Chromium and Chromium Picolinate: Health Benefit and Hazard

by Ben Best

Sales of chromium picolinate as a nutritional supplement was second only to calcium in the year 2000. Claims have been made that chromium picolinate can reduce body fat and increase lean body mass as well as prevent diabetes and cardiovascular disease. The evidence for many of these claims is questionable and there is evidence for chromium picolinate being a health hazard.

The element chromium commonly exists in oxidation states 2+, 3+ and 6+. In the 6+ oxidation state chromium is usually combined with oxygen, either as chromate (CrO₄^2-) or dichromate (Cr₂O₇^2-), both of which are strong oxidizing agents that are readily reduced to Cr³⁺. Cr³⁺ is the most stable oxidation state for chromium.

Chromium (Cr³⁺) is regarded to be an essential mineral in human nutrition, unlike (Cr²⁺) and (Cr⁶⁺), which are quite toxic. Chromium deficiency impairs removal of glucose from the bloodstream. Chromium deficiency during total parenteral nutrition has been shown to cause diabetes-like symptoms in humans which chromium supplementation can reverse. Otherwise, severe chromium deficiency is rare. Rat studies indicate insulin resistance results from a low chromium diet. Chromium is evidently physiologically active as an oligopeptide called chromodulin (sometimes called Glucose Tolerance Factor, GTF) that is composed of glycine, cysteine, glutamate, aspartate and four chromic (Cr³⁺) ions. Chromodulin can increase insulin receptor activity as much as eightfold [JOURNAL OF NUTRITION; Vincent,JB; 130(4):715-718 (2000)]. Chromium reportedly facilitates translocation of the glucose transporter GLUT4 to the cytoplasmic side of the cell membrane [MOLECULAR ENDOCRINOLOGY; Chen,G; 20(4):857-870 (2006)].

Picolinic acid	Zinc picolinate	Chromium picolinate

The enthusiasm for chromium picolinate supplementation began with reports by Dr. Gary Evans that the supplement could promote weight loss and muscle development. The picolinate molecule is a catabolite of L−Tryptophan, which acts as a chelating agent for zinc, chromium and other metal ions. When chromium is complexed with picolinate, assimilation into the bloodstream and into body cells is increased up to ten-fold. Nonetheless, numerous studies on the effects of chromium picolinate on body composition have failed to demonstrate any effect on muscle growth or fat loss [SPORTS MEDICINE; Vincent,JB; 33(3):213-230 (2003)]. Picolinic acid can increase nitric oxide expression in macrophages [JOURNAL OF BIOLOGICAL CHEMISTRY; Melillo,G; 269(11):8128-8133 (1994)], which can worsen ischemia/reperfusion injury. Picolinic acid has also been shown to cause birth defects in the offspring of pregnant mice [BIRTH DEFECTS RESEARCH (SERIES B); Bailey,MM; 77(3):244-249 (2006)].

Claims that chromium supplementation is of benefit for persons with type 2 diabetes have been the subject of considerable debate. The fact that chromium deficiency apparently leads to symptoms of diabetes and the fact that diabetics excrete elevated amounts of chromium in their urine have led investigators to suspect and test possible benefits of supplementation.

A meta-analysis of randomized clinical trials of dietary trivalent chromium (Cr³⁺) concluded that chromium supplementation is of no benefit for non-diabetic subjects and that the results for diabetic subjects are inconclusive [AMERICAN JOURNAL OF CLINICAL NUTRITION; Althuis,MD; 76(1):148-155 (2002)]. But for most of the studies included in the meta-analysis the chromium amounted to less than 200 micrograms per day -- and none of the studies including diabetics used chromium picolinate. Specifically excluded from the meta-analysis was a large study of type 2 diabetics in China which had shown a 22% reduction in glycated hemoglobin along with a comparable increase in insulin sensitivity with 1,000 micrograms of chromium picolinate per day for four months [DIABETES; Anderson,RA; 46(11):1786-1791 (1997)]. The authors of the meta-analysis justified excluding the Chinese study on grounds that the Chinese population are different from other subjects and that the 155 subjects in the Chinese trial would have overwhelmed the results of the total 38 subjects from all the other trials [AMERICAN JOURNAL OF CLINICAL NUTRITION; Althuis,MD; 78(1):193 (2003)]. Studies that distinguish between insulin-resistant and insulin-sensitive subjects having type 2 diabetes show benefit only for those who are insulin-resistant [CURRENT DIABETES REPORTS; Wang,ZQ; 10(2):145-151 (2010)].

Toxicity studies on rats with doses of chromium picolinate thousands of times greater than humans normally use for supplementation showed no effects on body mass, organ mass or blood variables as well as no evidence of tissue damage in liver or kidney [JOURNAL OF THE AMERICAN COLLEGE OF NUTRITION; Anderson,RA; 16(3):273-279 (1997)].

On the other hand, numerous studies have provided evidence that chromium picolinate, much more than other forms of chromium, can lead to DNA damage and mutation. Chinese hamster ovary cells (a standard assay model for chromosome damage) showed a 3−18-fold increase in chromosome damage with chromium picolinate in doses 3,000 times greater than serum levels seen in humans taking 200 micrograms per day. The authors justified their concerns on grounds that tissue levels can be 100 times greater than serum levels and that lymphocytes may be as much as 10 times more sensitive to chromosome damage as the Chinese hamster ovary cells [THE FASEB JOURNAL; Stearns,DM; 9(1):1643-1648 (1995)]. A follow-up study on Chinese hamster ovary cells showed that chromium picolinate is seven times more mutagenic than an equivalent dose (1 mM) of trivalent chromium (Cr³⁺) given as chromium chloride [MUTATION RESEARCH; Stearns,DM; 513(1−2):135-142 (2002)], but a subsequent study found no such damage [MUTATION RESEARCH; Gudi,R; 587(1-2):140-146 (2005)]. Another study similarly showed high DNA cleavage by chromium picolinate compared to other forms of trivalent chromium [JOURNAL OF INORGANIC BIOCHEMISTRY; Chandhary,S; 99(3):787-794 (2005)]. Adult fruit flies are able to ingest high concentrations of chromium picolinate with no effects on viability, fertility or behavior, but when chromium picolinate is fed to fruit fly larvae the result is lethal mutations and sterility [PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES (USA); Hepburn,DDD; 100(7):3766-3771 (2003)]. Chromium picolinate fed to pregnant mice in doses thousands of times what a human would ingest as a supplement resulted in skeletal defects in the offspring [BIRTH DEFECTS RESEARCH (SERIES B); Bailey,MM; 77(3):244-249 (2006)]. Chromium chloride had the same effect, but only one third as much as chromium picolinate.

Picolinic acid induces macrophage inflammatory protein, an effect that is opposed by interferon gamma [ ADVANCES IN EXPERIMENTAL BIOLOGY AND MEDICINE; Bosco,MC; 527:55-65 (2003)].

Chromium picolinate is a very stable hydrophobic molecule which allows it to be readily absorbed from the digestive tract and readily cross membranes. But it appears that once inside cells, trivalent chromium (Cr³⁺) picolinate can be reduced to divalent chromium (Cr²⁺) which can participate in the Fenton reaction in the presence of hydrogen peroxide to generate hydroxyl radicals which cause DNA damage [CHEMICAL RESEARCH IN TOXICOLOGY; Speetjens,JK; 12(6):483-487 (1999)].

Nonetheless, some scientists argue that the DNA damaging results seen in laboratory studies using massively high doses of chromium picolinate are not relevant to normal human dietary supplementation [MEDICAL HYPOTHESIS; McCarty,MF; 49(3):263-269 (1997)]. An 8 week study of ten obese women taking 400 micrograms of chromium picolinate per day showed no evidence of oxidative damage to DNA [EUROPEAN JOURNAL OF EPIDEMIOLOGY; Kato,I; 14(6):621-626 (1998)]. And researchers continue to report evidence that chromium picolinate can increase insulin sensitivity in diabetic patients [DIABETIC MEDICINE; Morris,BW; 17(9):684-685 (2000)] as well as in healthy subjects [JOURNAL OF THE AMERICAN COLLEGE OF NUTRITION; Frauchiger,MT; 23(4):351-357 (2004)].

Given that the benefits of chromium supplementation are so questionable, and given the potential for DNA damage, there seems to be little justification for non-diabetics to take more than the minimum daily requirement of 50 micrograms. (The average adult gets less than 50 micrograms daily, and may be suffering from subclinical chromium deficiency, even though clinical chromium deficiency is so rare.) If supplementation is desired, it might be prudent to avoid chromium picolinate and get chromium from an alternative bioavailable form such as brewer's yeast, oysters, peanuts or egg yolk.

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