Haem, not protein or inorganic iron, is responsible for endogenous intestinal N-nitrosation arising from red meat.

Many N-nitroso compounds (NOC) are carcinogens. In this controlled study of 21 healthy male volunteers, levels of NOC on a high (420 grams) red meat diet were significantly greater (P = 0.001) than on a low (60 grams) meat diet but not significantly greater when an equivalent amount of vegetable protein was fed. An 8-mg supplement of haem iron also increased fecal NOC (P = 0.006) compared with the low meat diet, but 35-mg ferrous iron had no effect. Endogenous N-nitrosation, arising from ingestion of haem but not inorganic iron or protein, may account for the increased risk associated with red meat consumption in colorectal cancer.

Effect of white versus red meat on endogenous N-nitrosation in the human colon and further evidence of a dose response.

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.