[1][2] Supplementation with trivalent chromium does not prevent or treat obesity, impaired prediabetes condition, type 2 diabetes or metabolic syndrome, and is not considered effective for maintaining or losing body weight.

[1][2] Although some research suggested that chromium(III) picolinate may assist in weight loss and increase muscle mass, a 2013 Cochrane review was unable to find "reliable evidence to inform firm decisions" to support such claims.

[12] The picolinate ligand coordinates to Cr3+ only when deprotonated and this is evident by the disappearance of IR bands ranging from 2400 to 2800 cm−1 (centered at 2500 cm−1) and 1443 cm−1, corresponding to the O-H stretching and bending, respectively, on the carboxyl functional group.

[13] Chromium was once proposed as an essential nutrient in maintaining normal blood glucose levels,[6] but this function has not been sufficiently demonstrated.

[9] Although absorption is low, CrPic3 absorbs more efficiently than other organic and inorganic sources (i.e. CrCl3 and chromium nicotinate) and thus accumulate at higher concentrations in tissues.

Organic sources tend to absorb better as they have ligands which are more lipophilic and usually neutralize the charge of the metal, thus permitting for easier passage through the intestinal membrane.

[15][17][18] The exact mechanism of release is currently unknown, however, it is believed not to occur by a single electron reduction, as in the case of Fe3+, due to the high instability of Cr2+.

[19] Each lobe contains aspartic acid, histidine, 2 tyrosine residues and a bicarbonate ion that acts as a bidentate ligand to allow iron or other metals to bind to transferrin in a distorted octahedral geometry.

[5] Furthermore, an in vivo study in rats showed that 80% of isotopically labelled Cr3+ ended up on transferrin while the rest were bound to albumin.

[1][2][25] Although chromium(III) picolinate has been marketed in the United States as an aid to body development for athletes, and as a means of losing weight, there is insufficient evidence that it provides this effect.

[3] The European Food Safety Authority reviewed the literature and concluded that there was insufficient evidence to support a claim of effect on body weight.

[2][27][28][29] Two reviews concluded that chromium(III) picolinate may be more effective at lowering blood glucose levels compared to other chromium-containing dietary supplements.

[28][30] In 2005, the U.S. Food and Drug Administration (FDA) approved a qualified health claim for chromium picolinate as a dietary supplement relating to insulin resistance and risk of type 2 diabetes.

FDA concludes, however, that the existence of such a relationship between chromium picolinate and either insulin resistance or type 2 diabetes is highly uncertain."

[2] Use of chromium picolinate may cause an allergic reaction, headache, insomnia, or irritability, and may interfere with normal thinking and muscular coordination.

This was due to concerns raised by the Expert Group on Vitamins and Minerals that chromium(III) picolinate might be genotoxic (cause cancer).