The nutritional supplement chromium picolinate causes deleterious effects in rat and fly models: Implications for the safety of the dietary supplement in humans

The nutritional dietary supplement chromium picolinate, [Cr(pic) ₃], has gained much notoriety as a safe dietary supplement that allegedly promotes fat loss and muscle enhancement in humans. Consequently, a significant industry has materialized around the incorporation of [Cr(pic)₃] in numerous sports foods and drinks and a variety of weight loss products. However, in vitro studies have suggested that low levels of [Cr(pic) ₃] in the presence of biological reducing agents can catalytically generate reactive oxygen species (ROS). In vitro studies have also shown the complex to be remarkably stable in neutral, basic, or weakly acidic solutions. Herein, in vivo studies in male Sprague Dawley rats revealed that [Cr(pic)₃] had an intracellular lifetime of less than 24 hours and the majority of Cr injected was retained whereas the organic portions of the complex were rapidly excreted. Subsequent studies revealed that the complex had a lifetime of less than two hours in vivo (much less than previously thought) and was found to accumulate for a time in DNA-rich regions of liver cells. Subsequent investigations determined that [Cr(pic)₃] treated rats suffered a significantly greater incidence of oxidative damage to their DNA and intracellular membranes compared to non-supplemented rats. The potential deleterious in vivo effects of this activity were also examined using Drosophila melanogaster . [Cr(pic)₃], but not CrCl₃, at levels of 260 μg Cr/kg food or less were found to lower the success rate of pupation and eclosion and to arrest development of pupae in a concentration dependent fashion. X-linked lethal analysis indicates that the supplement greatly enhances the rate of appearance of lethal mutations and dominant female sterility. Finally, studies examined damage to polytene chromosomes obtained from salivary glands of second generation third instar larval from parents exposed to [Cr(pic)₃]. The chromosomes from the flies had a myriad of aberrations that include deficiencies, complex inversions and translocations of chromosomal arms compared to those of untreated chromosomes. Thus, oxidative DNA damage and lipid damage and inheritable genetic damage from [Cr(pic)₃] in whole animals has been observed for the first time.