DIETARY-EFFECT ON MIXED-FUNCTION P450 1A2 ACTIVITY ASSAYED BY ESTIMATION OF CAFFEINE METABOLISM IN MAN

Two studies were performed in order to evaluate cytochrome P450 1A2 me diated caffeine metabolism during different nutritional conditions. 1 In the first study, 23 healthy male non-smokers, mean age 25, changed from a customary mixed diet to a standard diet in 6 days. The 6 day's standard diet was based on bread, potatoes, rice and boned meat. Thus, broccoli, cabbage and other cruciferous vegetables, spinach, leeks, o nion, parsley, grapefruit, toasted bread, fried and charcoal grilled f ood, smoked fish and meat, ham and sausages were avoided. 2 In the sec ond study, 33 healthy non-smoking subjects, 24 men and nine women mean age 25 years, volunteered. The study was designed to compare a custom ary home dietary period with the 6 day period of low dietary P450 indu ction and with a 5 day supplementary dietary period, i.e. ingestion of known dietary inducers. None of the women were using oral contracepti ves or were pregnant during the experimental period. In the period of diet supplementation, the volunteers received charcoal grilled hamburg er as a supplement to the standard low induction diet for lunch for 5 days. The hamburgers were made with 150 g beef (18-20% fat) and were g rilled on charcoal for 10 min on each side until they were 'well done' . In the present study P450 1A2 activity was estimated from the caffei ne metabolic ratio, the so-called CYP 1A2 index:(AFMU + I-MX + 1-MU/ 1 7 -DMU) of the caffeine metabolites formed after oral ingestion of 200 mg caffeine. Urine was collected 4-8 h after caffeine ingestion in st udy 1 and 5 h after caffeine ingestion in study 2. In study 1 the CYP 1A2 index decreased from 4.28 +/- 0.98 in the customary home dietary p eriod to 3.87 +/- 0.69 in the standard dietary period corresponding to 10.6% (P < 0.06) decrease in the CYP 1A2 index. In study 2 the CYP 1A 2 index decreased from 4.47 +/- 1.76 in the customary home dietary per iod to 3.90 +/- 1.12 in the standard dietary period corresponding to a 14.6% decrease (P < 0.2) in P450 1A2 activity. The female subjects ha d a mean index value of 3.89 +/- 1.14 which was 16.8% (P = 0.09) lower than the mean male index value of 4.68 +/- 1.76 during the home dieta ry period. After the 5 day period with charcoal grilled hamburgers as a dietary supplement, the CYP 1A2 index increased to almost the same l evel as in the customary home dietary period. The index increased to 4 .45 +/- 1.57 in the whole group of volunteers, corresponding to a 14.1 % (P < 0.05) increase. The mean increase in the CYP 1A2 index covered a large inter-individual variation in response to ingestion of charcoa l grilled meat ranging from a 29% decrease to a 147% increase.