Nutrition and oxidative drug metabolism in man: Relative influence of dietary lipids, carbohydrate, and protein

Effects of an increase in dietary lipid content relative to protein or carbohydrate, and consequences of an alteration in dietary fatty acid composition on oxidative metabolism of drugs in man were examined. Two studies were carried out in healthy subjects fed carefully controlled solid food diets. In the first, the isocaloric substitution of fat for carbohydrate produced little or no statistically significant change in the mean plasma half-lifes (t 1 2s), apparent volumes of distribution (aVD), or metabolic clearance rates (MCR) of antipyrine (t 1 2, 12.3 ± 0.5 hr and 11.7 ± 0.6 hr on the high carbohydrate and high fat diets, respectively) or theophylline (t 1 2, 7.9 ± 0.4 hr on both diets) after periods of 10 to 14 days on each diet; but when intake was changed to a high protein diet metabolism rates for both drugs were greater than on either the high fat or the high carbohydrate diet in that mean plasma antipyrine t 1 2 decreased to 9.9 ± 0.5 hr and theophylline 1 2 to 5.8 ± 0.3 hr, with increases in MCR for both drugs. In the second study, which was carried out with 9 subjects on high fat and high carbohydrate diets, the isocaloric substitution of either saturated fat (butter) or polyunsaturated fat (corn oil) for carbohydrate (without changing total protein content) produced no significant changes in rates of metabolism of these drugs, whereas the alterations in dietary fatty acid composition produced expected changes in plasma concentrations of cholesterol and triglycerides. Our observations suggest that protein, when substituted for either dietary carbohydrate or lipid, has a clear inducing influence on oxidative drug metabolism in man, and the degree of fatty acid unsaturation has little or no effect on rates of metabolism of these drugs despite marked changes in plasma lipids.