Systematic Reviews of Current Literature Fail to Establish Dietary Benzo[a]pyrene, Heterocyclic Aromatic Amines, or Heme Iron as Mechanisms Linking Red and Processed Meat Consumption with Cancer Risk

Dietary exposure to potentially high‐risk compounds such as heterocyclic aromatic amines (HAAs) or the polycyclic aromatic hydrocarbon, benzo[a]pyrene (BaP), formed in meat during cooking, or from exposure to hemeiron naturally occurring in meat, have all been proposed as possible mechanisms responsible for the reported weak association between red and processed meat consumption and increased cancer risk in observational studies. In this study, a systematic review of the mechanistic literature was used to examine the available evidence‐base to determine if sufficient evidence exists to link heme iron, BaP, or HAAs from red and processed meat to increased cancer risk. Inclusion criteria required that study designs accommodate exposure from a whole food or in the context of a well‐described diet and that outcomes adequately represent normal physiology of the tissue of interest. Results regarding dietary Ba Prevealed, of 51 studies published since 2000, only 4 met the full criteria for inclusion. The primary reasons for study exclusion were a failure to evaluate effects of BaP administered orally or as part of a diet and a failure to adequately represent non‐cancerous tissue physiology. Regarding dietary HAAs, of 294studies published since 2000, 29 publications met the full criteria for inclusion. Only 3 of the included studies utilized an animal model to investigate HAA intake from foods or as part of a well‐described diet and only one type of HAA was evaluated in the included animal studies. In the human studies there was near‐exclusive use of a single, non‐comprehensive database, rather than actual and/or direct analytical measurement of dietary HAAs. And regarding dietary heme iron, of 210 search results since 2000, only 13publications met the full criteria for inclusion. The type of heme iron supplemented in animal diets, as surrogates for naturally occurring heme iron, were found to independently affect the outcomes in some studies. The use of hemeiron surrogates has not been systematically validated against naturally occurring heme iron. For all compounds, the exclusive use of carcinogen‐treated animals was questioned as well as the use of in vitro cytotoxicity assays as surrogates for normal colon physiology. In each case, evidence was found to be weak and inadequate in both humans and animals concerning the mechanistic relationship between the dietary exposures of BaP, HAAs, or heme iron and human cancer. Support or Funding Information Support from the Beef Checkoff