TABLE 3.

Examples of the impact of specific nutrients on Phase 1/MFO metabolism¹

Nutrient	Effect on MFO metabolism	Potential mechanism(s)
Protein	Deficiency: ↓ rate of metabolism	↓ Protein synthesis; ↓ in synthesis of other elements, such as hormones, involved in enzyme induction
Excess: can ↑ rate of metabolism
Lipids	Deficiency (or diet high in saturated fatty acids): ↓	↓ Activity of MFO possibly connected to the requirement for polyunsaturated fatty acid in the β-position of phosphatidylcholine (lecithin), which is an essential component of the MFO system
Excess (or diet high in polyunsaturated fatty acids): ↑ activity and induction of MFO enzymes
Carbohydrates	Excess: ↓	Secondary effect due to ↓ protein or possibly inhibition of P450 via ↓ in supporting enzyme components
Vitamin C	Deficiency: ↓	Alterations in activities of P450 and P450 reductase mediated via either ↑ or ↓ in the expression of specific CYP isozymes in excess or deficiency states
Excess: ↑ P450 activity
Vitamin B-6	Deficiency: ↓	↓ Synthesis of heme; possible impairment of protein synthesis
Thiamine	Deficiency: ↑ activity of cytochrome P450	↑ Activity of specific P450 isozymes and perhaps other enzymes in deficiency by an unknown mechanism. Excess may be due to ↓ substrate binding
Excess: ↓ (both reductase and P450)
Riboflavin	Deficiency: ↓ or ↑ depending on the severity	↓ Reductase activity but ↑ P450 activity, such that the metabolism of some drugs will be ↑, whereas others may be ↓
Vitamin E	Deficiency: ↓	Because activities of P450 and reductase are unaffected, it may be due to reduction in antioxidative mechanisms (eg, protection of the lecithin component): lack of effect from excess may be due to rapid metabolic clearance of vitamin E isomers via P450 (3)
Excess: no reported effect
Iron	Deficiency: ↓ and ↑	Differential effects on various components of the MFO system. ↑ Lipid peroxidation could lead to damage to the integrity of the system
Excess: ↑ in microsomal lipid peroxidation

¹Reproduced with permission (2). MFO, mixed-function oxygenase.