Role of chromium in human health and in diabetes.

D espite widespread use by patients with diabetes and anecdotal reports in the past regarding its efficacy, until recently, data in humans concerning chromium’s effects on insulin action in vivo or on cellular aspects of insulin action were scarce. Consequently, significant controversy still exists regarding the effect of chromium supplementation on parameters assessing human health. Furthermore, elucidating the cellular and molecular mechanisms by which chromium supplements affect carbohydrate metabolism in vivo is necessary before specific recommendations can be made regarding its routine use in the management of diabetes. This review focuses on providing current information about this trace mineral’s specific mechanisms of action and clinical trials in patients with diabetes. Chromium, one of the most common elements in the earth’s crust and seawater, exists in our environment in several oxidation states, principally as metallic (Cr), trivalent ( 3), and hexavalent ( 6) chromium. The latter is largely synthesized by the oxidation of the more common and naturally occurring trivalent chromium and is highly toxic. Trivalent chromium, found in most foods and nutrient supplements, is an essential nutrient with very low toxicity. The interest in chromium as a nutritional enhancement to glucose metabolism can be traced back to the 1950s, when it was suggested that brewer’s yeast contained a glucose tolerance factor (GTF) that prevented diabetes in experimental animals (1). This factor was eventually suggested to be a biologically active form of trivalent chromium that could substantially lower plasma glucose levels in diabetic mice (2). Interest regarding chromium administration in patients with diabetes was kindled by the observation in the 1970s that it truly was an essential nutrient required for normal carbohydrate metabolism. A patient receiving total parenteral nutrition (TPN) developed severe signs of diabetes, including weight loss and hyperglycemia that was refractory to increasing insulin dosing (3). Based on previous animal studies and preliminary human studies, the patient was given supplemental chromium. In the following 2 weeks, signs and symptoms of diabetes were ameliorated, with markedly improved glycemic status and greatly reduced insulin requirements (exogenous insulin requirements decreased from 45 units/day to none). Other studies (4,5) of the beneficial effects of chromium in patients receiving TPN have also been documented in the scientific literature. Chromium is now routinely added to TPN solutions (5). The results of these studies strongly implicated chromium as a critical cofactor in the action of insulin (6,7). Whereas chromium replacement in deficiency states is well established, the role of chromium supplementation to enhance glucose metabo l i sm in sub jec t s i s controversial and serves as the basis for this review. Trivalent chromium is found in a wide range of foods, including egg yolks, whole-grain products, high-bran breakfast cereals, coffee, nuts, green beans, broccoli, meat, brewer’s yeast, and some brands of wine and beer (8,9). Chromium is also present in many multivitamin/ mineral supplements, and there are also specific chromium picolinate (CrP) supplements that contain 200–600 g chromium per tablet (10). The U.S. National Academy of Sciences has established the Recommended Daily Allowances for chromium as 50–200 g/day for adult men and women (11), which is also the Estimated Safe and Adequate Daily Dietary Intake (ESADDI) for chromium for children aged 7 years to adulthood (7,12). However, it appears that Americans normally ingest 50–60% of the minimum suggested daily intake of 50 g (7). Results from one study (10) indicated that daily chromium intakes for men and women in the U.S. were 33 and 25 g, respectively. Therefore, normal dietary intake of chromium for adults may be suboptimal. At dietary intakes 50 g/day, chromium absorption is 0.4%, but the trivalent formulation also significantly influences bioavailability. At a dose of 1,000 g/day, absorption of chromium from chromium chloride (CrCl3) is 0.4%, whereas that from CrP may be as high as 2.8% (7,13,14). Once absorbed, chromium is distributed widely in the body, with the highest levels being found in the kidney, liver, spleen, and bone (14).