving a better assessment of the possibilities for a vicariation effect.
Download the six phase table