Iron deficiency and iron overload: effects of diet and genes

Like most essential nutrients, Fe needs to be maintained in the body at a d efined level for optimal health, with appropriate adaptation to varying Fe needs and supply. The primary mechanism for controlling Fe level is the reg ulation of Fe absorption. Several different proteins have been identified a s contributors to the process. Despite a complex regulatory system, Fe diso rders (both Fe deficiency and Fe overload) occur. Fe deficiency is a common problem worldwide, resulting from inadequate dietary Fe and blood loss. Co mplications include pre-term labour, developmental delay, and impaired work efficiency. No specific genetic syndromes causing isolated Fe deficiency h ave been described, but animal studies and clinical observations suggest th at such a relationship may be a possibility. Conversely, the known causes o f Fe overload are genetic. Fe overload is less common than Fe deficiency, b ut can result in serious medical complications, including cirrhosis, primar y liver cancer, diabetes, cardiomyopathy and arthritis. The most common and best characterized syndrome of Fe overload is hereditary haemochromatosis (HHC). an autosomal recessive disorder. Mutations in the HFE protein cause HHC, but the clinical presentation is variable. Of particular interest is t he factor that some HFE genotypes appear to be associated with protection f rom Fe deficiency. Other genetic variants in the regulatory pathway may inf luence the likelihood of Fe deficiency and Fe overload. Studies of genetic variants in HFE and other regulatory proteins provide important tools for s tudying the biological processes in Fe regulation. This work is likely to l ead to new insights into Fe disorders and potentially to new therapeutic ap proaches. It will not be complete, however, until coordinated study of both genetic and nutritional factors is undertaken.