European Journal of Epidemiology

, Volume 14, Issue 6, pp 621–626 | Cite as

Effect of supplementation with chromium picolinate on antibody titers to 5-hydroxymethyl uracil

  • Ikuko Kato
  • Joseph H. Vogelman
  • Vladimir Dilman
  • Jerzy Karkoszka
  • Krystyna Frenkel
  • Nancy P. Durr
  • Norman Orentreich
  • Paolo Toniolo


Recent in vitro studies have shown that chromium (III) compounds such as chromium picolinate, a popular dietary supplement among people trying to lose weight, produce chromosome damage. We monitored levels of DNA damage in a chromium picolinate supplement trial by measuring antibodies titers to an oxidized DNA base, 5-hydroxymethyl-2'-deoxyuridine (HMdU), by enzyme-linked immunosorbent assays. Ten obese volunteer women completed a 8-week course of 400 μg chromium picolinate per day. In either absolute titers or percent of the baseline value, there were no changes in antibody titers at 4 or 8 weeks. The titers were very stable within individuals and those of one individual rarely crossed over others, which was reflected in an intraclass correlation coefficient of 0.99 (95% confidence interval: 0.96–1.00). There were no effects on glucose and lipid metabolism in this period. The results of this trial suggest that chromium (III) picolinate in a dose typically used for nutrient supplementation dose not increase oxidative DNA damage, as measured by anti-HMdU antibody levels.

Autoantibodies Chromium picolinate Dietary supplement DNA damage HMdU 


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  1. 1.
    Mertz W. Chromium in human nutrition: A review. J Nutr 1993; 123: 626–633.PubMedGoogle Scholar
  2. 2.
    Evans CW. Dietary supplementation with essential met al picolinates. Chem Abstr 1091; 95: 23384d.Google Scholar
  3. 3.
    IARC. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Vol 49: Chromium. Nickel and Welding. Lyon: IARC, 1990.Google Scholar
  4. 4.
    Cohen MD, Kargacin B, Klein CB, Costa M. Mechanisms of chromium carcinogenicity and toxicity. Crit Rev Toxicol 1993; 23: 255–281.PubMedGoogle Scholar
  5. 5.
    Cupo DY, Wetterhahn KE. Binding of chromium to chromatin and DNA from liver and kidney of rats treated with sodium dichromate and chromium (III) chloride in vivo. Cancer Res 1985; 45: 1146–1151.PubMedGoogle Scholar
  6. 6.
    Snow WT. A possible role of chromium (III) in genotoxicity. Env Health Perspect 1991; 92: 75–81.Google Scholar
  7. 7.
    Bridgewater LC, Manning FCE, Woo ES, Patierno SR. DNA polymerase arrest by adducted trivalent chromium. Mol Carcinog 1994; 9: 122–133.PubMedGoogle Scholar
  8. 8.
    Friedman J, Shabtai F, Levy LS, Djaldetti M. Chromium chloride induces chromosomal aberrations in human lymphocytes via indirect action. Mutat Res 1987; 191: 207–210.CrossRefPubMedGoogle Scholar
  9. 9.
    Tsou T-C, Chen C-L, Liu T-Y, Yang J-L. Induction of 8-hydroxydeoxyguanosine in DNA by chromium (III) plus hydrogen peroxide and its prevention by seavengers. Carcinogenesis 1996; 17: 103–108.PubMedGoogle Scholar
  10. 10.
    Borges KM, Wetterhahn KE. Chromium cross-links glutathione and cysteine to DNA. Carcinogenesis 1989; 10: 2165–2168.PubMedGoogle Scholar
  11. 11.
    Zhitkovich A, Voitkun V, Costa M. Formation of the amino acid-DNA complexes by hexavalent and trivalent chromium in vitro: Importance of trivalent chromium and phosphate group. Biochemistry 1996; 35: 7275–7282.CrossRefPubMedGoogle Scholar
  12. 12.
    Zhitkovich A, Voitkun V, Costa M. Glutathione and free amino acids from stable complexes with DNA following exposure of intact mammalian cells to chromate. Carcinogenesis 1995; 16: 907–913.PubMedGoogle Scholar
  13. 13.
    Liu S, Dixon K. Induction of mutagenic DNA damage by chromium (VI) and glutathione. Environ Molec Mutagen 1996; 28: 71–79.Google Scholar
  14. 14.
    Mattagajasingh SN, Mirsa HP. Mechanisms of the carcinogenic chromium (VI)-induced DNA-protein crosslinking and their characterization in cultured intact human cells. J Biol Chem 1996; 271: 33550–33560.CrossRefPubMedGoogle Scholar
  15. 15.
    Snow ET, Xu LS. Chromium (III) bound to DNA templates promotes increased polymerase processivity and decreased fidelity during replication in vitro. Biochemistry 1991; 30: 11238–11245.PubMedGoogle Scholar
  16. 16.
    Snow ET. Effects of chromium on DNA replication in vitro. Environmental Health Perspect 1994; 102(suppl 3): 41–44.Google Scholar
  17. 17.
    Connett PH, Wetterhahn KE. Metabolism of the carcinogen chromate by cellular constitutes. Struct Bonding 1983; 54: 93–124.Google Scholar
  18. 18.
    De Flora S, Wetterhahn KE. Mechanisms of chromium metabolism and genotoxicity. Life Chem Rep 1989; 7: 169–244.Google Scholar
  19. 19.
    Gargas ML, Norton RL, Paustenbach DJ, Finley BL. Urinary exertion of chromium by humans following ingestion of chromium picolinate: Implications for biomonitoring. Drug Metab Dispos 1994; 22: 522–529.PubMedGoogle Scholar
  20. 20.
    Mertz W. Effects and metabolism of glucose tolerance factor. Nutr Rev 1975 33: 129–135.PubMedGoogle Scholar
  21. 21.
    Stearns DM, Wise JP Sr, Patierno SR, Wetterhahn KE. Chromium(III) picolinate produces chromosome damage in Chinese hamster ovary cells. FASEB J 1995; 9: 1643–1648.PubMedGoogle Scholar
  22. 22.
    Ozawa T, Hanaki A. Spin-trapping studies on the reactions of Cr(III) with hydrogen peroxide in the presence of biological reductants: Is Cr(III) non toxic? Biochenm Int 1990; 22: 343–352.Google Scholar
  23. 23.
    Klein CB, Frenkel K, Costa M. The role of oxidative processes in metal carcinogenesis. Chem Res Toxicol 1991; 4: 592–604.PubMedGoogle Scholar
  24. 24.
    Frenkel K. Carcinogen-mediated oxidant formation and oxidative DNA damage. Pharmacol Ther 1992; 53: 127–166.CrossRefPubMedGoogle Scholar
  25. 25.
    Shirname-More L, Rossman TG, Troll W, Teebor GW, Frenkel K. Genetic effects of 5-hydroxyl-2′-deoxyuridine, a product of ionizing radiation. Mutat Res 1987; 178: 177–186.PubMedGoogle Scholar
  26. 26.
    Berkner KI, Falk WR. EcoRI cleavage and methylation of DNAs containing modified pyrimidines in the recognition sequence. J Biol Chem 1977; 252: 3185–3193.PubMedGoogle Scholar
  27. 27.
    Weitzman SA, Turk PW, Milkowski DH, Kozloski K. Free radical adducts induce alterations in DNA cytosine methylation. Proc Natl Acad Sci USA 1994; 91: 1261–1264.PubMedGoogle Scholar
  28. 28.
    Jones PA, Buckley JD. The role of DNA methylation in cancer. Adv Cancer Res 1990: 54: 1–23.PubMedGoogle Scholar
  29. 29.
    Frenkel K, Karkoszka J, Cohen B, Baranski B, Jakubowski M, Cosma G, Taioli E, Toniolo P. Occupational exposures to Cd, Ni, and Cr modulate titers of antioxidized DNA base autoantibodies. Env Health Perspect 1994; 102(Suppl): 221–225.Google Scholar
  30. 30.
    Frenkel K, Karkoszka J, Kim E, Taioli E. Recognition of oxidized DNA bases by sera of patients with inflammatory diseases. Free Radic Bio Med 1993; 14: 483–494.CrossRefGoogle Scholar
  31. 31.
    Frenkel K, Khasak D, Karkoszka J, Stiller, M. Enhanced antibody titers to an oxidized DNA base in inflammatory and neoplastic diseases. Exp Dermatol 1992; 1: 242–247.PubMedGoogle Scholar
  32. 32.
    Sasson M, Stiller MJ, Shupack JL, Khasak D, Karkoszka J, Frenkel K. Antibody titers to an oxidized thymidine moiety are altered by systemic pharmacotherapy and by ultraviolet B phototherapy. Arch Dermatol Res 1993; 285: 227–229.PubMedGoogle Scholar
  33. 33.
    Toniolo P, Levitz M, Zeleniuch Jacquotte A, Banerjee S, Koenig KL, Shore RE, Strax P, Pasternack BS. A prospective study of endogenous estrogens and breast cancer in postmenopausal women. JNCI 1995; 87: 190–197.PubMedGoogle Scholar
  34. 34.
    Erlanger BF, Beiser SM. Antibodies specific for ribonucleosides and ribonucleotides and their reaction with DNA. Proc Natl Acd Sci 1964; 52: 68–74.Google Scholar
  35. 35.
    Fleiss J. The Design and Analysis of Clinical Experiments. New York: Wiley, 1986.Google Scholar
  36. 36.
    Duthie SJ, Ma A, Ross MA, Collins A.R. Antioxidant supplementation decreases oxidative DNA damage in human lymphocytes. Cancer Res 1996; 56: 1291–1295.PubMedGoogle Scholar
  37. 37.
    Cadenas S, Rojas C, Pertz-Campo R, Lopez-Torres M, Barja G. Caloric and carbohydrate restriction in the kidney: effects on free radical metabolism. Exp Gerontol 1994; 29: 77–88CrossRefPubMedGoogle Scholar
  38. 38.
    Hart RW, Leakey JE, Chou M, Duffy PH, Allaben WT, Feuers RJ. Modulation of chemical toxicity by modification of caloric intake. Adv Exp Med Biol 1992; 322: 73–81.PubMedGoogle Scholar
  39. 39.
    Djuric Z, Heilbrun LK, Reading BA, Boomer A, Valeriote FA, Martino S. Effects of a low-fat diet on levels of oxidative damage to DNA in human peripheral nucleated blood cells. J Natl Cancer Inst 1991; 83: 766–769, 1991.PubMedGoogle Scholar
  40. 40.
    Abraham AS, Brooks BA, Eylath U. The effects of chromium supplementation on serum glucose and lipids in patients with and without non-insulin dependent dia betes. Metabolism 1992; 41: 768–771.CrossRefPubMedGoogle Scholar
  41. 41.
    Mossop RT. Effects of chromium (III) on fasting blood glncose, cholesterol and cholesterol HDL levels in diabetics. Cent Afr J Med 1983; 29: 80–82, 1983.PubMedGoogle Scholar
  42. 42.
    Press RI, Geller J, Evans GW. The effects of chromium picolinate on serum cholesterol and apolipoprotein factions in human subjects. West J Med 1990; 152: 41–45.PubMedGoogle Scholar
  43. 43.
    Riales R, Albrink MJ. Effect of chromium chloride supplementation on glucose tolerance and serum lipids including high-density lipoprotein of adult men. Am J Clin Nutr 1981; 34: 2670–2678.PubMedGoogle Scholar
  44. 44.
    Wang MM, Fox EA, Stoccker BJ, Menendez CE, Chan SB. Serum cholesterol of adults supplemented with brewer's yeast or chromium chloride. Nutr Res 1989; 9: 989–998.Google Scholar

Copyright information

© Kluwer Academic Publishers 1998

Authors and Affiliations

  • Ikuko Kato
    • 1
  • Joseph H. Vogelman
    • 2
  • Vladimir Dilman
    • 1
  • Jerzy Karkoszka
    • 1
  • Krystyna Frenkel
    • 1
  • Nancy P. Durr
    • 2
  • Norman Orentreich
    • 2
  • Paolo Toniolo
    • 1
  1. 1.Nelson Institute of Environmental Medicine, New York University School of MedicineNew York
  2. 2.Biomedical Research StationOrentreich Foundation for the Advancement of Science, Inc.Cold-Spring-on-HudsonUSA

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