Chromium

• How It Works

  There is no clear evidence to show that chromium supplementation is effective for improving glucose metabolism, losing weight, or building muscle mass.

  Chromium is an element required by the body in very small amounts (0.025 mg a day). Adequate amounts are usually obtained in the diet from foods such as American cheese, meat, fish, fruits, and whole grains. Lab experiments suggest chromium is involved in maintaining adequate levels of glucose, fats, and insulin in the body. In theory, this could help patients with type 2 diabetes, but the current evidence in human studies is mixed.

  Chromium is sometimes combined with GTF (Glucose Tolerance Factor) in over-the-counter products. GTF is a yeast extract that helps with glucose metabolism in lab studies, but this effect has not been confirmed in humans.

• Purported Uses
  • To treat diabetes
    Clinical trials produced conflicting results regarding chromium’s ability to lower blood glucose, cholesterol, and triglycerides.
  • To treat polycystic ovarian syndrome
    Data suggest that any effect of chromium on PCOS symptoms is small, with clinical relevance uncertain.
  • To improve muscle mass
    Clinical trials do not support this use.
  • To improve weight loss
    Clinical trials do not support this use.
• Do Not Take If
  • You have liver or kidney problems: There have been some case reports of liver and kidney toxicities with chromium supplements.
  • You are taking sulfonylureas or insulin: Chromium can lower your blood sugar even more.
• Side Effects

  In rare cases, liver toxicity has occurred.

  Case reports

  • Kidney failure: In two patients who took chromium supplements to enhance weight loss.
  • Red skin lesions: Accompanied with fever, swelling, and high white blood cell counts.
  • Destruction of skeletal muscle: In one patient while taking chromium picolinate in addition to other dietary supplements. Therefore, whether chromium caused this condition is not clear.
  • Low blood sugar: In a 29-year-old man with type 2 diabetes who took chromium supplements in addition to insulin.
• Clinical Summary

  Chromium is a trace element that is necessary for glucose, insulin, and lipid metabolism in humans ^(1) (9). It is marketed as a dietary supplement for diabetes, weight loss, and to improve muscle mass. Trivalent chromium from yeast extract is sometimes referred to as glucose tolerance factor (GTF) in over-the-counter products.

  Although most people consume adequate amounts through diet, chromium deficiency has been implicated in the development of diabetes ⁽²⁵⁾. In vitro studies suggest that chromium produces beneficial modulatory effects under hyperglycemic conditions ⁽²⁶⁾. Animal models also suggest antidiabetic ^(27) (28), antidepressant ^{(29) (30) (31)}, and anxiolytic ⁽³²⁾ properties.

  In human studies, chromium supplementation with biotin may help to improve glycemic control in type 2 diabetes (T2D) ^{(4) (5) (6)}, but results from other studies on chromium alone are mixed ^(33) (44). Another study showed that chromium picolinate may increase satiety ⁽¹⁵⁾. However, many clinical studies failed to demonstrate improvements in glucose metabolism, weight loss, or muscle mass ^{(3) (7) (8) (9) (10) (11) (12) (13) (14)}. More recently one meta-analysis suggested that overall, chromium monosupplementation improved glycemic control and lipid profiles ⁽³⁴⁾, while another determined that chromium picolinate did not affect A1C or fasting plasma glucose ⁽³⁵⁾. It has been posited that mixed and modest effect sizes may reflect a greater glucoregulatory effect in complex patients with comorbid diabetes, depression, and binge eating ⁽³⁶⁾. A large population study suggests that those who consumed chromium-containing supplements had a reduced risk of T2D compared with those who did not, and that more study is needed ⁽³⁷⁾.

  In women with polycystic ovary syndrome (PCOS), chromium supplementation did not affect endocrine profiles, and nitric oxide or glutathione levels, but did reduce acne, hirsutism, C-reactive protein, total antioxidant capacity, and malondialdehyde levels ⁽⁴⁵⁾. However, meta-analyses suggest that for PCOS patients, chromium supplementation may not have significant benefits ⁽⁴⁶⁾ or the magnitude of effect is small, with clinical relevance uncertain ⁽⁴⁷⁾.

  Chromium is poorly absorbed following oral administration, but salt forms such as chromium picolinate, niacin-bound chromium, and chromium chloride, appear to have better bioavailability. Other novel chromium compounds also have improved bioavailability ^(40) (41). Adverse effects are rare but can include renal failure ^(18) (19), rhabdomyolysis ⁽²⁰⁾, liver damage ⁽²¹⁾, and dermatitis ⁽²²⁾.

• Food Sources

  Liver, American cheese, broccoli, brewer’s yeast, wheat germ, meat, eggs, chicken, fish, fruits, whole grains, brown sugar, alfalfa, and animal fats ^(1) (25)

• Purported Uses
  • Diabetes
  • Polycystic ovarian syndrome
  • Muscle mass
  • Weight loss
• Mechanism of Action

  Chromium is an essential trace element involved with glucose and lipid metabolism, circulating insulin levels, and the peripheral activity of insulin ⁽¹⁾. In vitro and in vivo studies suggest that chromium potentiates the activity of insulin ^(23) (42). This is thought to occur via enhanced intracellular tyrosine kinase activity that results from an interaction between chromium, low molecular weight chromium-binding substance, and activated cell surface insulin receptors ⁽²⁾.

  In animal models of diabetes, chromium recovered beta cell functioning and alleviated macroangiopathy ⁽²⁷⁾. It also augmented the insulin signaling pathway, dulled negative-regulators of insulin signaling, enhanced adenosine monophosphate-activated protein kinase (AMPK) activity to increase cellular glucose uptake, and attenuated oxidative stress ⁽⁴²⁾. Chromium may also modulate peroxisome proliferator-activated receptor-gamma (PPAR-gamma), insulin receptor substrate (IRS-1), and nuclear factor-kappaB (NF-κB) proteins ⁽²⁸⁾. Antidepressant effects occur via modified brain 5-hydroxytryptamine receptor (5-HT) function and increased serotonergic and noradrenergic functioning ^(30) (31). Additional mechanisms for antidepressant and anxiolytic effects include the lowering of plasma corticosterone levels via reversal of hypothalamic–pituitary–adrenal axis (HPA) axis overactivity ⁽³²⁾. In humans, suggested antidepressant mechanisms include 5HT2A downregulation and increased insulin sensitivity ⁽³⁸⁾.

• Contraindications

  Patients with liver or renal insufficiency may have increased susceptibility to adverse effects ⁽²⁴⁾.

• Adverse Reactions

  Rare: Hepatic toxicity ⁽²¹⁾

  Case reports
  Renal failure: In a 33-year-old white woman who also presented with weight loss, anemia, thrombocytopenia, hemolysis, and liver dysfunction after chronic high doses of chromium picolinate to enhance weight loss ⁽¹⁸⁾ ; and in a 49-year-old female nurse who took chromium picolinate 600 mcg daily for 6 weeks for weight reduction ⁽¹⁹⁾.
  Acute generalized exanthematous pustulosis: Characterized by erythematous lesions, fever, edema, leukocytosis, and eosinophilia ⁽²²⁾.
  Rhabdomyolysis: In a 24-year old patient taking chromium picolinate in addition to other dietary supplements ⁽²⁰⁾.
  Hypoglycemia: In a 29-year-old man with T2D after ingesting oral chromium 1000 mcg daily in addition to taking insulin ⁽⁴³⁾.

• Herb-Drug Interactions

  Sulfonylureas/insulin: Chromium can have additive hypoglycemic effects ⁽⁴³⁾.

• References

  1. Porter DJ, Raymond LW, Anastasio GD. Chromium: friend or foe? Arch Fam Med 1999;8:386-90.

  2. Vincent JB. The biochemistry of chromium. J Nutr 2000;130:715-8.

  3. Christopher H. Bailey. Improved Meta-Analytic Methods Show No Effect of Chromium Supplements on Fasting Glucose. Biological Trace Element Research, 2013; 157 (1):1-8.

  4. Anderson RA, et al. Elevated intakes of supplemental chromium improve glucose and insulin variable in individuals with type 2 diabetes. Diabetes 1997;46:1786-91.

  5. Albarracin CA, Fuqua BC, Evans JL, Goldfine ID. Chromium picolinate and biotin combination improves glucose metabolism in treated, uncontrolled overweight to obese patients with type 2 diabetes. Diabetes Metab Res Rev. Jan-Feb 2008;24(1):41-51.

  6. Wang ZQ, Qin J, Martin J, et al. Phenotype of subjects with type 2 diabetes mellitus may determine clinical response to chromium supplementation. Metabolism. Dec 2007;56(12):1652-1655.

  7. Campbell WW, et al. Effects of resistance training and chromium picolinate on body composition and skeletal muscle in older men. J Appl Physiol 1999;86:29-39.

  8. Clancy SP, et al. Effects of chromium picolinate supplementation on body composition, strength, and urinary chromium loss in football players. Int J Sport Nutr 1994;4:142-53.

  9. Grant KE, et al. Chromium and exercise training: Effect on obese women. Med Sci Sports Exercise 1997;29:992-8.

  10. Lukaski HC, et al. Chromium supplementation and resistance training: effects on body composition, strength, and trace element status of men. Am J Clin Nutr 1996;63:954-65.

  11. Pasman WJ, et al. The effectiveness of long-term supplementation of carbohydrate, chromium, fibre and caffeine on weight maintenance. Int J Obes Rel Metab Dis 1997;21:1143-51.

  12. Volpe SL, et al. Effect of chromium supplementation and exercise on body composition, resting metabolic rate and selected biochemical parameters in moderately obese women following an exercise program. J Am Coll Nutr 2001;20:293-306.

  13. Ali A, Ma Y, Reynolds J, et al. Chromium effects on glucose tolerance and insulin sensitivity in persons at risk for diabetes mellitus. Endocr Pract. 2011 Jan-Feb;17(1):16-25.

  14. Iqbal N, Cardillo S, Volger S, et al. Chromium picolinate does not improve key features of metabolic syndrome in obese nondiabetic adults. Metab Syndr Relat Disord. 2009 Apr;7(2):143-50.

  15. Anton SD, Morrison CD, Cefalu WT, et al. Effects of chromium picolinate on food intake and satiety. Diabetes Technol Ther. Oct 2008;10(5):405-412.

  16. Letter from FDA. Chromium picolinate and Insulin resistance. Accessed December 8, 2009.

  17. Krikorian R, Eliassen JC, Boespflug EL, et al. Improved cognitive-cerebral function in older adults with chromium supplementation. Nutr Neurosci. 2010 Jun;13(3):116-22.

  18. Cerulli J, et al. Chromium picolinate toxicity. Ann Pharmacother 1998; 32:428-31.

  19. Wasser WG, Feldman NS, D’Agati VD. Chronic renal failure after ingestion of over-the-counter chromium picolinate. Ann Int Med 1997;126:410.

  20. Martin WR, Fuller RE. Suspected chromium picolinate-induced rhabdomyolysis. Pharmacotherapy 1998;18:860-2.

  21. Jeejeebhoy KN. The role of chromium in nutrition and therapeutics and as a potential toxin. Nutr Rev 1999;57:329-35.

  22. Young PC, et al. Acute generalized exanthematous pustulosis induced by chromium picolinate. J Am Acad Dermatol 1999;41:820-3.

  23. Cefalu WT, et al. Oral chromium picolinate improves carbohydrate and lipid metabolism and enhances skeletal muscle Glut-4 translocation in obese, hyperinsulinemic (JCR-LA corpulent) rats. J Nutr 2002 ;132:1107-14.

  24. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. Washington: National Academy Press; 2001.

  25. Mlyniec K, Davies CL, de Aguero Sanchez IG, et al. Essential elements in depression and anxiety. Part I. Pharmacol Rep. Aug 2014;66(4):534-544.

  26. Ganguly R, Sahu S, Chavez RJ, et al. Trivalent chromium inhibits TSP-1 expression, proliferation, and O-GlcNAc signaling in vascular smooth muscle cells in response to high glucose in vitro. Am J Physiol Cell Physiol. Jan 15 2015;308(2):C111-122.

  27. Huang S, Peng W, Jiang X, et al. The effect of chromium picolinate supplementation on the pancreas and macroangiopathy in type II diabetes mellitus rats. J Diabetes Res. 2014;2014:717219.

  28. Sahin K, Tuzcu M, Orhan C, et al. Anti-diabetic activity of chromium picolinate and biotin in rats with type 2 diabetes induced by high-fat diet and streptozotocin. Br J Nutr. Jul 28 2013;110(2):197-205.

  29. Iovieno N, Dalton ED, Fava M, et al. Second-tier natural antidepressants: review and critique. J Affect Disord. May 2011;130(3):343-357.

  30. Khanam R, Pillai KK. Effect of chromium picolinate on modified forced swimming test in diabetic rats: involvement of serotonergic pathways and potassium channels. Basic Clin Pharmacol Toxicol. Feb 2006;98(2):155-159.

  31. Franklin M, Odontiadis J. Effects of treatment with chromium picolinate on peripheral amino acid availability and brain monoamine function in the rat. Pharmacopsychiatry. Sep 2003;36(5):176-180.

  32. Dubey VK, Ansari F, Vohora D, et al. Possible involvement of corticosterone and serotonin in antidepressant and antianxiety effects of chromium picolinate in chronic unpredictable mild stress induced depression and anxiety in rats. J Trace Elem Med Biol. Jan 2015;29:222-226.

  33. Paiva AN, Lima JG, Medeiros AC, et al. Beneficial effects of oral chromium picolinate supplementation on glycemic control in patients with type 2 diabetes: A randomized clinical study. J Trace Elem Med Biol. Oct 2015;32:66-72.

  34. Suksomboon N, Poolsup N, Yuwanakorn A. Systematic review and meta-analysis of the efficacy and safety of chromium supplementation in diabetes. J Clin Pharm Ther. Jun 2014;39(3):292-306.

  35. Yin RV, Phung OJ. Effect of chromium supplementation on glycated hemoglobin and fasting plasma glucose in patients with diabetes mellitus. Nutr J. 2015;14:14.

  36. Brownley KA, Boettiger CA, Young L, et al. Dietary chromium supplementation for targeted treatment of diabetes patients with comorbid depression and binge eating. Med Hypotheses. Jul 2015;85(1):45-48.

  37. McIver DJ, Grizales AM, Brownstein JS. Risk of Type 2 Diabetes Is Lower in US Adults Taking Chromium-Containing Supplements. J Nutr. Dec 2015;145(12):2675-2682.

  38. Davidson JR, Abraham K, Connor KM, et al. Effectiveness of chromium in atypical depression: a placebo-controlled trial. Biol Psychiatry. Feb 1 2003;53(3):261-264.

  39. Brownley KA, Girdler SS, Stout AL, et al. Chromium supplementation for menstrual cycle-related mood symptoms. J Diet Suppl. Dec 2013;10(4):345-356.

  40. Ulas M, Orhan C, Tuzcu M, et al. Anti-diabetic potential of chromium histidinate in diabetic retinopathy rats. BMC Complement Altern Med. 2015;15:16.

  41. Peng M, Yang X. Controlling diabetes by chromium complexes: The role of the ligands. J Inorg Biochem. May 2015;146:97-103.

  42. Hua Y, Clark S, Ren J, et al. Molecular mechanisms of chromium in alleviating insulin resistance. J Nutr Biochem. Apr 2012;23(4):313-319.

  43. Bunner SP, McGinnis R. Chromium-induced hypoglycemia. Psychosomatics. May-Jun 1998;39(3):298-299.

  44. Guimaraes MM, Carvalho AC, Silva MS. Effect of chromium supplementation on the glucose homeostasis and anthropometry of type 2 diabetic patients: Double blind, randomized clinical trial: Chromium, glucose homeostasis and anthropometry. J Trace Elem Med Biol. Jul 2016;36:65-72.

  45. Jamilian M, Bahmani F, Siavashani MA, et al. The Effects of Chromium Supplementation on Endocrine Profiles, Biomarkers of Inflammation, and Oxidative Stress in Women with Polycystic Ovary Syndrome: a Randomized, Double-Blind, Placebo-Controlled Trial. Biol Trace Elem Res. Jul 2016;172(1):72-78.

  46. Tang XL, Sun Z, Gong L. Chromium supplementation in women with polycystic ovary syndrome: Systematic review and meta-analysis. J Obstet Gynaecol Res. Jan 2018;44(1):134-143.

  47. Heshmati J, Omani-Samani R, Vesali S, et al. The Effects of Supplementation with Chromium on Insulin Resistance Indices in Women with Polycystic Ovarian Syndrome: A Systematic Review and Meta-Analysis of Randomized Clinical Trials. Horm Metab Res. Mar 2018;50(3):193-200.