Multiple hypotheses for chromium(III) biochemistry: Why the essentiality of chromium(III) is still questioned

This chapter discusses multiple hypotheses for chromium (III) biochemistry and why the essentiality of chromium (III) is still questioned. The original hypothesis that the effects of chromium on parameters related to diabetes may, in fact, be due to either influences of chromium on iron metabolism or influences of iron on chromium metabolism has not yet been fully explored. A growing number of studies have reported a link between high iron levels and both type II and gestational diabetes. It has been well established that iron-binding proteins are involved in chromium binding, transport, and storage. Chromium blood plasma levels have been reported to be lower in diabetics than in non-diabetic controls. Thus, decreased chromium stores in diabetics could be an indirect indication of increased iron stores, not necessarily a cause of diabetes. Also, positive effects attributed to chromium supplementation could be a result of lowered iron absorption rather than an improvement in a chromium deficiency. The concept of dose-response, that there is a proportional relationship between the amount of exposure to a chemical or physical agent and the degree of response in a given experimental system, is a central tenet of pharmacology and toxicology. Hormesis, derived from the Greek word hormaein), is the observation of a stimulatory or “beneficial” response elicited by a low dose range of a chemical, even if that chemical produces an inhibitory or adverse response at a higher dose range.