The safety and efficacy of high-dose chromium - High-Dose Chromium

Alternative Medicine Review, June, 2002 by Davis W. Lamson, Steven M. Plaza

Presently the EPA Federal-State Toxicology and Risk Analysis Committee has set state and federal drinking water standards for all chromium regardless of valence at 100 mcg/L, while Minnesota has refined its standards to include chromium III at 20,000 mcg/L. (50) The higher range of safety set by Minnesota stems from a number of studies that have examined the effects of chronic ingestion of chromium III in water. Schroeder et al (8) found that 461 rats given drinking water containing 5-ppm Cr III for a period of three years were found to have no signs of sub-clinical toxicity or microscopic abnormalities in tissue, while the rats demonstrated an increase in growth rate and mature weight as well as increased longevity as compared to controls.

Subcutaneous, Intravenous and Intraperitoneal Injection of Cr III

The lethal dose of chromium III chloride, subcutaneously injected, was reported to be 0.8 gm/kg for dogs and 0.5 gm/kg for rabbits. Rats and mice intravenously injected with Cr Ill showed an LD50 of 10-30 mg/kg. (4) Another study demonstrated the chromium III chloride LD50 to be 1.75 mg/100 g and the chromium III hexaurea chloride complex LD50 to be 1.0 mg/100 g. (4) In an attempt to study chronic toxicity, mice were given intraperitoneal injections of Cr III and Cr VI compounds. Along with the obvious acute toxicity of Cr VI, the median lethal dose in distal time, regardless of oxidation state (more than 10 days after treatment), averaged (17.9 /- 1.8) mcg chromium/g body weight. (51)

Mutagenic Potential: In vitro Studies

The results of many studies support the conclusion that Cr III is relatively nontoxic. Most Cr III compounds have failed to induce genetic defects in bacteria, yeast, or mammalian cell lines. (52) Recently, the safety of chromium picolinate has been questioned with the research of both Stearns and Speetjens. Stearns et al (53,54) cites that organic forms of Cr III such as chromium picolinate and nicotinate have much higher absorption (2-5%) as compared to 0.5- l percent for chromium Ill chloride and carbonate or phosphate salts. (4) Stearns contends this increased absorption of organic-complexed chromium could cause toxicity due to the concentration of this heavy metal in various tissues. She also argues that concentration of Cr III in various tissues over time could lead to eventual damage through chromosomal aberrations from clastogenic action of the metal, as has been observed in vitro. (53-55) (A clastogen is a specific mutagen that causes breaks in chromosomes.) Chromium picolinate is thought to become clastogenic due to the redox potential of the compound, which can enter the cell intact and possibly generate hydroxyl radicals (Figure 1).

[FIGURE 1 OMITTED]

Hydrophobic complexes such as those with the pyridine nitrogen ligands of chromium picolinate are thought to readily enter the lipid bilayer of the cellular membrane. Chromium tightly binds to picolinic acid forming a complex with three picolinate molecules (Figure 2).

[FIGURE 2 OMITTED]