Urinary chromium excretion in response to an insulin challenge is not a biomarker for chromium status.

Over 50 years ago, chromium (Cr) was proposed to be an essential trace element; however, recent studies indicate that this status should be removed as the effects of Cr supplementation appear to be pharmacological rather than nutritional. The pharmacological basis for Cr's effects can explain the inability of investigators to discover a biomarker for Cr status. One potential biomarker has not been examined to date. Cr is known to be mobilized in the body in response to insulin (or insulin release in response to a glucose challenge), resulting in an increase in urinary Cr excretion. The magnitude of increase in urinary Cr loss as a function of dietary Cr intake was tested as a potential biomarker for Cr. Zucker lean rats housed in carefully controlled metal-free conditions were provided a series of purified diets containing variable Cr contents (from 16 µg/kg diet to 2,000 µg/kg) for 23 weeks. The 16 µg/kg diet contained less Cr than any diet examined to date. Urine samples were collected before and after insulin and glucose challenges (0, 2, 6, and 12 h postinjection). Urinary Cr levels were analyzed by the standard method of addition using graphite furnace atomic absorption. The rate of urinary Cr loss after a glucose or insulin challenge was found to not be dependent on the Cr content of the rats' diets. Blood iron levels of the rats were also measured to determine if the addition of Cr to the diet altered iron status. The Cr content of the diet was found to have no affect on blood iron levels. Overall, the study demonstrated that insulin-stimulated urinary Cr excretion cannot be used as a biomarker for Cr status.

Comparison of tissue metal concentrations in Zucker lean, Zucker obese, and Zucker diabetic fatty rats and the effects of chromium supplementation on tissue metal concentrations.

Diabetes results in several metabolic changes, including alterations in the transport, distribution, excretion, and accumulation of metals. While changes have been examined in several rat models of insulin resistance and diabetes, the metal ion concentrations in the tissues of Zucker lean, Zucker obese (an insulin resistance and early stage diabetes model), and Zucker diabetic fatty (ZDF, a type 2 diabetes model) have not previously been examined in detail. The concentration of Cu, Zn, Fe, Mg, and Ca were examined in the liver, kidney, heart and spleen, and Cr concentration in the liver and kidney of these rats were examined. Zucker obese rats have a reduction in the concentration of Cu, Zn, Fe, Mg in the liver compared to ZDF and/or lean Zucker rats, presumably as a result of the increased fat content of the liver of the obese rats. ZDF rats have increased concentrations of kidney Cu compared to the lean rats, while kidney Ca concentrations are increased in the Zucker obese rats. Spleen Fe concentrations are decreased in Zucker obese rats compared to the lean rats. No effects on metal concentrations in the heart were observed between the lean, obese, and ZDF rats, and no effects on Cr concentrations were identified. Cr(III) complexes have previously been shown to have beneficial effects on the signs of insulin resistance in Zucker obese and ZDF rats. The effects of daily gavage administration of chromium picolinate ([Cr(pic)(3)]) (1 mg Cr/kg body mass), CrCl(3) (1 mg Cr/kg body mass), and Cr3 ([Cr(3)O(propionate)(6)(H(2)O)(3)](+)) (33 µg and 1 mg Cr/kg body mass) on metal concentrations in these tissues were examined. Treatment with CrCl(3) and Cr3, but not [Cr(pic)(3)], at 1 mg Cr/kg resulted in a statistically significant accumulation of Cr in the kidney of lean and obese but not ZDF rats but resulted in lowering the elevated levels of kidney Cu in ZDF rats, suggesting a beneficial effect on this symptom of type 2 diabetes.

The need for combined inorganic, biochemical, and nutritional studies of chromium(III).

The history of biochemical and nutritional studies of the element is unfortunately full of twists and turns, most leading to dead ends. Chromium (Cr), as the trivalent ion, has been proposed to be an essential element, a body mass and muscle development agent, and, in the form of the most popular Cr-containing nutritional supplement, to be toxic when given orally to mammals. None of these proposals, despite significant attention in the popular media, has proven to be correct. Trivalent chromium has also been proposed as a therapeutic agent to increase insulin sensitivity and affect lipid metabolism, although a molecular mechanism for such actions has not been elucidated. Greater cooperative research interactions between nutritionists, biochemists, and chemists might have avoided the earlier issues in nutritional and biochemical Cr research and is necessary to establish the potential role of Cr as a therapeutic agent at a molecular level.