Effect of White Versus Red Meat on Endogenous N-Nitrosation in the Human Colon and Further Evidence of a Dose Response

Abstract

N-nitroso compounds are found in the colon and are formed endogenously because amines and amides are produced by bacterial decarboxylation of amino acids in the large gut. They can be N-nitrosated in the presence of a nitrosating agent. To test the hypothesis that increased nitrogenous residues from red meat would increase endogenous N-nitrosation, thus accounting for the epidemiologic association between red meat consumption and colorectal cancer, we fed increased levels of red meat and measured apparent total N-nitroso compounds (ATNCs) in fecal samples in a series of studies of volunteers maintained under controlled conditions. A result of these studies is that we have shown a consistent dose response to red meat consumption. Fiber, in the form of vegetables, bran or resistant starch, does not reduce the level of ATNCs formed, although transit time is reduced and fecal weight are increased. Here we show that the equivalent amount (420-600 g) of meat as white meat has no effect on fecal ATNCs in 12 volunteers (P = 0.338). At dosages of 0, 60, 120, 240 and 420 g of red meat/d, mean levels of ATNC output are highly correlated with dose of meat: for concentration ATNC versus dose of meat in g/d, r = 0.972, beta = 0.252 ng/g (SE 0.035); for total ATNC output versus dose of meat in g/d, r = 0.963, beta = 2.605 microg/d (SE 0.419). The effects of nonmeat protein and of heme on increased N-nitrosation and the genotoxic effects of the ATNCs produced are presently being investigated.