Chromium is known as a trace element that is essential in human health. Chromium can be used to regulate glucose levels in patients with diabetes. It also helps boost energy levels. Chromium use by pregnant and nursing women should be limited. Chromium can also interact with beta-blockers so caution should be used when combining these supplements.
Chromium is an essential trace mineral in human nutrition. Evidence suggests that it plays an important role in normal carbohydrate metabolism. In the 1950s it was found that chromium was necessary for the maintenance of normal glucose tolerance in rats; chromium-deficient rats had impaired glucose tolerance. Subsequently, it was found that patients receiving long-term total parenteral nutrition (TPN) without chromium developed glucose intolerance, weight loss and peripheral neuropathy. These symptoms were reversed when the patients were given intravenous chromium chloride.
Chromium is a metal with atomic number 24 and an atomic mass of 52 daltons. Its symbol is Cr. It occurs in nature chiefly as a chrome-iron ore. Chromium exists in several valence states, of which the trivalent and hexavalent states are the most common. Most chromium in the food supply is in the trivalent state. Hexavalent chromium compounds are recognized as toxic and are potential carcinogens. Chromium is found in many foods, typically in small amounts. Good food sources of chromium include whole grains, cereals, spices (black pepper, thyme), mushrooms, brown sugar, coffee, tea, beer, wine and meat products. Brewer's yeast is also a good source of chromium. Fruits and vegetables are generally poor sources of chromium, as are most refined foods.
Actions & Pharmacology
Chromium may have glucose-regulatory activity. It may also have hypocholesterolemic and anti-atherogenic activities.
Mechanism of Action
The mechanism of chromium's possible glucose-regulatory activity is not well understood, but there are some theories. It is thought that the possible action of chromium on the control of blood glucose concentrations is the potentiation of insulin. Chromium is thought to be a cofactor necessary for optimal insulin action. One proposed mechanism involves increased insulin binding, increased insulin receptor number and increased insulin receptor phosphorylation. Chromium stimulates protein kinase activity of rat adipocytes in the presence of insulin. Chromium also inhibits phosphotyrosine phosphatase, a rat homolog of tyrosine phosphatase that inactivates the insulin receptor. The activation by chromium of insulin receptor kinase activity and the inhibition of insulin receptor tyrosine phosphatase would lead to increased phosphorylation of the insulin receptor, which is associated with increased insulin sensitivity.
It has also been suggested that chromium may decrease hepatic extraction of insulin and improve glucose tolerance by such a mechanism. Earlier, it was found that glucose tolerance could be restored in chromium-deficient rats by feeding them an extract of brewer's yeast. Brewer's yeast is rich in chromium, and it was proposed that it contained an organic factor which potentiated the action of insulin. This factor was called the glucose tolerance factor or GTF. GTF was hypothesized to contain trivalent chromium bound to nicotinic acid and the amino acids glycine, cysteine and glutamic acid. However, an organic glucose tolerance factor has, to date, not been isolated from brewer's yeast.
Recently, an oligopeptide low-molecular-weight chromium-binding substance (LMWCr) has been isolated from animal tissues. The oligopeptide is comprised of the amino acids glycine, cysteine, glutamic acid, and aspartic acid, with the two carboxylic acids (glutamic, aspartic) comprising more than half the amino acid residues. It is proposed that LMWCr is part of an insulin signal amplification system. Its possible participation in the glucose-regulatory activity may be as follows: chromium ions are transferred from transferrin to LMWCr. LMWCr normally exists in insulin-dependent cells in the apo or inactive form. Binding to chromic ions converts the inactive form to its holo or active form. Chromic-containing LMWCr then binds to insulin-activated insulin receptor, stimulating its tyrosine kinase activity and potentiating the activity of insulin. LMWCr is also called chromodulin because its proposed action is similar to that of calmodulin.
The mechanism of the possible hypocholesterolemic activity of chromium is unknown. The possible anti-atherogenic activity of chromium may be accounted for by its possible glucose-regulatory activity.
Very little chromium in the form of inorganic compounds, such as chromic chloride, is absorbed. The efficiency of absorption of chromium from chromic chloride is less than 2%. The efficiency of absorption of chromium from organic compounds is higher. For example, approximately 2.8% of an ingested dose of chromium picolinate is absorbed. Following absorption, chromium is bound to transferrin and albumin. Chromium is transported primarily by transferrin.
Chromium is distributed to various tissues of the body but appears to have a preference for bone, spleen, liver and kidney. Pharmacokinetic studies indicate that chromium is distributed into four different compartments that have rapid, medium, slow and very slow turnover, respectively. Bone, spleen, liver and kidney appear to contain all four compartments. The half-life of the rapid compartment is less than one day, that of the medium compartment approximately one week and that of the slow compartment from 7 to 12 weeks. The half-life of chromium in the compartment which appears to turn over most slowly is approximately one year. This compartment is probably related to long-term tissue deposition.
Most of an ingested dose of chromium is excreted in the feces. Chromium that has been absorbed is excreted mainly in the urine. Little excretion occurs via the biliary route.
There is much that remains unknown regarding the pharmacokinetics of chromium and its various trivalent forms in humans. More research in this area is needed.
Indications & Usage
There is some evidence that chromium may improve glucose tolerance and may be helpful in some with diabetes. There is preliminary evidence it may have some favorable effects on lipids. Claims that it boosts athletic performance, builds muscle and promotes weight loss have little, if any, credible support. The Federal Trade Commission has, in fact, declared such claims to be unsubstantiated and deceptive. Evidence is mixed with respect to claims that chromium picolinate may be mutagenic. The suggestion that chromium is nephrotoxic is based on isolated case studies and requires further investigation.
There are a few forms of chromium available for nutritional supplementation. They include chromium picolinate, chromium polynicotinate, chromium chloride and high-chromium yeast. These forms are available as stand-alone supplements or in combination products. Typical doses of chromium range from 50 to 200 micrograms daily, expressed as elemental chromium.
Dietary intake of chromium is approximately 25 micrograms daily.
The Food and Nutrition Board of the U.S. National Academy of Sciences has recommended the following Dietary Reference Intakes (DRI) for chromium. A summary of DRIs for various age groups is as follows:
|DRI values (micrograms/day)|
|Infants||Adequate Intake (AI)|
|Older than 70 years||30|
|Older than 70 years||20|
The DV (Daily Value) for chromium, which is used for determining percentage of nutrient daily values on nutritional supplement and food labels, is 120 micrograms. The basis for the DV for chromium is the 1989 Estimated Safe and Adequate Daily Dietary Intake (ESADDI).
LiteratureAnderson RA. Chromium, glucose intolerance and diabetes. J Amer Coll Nutr. 1998;17:548-555.Anderson RA. Effects of chromium on body composition and weight loss. Nutr Rev. 1998;56:266-270.Anderson RA, Bryden NA, Polansky MM. Lack of toxicity of chromium chloride and chromium picolinate in rats. J Amer Coll Nutr. 1997;16:273-279.Anderson RA, Cheng N, Bryden NA, et al. Elevated intakes of supplemental chromium improve glucose and insulin variables in individuals with type II diabetes. Diabetes. 1997;46:1786-1791.Balk EM, Tatsioni A, Lichtenstein AH, et al. Effect of chromium supplementation on glucose metabolism and lipids: a systematic review of randomized controlled trials. Diabetes Care. 2007;30(8):2154-2163.Cerulli J, Grabe DW, Gauthier I, et al. Chromium picolinate toxicity. Ann Pharmacother. 1998;32:428-431.Donaldson RM Jr, Barreras RF. Intestinal absorption of trace quantities of chromium. J Lab Clin Med. 1966;68:484-493.Guan X, Matte JJ, Ku PK, et al. High chromium yeast supplementation improves glucose tolerance in pigs by decreasing hepatic extraction of insulin. J Nutr. 2000;130:1274-1279.Institute of Medicine, Food and Nutrition Board. Dietary Reference Intakes for vitamin A, vitamin K, arsenic, boron, chromium, copper, iodine, iron, manganese, molybdenum, nickel, silicon, vanadium, and zinc. Washington, DC: National Academy Press, 2001.International Symposium on the Health Effects of Dietary Chromium. J Trace Elem Exp Med. 1999;12:53-169.Jeejeebhoy KN. The role of chromium in nutrition and therapeutics and as a potential toxin. Nutr Rev. 1999;57:329-335.Kaats GR, Blum K, Fisher JA, et al. Effects of chromium picolinate supplementation on body composition: a randomized, double-masked, placebo-controlled study. Curr Therap Res. 1996;57:747-756.Lukaski HC. Chromium as a supplement. Annu Rev Nutr. 1999;19:279-302.Martin WR, Fuller RE. Suspected chromium picolinate-induced rhabdomyolysis. Pharmacotherapy. 1998;18:860-862.Merz W. Chromium in human nutrition: a review. J Nutr. 1993;123:626-633.Nielsen FH. Controversial chromium. Nutr Today. 1996;31:226-233.Press RI, Geller J, Evans GW. The effect of chromium picolinate on serum cholesterol and apolipoprotein fractions in human subjects. West J Med. 1990;152:41-45.Porter DJ, Raymond LW, Anastasio GD. Chromium: Friend or foe? Arch Fam Med. 1999;8:386-390.Roeback JR Jr, Hla KM, Chambless LE, et al. Effects of chromium supplementation on serum high-density lipoprotein cholesterol levels in men taking beta-blockers. Ann Intern Med. 1991;115:917-924.Speetjens JK, Collins RA, Vincent JB, et al. The nutritional supplement chromium (III) tris (picolinate) cleaves DNA. Chem Res Toxicol. 1999;12:483-487.Stallings DM, Hepburn DD, Hannah M, et al. Nutritional supplement chromium picolinate generates chromosomal aberrations and impedes progeny development in Drosophila melanogaster. Mutat Res. 2006;610(1-2):101-113.Stearns DM, Belbruno JJ, Wetterhahn KE. A prediction of chromium (III) accumulation in humans from chromium dietary supplements. FASEB J. 1995;9:1650-1657.Stearns DM, Wise JP Sr, Patierno SR, et al. Chromium (III) picolinate produces chromosome damage in Chinese hamster ovary cells. FASEB J. 1995;9:1643-1649.Stoecker BJ. Chromium. In: Shils ME, Olson JA, Shike M, Ross AC, eds. Modern Nutrition in Health and Disease. 9th ed. Baltimore, MD: Williams and Wilkins; 1999:277-282.Verhage AH, Cheong WK, Jeejeebhoy KN. Neurologic symptoms due to possible chromium deficiency in long-term parenteral nutrition that closely mimic metronidazole-induced syndromes. J Parenter Enter Nutr. 1996;20:123-127.Vincent J. The biochemistry of chromium. J Nutr. 2000;130:715-718.Vincent JB. Quest for the molecular mechanism of chromium action and its relationship to diabetes. Nutr Rev. 2000;58:67-72.Wasser WG, Feldman NS, D'Agati VD. Chronic renal failure after ingestion of over-the-counter chromium picolinate [letter]. Ann Intern Med. 1997;126:410.Young PC, Turiansky GW, Bonner MW, et al. Acute generalized exanthematous pustulosis induced by chromium picolinate. J Am Acad Dermatol. 1999;41(5 pt 2):820-823.
Research & Summary
The American Diabetes Association asserted in 1996 that ""chromium supplementation has no known benefit in patients who are not chromium deficient.'' Some patients on long-term parenteral nutrition have developed chromium deficiency and diabetic symptoms that were reversed with chromium supplementation. In general, plasma chromium levels are about 40% lower in diabetic subjects, compared with healthy individuals.
A double-blind, placebo-controlled study of 180 subjects with type 2 diabetes demonstrated that supplemental chromium significantly improved fasting glucose, postprandial glucose, insulin, hemoglobin A1c and cholesterol levels. Subjects in this study, conducted in China, received placebo, 200 micrograms of chromium picolinate or 1,000 micrograms of chromium picolinate daily. Subjects had suffered from diabetes for five to eight years. Better results were achieved with the higher dose of chromium.
This trial, while encouraging, was flawed in that baseline chromium status was not assessed; neither was postsupplemental status evaluated. Extrapolation of these results to Western populations is not possible. Additionally, the best designed prior studies have failed to show consistent results. Two of the best studies were largely negative. Variations may be due to divergence in chromium status at baseline and to the type and dose of chromium used. No beneficial effect was seen in diabetic patients taking 200 micrograms of chromium chloride, for example, but some positive effects were noted in those getting 400 micrograms or more of chromium chloride daily. With respect to the study in China, some hypothesized that the more dramatic effects achieved in that trial may be due to possible greater chromium deficiency in that country. More research is needed.
Chromium picolinate supplementation (200 micrograms daily) significantly decreased levels of total cholesterol, LDL-cholesterol and apolipoprotein B, compared with controls, in one small study. There was no significant effect on HDL-cholesterol. In a subsequent trial, 600 micrograms of chromium daily reportedly increased serum levels of HDL-cholesterol in patients taking beta-blockers. Again, however, studies have produced mixed results so that no persuasive conclusion can yet be reached with respect to chromium's effects on lipids.
One study reported that six weeks of chromium supplementation resulted in a significant increase in lean body mass and a decrease in body fat among athletes. Numerous, better designed follow-up studies, however, failed to confirm this finding. The original study used skinfold measurements (anthropometry) to assess changes in body composition. The subsequent studies used more sensitive measures, e.g., dual x-ray absorptiometry (DXA) and underwater weighing (hydrodensitometry). Even a study using the same anthropometry measurements that were employed in the original study also produced negative results.
Claims that chromium can be useful in treating obesity have similarly met with largely negative results. In some of these studies subjects have actually gained weight. Claims related to obesity were fueled by a study in which 200 micrograms of chromium daily reportedly led to weight loss even without alterations in food intake and exercise. In fact, however, weight loss in this small study was very modest, with a consequent high dropout rate. The same researchers conducted another study in which greater weight loss was achieved, but in this study chromium supplementation was used in conjunction with caloric restriction, dietary fiber and other nutritional support, making it impossible to assess the role of chromium, if any, in the final results.
There are two in vitro reports that, in high concentrations, chromium picolinate, but not chromium chloride or chromium nicotinate, is clastogenic. Thus some have concluded that picolinate, rather than chromium itself, might be mutagenic and should thus be avoided. Some have suggested that long-term use of chromium picolinate, particularly at doses higher than 200 micrograms daily, could be hazardous. More research is needed to clarify this issue.
Additional warnings have been issued based upon scattered case reports. In one of these cases, a 33-year-old woman taking 1,200-2,400 micrograms of chromium picolinate daily for four to five months in an effort to lose weight developed renal failure. In another case, a 49-year-old woman who took 600 micrograms of chromium picolinate daily for six weeks was also diagnosed with chronic renal failure.
It has not been demonstrated conclusively that chromium picolinate caused the renal failure, but some have speculated that the greater absorbability of the picolinate form of chromium may, when used at higher doses long term, increase the incidence of any possible side effects. One researcher has speculated that supplementation with 600 micrograms of chromium picolinate daily for five years could result in tissue accumulation of chromium picolinate possibly sufficient to cause chromosomal damage similar to that seen in in vitro studies.
Though these precautions need to be further investigated, the observation of one reviewer should also be noted. In reviewing the safety data, he concluded, ""in contrast, better evidence exists that chromium is safe rather than toxic at very high doses.'' In contrast with the in vitro studies showing clastogenic effects, experimental in vivo results have differed. In one of these experiments, rats were fed either chromium chloride or chromium picolinate at high doses for 20 weeks. These doses were calculated to be several thousand times greater than the ESSADI (Estimated Safe and Adequate Daily Dietary Intake) for humans. After being killed, the animals were examined for toxic effects. Whether the animals received 0, 5, 25, 50 or 100 mg/kg of chromium, there were no significant differences in body weight, organ weight or blood variables. Histologic evaluations of liver and kidneys of controls and those fed the highest chromium doses, whether chloride or picolinate, also failed to find significant differences. Again, more research is needed.
The FDA recently gave chromium picolinate the food-related qualified health claim that ""it may reduce the risk of insulin resistance, and therefore may reduce the risk of type 2 diabetes . . . however, the existence of such a relationship between chromium picolinate and either insulin resistance or type 2 diabetes is highly uncertain.''
Finally, a recent systematic review of randomized controlled trials on the effect of chromium supplementation on glucose metabolism and lipids came to the following conclusions: supplementation in patients with type 2 diabetes may have a modest beneficial effect on glycemia and dyslipidemia; there was no beneficial effect of chromium supplementation on serum glucose or lipid levels on those without diabetes; 41 studies met the criteria for the review, almost half of which were of poor quality; larger effects were more commonly observed in poor-quality studies; and future studies that address the limitations in the current evidence are needed before definitive claims can be made about the effect of chromium supplementation. And, it should be added, future research should focus on how to determine which patients are chromium deficient. It is very important and certainly warranted to develop a good method to define an individual's chromium status.
Contraindications, Precautions & Adverse Reactions
Chromium is contraindicated in those hypersensitive to any component of a chromium-containing supplement.
Pregnant women and nursing mothers should avoid doses of chromium above the upper limit of the estimated safe and adequate daily dietary intake (ESADDI). The ESADDI for chromium is 50 to 200 micrograms daily.
Those with a history of hypoglycemia should exercise caution in the use of chromium supplements.
Those with a history of hyperglycemia or type 2 diabetes mellitus should only use chromium supplements for the possible management of abnormal glucose tolerance under medical supervision.
Chromium supplements are generally well tolerated. There are a few reports of adverse reactions particularly with use of chromium picolinate. There is one report of a 24-year-old body builder who developed rhabdomyolysis after ingesting 1,200 micrograms of chromium in the form of chromium picolinate. Acute generalized exanthematous pustulosis was reported to be associated with the use of chromium picolinate. A case of interstitial nephritis was reported to occur five months after a subject received a six-week course of 600 micrograms of chromium in the form of chromium picolinate daily. Another report described anemia, thrombocytopenia, hemolysis, liver dysfunction, renal failure and weight loss after the use of 1,200-2,400 micrograms of chromium picolinate daily for four to five months.
Beta-Blockers: One study reported that those on beta-blockers who took 600 micrograms daily of chromium in the form of high-chromium yeast were found to have modestly elevated HDL-cholesterol levels after two months of chromium use.
Ascorbate: Concomitant intake of ascorbate and chromium may increase the absorption of chromium.
Concomitant intake of chromium with foods rich in phytic acid (unleavened bread, raw beans, seeds, nuts and grains and soy isolates) may decrease the absorption of chromium.