The Comprehensive Detoxification Profile

Why are toxins serious? It is estimated that 60 to 80 percent of all cancers are a direct result of chemicals in our air, water and food. Further, neuroscientists are now studying the role of environmental toxins in the development of neurological disorders such as Alzheimer's and Parkinson's diseases, and in mental/behavioral disorders such as depression, anxiety, schizophrenia and attention deficit disorder. Toxins that directly affect the nervous system are called neurotoxins. Since the nervous system is intricately connected to the immune system, neurotoxins also affect our immune functions. Thus, our very ability to think and feel normally can be drastically affected by exposure to toxins. It does not take a giant leap of logic to realize that we could soon be in such a state of toxic poisoning that we would be unable to "problem-solve" our way out.

Chronic health problems can develop from your body's impaired detoxification ability. Uncover the link between your symptoms and your liver function.

What role does the liver play in detoxification? The liver is a key organ in your body's self-defense system. It changes, or detoxifies, many harmful substances into forms which your body can safely eliminate.

In today's world of processed foods and pollution, toxic substances exist almost everywhere. They are in the food you eat, the water you drink (from fertilizers, chemicals and other additives such as colorings and preservatives), and the air you breathe (from automobile emissions, pesticides and industrial pollutants). Some of the body's own compounds must be detoxified as well.

A healthy liver uses two mechanisms, called Phase I and Phase II detoxification, to remove toxins. In Phase I, your body's enzymes activate toxic substances to make them more accessible to Phase II. In Phase II, other enzymes convert toxins to more water-soluble forms, which your body eliminates through urine or stool.

An unhealthy liver does not detoxify substances as rapidly or as completely as a healthy liver. Slower detoxification results in more toxic substances circulating in the body. Unchanged or partially changed toxins are not easily eliminated and instead pass from the liver into the body. Eventually, the toxins are stored in fatty body tissue, including the brain and central nervous system cells. Stored toxins may be slowly released into the blood, contributing to many chronic illnesses.

A number of conditions affect how well the liver performs its detoxifying duties. Repeated exposure to chemicals and toxins in food, water and the environment increases the detoxification burden.

If you have a "leaky gut," your intestine allows large, undigested molecules to pass into the body. Increased amounts of toxic substances can travel through the liver and overload its capacity to detoxify them.

One method to assess the liver's detoxifying ability is to examine the overall state of your health. Toxic substances are contributing factors in a wide range of health problems.

You may have heard of several different liver tests (such as liver enzyme analysis) which look for clinical evidence of existing liver damage. Standard "liver function" tests measure levels of enzymes such as SGOT and SGTT. Unfortunately, by the time these tests register "abnormal," liver damage is already present.

A definitive assessment of function can be made using the Detoxification Profile. This test uses common substances to challenge the liver's detoxification ability using urine and saliva samples. You simply swallow the tablets, collect urine and saliva specimens, and return the test kit to Great Smokies Diagnostic Laboratory. The specimens are analyzed, and the results are sent to your health care professional. The specific results can be used to develop a treatment plan. In addition to detoxification testing, your health care professional may want to test your level of oxidative stress. Impaired liver function can lead to higher levels of free radicals, substances in the blood which have been linked to chronic illness. Analysis of a blood and/or urine sample provides important information about damage resulting from a dysfunctional liver.

Talk to your health care professional about your symptoms and ask if a Detoxification Profile from Great Smokies Diagnostic Laboratory would be useful for you. Your body's natural self-defense system may be overwhelmed by toxins in food, water and air. Take this quiz to determine your level of toxic exposure and its effect on your body.

If you answered Yes to two or more of these questions, you may be reacting to increased toxic exposure and burdening your body's detoxification ability.

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The Comprehensive Detoxification Profile analyzes saliva, blood, and after-challenge doses of caffeine, aspirin, and acetaminophen in order to assess the Phase I and Phase II functional capacity of the liver to convert and clear toxic substances from the body. This profile includes markers for oxidative stress and important antioxidants. The standard profile analyzes saliva and urine to assess the Phase I and Phase II functional capacity of the liver to convert and clear toxic substances from the body.

In the Comprehensive version of this profile, the urine specimen is analyzed for levels of lipid peroxides. In addition, various oxidative markers are assessed from fasting blood specimens taken the morning after the challenge. These tests are sensitive indicators of biological detoxification status.

Our bodies must be able to detoxify xenobiotics (environmental toxins), endotoxins (gut-derived toxins), endogenous hormones (hormones produced by the body), and other phenolic compounds. This test reflects the degree of toxin exposure and the body’s ability to handle this load. When the two phases of detoxification are out of balance, our bodies are more prone to illness. This test is the only means of assessing this balance. An insufficiency of critical nutrients required for detoxification results in an increased toxic burden on the body and illness. This test can assess the demand upon, and the availability of, these nutrients.

All ingested and microbially-produced toxins are presented to the first-pass clearance system. First-pass clearance involves the biotransformation and clearance of a chemical from the body before it reaches the systemic circulation. This clearance may take place in several organ tissues including the wall of the intestines and the liver.

The liver is the body's primary detoxifying organ. Here, detoxification is carried out in two related processes known as Phase I and Phase II. Phase I serves to break down toxic substances through a process that utilizes what is known as the cytochrome P450 enzymes. This process increases the solubility of molecules and prepares them for Phase II reactions which will further increase their solubility.^4-8

The Phase I reactions are necessary for detoxification, but the resulting production of reactive oxygen species can at times be very damaging. Thus, the liver needs to be able to generate oxidation capacity when needed, yet at the same time generate no more than what is needed. Perhaps this is why Phase I systems are inducible by different compounds.

In Phase II, conjugation reactions add a polar hydrophilic molecule to the metabolite or toxin, converting lipophilic (attracting fat) substances to water-soluble forms for excretion and elimination. Phase II reactions may follow Phase I for some molecules or act directly on the toxin or metabolite. Major Phase II pathways include glutathione, sulfate, glycine, and glucuronide conjugations.9 Individual xenobiotics and metabolites usually follow one or two distinct pathways. While the modification of Phase I and II enzyme activities has its basis in the research setting, there is growing appreciation of the clinical applications of such strategies.

Although exhaustive clinical studies have yet to be performed, we have the biochemical and logical basis upon which to recommend interventions in order to help patients with evidence of chemical sensitivity or high exposures to toxic compounds.^10-12 It should be noted, however, that nutritional modification of the P-450 and/or conjugation pathways has strong potential to change drug metabolism. Due to this potential metabolic impact, practitioners should use caution and awareness when recommending such strategies in patients taking prescription medications.¹³

Assessment of the metabolic status of these major detoxification processes assists with our understanding of the body's capacity to detoxify foreign substances. (See Figure 1 below.) ^4-8

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Saliva samples are collected following the ingestion of a pre-measured amount of caffeine, urine is collected following the ingestion of aspirin and acetaminophen, and, depending upon the profile selected, a blood draw may be required. The report includes caffeine clearance (Phase 1 activity), conjugates of four Phase 2 detoxification pathways, ratios of Phase 1 to Phase 2, and, depending upon the profile selected, plasma cysteine and sulfate, a cysteine/sulfate ratio, reduced glutathione, superoxide dismutase, glutathione peroxidase, and markers for free radical activity.

Toxic exposure results in free radical production which can be damaging to the body as antioxidants are depleted. This can result in disorders such as arteriosclerosis, allergies, inflammatory joint disease, neurological diseases, fibromyalgia, and chronic fatigue. An increased exposure to toxins can deplete glutathione, sulfate, and other critical nutrients used in detoxification. The resulting accumulation of toxic intermediate metabolites can contribute to chronic fatigue, environmental sensitivities, or other chronic illnesses.

The intestinal mucosa is the primary barrier to permeation of toxic compounds and macromolecules. Abnormalities of the intestinal barrier system as detected by intestinal permeability assessment may lead to enhanced uptake of inflammatory luminal macromolecules, endotoxins and xenobiotics. Impairment of intestinal integrity dramatically increases mucosal absorption of substances that are normally excluded.

These foreign chemicals are presented to the liver's detoxifying system for processing and elimination. They can stress the detoxification capability of the liver or be partially processed and accumulate in the liver and adipose tissue. It has been speculated that the combination of leaky gut and dysfunctional liver detoxification can lead to increased tissue stores of toxic compounds and depressed immune status.

Substances which may induce P-450 enzymes

• Acetate
• Alcohol
• Barbiturates
• Carbon Tetrachloride
• Charcoal-broiled meats
• Dioxin
• Exhaust fumes
• High protein diets
• Niacin
• Oranges
• Organophosphorus pesticides
• Paint fumes
• Riboflavin
• Sassafras
• Saturated fats
• Steroid hormones
• Sulfonamides
• Tangerines

In the Detoxification Profile, one caffeine caplet (200 mg) is taken in the morning and its clearance is assessed from two salivary specimens collected two and eight hours after ingestion.

Aspirin and acetaminophen are ingested in the evening and the products of detoxifying reactions are assessed in a 10-hour overnight urine specimen. The challenge dose consists of two capsules of aspirin (650 mg total) and two capsules of acetaminophen (650 mg total). The only side effect is potential drowsiness.

In the Comprehensive version of this profile, the urine specimen is analyzed for levels of lipid peroxides. In addition, glutathione, glutathione peroxidase, superoxide dismutase, plasma cysteine, and plasma sulfate are assessed from fasting blood specimens.

Low caffeine clearance (Phase I): Indicates slow P-450 enzyme activity and metabolic detoxification difficulty; may also reflect use of medications such as amphetamines, cimetidine, and oral contraceptives.

High caffeine clearance (Phase I): Reflects excessive P-450 enzyme induction, possibly due to toxin exposure; also implies greater production of free radicals.

Low acetaminophen mercapturate, salicyluric acid, acetaminophen sulfate or acetaminophen glucuronide (Phase II): Indicate inadequate Phase II conjugation reactions. Low levels may reflect depletion of the particular amino acids or nutrient cofactors used in the reactions, or diminished enzymatic capacity for conjugation.

Elevated Phase I/Phase II ratios: May reflect elevated (induced) Phase I processes or diminished Phase II conjugation reactions. The ratio of Phase I to Phase II detoxification processes is important in determining the toxicity of certain drugs, and these ratios may be significant indicators of the balance of biological processes.

Elevated plasma cysteine/sulfate ratio: Suggests possible impairment of the sulfoxidation reaction that converts cysteine to the inorganic sulfate required for sulfation. Elevated ratios have been noted in neurological disorders such as Parkinson's disease, Alzheimer's, and motor neuron disease.

Elevated plasma cysteine: Indicates sulfoxidation impairment, other blocks in cysteine metabolism, excess intake of cysteine and related molecules, or excessive catabolism. Checking the levels of plasma sulfate and glutathione provides further information.

Depressed plasma sulfate: Suggests sulfoxidation impairment, especially when plasma cysteine is elevated. Organic sulfate precursors such as L-cysteine, N-acetyl cysteine, or glutathione may be contraindicated in these cases.

Low reduced glutathione: Suggests low amount of glutathione available for removal of toxic intermediates, generation of cysteine and sulfate reserves, and antioxidant activity.

Low glutathione peroxidase (GSH-Px): Implies inadequate defense against accumulation of oxidized lipids in cell membranes. Low levels are found in conditions such as Down's syndrome, Alzheimer's dementia, and beta-thalassemia minor and may indicate insufficient nutrient cofactors.

High/low superoxide dismutase (SOD): Decreased in conditions associated with inflammation, impaired glucose metabolism, and zinc deficiency. High levels occur in systemic sclerosis, myositis and malignant melanoma, and may also indicate exposure to agricultural pesticides.

Elevated Urine Lipid Peroxides: Suggest increased cellular lipid peroxidation and the need for antioxidant protection of body lipids.

High Hydroxyl Radicals: Indicate the potential for oxidative damage, such as that occurring in the pathogenesis of diabetes and other illnesses. May also reflect the presence of an inflammatory process.

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