Iron is involved in the entire process of respiration, including oxygen transport and electron transport. It is essential to the synthesis of hemoglobin. Iron is also considered to have a role in immune function, DNA synthesis and brain development.Deficiency may cause anemia (the most common nutritional disorder in the world), while excessive amounts may result in cirrhosis, heart disease and cancer. Rich sources are red meat, liver, eggs, seafood (tuna, salmon), legumes (wheat, oats, lentil), green vegetable (spinach, broccoli). Recommended daily allowance is 6-15 milligrams/day based on age. (For more detailed information, please visit ISM’s searchable database: Nutraceutical Search.)
Iron can react with citric acid, interfering with the Krebs cycle, hence with oxidative phosphorylation. Free iron (Fe) can cause considerable oxidative damage both through Fenton reactions and by activating xanthine oxidase, which produces both superoxide (O(2-)) and uric acid (abundant in many cancers). It can also react with lactic acid, reducing its elimination and increasing the acidity of the cytoplasm. Fe can also wreak havoc by reacting with tryptophan, the least abundant and most delicate essential amino acid, which is necessary for the production of serotonin and other substances required by the immune system to fight cancer. On the other hand, in the presence of iron, the tryptophan metabolite quinolinate causes intense lipid peroxidation. Similarly, several other carcinogenic metabolites of tryptophan are particularly dangerous in the presence of Fe. Excess Fe may also interfere with manganese superoxide dismutase and impair the initiation of apoptosis by the mitochondrion, rendering the cells impervious to all the signals to undergo apoptosis from without and from within the cell. Moreover, Fe may also play a crucial role on telomere repair, by activating telomerase. Therefore, by inhibiting apoptosis and enhancing chromosome repair, Fe may bestow immortality upon the cancer cell. Furthermore, Fe is one of the triggers for mitosis. Therefore, increased Fe levels may be essential for the rapid growth characteristic of many malignancies. In turn, the rapid growth further depletes resources from the healthy tissues, exacerbating the deficiencies of the other elements and reducing the ability to fight the malignancy. [Med Hypotheses. 2001 Nov;57(5):539-43.]
Because of evidence that increased body iron stores are associated with an increased risk of cancer, we examined iron status and cancer risk in the first National Health and Nutrition Examination Survey, a survey of more than 14,000 adults begun in 1971, with follow-up between 1981 and 1984...These results are consistent with the hypothesis that high body iron stores increase the risk of cancer in men. The possibility that a similar association exists in women requires further study. [Stevens, RG, Jones, DY, Micozzi, MS, & Taylor, PR (1988). Body iron stores and the risk of cancer. New England Journal of Medicine, 319(16), 1047-52.]
Oxidative stress resulting from excess reactive oxygen species and/or deficiencies in antioxidant capabilities may play a role in breast cancer etiology. In a nested case-control study of postmenopausal women (505 cases and 502 controls) from the American Cancer Society Prevention II Nutrition Cohort, we examined relationships between breast cancer risk and genetic polymorphisms of enzymes involved in the generation and removal of iron-mediated reactive oxygen species… These results indicate that women with genotypes resulting in potentially higher levels of iron-generated oxidative stress may be at increased risk of breast cancer and that this association may be most relevant among women with high iron intake. [Hong, CC et al (2007).Genetic Variability in Iron-Related Oxidative Stress Pathways (Nrf2, NQ01, NOS3, and HO-1), Iron Intake, and Risk of Postmenopausal Breast Cancer. Cancer Epidemiology Biomarkers & Prevention, 16(9), 1784-94.]
The aim of the present study was to evaluate the relation between iron status and cancer in a population of middle-aged adults living in France where iron supplementation and iron-fortified foods are rarely used. The SU.VI.MAX study is a randomized, double-blind, placebo-controlled primary prevention trial evaluating the effect of antioxidant supplementation on chronic diseases in women aged 35–60 and men aged 45–60 years… No relation was found between dietary iron intake and risk of all cancer sites combined for either men or women. Our results suggest that iron status is not a predictor of cancer risk in men, whereas a serum ferritin concentration > 160 µg/L may be associated with an increase in cancer risk in women. [Hercberg, S et al (2005).Iron Status and Risk of Cancers in the SU.VI.MAX Cohort. J Nutr, 135, 2664-8.]
Iron overload may increase prostate cancer risk through stimulation of oxidative stress, and endogenous pro- and antioxidant capabilities, i.e. manganese superoxide dismutase (MnSOD) and myeloperoxidase (MPO), may modify these associations. We investigated this hypothesis in the Carotene and Retinol Efficacy Trial cohort in a nested case–control study. Although there was no association between iron intake and risk overall, there was a suggestion of increased risk of clinically aggressive prostate cancer with higher iron intake… Findings suggest that higher iron intake may be associated with risk of clinically aggressive prostate cancer, and that endogenous antioxidant capabilities may modify these associations. [Choi, JY et al (2008).Iron intake, oxidative stress-related genes (MnSOD and MPO) and prostate cancer risk in CARET cohort. Carcinogenesis, 29(5), 964-70.]
Excess iron has been implicated in cancer risk through increased iron-catalyzed free radical–mediated oxidative stress. A multicenter randomized, controlled, single-blinded clinical trial (VA Cooperative Study #410) tested the hypothesis that reducing iron stores by phlebotomy would influence vascular outcomes in patients with peripheral arterial disease… Iron reduction was associated with lower cancer risk and mortality. Further studies are needed to define the role of body iron in cancer risk. [Zacharski, LR et al (2008).Decreased Cancer Risk After Iron Reduction in Patients With Peripheral Arterial Disease: Results From a Randomized Trial. Journal of the National Cancer Institute , 100(14), 996-1002.]
Recent studies suggest that elevated body iron levels may contribute to breast carcinogenesis; however, epidemiologic evidence is lacking. We used data from a large cohort study of Canadian women to assess breast cancer in association with total iron and heme iron intake. Among 49,654 women ages 40 to 59 followed for an average of 16.4 years, we identified 2,545 incident breast cancer cases. Data from a food frequency questionnaire administered at baseline were used to calculate total dietary iron and heme iron intake. Using Cox proportional hazards models, we found no association of iron or heme iron intake with risk of breast cancer overall, in women consuming 30+ g of alcohol per day, or in women who had ever used hormone replacement therapy. The present study offers no support for an association of iron or heme iron intake with breast cancer risk or for a modification by iron of the effect of alcohol or estrogen. However, further cohort studies with repeated measurement of iron intake are warranted. [Kabat, GC et al (2007).Dietary Iron and Heme Iron Intake and Risk of Breast Cancer: A Prospective Cohort Study. Cancer Epidemiology Biomarkers & Prevention , 16(6), 1306-8.]
Prospectively gathered data from the National Health and Nutrition Examination Survey I and the National Health Evaluation Follow-Up Study were analyzed to evaluate the risk of colorectal cancer due to consumption of iron. Morbidity and mortality data due to colorectal cancer were available on 14,407 persons first interviewed in 1971 and followed through 1986. A total of 194 possible colorectal cancers occurred in this group over the 15-year period… Data suggest that iron may confer an increased risk for colorectal cancer, and that the localization of risk may be attributable to the mode of epithelial exposure. It seems that luminal exposure to iron increases risk proximally, whereas humoral exposure increases risk distally. [Wurzelmann, JI, Silver, A, Schreinemachers, DM, Sandler, RS, & Everson, RB (1996). Iron intake and the risk of colorectal cancer. Cancer Epidemiology Biomarkers & Prevention, 5 (7), 503-7.]
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