Phase II reactions involve a chemical reaction called conjugation, in which fat-soluble substances formed in Phase I or present independent of Phase I are combined with certain substances to form water-soluble compounds. To carry out these conjugating reactions, the liver uses glutathione, sulfate, glycine, acetate, cysteine and glucuronic acid molecules. If some of these substances are lacking, then phase II reactions may be impaired, resulting in what is called a pathological detoxifier situation.
The important thing here is that with relatively simple tests, one can determine how well each phase of liver detoxification is working. Then appropriate therapeutic measures may be taken to correct the problem, improve liver detoxification and thus improve the health of the patient.
Tests to Assess Liver Detoxification and Some Therapeutic Measures
The Functional Liver Detoxification Profile uses two common challenge substances to evaluate liver detoxifying ability. Caffeine, which is acted on by P-450 enzymes, is used to assess Phase I. Sodium benzoate, a common food additive, is used to assess Phase II, since it is conjugated with glycine to produce hippuric acid. The patient can carry out the testing procedure at home with the help of a testing kit. Samples collected by the patient are sent to a certain laboratory for measurements of caffeine and hippuric acid. The test results and interpretation are sent to the ordering physician. The patient drinks a known amount of caffeine and benzoic acid solution. Subsequently, during the next few hours, the patient collects a saliva specimen to measure the caffeine and a urine specimen to measure the hippuric acid.
If the caffeine is relatively high, this indicates an overactive phase I due to enzyme induction, probably due to exposure to internal or external toxins. This also suggests potential increase free radical production due to excessive P-450 activity. A low caffeine clearance indicates slow dysfunctional P-450 enzyme activity. This suggests metabolic difficulty in removing toxic chemicals from the system. So, the caffeine clearance helps us to understand the status of Phase I liver detoxification.
A slow conversion of benzoate to hippurate after the sodium benzoate challenge is indicative of inadequate Phase II detoxifying reactions. A high hippurate level in the urine has no pathological significance and probably indicates that phase II detoxification is adequate. An elevated caffeine clearance to benzoate conversion ratio indicates increased liver cytochrome P-450 activity relative to phase II conjugation with glycine. These individuals have been termed "pathological detoxifiers." A reduced caffeine clearance to benzoate conversion ratio indicates decreased liver cytochrome p-450 activity relative to the glycine conjugation. These individuals have been termed "slow detoxifiers."
The treatment of these imbalances are different. For example, when Phase I is increased, attempts should be made to reduce the drug, chemical or toxic load and antioxidants, such as Vitamins A, C, E, beta carotene flavonoids, pycnogenol and selenium should be supplemented. When the Phase I system is decreased, a nutritional detox program is usually recommended with biochemical liver support such as milk thistle herbs and lipotropic nutrients like choline, inositol and methionine. When Phase II conversion is slow, liver support is also helpful, along with conjugating nutrients, which are likely in short supply. These include glycine, glutathione, N-acetyl cysteine, glucuronic acid, taurine and others. It is important to understand the status of the liver detoxification system because if for example you use the treatment to upregulate Phase I when Phase II is inadequate, then the patient may get worse. With proper understanding, an intelligent treatment program may be planned.