Chromium in Metabolic and Cardiovascular Disease

Abstract

Chromium is an essential mineral that appears to have a beneficial role in the regulation of insulin action, metabolic syndrome, and cardiovascular disease. There is growing evidence that chromium may facilitate insulin signaling and chromium supplementation therefore may improve systemic insulin sensitivity. Tissue chromium levels of subjects with diabetes are lower than those of normal control subjects, and a correlation exists between low circulating levels of chromium and the incidence of type 2 diabetes. Controversy still exists as to the need for chromium supplementation. However, supplementation with chromium picolinate, a stable and highly bioavailable form of chromium, has been shown to reduce insulin resistance and to help reduce the risk of cardiovascular disease and type 2 diabetes. Since chromium supplementation is a safe treatment, further research is necessary to resolve the confounding data. The existing data suggest to concentrate future studies on certain forms as chromium picolinate and doses as at least 200 mcg per day.

Key words

chromium - chromium picolinate - diabetes - cardiovascular risk - insulin - metabolic syndrome

References

• 1 Food and Nutrition Board . Recommended dietary allowances. 10th ed. Washington, DC: National Academy Press 2000
• 2 Anderson RA. Chromium, glucose intolerance and diabetes.  J Am Coll Nutr. 1998;  17 548-555
• 3 Jeejeebhoy KN, Chu RC, Marliss EB, Greenberg GR, Bruce-Robertson A. Chromium deficiency, glucose intolerance, and neuropathy reversed by chromium supplementation in a patient receiving long-term total parenteral nutrition.  Am J Clin Nutr. 1977;  30 531-538
• 4 Freund H, Atamian S, Fischer JE. Chromium deficiency during total parenteral nutrition.  JAMA. 1979;  241 496-498
• 5 Brown RO, Forloines-Lynn S, Cross RE, Heizer WD. Chromium defi-ciency after long-term total parenteral nutrition.  Dig Dis Sci. 1986;  31 661-664
• 6 Anderson RA. Chromium and parenteral nutrition.  Nutrition. 1995;  11 83-86
• 7 Nielsen F. Controversial chromium: does the superstar mineral of the mountebanks receive appropriate attention from clinicians and nutritionists?.  Nutr Today. 1996;  31 226-233
• 8 Anderson R, Cheng N, Bryden N. et al . Elevated intakes of supplemental chromium improve glucose and insulin variables in individuals with type 2 diabetes.  Diabetes. 1997;  46 1786-1791
• 9 Anderson RA. Nutritional factors influencing the glucose/insulin system: chromium.  J Am Coll Nutr. 1997;  16 404-410
• 10 Vincent JB. Elucidating a biological role for chromium at a molecular level.  Acc Chem Res. 2000;  33 503-510
• 11 Anderson RA, Polansky MM, Bryden NA. Stability and absorption of chromium and adsorption of chromium histidinate complexes by humans.  Biol Trace Elem Res. 2004;  101 211-218
• 12 Anderson RA, Bryden NA, Evock-Clover M, Steele NC. Beneficial effects of chromium on glucose and lipid variables in control and somatotropin-treated pigs are associated with increased tissiue chromium and altered tissiue copper, iron, and zinc.  J Anim Sci. 1997;  75 657-661
• 13 Anderson RA, Bryden NA, Polansky MM, Gautschl K. Dieatary chromium effects on tissue chromium concentrations and chromium absorption in rats.  J Trace Elem Exp Med. 1996;  9 12-25
• 14 Rajpathak S, Rimm EB, Li T, Morris JS, Stampfer MJ, Willett WC, Hu FB. Lower toenail chromium in men with diabetes and cardiovas-cular disease compared with healthy men.  Diabetes Care. 2004;  27 2211-2216
• 15 Doisy RJ, Streeten DHP, Freiberg JM, Schneider AJ. Chromium metabolism in man and biochemical effects. In: Prasad AS, Oberleas D (eds). Trace Elements in Human Health and Disease: Essential and Toxic Elements. Vol. 2 New York: Marcel Dekker 1976
• 16 Bunker VW, Lawson MS, Delves HT, Clayton BE. The uptake and excretion of chromium in the elderly.  Am J Clin Nutr. 1984;  39 797-802
• 17 Saad MJA. Molecular mechanisms of insulin resistance.  Braz J Med Biol Res. 1994;  27 941-957
• 18 Kahn CR. Current concepts of the molecular mechanism of insulin action.  Ann Rev Med. 1985;  36 429-451
• 19 Roth RA, Lui F, Chin JE. Biochemical mechanisms of insulin resistance.  Horm Res. 1994;  41 ((Suppl 2)) 51-55
• 20 Davis CM, Vincent JB. Chromium oligopeptide activates insulin receptor kinase activity.  Biochemistry. 1997;  36 4382-4385
• 21 Vincent JB. The quest for the molecular mechanism of chromium action and its relationship to diabetes.  Nutr Rev. 2000;  58
• 22 Yamamoto A, Wada O, Ono T. Isolation of a biologically active low-molecular-mass chromium compound from rabbit liver.  Eur J Biochem. 1987;  165 627-631
• 23 Davis CM, Vincent JB. Chromium oligopeptide activates insulin receptor tyrosine kinase activity.  Biochemistry. 1997;  36 4382-4385
• 24 Rabinowitz MB, Gonick HC, Levine SR, Davidson MB. Clinical trial of chromium and yeast supplements on carbohydrate and lipid metabolism in diabetic men.  Biol Trace Elem Res. 1983;  5 449-466
• 25 Uusitupa MIJ, Kumpulainen JT, Voutilainen E, Hersio K, Sarlund H, Pyorala KP, Koivistoinen P, Lehto JT. Effect of inorganic chromium supplementation on glucose tolerance, insulin response and serum lipids in noninsulin-dependent diabetics.  Am J Clin Nutr. 1983;  38 404-410
• 26 Mossop RT. Effects of chromium (III) on fasting glucose, cholesterol and cholesterol HDL levels in diabetics.  Cent Afr J Med. 1983;  29 80-82
• 27 Nath R, Minocha J, Lyall V, Sunder S, Kumar V, Kapoor S, Dhar KL. Assessment of chromium metabolism in maturity onset and juvenile diabetes using chromium-51 and therapeutic response of chromium administration on plasma lipids, glucose tolerance and insulin levels. In Shapcott D, Hubert J (eds) Chromium in Nutrition and Metabolism. Amsterdam: Elsevier/North Holland 1979: 213-222
• 28 Wang ZQ, Zhang XH, Russell JC, Hulver M, Cefalu WT. Chromium picolinate enhances skeletal muscle cellular insulin signaling in vivo in obese, insulin-resistant JCR:LA-cp rats.  J Nutr. 2006;  136 415-420
• 29 Chen G, Liu P, Pattar GR, Tackett L, Bhonagiri P, Strawbridge AB, Elmendorf JS. Chromium activates glucose transporter 4 trafficking and enhances insulin-stimulated glucose transport in 3T3-L1 adipocytes via a cholesterol-dependent mechanism.  Mol Endocrinol. 2006;  20 857-870
• 30 Pattar GR, Tackett L, Liu P, Elmendorf JS. Chromium picolinate positively influences the glucose transporter system via affecting cholesterol homeostasis in adipocytes cultured under hyperglycemic diabetic conditions.  Mutat Res. 2006;  610 93-100
• 31 Glinsmann W, Mertz W. Effect of trivalent chromium on glucose tolerance.  Metabolism. 1966;  15 510-520
• 32 Sherman L, Glennon JA, Brech WJ, Klomberg GH, Gordon ES. Failure of trivalent chromium to improve hyperaglycemia in diabetes mellitus.  Metabolism. 1968;  17 439-442
• 33 Offenbacher KG, Pi-Sunyer X. Beneficial effect of chromium-rich yeast on glucose tolerance and blood lipids in elderly subjects.  Diabetes. 1980;  29 919-925
• 34 Elias AN, Grossman MK, Valenta LJ. Use of the artificial beta cell (ABC) in the assessment of peripheral insulin sensitivity; effect of chro-mium supplementation in diabetic patients.  Gen Pharmacol. 1984;  15 535-539
• 35 Evans GW. The effect of chromium picolinate on insulin controlled parameters in humans.  Int J Biosoc Med Res. 1989;  11 163-180
• 36 Roeback  Jr  JR, Mae K, Chambless LE, Fletcher RH. Effects of chro-mium supplementation on serum high-density lipoprotein cholesterol levels in men taking beta-blockers.  Ann Intern Med. 1991;  115 917-924
• 37 Abraham AS, Brooks BA, Eylath U. The effects of chromium supplementation on serum glucose and lipids in patients with and without non-insulin-dependent diabetes.  Metabolism. 1992;  41 768-771
• 38 Lee NA, Reasner CA. Beneficial effect of chromium supplementa-tion on serum triglyceride levels in NIDDM.  Diabetes Care. 1994;  17 1449-1452
• 39 Ravina A, Slezak L, Rubal A, Mirsky N. Clinical use of the trace element chromium (III) in the treatment of diabetes mellitus.  J Trace Elem Exp Med. 1995;  8 183-190
• 40 Jovanovic-Peterson L, Gutierry M, Peterson CM. Chromium supplementation for gestational diabetic women (GDM) improves glucose tolerance and decreases hyperinsulinemia.  Diabetes. 1996;  43 337
• 41 Thomas VLK, Gropper SS. Effect of chromium nicotinic acid supplementation on selected cardiovascular disease risk factors.  Biol Trace Elem Res. 1997;  55 297-305
• 42 Anderson RA, Cheng N, Bryden NA, Polansky MM, Chi J, Feng J. Beneficial effects of chromium for people with diabetes.  Diabetes. 1997;  46 1786-1791
• 43 Ravina A, Slezak L, Mirsky N, Bryden NA, Anderson RA. Reversal of corticosteroid-induced diabetes mellitus with supplemental chromium.  Diabet Med. 1999;  16 164-167
• 44 Cheng N, Zhu X, Shi H, Wu W, Chi J, Cheng J, Anderson R. Follow-up survey of people in China with type 2 diabetes mellitus con-suming supplemental chromium.  J Trace Elem Exp Med. 1999;  12 55-60
• 45 Cefalu WT, Bell-Farrow AD, Stegner J, Wang ZQ, King T, Morgan T, Terry JG. Effect of chromium picolinate on insulin sensitivity in vivo.  J Trace Elem Exp Med. 1999;  12 71-83
• 46 Trow LG, Lewis J, Greenwood RH, Sampson MJ, Self KA, Crews HM, Fairweather-Tait SJ. Lack of effect of dietary chromium supplementation on glucose tolerance, plasma insulin and lipoprotein levels in patients with type 2 diabetes.  Int J Vitam Nutr Res. 2000;  70 14-18
• 47 Morris BW, Kouta S, Robinson R, MacNeil S, Heller S. Chromium supplementation improves insulin resistance in patients with type 2 diabetes mellitus.  Diabet Med. 2000;  17 684-685
• 48 Ghosh D, Bhattacharya B, Mukherjee B, Manna B, Sinha M, Chowdhury J, Showdhury S. Role of chromium supplementation in Indians with type 2 diabetes mellitus.  J Nutr Biochem. 2002;  13 690-697
• 49 Gunton JE, Cheung NW, Hitchman R, Hams G, O’Sullivan C, Foster-Powell K, MacElduff A. Chromium supplementation does not improve glucose tolerance, insulin sensitivity, or lipid profile: a randomized, placebo-controlled, double-blind trial of supplementation in subjects with impaired glucose tolerance.  Diabetes Care. 2005;  28 712-713
• 50 Kleefstra N, Houweling ST, Jansman FG, Groenier KH, Gans RO, Meyboom-de Jong B, Bakker SJ, Bilo HJ. Chromium treatment has no Effect in patients with poorly controlled, insulin-treated type 2 diabetes in an obese western population. A randomized, double-blind, placebo-controlled trial.  Diabetes Care. 2006;  29 521-525
• 51 Vrtovec M, Vrtovec B, Briski A, Kocijancic A, Anderson RA, Radovancevic B. Chromium supplementation shortens QTc interval duration in patients with type 2 diabetes mellitus.  Am Heart J. 2005;  149 632-635
• 52 Martin J, Wang ZQ, Zhang XH. et al . Chormium picolinate supplementation attenuates body weight gain and increases insulin sensiti-vity in subjects with type 2 diabetes.  Diabetes Care. 2006;  29 1826-1832
• 53 Bahijri SM, Mira SA, Mufti AM, Ajabnoor MA. The effects of inorganic chromium and brewer's yeast supplementation on glucose tolerance, serum lipids and drug dosage in individuals with type 2 diabetes.  Saudi Med J. 2000;  21 831-837
• 54 Bahijri SM, Mufti AM. Beneficial effects of chromium in people with type 2 diabetes, and urinary chromium response to glucose load as a possible indicator of status.  Biol Trace Elem Res. 2002;  85 97-109
• 55 Komorowski J, Juturu V. Chromium supplementation does not improve glucose tolerance, insulin sensitivity, or lipid profile: a randomized, placebo-controlled, double-blind trial of supplementation in subjects with impaired glucose tolerance. Response to Gunton et al.  Diabetes Care. 2005;  28 1841-1842
• 56 Althuis MD, Jordan NE, Ludington EA, Wittes JT. Glucose and insulin responses to dietary chromium supplements: a meta-analysis.  Am J Clin Nutr. 2002;  76 148-155
• 57 Pittler MH, Stevinson C, Ernst E. Chromium picolinate for reducing body weight: meta-analysis of randomized trials.  Int J Obes Relat Metab Disord. 2003;  27 522-529
• 58 Uusitupa MI, Mykkanen L, Siitonen O, Laakso M, Sarlund H, Kolehmainen P, Rasanen T, Kumpulainen J, Pyorala K. Chromium supplementation in impaired glucose tolerance of elderly: effects on blood glucose, plasma insulin, C-peptide and lipid levels.  Br J Nutr. 1992;  68 209-216
• 59 Volpe SL, Huang HW, Larpadisorn K, Lesser II. Effect of chromium supplementation and exercise on body composition, resting meta-bolic rate and selected biochemical parameters in moderately obese women following an exercise program.  J Am Coll Nutr. 2001;  20 293-306
• 60 Cefalu WT, Hu FB. Role of chromium in human health and in diabetes.  Diabetes Care. 2004;  27 2741-2751
• 61 Anderson RA. Chromium, glucose tolerance, diabetes and lipid metabolism.  J Adv Med. 1995;  8 37-49
• 62 Kaats GR, Keith SC, Wise JA, Pullin D, Squires WG. Effects of baseline total cholesterol levels on diet and exercise interventions.  JANA. 1999;  2 42-49
• 63 Boyd SG, Boone BE, Smith AR, Conners J, Dohm GL. Combined dietary chromium picolinate supplementation and an exercise program leads to a reduction of serum cholesterol and insulin in college-aged subjects.  J Nutr Biochem. 1998;  9 471-475
• 64 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
• 65 Guallar E, Jimenez FJ, Veer P van’t, Bode P, Riemersma RA, Gomez-Aracena J, Kark JD, Arab L, Kok FJ, Martin-Moreno JM. EURAMIC-Heavy Metals and Myocardial Infarction Study Group . Low toenail chromium concentration and increased risk of nonfatal myocardial infarction.  Am J Epidemiol. 2005;  162 157-164
• 66 Jain SK, Patel P, Rogier K, Jain SK. Trivalent chromium inhibits protein glycosylation and lipid peroxidation in high glucose-treated erythrocytes.  Antioxid Redox Signal. 2006;  8 238-241
• 67 American Diabetes Association . Standards of medical care in diabetes (Position Statement).  Diabetes Care. 2006;  29 ((Suppl 1)) 14
• 68 Vincent JB. The Biochemistry of Chromium.  J Nutr. 2000;  130 715-718
• 69 http://www.cfsan.fda.gov/~dms/qhccr.html

Correspondence