Dietary sources of iron and vitamin B12: Is this the missing link in colorectal carcinogenesis?

Colorectal cancer (CRC) is distinctive for its strikingly high correlation with the diet. Heme-iron from red and processed meat was found to strongly increase the risk of CRC, yet only 20% of the total dietary iron is heme-iron. However, the results are still inconclusive in terms of the total dietary iron and CRC risk. On the other hand, vitamin B12 has been proposed as cytoprotector, and iron and vitamin B12 share their dietary sources. Meat and animal-derived products are the only foods that naturally provide vitamin B12. While iron is abundant in a variety of foods, its bioavailability (i.e. utilization) is the highest from meat and animal foods. We hypothesize that specific combinations of foods of animal origin could alter the risk of CRC, and even modulate the progression of CRC, by simultaneously altering iron and vitamin B12. All cells are iron dependent but iron's metabolism is one of the most complex, and tightly regulated. No nutrient has so many dietary factors that inhibit its bioavailability which results in almost 80% of all dietary iron ending in the feces, which is 10-fold higher than in most tissues. Luminal exposure to iron, which was found to affect crypt fission and increases the risk of CRC, is influenced by colonic transit time, the composition of feces, and the pH in the large bowel. Therefore, "inactivating" iron in the feces by specific dietary inhibitors disables adverse alterations during the luminal exposure. Only one inhibitor has the ability to bind both forms of iron, heme and non-heme to insoluble complexes, calcium. Milk and dairy as the best dietary sources of calcium contain vitamin B12 of the highest bioavailability. While calcium (both dietary and supplemental) has been studied separately on the risk of CRC, it has not been considered from the aspect of iron bioavailability or supplying vitamin B12. Preliminary, the hypothesis was tested on the diet quality assessment in adults from two Croatia's regions with distinctive dietary characteristics and CRC risk. Diet in the first region is considered to increase the risk of CRC (e.g. high intake of red and processed meat), while a traditional Mediterranean pattern prevails in the second region. However, CRC incidence rate is higher in the second region. Comparison of the regions showed that in the first region adults have significantly higher intake of vitamin B12, and as expected, the highest contribution is from meat. Still, the contribution of milk and dairy is significantly higher in the first than in the second region. These results suggest that high intake of vitamin B12 could have a protective role on CRC, when dietary intake of meat is high. Therefore, by specifically designing a diet to combine dietary sources with high content of both iron and vitamin B12 could result with a cumulative effect: the cytoprotective effect of vitamin B12, and diminished negative effect of high iron content in the feces. Clarifying the relevance of various dietary sources of iron from the aspect of high vitamin B12 content might provide answers we are still missing in the CRC.