Metabolic Tests / The Comprehensive Detoxification Profile

submitted by Dr. Gary Farr Last Updated August, 29, 2005

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What Does This Test Involve?

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.

What Are The Consequences Of Impaired Detoxification?

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.

Detoxification-intestinal permeability relationship

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.

Using the Detoxification Profile

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.

Interpreting the Detoxification Profile

Findings commonly found in the standard version of this test include:

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.

Findings commonly found in the comprehensive version of this test include:

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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