Phase 1 Detoxification

In general, phase 1 detoxification arises from the function of a group of some 50-100 enzymes referred to as cytochrome P450. The healthy functioning of this pathway depends upon an individual's nutritional status, genetics, and level of exposure to chemical toxins. Thus, an individual's risks of developing disease states arising from insufficient detoxification varies greatly. Indeed, this can explain the great variability in patients' susceptibility to, and manifestation of, disease processes such as cancer from environmental pollutants, such as smoking.

Clinical evaluation of a patient's risk entails a twofold consideration: (1) that of total toxin load and (2) that of his or her ability to process the exposure. Phase 1 detoxification becomes less active with aging. Complicating this decreased function is that blood flow through the liver also diminishes with age. Not surprisingly, there is an increased susceptibility to adverse drug reactions among older adults, whose detoxification capabilities have diminished. Studies have shown a fivefold variability of phase 1 functioning among healthy individuals.7 In light of this range of activity, there is also a significant oscillating need for antioxidant protection, because each toxin that is processed via phase 1 detoxification generates a free radical that either requires quenching or neutralization by phase 2 conjugation. Thus, phase 1 and phase 2 processing must be kept in balance to prevent the accumulation of highly reactive intermediates and to minimize the requirement for antioxidants to protect against free radicals. Many drugs, foods, nutrients, and chemicals can cause phase 1 and phase 2 detoxification processes to become desynchronized. Factors that affect the efficiency of phase 1 and phase 2 detoxification processes are summarized in Table 9-3.

There are clearly numerous substances that both affect induction and inhibition of these pathways positively and negatively.

When grapefruit or grapefruitjuice rich in naringenin is consumed while a patient is taking certain medications, there can be potentially serious deleterious consequences; for example, this could happen in the case of nifedipine.8

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