The Nutritional Supplement Chromium(III) Tris(picolinate) Cleaves DNA

Abstract

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.

A newly synthetic chromium complex – chromium(phenylalanine)3 improves insulin responsiveness and reduces whole body glucose tolerance

“…DNA cleavage-stimulated by chromium compounds was assessed as described previously [14]. All solutions were prepared using Chelex-100 treated water to remove any traces of metal ions.…”

“…Cr(pa) 3 does not cleave DNA under physiologically relevant conditions Recent studies have indicated that the nutritional supplement chromium picolinate can cause DNA damage by generating hydroxyl radicals [14]. The mutagenic potential of chromium picolinate has been attributed by the picolinate ligand, which primes the redox potential of the chromic center for reduction by biological reductants [22].…”

Metabolic pathways of carcinogenic chromium.

“…In the early 1980s a new chromiumbinding oligopeptide, named "low-molecularweight chromium" (LMWCr) (15,(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31), also known as chromodulin (32), was isolated in tissues, mainly in the liver, of several mammals (24). Moreover, the use of Cr(pic) 3 as a dietary supplement has been challenged by its proven features of a) catalytically producing hydroxyl radicals and b) being potentially mutagenic as are all other Cr(III) compounds (33).…”

O impacto do crômio nos sistemas biológicos

“…Um suplemento nutricional que se tornou alvo de indústrias farmacêuticas nos EUA é o tripicolinato de Cr(III), Cr(pic) 3 72 . No entanto, comprovou-se que este mesmo complexo é capaz de clivar a molécula do ADN, complementando outros experimentos que reportaram a capacidade do Cr(pic) 3 de induzir dano em cromossomos 73,74 . Devido às evidências da toxidez do tripicolinato de Cr(III), tem havido um interesse renovado na obtenção de novos suplementos e entre os mais promissores estão o oligopeptídeo LMWCr e os complexos trinucleares de Cr(III) do tipo "básico" 70,75,76 .…”