Chromium(III) tris(picolinate) [Cr(pic)3] is currently a very popular nutritional supplement; however, its safety has recently been questioned, especially with regard to its ability to act as a clastogen. At physiologically relevant concentrations, Cr(pic)3 is reduced by biological reductants, including ascorbate and thiols, to Cr(II)-containing species. These species are susceptible to air oxidation, resulting in the catalytic generation of the potent DNA-damaging agent hydroxyl radical. In the absence of reductants, H2O2 can interact with Cr(pic)3 to produce hydroxyl radicals by a second, less efficient mechanism. Cr(pic)3 is extremely stable, which allows the complex to be readily absorbed but also to potentially be incorporated into cells intact. In this form, Cr(pic)3 is primed by its redox potential to enter into the generation of hydroxyl radicals. This study suggests that investigation of the long-term effects of supplementation of the diet with Cr(pic)3 are needed to assess the safety of this material.

Chromium is essential for proper carbohydrate and lipid metabolism in mammals, although the mechanism of this action has previously proved elusive. Low-molecular-weight chromium-binding protein (LMWCr), a biologically active form of chromium in mammals, potentiates the effect of insulin on the conversion of glucose into lipid and into carbon dioxide in isolated adipocytes. Kinetics studies indicate that LMWCr isolated from bovine liver activates phosphotyrosine phosphatase (PTP) activity in adipocyte membranes while having no intrinsic phosphatase activity. This activation is directly proportional to the amount of added LMWCr. The pattern of inhibition of this activity in the presence of a number of known phosphatase inhibitors suggests the involvement of a membrane phosphotyrosine phosphatase similar to PTP1A' or PTP1B. We propose that chromium plays a biological role in the activation of a membrane phosphotyrosine phosphatase.

Background: A number of genes have been implicated in recent genome-wide association studies of suicide attempt in bipolar disorder. More focused investigation of genes coding for protein targets of existing drugs may lead to drug repurposing for the treatment and/or prevention of suicide. Methods: We analyzed 2,457 DNA variants across 197 genes of interest to GlaxoSmithKline across the pipeline in our sample of European patients suffering from bipolar disorder (N = 219). We analyzed these variants for a possible association with the suicide severity score (ranging from suicidal ideation/plan to serious suicide attempt) from the Schedule for Clinical Assessment in Neuropsychiatry. We conducted tests of individual variants and gene-based tests. Results: We found a number of DNA variants in the transforming growth factor beta receptor 1 gene (TGFBR1) to be suggestively associated with suicide severity scores (p < 0.005). The gene-based tests also pointed to TGFBR1 to be associated with suicide severity (p = 0.0001). However, these findings were not replicated in an independent bipolar disorder sample. Conclusions: We report no significant association between DNA sequences of drug target genes and suicidal behavior. Additional larger sequencing studies could further interrogate associations between variants in drug target genes and suicidal behavior.