Dose-dependent effect of dietary meat on endogenous colonic N-nitrosation

Human male volunteers were studied in a metabolic facility whilst they were fed randomized controlled diets. In eight volunteers there was a significant increase in faecal apparent total N-nitroso compounds (ATNC) and nitrite excretion (P < 0.0001 and P = 0.046, respectively) when randomized doses of meat were increased from 0 to 60, 240 and 420 g/day over 10 day periods. Mean (+/- SE) faecal ATNC levels were 54 +/- 7 <mu>g/day when the diets contained no meat, 52 +/- 11 mug/day when the diets contained 60 g meat/ day, 159 +/- 33 mug/day with 240 g meat and 199 +/- 36 mug/ day with 420 g meat, Higher concentrations of NOC were associated with longer times of transit in the gut (r = 0.55, P = 0.001) and low faecal weight (r = -0.51, P = 0.004). There was no significant decline in levels in individuals fed 420 g meat for 40 days. The exposures found on the higher meat diets were comparable with other sources of N-nitroso compounds (NOC), such as tobacco smoke. Many NOC are known large bowel initiators and promoters in colon cancer, inducing G-->A transitions in codons 12 and 13 of K-ras, Endogenous NOC formation, combined with prolonged transit times in the gut, may explain the epidemiological associations between high meat/low fibre diets and colorectal cancer risk.