to adverse effects of chromium picolinate that might manifest after long-term consumption. Similarly, no clear or distinct patterns were observed from the diverse congeries of literature.
Possible concerns arise from in vitro data that suggest Cr(III) increases oxidative stress and carcinogenesis (including carcinogenesis that may not be mediated by oxidative stress). However, data about such intracellular effects of Cr(III) (e.g., DNA fragmentation) are difficult to integrate into the evaluation of the safety of chromium picolinate as a dietary supplement; it is not clear whether intracellular Cr(III) concentrations sufficient to cause nuclear mutations and/or oxidative stress would result from chromium picolinate ingestion at doses found in the dietary supplements. Controversy concerning the relevance of in vitro studies to human health commonly evolves from a general skepticism about the physiologic relevance of high intracellular concentrations attained during in vitro studies. In the case of chromium picolinate, the controversy comes from a different source; a particular question arises about picolinate as a carrier of chromium into the cell and the subsequent release of Cr(III). At this time, there is insufficient experimental data to evaluate the long-term safety of chromium picolinate regarding carcinogenesis.
The human studies evaluated would not have detected carcinogenesis; only two of the studies might have detected oxidative stress if it did occur. These two studies examined measures indicative of oxidative stress and did not detect them; an 8-week study using 400 μg/day of Cr(III) failed to demonstrate oxidative damage to DNA (Kato et al., 1998), and a 12-week study using 924 μg/day Cr(III) failed to demonstrate a shift from proteinbound iron to the free (reactive) metal ion (Campbell et al., 1997). Additionally, animal studies provide some mitigation of the concern raised by in vitro studies; a 24-week study in female Sprague-Dawley rats with chromium picolinate (up to 100 μg Cr(III)/g diet) and lifespan studies in several strains of rats with chromium chloride (at 5–25 ppm Cr(III) in the drinking water) or chromium oxide (up to 5 percent w/w in bread dough) failed to demonstrate toxicity or carcinogenicity.
Considering the totality of the data reviewed, there is no consistent evidence of reasonable expectation of harm from chromium picolinate. There is also not sufficient evidence to raise concern regarding the safety or toxicity of chromium picolinate when used in the intended manner for a length of time consistent with the published clinical data, that is, up to 1.6 mg of chromium picolinate/day (200 μg of Cr(III)/day) for 3 to 6 months.
This conclusion is consistent with the findings of the Agency for Toxic