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 microg/day when the diets contained no meat, 52 +/- 11 microg/day when the diets contained 60 g meat/day, 159 +/- 33 microg/day with 240 g meat and 199 +/- 36 microg/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 promotors 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.
Hughes
R
R
Medical Research Council, Dunn Human Nutrition Unit, Welcome Trust/MRC Building, Hills Road, Cambridge CB2 2XY, UK.
Cross
A J
AJ
Pollock
J R
JR
Bingham
S
S
D000328:Adult; D000818:Animals; D002417:Cattle; D003106:Colon / Q000378:metabolism*; D018592:Cross-Over Studies; D004032:Diet; D005243:Feces; D006801:Humans; D008297:Male; D008460:Meat / Q000009:adverse effects*; D008875:Middle Aged; D009573:Nitrites / Q000378:metabolism; D009584:Nitrogen / Q000652:urine; D009603:Nitroso Compounds / Q000009:adverse effects / Q000378:metabolism*; D013552:Swine
D009573:Nitrites; D009603:Nitroso Compounds; D009584:Nitrogen