A hypothesis: Interaction between supplemental iron intake and fermentation affecting the risk of colon cancer. The Iowa women's health study

Fermentation in the large intestine can increase absorption of ferrous iron, which is the main form in supplements, because the solubility of ferrous iron is enhanced in the mildly acidic environments caused by fermentation. We therefore hypothesized that higher supplemental iron intake would increase the risk of colon cancer among those who consume large amounts of fermentable substrates, namely, dietary fiber and resistant starch. Among 34,708 postmenopausal women, supplemental iron was unrelated to proximal colon cancer in all women and to distal colon cancer among those consuming below the median of fermentable substrates. However, supplemental iron was positively associated with distal colon cancer among women who consumed above the median of fermentable substrates (P for interaction < 0.01); the adjusted relative risks across categories of supplemental iron (0 g/day, 1-19 g/day, 20-49 g/day, and greater than or equal to50 g/day) were 1.0, 1.24, 1.78, and 3.78 (P for trend < 0.01). This hypothesis needs confirmation in other cohort studies because, despite the significant trend, only nine cases were included in the top category of greater than or equal to50 mg supplemental iron, and this finding could have arisen by chance.