, Volume 25, Issue 5, pp 1051–1060 | Cite as

Bioavailability of chromium(III)-supplements in rats and humans

  • Niels Laschinsky
  • Karin Kottwitz
  • Barbara Freund
  • Bernd Dresow
  • Roland Fischer
  • Peter Nielsen


Chromium(III) is long regarded as essential trace element but the biochemical function and even basic transport ways in the body are still unclear. For a more rational discussion on beneficial as well as toxic effects of Cr(III), we re-investigated the bioavailability of the most important oral Cr supplements by using radiolabeled compounds and whole-body-counting in rats and in the first time also in humans. The apparent absorption of 51Cr(III) from Cr-picolinate, Cr-nicotinate, Cr-phenylalaninate, Cr-proprionate, or Cr-chloride was generally low (0.04–0.24 %) in rats with slightly higher values for Cr-chloride and -phenylalaninate. Taking a fast urine excretion into account, the true absorption of 51Cr was clearly higher for CrPic3 (0.99 %), probably indicating a different uptake mechanism of this rather stable organic Cr complex. The bioavailability of CrPic3 and Cr(d-Phen)3, the leading compounds in actual investigations, was analysed also in human volunteer by intraindividual comparison. The apparent absorption (=Cr bioavailability) of 51Cr from both compounds was substantially higher in humans (0.8–1 %) than in rats. Again, most of freshly absorbed CrPic3 was excreted into the urine resulting in the same low whole-body retention after 7 days for both compounds. In summary, the bioavailability of Cr from pharmaceutical Cr compound is lower than hitherto assumed. Importantly, humans absorb Cr(III) clearly better than rats. The absorption mechanism of CrPic3 seems to be different from ionic Cr(III) but, as only the same low amount of Cr is retained from this compound, it is also not more bioavailable than other Cr compounds.


Chromium Cr-picolinate Cr-nicotinate Cr-phenylalaninate 51Cr-absorption Whole-body-counting 



The technical assistance of Angelika Schmidt is grateful acknowledged. Parts of the data are including in the medical thesis of N.L., N.F., and G.C. at the University Hamburg, Germany. N.L., K.K., P.N. designed research; N.L., K.K., B.F., B.D., P.N. conducted research; R.F. analyzed data; B.F. and P.N. wrote the paper; all authors read and approved the final manuscript.


  1. Anderson RA, Bryden NA, Polansky MM, Gautschi K (1996) Dietary chromium effects on tissue chromium concentrations and chromium absorption in rats. J Trace Elem Exp Med 9:11–25CrossRefGoogle Scholar
  2. Braunsfurth JS, Gabbe EE, Heinrich HC (1977) Performance parameters of the Hamburg 4π whole body radioactivity detector. Phys Med Biol 22:1–17PubMedCrossRefGoogle Scholar
  3. Broadhurst CL, Domenico P (2006) Clinical studies on chromium picolinate supplementation in diabetes mellitus-a review. Diabetes Technol Ther 8:677–687PubMedCrossRefGoogle Scholar
  4. Cefalu WT, Hu FB (2004) Role of chromium in human health and in diabetes. Diabetes Care 27:2741–2751Google Scholar
  5. Clancy SP, Clarkson PM, DeCheke ME, Nosaka K, Freedson PS, Cunningham JJ, Valentine B (1994) Effects of chromium picolinate supplementation on body composition, strength, and urinary chromium loss in football players. Int J Sport Nutr 4:142–153PubMedGoogle Scholar
  6. Clodfelder BJ, Vincent JB (2005) The time-dependent transport of chromium in adult rats from the bloodstream to the urine. J Biol Inorg Chem 10:383–393PubMedCrossRefGoogle Scholar
  7. Clodfelder BJ, Gullick BM, Lukaski HC, Neggers Y, Vincent JB (2005) Oral administration of the biomimetic [Cr3O(O2CCH2CH3)6(H2O)3]+ increases insulin sensitivity and improves blood plasma variables in healthy and type 2 diabetic rats. J Biol Inorg Chem 10:119–130PubMedCrossRefGoogle Scholar
  8. Davis CM, Royer AC, Vincent JB (1997) Synthetic multinuclear chromium assembly activates insulin receptor kinase activity: functional model for low-molecular-weight chromium-binding substance. Inorg Chem 36:5316–5320CrossRefGoogle Scholar
  9. DiSilvestro RA, Dy E (2007) Comparison of acute absorption of commercially available chromium supplements in humans. J Trace Elem Exp Med 21:274–275Google Scholar
  10. Dogukan A, Tuzcu M, Juturu V, Cikim G, Ozercan I, Komorowski J, Sahin K (2010) Effects of chromium histidinate on renal function, oxidative stress, and heat-shock proteins in fat-fed and streptozotocin-treated rats. J Ren Nutr 20(2):112–120PubMedCrossRefGoogle Scholar
  11. Doisy RJ, Streeten DHP, Souma ML, Kalafer ME, Rekant SL, Dalakos TG (1971) Metabolism of 51chromium in human subjects. In: Mertz W, Cornatzer WE (eds) Newer trace elements in nutrition. Dekker, New York, pp 155–168Google Scholar
  12. Donaldson RM, Barreras RF (1966) Intestinal absorption of trace quantities of chromium. J Lab Clin Med 68:484–493PubMedGoogle Scholar
  13. Dong F, Xiaoping MR, Nair S, Ren J (2007) Chromium (d-phenylalanine)3 improves obesity-induced cardiac contractile defect in ob/ob mice. Obesity 15:2699–2711PubMedCrossRefGoogle Scholar
  14. Dong F, Kandadi MR, Ren R, Sreejayan N (2008) Chromium (d-phenylalanine)3 supplementation alters glucose disposal, insulin signaling, and glucose transporter-4 membrane translocation in insulin-resistant mice. J Nutr 138:1846–1851PubMedGoogle Scholar
  15. Dowling HJ, Offenbacher EG, Pi-Sunyer FX (1989) Absorption of inorganic, trivalent chromium from the vascularly perfused rat small intestine. J Nutr 119:1138–1145PubMedGoogle Scholar
  16. Evans GW (1982a) The role of picolinic acid in metal metabolism. Life Chem Rep 1:57–67Google Scholar
  17. Evans GW (1982b) Dietary supplementation with essential metal picolinates. US Patent 4,315,927, 1982Google Scholar
  18. Evans GW, Pouchnick DJ (1993) Composition and biological activity of chromium-pyridine carboxylate complexes. J Inorg Biochem 49:177–187PubMedCrossRefGoogle Scholar
  19. Gammelgaard B, Jensen K, Steffansen BJ (1999) In vitro metabolism and permeation studies in rat jejunum: organic chromium compared to inorganic chromium. J Trace Elem Med Biol 13:82–88PubMedCrossRefGoogle Scholar
  20. Gargas ML, Norton RL, Paustenbach DJ, Finley BL (1995) Urinary excretion of chromium by humans following ingestion of chromium picolinate. Implications for biomonitoring. Drug Metab Dispos 23:607–609Google Scholar
  21. Hatfield MJ, Gillespie S, Chen Y, Li Z, Cassady CJ, Vincent JB (2006) Low-molecular-weight chromium-binding substance from chicken liver and American alligator liver. Comp Biochem Physiol 144:423–431Google Scholar
  22. Hepburn DD, Vincent JB (2002) In vivo distribution of chromium picolinate in rats and implications for the safety of the dietary supplement. Chem Res Toxicol 15:93–100PubMedCrossRefGoogle Scholar
  23. Jain SK, Croad JL, Velusamy T, Rains JL, Bull R (2010) Chromium dinicocysteinate supplementation can lower blood glucose, CRP, MCP-1, ICAM-1, creatinine, apparently mediated by elevated blood vitamin C and adiponectin and inhibition of NFkappaB, Akt, and Glut-2 in livers of zucker diabetic fatty rats. Mol Nutr Food Res 54(9):1371–1380PubMedCrossRefGoogle Scholar
  24. Jeejeebhoy KN, Chu RC, Marliss EB, Greenberg GR, Bruce-Robertson A (1977) Chromium deficiency, glucose intolerance, and neuropathy reversed by chromium supplementation, in a patient receiving long-term total parenteral nutrition. Am J Clin Nutr 30:531–538PubMedGoogle Scholar
  25. Kottwitz K, Laschinsky N, Fischer R, Nielsen P (2009) Absorption, excretion and retention of 51Cr from labelled Cr-(III)-picolinate in rats. Biometals 22:289–295PubMedCrossRefGoogle Scholar
  26. Lau FC, Bagchi M, Bagchi D (2007) Letter to the editor: comparison of acute absorption of chromium(III) supplements. J Trace Elem Med Biol 21:274–276PubMedCrossRefGoogle Scholar
  27. Li F, Wu X, Zhao T, Zhang M, Zhao J, Mao G, Yang L (2011) Anti-diabetic properties of chromium citrate complex in alloxan-induced diabetic rats. J Trace Elem Med Biol 25(4):218–224PubMedCrossRefGoogle Scholar
  28. Mertz W (1969) Chromium occurrence and function in biological systems. Physiol Rev 49:163–239PubMedGoogle Scholar
  29. Mertz W, Roginski EE, Reba RC (1965) Biological activity and fate of trace quantities of intravenous chromium(III) in the rat. Am J Physiol 209:489–494PubMedGoogle Scholar
  30. National Research Council (2002) Dietary reference intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. A Report of the Panel on Micronutrients, Subcommittees on Upper Reference Levels of Nutrients and of Interpretation and Uses of Dietary Reference Intakes, and the Standing Committee on the Scientific Evaluation of Dietary Reference Intakes Food and Nutrition Board Institute of Medicine. National Academy Press, WashingtonGoogle Scholar
  31. NIH Publication No. 08-5897 (2008) NTP technical report on the toxicology and carcinogenesis. Studies of chromium picolinate monohydrate (CAS NO. 27882-76-4) in F344/N rats and B6C3F1 mice Scheduled Peer Review Date: February 27–28Google Scholar
  32. Olin KL, Stearns DM, Armstrong WH, Keen CL (1996) Comparative retention/absorption of 51chromium from 51Cr chloride, 51Cr nicotinate and 51Cr picolinate in a rat model. Trace Elem Electrolytes 11:182–186Google Scholar
  33. Onkelinx C (1977) Compartment analysis of metabolism of chromium(III) in rats of various ages. Am J Physiol 232(5):E478–E484PubMedGoogle Scholar
  34. Phung OJ, Quercia RA, Keating K, Baker WL, Bell JL, White CM, Coleman CI (2010) Improved glucose control associated with i.v. chromium administration in two patients receiving enteral nutrition. Am J Health Syst Pharm 67(7):535–541PubMedCrossRefGoogle Scholar
  35. Radimer K, Bindewald B, Hughes J, Ervin B, Swanson C, Picciano MF (2004) Dietary supplement use by US adults: data from the national health and nutrition examination survey, 1999–2000. Am J Epidemiol 160:339–349PubMedCrossRefGoogle Scholar
  36. Rhodes NR, McAdory D, Love S, Di Bona KR, Chen Y, Ansorge K, Hira J, Kern J, Kent J, Lara P, Rasco JF, Vincent JB (2010) Urinary chromium loss associated with diabetes is offset by increases in absorption. J Inorg Biochem 104:790–797PubMedCrossRefGoogle Scholar
  37. Sargent T, Lim TH, Jenson RL (1979) Reduced chromium retention in patients with hemochromatosis, a possible basis of hemochromatotic diabetes. Metabolism 28:70–79PubMedCrossRefGoogle Scholar
  38. Schwarz K, Mertz W (1957) A glucose tolerance factor and its differentiation from factor 3. Arch Biochem Biophys 72(2):515–518PubMedCrossRefGoogle Scholar
  39. Sreejayan N, Dong F, Kandadi MR, Yang X, Ren J (2008) Chromium alleviates glucose intolerance, insulin resistance, and hepatic er stress in obese mice. Obesity 16:1331–1337PubMedCrossRefGoogle Scholar
  40. Stanieka H, Krejpcioa Z (2009) The effects of tricentric chromium(III) propionate complex supplementation on pregnancy outcome and maternal and foetal mineral status in rat. Food Chem Toxicol 47:2673–2678CrossRefGoogle Scholar
  41. Stearns DM, Belbruno JJ, Wetterhahn KE (1995) A prediction of chromium(III) accumulation in humans from chromium dietary supplements. FASEB J 9:1650–1657PubMedGoogle Scholar
  42. Sun Y, Ramirez J, Woski SA, Vincent JR (2000) The binding of trivalent chromium to low-molecular-weight chromium-binding substance (LMWCr) and the transfer of chromium from transferrin and chromium picolinate to LMWCr. J Biol Inorg Chem 5:129–136PubMedCrossRefGoogle Scholar
  43. Tkaczyk C, Huk OL, Mwale F, Antoniou J, Zukor DJ, Petit A, Tabrizian M (2010) Investigation of the binding of Cr(III) complexes to bovine and human serum proteins: a proteomic approach. J Biomed Mater Res A 94:214–222PubMedGoogle Scholar
  44. Trumbo PR, Ellwood KC (2006) Chromium picolinate intake and risk in type 2 diabetes: an evidence-based review by the United States food and drug administration. Nutr Rev 64:357–363PubMedCrossRefGoogle Scholar
  45. Tuzcu M, Sahin N, Orhan C, Agca CA, Akdemir F, Tuzcu Z, Komorowski J, Sahin K (2011) Impact of chromium histidinate on high fat diet induced obesity in rats. Nutr Metab 8:28. doi: 10.1186/1743-7075-8-28 CrossRefGoogle Scholar
  46. Vincent J (2000) The biochemistry of chromium. J Nutr 130:715–718PubMedGoogle Scholar
  47. Vincent JB (2003) The potential value and toxicity of chromium picolinate as a nutritional supplement, weight loss agent and muscle development agent. Sports Med 33(3):213–230PubMedCrossRefGoogle Scholar
  48. Vincent JB (2010) Chromium: celebrating 50 years as an essential element? Dalton Trans 39:3787–3794PubMedCrossRefGoogle Scholar
  49. Wang Y, vanOort MM, Yao M, van der Horst DJ, Rodenburg KW (2010) Insulin and chromium picolinat induce translocation of CD36 to plasma membrane trough different signiling pathways in 3T3-L1 adipocytes and with differential functionality of the CD36. Biol Trace Elem Res. doi: 10.1007/s12011-010-8809-8 Google Scholar
  50. Yang X, Palanichamy K, Ontko AC, Rao MN, Fang CX, Ren J, Sreejayan N (2005) A newly synthetic chromium complex-chromium(phenylalanine)3 improves insulin responsiveness and reduces whole body glucose tolerance. FEBS Lett 579:1458–1464PubMedCrossRefGoogle Scholar
  51. Zimmet P, Alberti KG, Shaw J (2001) Global and societal implications of the diabetes epidemic. Nature 414:782–787PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC. 2012

Authors and Affiliations

  • Niels Laschinsky
    • 1
  • Karin Kottwitz
    • 1
  • Barbara Freund
    • 1
  • Bernd Dresow
    • 1
  • Roland Fischer
    • 1
  • Peter Nielsen
    • 1
  1. 1.Institut für Biochemie und Molekulare ZellbiologieZentrum für Experimentelle Medizin, Universitätsklinikum Hamburg-EppendorfHamburgGermany

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