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The Liver's Detoxification Function

Your body doesn't like to keep any molecules around for a long time. Even "good" molecules, such as hormones, are constantly being disassembled and reconstructed to prepare them to be recycled or eliminated. Thanks to detoxification enzymes, the liver is able to break tip most molecules, even toxic and dangerous ones. Enzymes are molecules that act as catalysts in the transformation process. There are thousands of different enzymes, each with a unique role.

Think of this detoxification process as a two-phase wash cycle. Enzymes are like the soap that liberates grease into little droplets, removing impurities that the water can't remove on its own. In the first part of the wash cycle (Phase 1), enzymes break toxins down into intermediate forms. Figure 5.2 illustrates the complicated process of how some common toxins are broken down during Phase I detoxification. Some toxins are ready for elimination at this stage, but others require a second wash cycle. In Phase 2, these intermediate compounds are routed along one of six chemically driven detoxification pathways, where they are further broken down, and then bound to specific types of' protein molecules which act as "escorts" to guide them out of the body, allowing them to exit through the kidneys (in the form of urine) or the bile (in the form of feces). This process is called conjugation and is illustrated in figure 5.3. Of the six pathways, three warrant special mention.

One of the most important systems in Phase 2 is the glutathione conjugation pathway, which utilizes glutathione for the detoxification of deadly industrial toxins such as PCBs, and the breakdown of carcinogens. Its activity accounts for up to 60 percent of the toxins excreted in the bile. Glutathione also circulates through the bloodstream combating free radicals. No other conjugating substance is as versatile as glutathione and the body's supply of it, most of which is produced by the liver, is easily depleted. Exposure to high levels of toxins exhausts reserves of glutathione, possibly increasing susceptibility to cancer. Chronic disease, HIV, and cirrhosis use up reserves of glutathione. Excessive exercise, which increases oxidative stress and free radical production, and alcohol consumption, which blocks glutathione production, also deplete glutathione in the blood.

The weakest pathway in most people, from a dietary standpoint, is sulfation, the one responsible for the transformation of neurotransmitters, steroid hormones, drugs, industrial chemicals, phenolics (compounds derived from benzene, commonly used in plastics, disinfectants, and pharmaceuticals), and especially toxins from intestinal bacteria and the environment. Intake of too little dietary sulfur, a molecule that must come from our diets, is a cause of ineffective detoxification. If your exposure to substances that need to be deoxified via the sulfation pathway is high, but your sulfate reserves are low due to an inadequate diet, you will not be able to break down these toxins.

Studies have established a strong association between the function of the sulfation pathway and a variety of illnesses including Alzheimer's disease, Parkinson's disease, motor neuron disease, autism, primary biliary cirrhosis, rheumatoid arthritis, food sensitivity, and multiple chemical sensitivity. The detoxification profile test described in Chapter 7 identifies alterations in this pathway.

The body manufactures five different types of amino acids that form a third  detoxification pathway: glycine, taurine, glutamine, arginine, and ornithine. Of these, glycine is the most important for the neutralization of toxins. In some cases, the body cannot make enough glycine to keep up with its own detoxification needs. Though not considered an essential amino acid because the body can make it, glycine production depends on an adequate intake of dietary protein. Individuals who eat a protein-deficient diet have trouble detoxifying environmental pollutants.

Glycine supplies can be depleted by lifestyle stresses. Benzoates for example, found in soft drinks, bind with glycine and rob the body's store of it. One study found that people who consumed a large number of soft drinks had problems breaking down toluene, a common industrial organic solvent. Aspirin also slows down this detoxification pathway because it competes for available glycine in the liver. When the diet is supplemented with glycine, as well as the other nonessential amino acids, there is a noticeable improvement in the detoxification capabilities of many people.

Problems in Phase I and Phase 2

Detoxification

When the liver is "sluggish," Phase I of the detoxification cycle may not be processing toxins at a normal and necessary speed. This causes toxins to accumulate in the bloodstream. If the hormone estrogen, for example, is not dismantled during Phase 1, the buildup can reach potentially harmful levels. Premenstrual tension can be an expression of this. Many factors can cause Phase I to become sluggish. As we age, our detoxification processes slow. Use of medications such as anti-ulcer drugs (cimetidine) and oral contraceptives; exposure to cadmium, lead, and mercury; and consumption of large amounts of sugar and hydrogenated fats hinder Phase I detoxification.

Substances that slow down Phase I detoxification, setting the stage for a toxic buildup, are called Phase I inhibitors. They affect the DNA of the liver cells, causing less detoxification enzymes to be produced. In addition to those mentioned previously, Phase I inhibitors include:

Pancreatitis and the Detoxification Bottleneck

Mainstream medicine generally does not factor in bottleneck detoxification problems in diagnosis and treatment. Our clinical experience, however, has shown us that when treatment focuses on eliminating this problem, other disease conditions improve. For example, we believe that many cases of pancreatitis are caused by a bottleneck detoxification problem. The use of alcohol, cigarettes, and a body-abusing lifestyle creates this bottleneck, and the free radicals generated in this process cause inflammation in the pancreas.

We had a patient who had been in the hospital several times for acute pancreatitis. He was always alternating between a healthy lifestyle and use of alcohol and cigarettes. After every binge, he would end up in the hospital with pancreatitis. We put him on a detoxification program with great success. Patients with pancreatitis often report exposure to diesel fumes, solvents, and trichloroethelene. These toxins also seem to accentuate the susceptibility to alcohol-related pancreatitis. The treatment of pancreatitis with detoxification medicine is not mentioned in medical literature. However, we believe there's ample evidence to make it a first-line treatment consideration.

A different type of detoxification problem develops if Phase I breaks down toxins at so fast a rate that Phase 2 cannot keep up. In this situation, the toxic intermediates produced during Phase I waiting to be washed out in Phase 2 flood the system. Many of these intermediate compounds-stuck in between Phase I and Phase 2-are more dangerous than the original toxin. This bottleneck can become a biochemical nightmare, damaging the liver, brain, and immune system.

Some of the substances that accelerate the breakdown of toxins in the liver by increasing the production of Phase I enzymes, without a concurrent increase in Phase 2 enzymes, are known carcinogens- paint fumes, and cigarette smoke. Others are well known for their detrimental effects, such as alcohol and steroids. Even some otherwise harmless substances such as limonene from lemons, increase Phase I detoxification. But unlike cigarette smoke, limonene does not create dangerous intermediate molecules. As you read the following list, keep in mind that it is not strictly a list of "bad" things, but of those that increase the rate of Phase I detoxification, and that this becomes a problem only when Phase 2 can't keep up.

• Phenobarbital
• Steroids
• Sulfonamide medications
• Foods in the cabbage family
• Charbroiled meats
• High-protein diets
• Citrus fruits
• Vitamin B1
• Vitamin B3
• Vitamin C
• Environmental toxins (exhaust fumes, paint fumes, dioxin, pesticides)
• Cigarette smoke
• Alcohol
• Endotoxins from intestinal bacteria in the bloodstream

Exposure to a toxin, when coupled with exposure to another substance that speeds up Phase 1, is especially dangerous. The combination of alcohol and acetaminophen provides a good example. It's not uncommon to drink heavily, and later take acetaminophen for the headache that follows. The intermediate compound (from acetaminophen) is an extremely toxic substance called n-acetyl-p-benzoquinoneimine (NAPQI). Under normal conditions, NAPQ1 is removed quickly during Phase 2, but alcohol intake forces more NAPQI into the liver than Phase 2 can handle.

Research has shown that specific foods and nutrients not only have a beneficial effect on detoxification capability, but can also provide a safe and viable approach to treating a variety of immune disorders and toxicity syndromes.

If two or more detoxification accelerants are combined, they can interact, with serious consequences. An individual on a prescription medication who smokes, for example, actually needs higher dosages of the medication because smoking causes the medication to be broken down faster than it normally would be during Phase 1. If Phase 2 can't handle the extra burden, a detoxification bottleneck results. We predict that in the future, medical specialists will check detoxification capabilities in order to give more accurate drug prescriptions.

Case History

Joanie was a forty-eight-year-old female who had a history of hepatitis B, a disease of the liver. She had worked for many years in the graphic arts field, and was regularly exposed to volatile organic solvents. She came to our clinic with symptoms of chronic fatigue. We did a comprehensive liver detoxification screening. The test clearly showed which pathways were out of balance. After recommending the correct nutrients, Joanie was on the road to repairing her damaged liver function and rebuilding her health.

Problems in Phase I and Phase 2 liver detoxification are so prevalent, and have such a major impact on health that we believe it's a good idea for everyone to have liver detoxification tests as part of a standard medical workup. This lab test, described in Chapter 7, can identify problems localized in the different detoxification pathways. If you suffer from chronic liver and gallbladder problems, you're probably a candidate for this test. Abnormal results, of course, will require ruling out a liver disease before going ahead with detoxification therapy. Assessing detoxification function makes it possible to diagnose a problem before symptoms actually appear. Tests that measure Phase I and Phase 2 enzymes take much of the guesswork out of estimating the severity of liver detoxification dysfunction, and can to some extent indicate whether a person is at special risk for cancer, neurological disease, chemical and drug sensitivity, and immune problems.

Diet and Detoxification: Feeding Phase 1 and 2

You can take steps to keep your liver detoxification system running smoothly. Diet has a strong effect on detoxification enzymes, and foods can help "regulate" or balance Phase 1 and 2 activity. Eating foods that support the liver can reduce your susceptibility to damage from toxins and to conditions Such as multiple chemical sensitivity syndrome, chronic fatigue syndrome, and cancer. Research has shown that specific foods and nutrients not only have a beneficial effect on detoxification capability, but can also provide a safe and viable approach to treating a variety of immune disorders and toxicity syndromes.

Essential fatty acids are vital for Phase 1 detoxification, and the standard American diet does not provide an adequate supply of these vital nutrients. Essential fatty acid intake in the form of cold-water fish and flaxseed oils have a demonstrated ability to heighten detoxification. Other sources of essential fatty acids include edible oils, such as those made from sunflower seeds, walnuts, and sesame seeds; wheat germ; and supplements of black current seed, borage, or evening primrose oil.

Eating fresh fruits and vegetables daily is a good way to continually replenish your body's store of glutathione, necessary for one of Phase 2 pathways. High-quality protein nourishes both the amino acid and the sulfation pathways. Vegetable sources of sulfur for the sulfation pathways include radishes, turnips, onions, celery, horseradish, string beans, watercress, kale, and soybeans. Eggs, fish, and meat are also excellent sulfur sources.

Cabbage, Brussels sprouts, broccoli, citrus fruits, and lemon peel oils support Phase 2 activity. Studies have shown dramatic results from consuming broccoli sprout extract, which inhibits the activity of Phase 1 enzymes and, simultaneously enhances the Phase 2 glutathione pathway. Broccoli sprout extracts are especially beneficial for people who have frequent or high-level exposure to pesticides, exhaust fumes, paint fumes, cigarette smoke, or alcohol. Anyone who is exposed to known carcinogens will benefit from broccoli sprout extract.

Foods to Support Liver Detoxification

• Cabbage family
• Cold-water fish
• Flaxseed oil
• Fruits (fresh)
• Garlic
• Nuts and seeds
• Onions
• Safflower oil
• Sesame seed oil
• Sunflower seed oil
• Vegetables (fresh)
• Walnut oil
• Wheat germ and wheat germ oil

Nutritional Supplements to Support Liver Detoxification

• Bioflavonoids
• Black currant seed oil
• Borage oil
• Carotenes
• Coenzyme Q10
• Copper
• Evening primrose oil
• Folic acid
• Iron
• Lecithin
• Magnesium
• Manganese
• N-acetyl-cysteine
• Niacin
• Riboflavin
• Selenium
• Silymarin (milk thistle)
• Trace minerals
• Vitamin A
• Vitamin B6 (pyridoxine)
• Vitamin B12
• Vitamin C (ascorbic acid)
• Vitamin D
• Vitamin E
• Vitamin K
• Zinc

The Gallbladder, Bile, and Gallstones

The gallbladder is the end of the detoxification road that begins in the liver. Bile is the fluid into which the liver excretes its toxins. (The other routes of elimination are the sweat glands and the kidneys.) After bile is produced in the liver, it runs into the gallbladder and eventually into the intestinal tract. We have found that in many cases people with liver problems also have gallbladder problems, and vice versa.

Bile is made in the liver from cholesterol, bilirubin, and lecithin, and is then secreted into the gallbladder. While in the gallbladder, bile is concentrated by a re-absorption of the liquids back into the circulatory system. A proper ratio of bile components is necessary for it to remain in solution. Abnormal ratios promote the formation of cholesterol crystals or stones in the gallbladder. During a meal, bile is secreted by the gallbladder into the intestines to promote the digestion and breakdown of oils and fats. After the intestines absorb them, these bile-digested fats are used in the body to build cells, hormones, and prostaglandins (a group of chemicals that act like hormones).

When constipation occurs, bacteria in the intestines split the toxins that are bound up in the bile, in turn causing reabsorption of these already detoxified poisons. A diet high in vegetables will prevent constipation. Beta-glucuronidase is an intestinal bacterial enzyme that releases compounds for reabsorption. To prevent this reabsorption of toxins, an adequate supply of calcium d-glucarate, a natural ingredient in vegetables that inhibits beta-glucuronidase activity, is necessary. Charcoal will also bind up the bile and prevent toxins from being reabsorbed into the bloodstream.

Gallstones-a common complaint in North America-easily disrupt the flow of bile. They are found in sixteen to twenty million Americans and are twice as common for women as men. Usually the stones are a mixture of cholesterol, calcium, bilirubin, and lecithin. Occasionally, however, the gallbladder also forms a stone consisting mainly of calcium with a little bit of cholesterol. If you have gallstones, observe the following instructions:

1. Take lecithin daily. Cholesterol stones are caused when your liver excretes more cholesterol into the gallbladder than it does lecithin and bile acids. The cholesterol tends to "supersaturate" and form stones. A daily supplement of 500 mg of lecithin with meals keeps the bile flowing smoothly.
2. Limit dietary sugar. Sugar intake correlates with gallstone formation, suggesting that sugar stimulates cholesterol synthesis.
3. Take 5 g of soluble fiber (pectin in fruits, beans, or oat bran) daily with meals.
4. Eat a low-fat diet to prevent obesity.
5. Eat small meals to ensure proper digestive capacity.
6. Avoid food allergens, which are notorious for provoking acute attacks of gallbladder inflammation. Eggs are considered the worst offender.
7. Take 500 mg of bile acids with every meal; this is usually 50 percent effective in reducing the size of the cholesterol variety of gallstones.
8. Take supplements of the amino acids methionine and taurine. Because women's bodies make less taurine than men's, this might be the clue to their twofold increased risk for gallstones. The dose is 1 g of each, between meals, twice daily.
9. Take dandelion root (Taraxacum officinalis) extract. It's a superb cholegogue (releases stored bile), gentle in action, and safe to use. The dose of the solid extract is 1 teaspoon, 3 times a day. The solid extract is hard to find in the store, but the next best thing is to use the powdered root. The dose is 8 g as a tea, 3 times a day.

Detoxification and You

Human beings are not created biochemically alike. Everyone has a liver and a gallbladder; all livers and gallbladders are designed to do the same work; but not all livers and gall bladders work the same. Some of us are genetic warriors, naturally equipped to stay up all night, drink alcohol, eat whatever we like, smoke, work brutal hours under tremendous stress, and even so die peacefully in our sleep at the age of ninety-five. But for others, not born with a hardy, resilient constitution, such a lifestyle is a prescription for poor health and an early death. Despite the fact that advertisements for everything from painkillers to breakfast cereals create the impression that what's good for one is good for all, there is really a large range of variability in how we function metabolically and what we need.

Genetic biocapabilities determine, to a large extent, our ability to handle the onslaught of environmental toxins. Each of us faces the physical, mental, and emotional stresses of life equipped with a unique molecular system characterized by its own inherent weaknesses and strengths. These genetic biocapabilities determine, to a large extent, our ability to handle the onslaught of environmental toxins. For example, much of the variability in the activity of both the glutathione and sulfation pathways is inherited. Your inborn capacity to manage toxins creates the climate in which either health or disease will flourish. A family history of estrogen-related breast cancer, smoking-induced lung cancer, and other types of cancer can be related to inherited weaknesses of detoxification capability.

These genetic differences are a result of the wide variance in how detoxifying enzymes in the liver express themselves. The term to describe this is metabolic polymorphism. This means that there is a variety (poly) of forms (morphism) that humans have in detoxifying their environment (metabolic).

In the book entitled Genome, authors Jerry E. Bishop and Michael Waldholtz, propose that genetic susceptibility factors should be the major focus of medicine in the future. This, they suggest, would make it possible to modify the environment appropriately to protect individuals against diseases related to genetic polymorphism. Yet hereditary variations in the biochemical breakdown and transformation of toxins is still one of the most undervalued and under-utilized areas of prevention and treatment.

Medical doctors could be individualizing health care plans and minimizing risks using laboratory tests (described in Chapter 7) to assess detoxification functions. This screening process would identify those individuals who have very strong detoxification abilities as well as those who require special help to discourage the onset of disease. Not taking genetics and detoxification abilities into consideration sets the stage for illnesses that are preventable.

It is possible to minimize the impact of our biological weak links. The "Achilles' Heel" that's encoded in our DNA that makes each of us more susceptible to certain stressors can be countered by our daily lifestyle choices and compensated for with nutritional medicine and detoxification support. Naturopathic doctors have many ways to stimulate the liver, for example, using herbs, special diets, physiotherapy, and homeopathic medicines.

Treatment of gall bladder disease frequently includes the same herbal medicines that are used for liver detoxification problems. If you have an inherited weakness in these organs, the EcoTox program will help. It is designed to stimulate the liver and gall bladder, as well as the proper digestion of foods and nutrients necessary for their activity. In the following chapter, you'll learn more about the sources of toxins that place such a heavy burden on the liver, and the toll they take on your health.

To learns more about detoxification visit http://www.detox.org/