Chromium Biochemistry In Brief:
The biologically active form of chromium is Cr(III). It was observed that rats fed on yeast could not process glucose, which was reversed by feeding chromium or Cr(III) or chromium-rich food1 and patients on prolonged total parenteral nutrition (TPN) developed insulin resistance which was reversed by chromium2. Diabetes patients tend to be deficient in chromium levels due to enhanced excretion of chromium3. Taken together these observations suggest a role for chromium in glucose metabolism.
Glucose tolerance factor (GTF) is a complex of various molecules including a 1500 Da chromium binding peptide of glycine, cysteine, glutamic and aspartic acid called low molecular weight Cr (LMWCr) binding substance. In plasma, transferrin acts as a carrier for chromium. Upon binding transferrin receptors on cell surface the chromium-transferrin complex is endocytosed into low pH vesicles where chromium is released. The freed chromium is then bound by LMWCr 4, converting it to a holopeptide.
Chromium potentiates insulin sensitivity and insulin-dependent signaling via two activities: the holopeptide LMWCr is thought to stimulate tyrosine kinase activity of insulin- bound active insulin receptors, with downstream activation of insulin receptor kinase and enhanced insulin action5. In addition, chromium inhibits phosphotyrosine phosphatase, which decreases insulin sensitivity6. Chromium may also stimulate insulin binding and internalization, increase insulin receptor number, and beta-cell sensitivity7.
Chromium is concentrated in the spleen, kidney, liver and bone8. Chromium deficiency occurs in the elderly, as the ability to absorb chromium is impaired 9. Chromium picolinate, a popular chromium source is reduced by ascorbates and thiols, with generation of reactive hydroxyl radicals that can cleave cellular DNA 10.
Role And Benefits Of Chromium In Various Diseases
Efficacy Of Chromium In Controlling Diabetes:
There is sufficient evidence for some efficacy of chromium in controlling diabetes. Low chromium levels often occur in patients with diabetes 11. Over 15 trials have found that chromium or Cr(III) reduces fasting blood glucose levels in patients with type I and II diabetes and improves insulin sensitivity in type II patients. 12
Oral intake of Cr (III) decreases insulin levels, and glycosylated hemoglobin (HbA1C). HbA 1c, plasma glucose (fasting glucose, 2-h glucose) and insulin (fasting and 2-h insulin) levels decreased in type II diabetes in a Chinese population upon chromium picolinate (CrP) treatment. 13
Insulin sensitivity increased in 10 days upon CrP (200 ug/day) treatment in another trial14, while 10 months of CrP (500 ug/day) treatment in 833 patients improved glucose metabolism and alleviated diabetes symptoms 15. Two randomized trials administered 100 ug/day chromium or Cr(III) to patients- one study found a 70% increase in insulin sensitivity of individuals with first degree relatives suffering diabetes.16
The second study in type II diabetes patients showed that supplementation of chromium with sufonylurea increases glucose control and insulin sensitivity using the most reliable measure- the euglycemic-hyperinsulinemic clamp. Decrease in gain of body weight and visceral fat was noted 17.
Brewer's yeast and Cr chloride significantly reduced fasting glucose (and 2h glucose), and the required dose required of antidiabetic drugs in a double-blind cross over, randomized trial involving 78 type II diabetes patients. 18
Another such study in 43 diabetes patients given placebo and brewer's yeast without GTF over 16 months, showed decrease in blood glucose and insulin levels.19
A trial of 188 type II diabetes patients treated with jiangtangkang (which contains chromium) 20 for 2 months, showed decrease in fasting and post-meal glucose, and HbA1c.
Supplementing Cr(III) with biotin lowered fasting blood glucose and HbA1C levels in overweight or obese type II diabetes patients. 21
Benefits Of Chromium In Decreasing Triglyceride, Serum Cholesterol And HbA1c Levels:
High doses of chromium can decrease triglyceride, serum cholesterol (10% reduction) and HbA1c levels, while increasing HDL (2% increase) in diabetic patients 22. This effect is also seen in non-diabetic individuals, and in the elderly 23, including those suffering low nutrition status. Glucose metabolism was also improved in women with gestational diabetes at 4 or 8 ug/kg CrP 24, and in steroid-induced diabetes (steroid leads to chromium loss) at 600 ug/day25. A decrease in insulin and C-peptide levels was also reported in gestational diabetes.
What Does Chromium Content In Toenail Indicate?
In a large study, 33737 individuals were monitored for toenail content of chromium or Cr(III) levels, with incidence of heart disease over 7 years and an inverse relationship was noted 26. Another study 27 compared chromium content in toenail of 688 diabetic patients to 361 healthy individuals. The diabetic/healthy subject OR was 0.74 (95% CI 0.49–1.11; P= 0.18 for trend) and diabetic with cardiovascular disease/healthy OR was 0.45 (95% CI 0.24–0.84; P= 0.003 for trend). However there is no study on the effect of chromium on cardiovascular disease, or any evidence that toenail chromium content reflects body content of chromium.
Can Chromium Control Prediabetes?
Prediabetes (Glucose intolerance) and normal glucose tolerance:
Most evidence suggests chromium is not effective in controlling prediabetes. Among nine studies on glucose intolerance in prediabetics, only two studies by one group28 reported significant reduction in post-load glucose levels with Cr treatment. Glucose tolerance, triglyceride or cholesterol levels are not improved in elderly glucose intolerant patients 29. Fourteen studies showed no effect of Cr on post-load glucose levels in subjects with normal glucose tolerance.
Chromium And Lipid Metabolism:
In two studies, brewer's yeast increased HDL cholesterol significantly in patients with type 2 diabetes30.
As already mentioned, high doses of chromium can decrease triglyceride and serum cholesterol by 10% while increasing HDL by 2% 31 in diabetic patients, and non-diabetic individuals suffering low nutrition status. Intake of chromium at 600 ug for 2 months increased HDL by 16% in patients on beta-blockers 32. Similarly an HDL increase of 21% was seen in atherosclerosis patients treated with 250 ug chromium daily in 7-16 months 33. This effect is not seen in prediabetics or individuals with normal glucose tolerance. In the latter study triglyceride levels were lower in treated patients compared to placebo (1.68 +/- 0.11 vs 2.10 +/- 0.14 nmol/L).34
In a study of type II diabetes patients, supplementing 1000 ug/day Cr(III) with sulfonylurea decreased free fatty acids (-0.2mmol/L vs. -0.12 mmol/L) as compared to placebo with sulfonylurea. However, triglycerides showed an opposite trend in this study. No statistically significant changes were seen in LDL cholesterol in any study35
Chromium For Weight Loss (Including Obesity), Fat Loss, And Lean Body Mass:
In a study of type II diabetes patients supplementing 1000 ug/day Cr(III) with sulfonylurea (n=17) lowered rate of fat accumulation (0.12% vs 1.17%), and gain in body weight (0.9 kg vs. 2.2 kg) as well as fat-free body mass (1.07 vs. 0.68) as compared to placebo with sulfonylurea (n=12), over 6 months.36
Chromium picolinate treatment at 200-400 ug/day in combination with strength training has been shown to induce weight loss (1.1-1.2kg over 10-13 weeks) and fat loss, with increase in lean body mass in some studies, even in the elderly, but the methodology used is questionable37. Other studies indicate no effect38.
One study provides tentative benefit of chromium in preventing weight gain upon cessation of cigarette smoking 39. Further studies are needed to resolve the effect of chromium on weight loss and gain of lean muscle mass 40.
Effects Of Chromium Picolinate In Treating Atypical Depression:
A small double-blind study in patients (n=15) suffering atypical depression found antidepressant activity of chromium picolinate in 70% patients, while placebo had no effect, over an 8 week treatment period. It is speculated that chromium picolinate may downregulate 5HT2A , or increase insulin sensitivity, resulting in antidepressant effects41 . A randomized, double-blind, multicenter study in patients with atypical depression (n=113) receiving 600 ug/day chromium picolinate or placebo showed improvement in carbohydrate craving and appetite regulation upon chromium treatment. It is suggested that studies with larger dose of chromium may affect mood 42.
Effectiveness Of Chromium Picolinate In Treating Dysthymia/Mild Depression:
There is tentative evidence that chromium picolinate or polynicotinate at 200 ug-400 ug/day may act as antidepressant. Only 5 patients were tested who were partial responders to psychiatric drugs nortrityline or sertraline 43.
Effectiveness Of Chromium In Treating Hypoglycemia:
200 ug chromium chloride treatment over 3 months alleviated hypoglycemia and increased serum glucose levels post-glucose load in hypoglycemic patients (n=8) in a double crossover study, with increase in insulin binding and insulin receptor number44. Chromium salts protect against cerebral injury and induce regeneration of cerebral tissues caused by hypoglycemic injury. Chromium appears to modulate transcription factors, neuroplasticity markers and glucose transporters45. However it should be noted that a case has been reported where hypoglycemia occurred upon fasting and insulin suppression which was reversed by withdrawing chromium supplements 46.
Effectiveness Of Chromium In Treating Polycystic Ovary Syndrome (PCOS):
Insulin resistance is commonly associated with PCOS. Insulin resistant women with PCOS have significantly increased fasting insulin and decreased serum levels of chromium 47. Obese women with PCOS were treated with chromium picolinate 1000 ug/day with 38% improvement in glucose disposal rate, using the euglycemic hyperinsulinemic clamp technique suggesting improved insulin sensitivity 48.
Benefits Of Chromium In Treating Turner's Syndrome:
Turner's syndrome is a genetic disorder with high incidence of diabetes. Patients suffering this syndrome (n=14) dosed with 30 g brewer's yeast (50 ug of chromium) daily for 8 weeks showed improved glucose tolerance. In three patients with high cholesterol, a decrease in cholesterol and/or triglyceride levels with an increase in high-density lipoprotein cholesterol was noted 49.
1 (Schwarz, K. & Mertz, W. (1959) Chromium(III) and glucose tolerance factor. Arch. Biochem. Biophys. 85: 292–295.; Mertz, W., Roginski, E. E. & Schwarz, K. (1961) Effect of trivalent chromium on glucose uptake by epididymal fat tissue of rats. J. Biol. Chem. 236:318–322.),
2 (Freund H, Atamian S, Fischer JE. Chromium deficiency during total parenteral nutrition. JAMA 1979;241:496-8; Jeejeebhoy KN. Chromium and parenteral nutrition. J Trace Elem Exp Med 1999;12:85–9.)
3 (Morris BW, Kemp GJ, Hardisty CA. Plasma chromium and chromium excretion in diabetes. Clin Chem 1985;31:334-5)
4 (Vincent JB: Elucidating a biological role for chromium at a molecular level. Acc Chem Res 33:503–510, 2000; Clodfelder BJ, Emamaullee J, HepburnDD, Chakov NE, Nettles HS, Vincent JB: The trail of chromium (III) in vivo from the blood to the urine: the roles of trans-ferrin and chromodulin. J Biol Inorg Chem 6:608–617, 2001)
5 (Vincent JB: Elucidating a biological role for chromium at a molecular level. Acc Chem Res 33:503–510, 2000; Vincent JB: The biochemistry of chromium. J Nutr 130:715–718, 2000; Vincent JB: Mechanisms of chromium action: low-molecular-weight chromium-binding substance. J Am Coll Nutr 18:6–12, 1999)
6 (Davis CM, Sumrall KH, Vincent JB: A biologically active form of chromium may activate a membrane phosphotyrosine phosphatase (PTP). Biochemistry 35: 12963–12969, 1996)
7 (Anderson RA: Nutritional factors inﬂuencing the glucose/insulin system: chromium. J Am Coll Nutr 16:404–410, 1997)
8 (PDRhealth: Chromium [Internet]. Available from http://www.pdrhealth.com/drug_info/nmdrugproﬁles/nutsupdrugs/chr_0073.shtml. Accessed 3 February 2004)
9 (Ding W, Chai Z, Duan P, Feng W, Qian Q: Serum and urine chromium concentrations in elderly diabetics. Biol Trace Elem Res 63:231–237, 1998; Davies S, McLaren Howard J, Hunnisett A, Howard M: Age-related decreases in chromium levels in 51,665 hair, sweat, and serum samples from 40,872 patients: implications for the prevention of cardiovascular disease and type II diabetes mellitus. Metabolism 46:469–473, 1997)
10 (Speetjens, J. K., Collins, R. A., Vincent, J. B. & Woski, S. A. (1999). The nutritional supplement chromium(III) tris(picolinate) cleaves DNA. Chem. Res.Toxicol. 12: 483–487.)
11 (Morris BW, Kemp GJ, Hardisty CA. Plasma chromium and chromium excretion in diabetes. Clin Chem 1985;31:334-5)
12 (Mertz W. Chromium in human nutrition: a review. J Nutr 1993;123:626-33.; Anderson RA, Cheng N, Bryden NA, et al. Elevated intakes of supplemental chromium improve glucose and insulin variables in individuals with type 2 diabetes. Diabetes 1997;46:1786-91.; Martin J, Wang ZQ, Zhang XH, et al. Chromium picolinate supplementation attenuates body weight gain and increases insulin sensitivity in subjects with type 2 diabetes. Diabetes Care 2006;29:1826-32; Albarracin C, Fuqua B, 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 2008;24:41-51; Geohas J, Finch M, Juturu V, et al. Improvement in Fasting Blood Glucose with the Combination of Chromium Picolinate and Biotin in Type 2 Diabetes Mellitus. American Diabetes Association 64th Annual Meeting, June 2004, Orlando, Florida, abstract 191-OR; Althius MD, Jordon NE, Ludington EA, Wittes JT. Glucose and insulin responses to dietary chromium supplements: a meta-analysis. Am J Clin Nutr 2002;76:148-55.; Balk, E. M.; Tatsioni, A.; Lichtenstein, A. H.; Lau, J.; Pittas, A. G. (2007). Effect of Chromium Supplementation on Glucose Metabolism and Lipids: A systematic review of randomized controlled trials. Diabetes Care 30 (8): 2154–2163; Rabinovitz H, Friedensohn A, Leibovitz A, et al. Effect of chromium supplementation on blood glucose and lipid levels in type 2 diabetes mellitus elderly patients. Int J Vitam Nutr Res 2004;74:178-82; Liu VJ, Abernathy RP. Chromium and insulin in young subjects with normal glucose tolerance. Am J Clin Nutr 1982;35:661-7; Cefalu WT, Hu FB. (2004) Role of chromium in human health and in diabetes. Diabetes Care 27:2741-51.)
13 (Anderson RA, Cheng N,Bryden NA, Polansky MM, Cheng N, Chi J, Feng J: Elevated intakes of supplemental chromium improve glucose and insulin variables in individuals with type 2 diabetes. Diabetes 46:1786–1791, 1997; Anderson RA. Chromium, glucose tolerance, and diabetes. Biological Trace Element Research 1992;32:19-24.)
14 (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 8: 183–190, 1995)
15 (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 consuming supplemental chromium. J Trace Elem Exp Med 12:55–60, 1999)
16 (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 12:71–83, 1999)
17 (Martin J, Wang ZQ, Zhang XH, et al. Chromium picolinate supplementation attenuates body weight gain and increases insulin sensitivity in subjects with type 2 diabetes. Diabetes Care 2006;29:1826-32.)
18 (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 85:97–109, 2002; 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 21:831–837, 2000)
19 (Rabinowitz MB, Gonick HC, Levin SR, Davidson MB: Effects of chromium and yeast supplements on carbohydrate and lipid metabolism in diabetic men. Diabetes Care 6:319–327, 1983)
20 (Chen SH, Sun YP, Chen XS: Effect of jiangtangkang on blood glucose, sensitivity of insulin and blood viscosity in non-insulin dependent diabetes mellitus [in Chinese]. Zhongguo Zhong Xi Yi Jie He Za Zhi 17:666–668, 1997)
21 (Albarracin C, Fuqua B, 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 2008;24:41-51; Singer GM, Geohas J. The effect of chromium picolinate and biotin supplementation on glycemic control in poorly controlled patients with type 2 diabetes mellitus: a placebo-controlled, double-blinded, randomized trial. Diabetes Technol Ther 2006;8:636-43; McCarty MF, Med Hypotheses. 2000 May;54(5):786-93.Toward practical prevention of type 2 diabetes.)
22 (Lee NA, Reasner CA. Beneficial effect of Chromium supplementation on serum triglyceride levels in NIDDM. Diabetes Care 1994;17:1449-52.; Anderson RA, Cheng N, Bryden NA, et al. Elevated intakes of supplemental chromium improve glucose and insulin variables in individuals with type 2 diabetes. Diabetes 1997;46:1786-91; Rabinovitz H, Friedensohn A, Leibovitz A, et al. Effect of chromium supplementation on blood glucose and lipid levels in type 2 diabetes mellitus elderly patients. Int J Vitam Nutr Res 2004;74:178-82; 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;41:768-71.)
23 (Press RI, Geller J, Evans GW. The effect of Chromium picolinate on serum cholesterol and apolipoprotein fractions in human subjects. Western J Med 1993;152:41-5.; Lefavi RG, Wilson GD, Keith RE, Anderson RA, Blessing DL, Hames CG, et al. Lipid-lowering effect of a dietary Chromium (III) Nicotinic Acid complex in male athletes. Nutr Res 1993;13:239-49; Offenbach E, Pistunyer F. Beneficial effect of Chromium-rich yeast on glucose tolerance and blood lipids in elderly patients. Diabetes 1980;29:919-25; Wang MM, Fox EA, Stoecker BJ, Menendez CE, Chan SB. Serum cholesterol of adults supplemented with brewer's yeast or Chromium Chloride. Nutr Res 1989;9:989-98.)
24 (Jovanovic L, Gutierrez M, Peterson CM: Chromium supplementation for women with gestational diabetes mellitus. J Trace Elem Exp Med 12:91–97, 1999)
25 (Ravina A, Slezak L, Mirsky N, Bryden NA, Anderson RA: Reversal of corticosteroid-induced diabetes mellitus with supplemental chromium. Diabet Med 16:164–167, 1999)
26 (Rimm EB, Guallar E, Giovannucci E, Ascherio A, Stampfer MJ, Willet WC, Hu F: Toenail chromium levels and risk of coronary heart disease among normal and overweight men. Presented at the American Heart Association 42nd Annual Conference on Cardiovascular Disease, Epidemiology and Prevention, 23–26 April, 2002, Honolulu, Hawaii)
27 (Rajpathak S, Rimm EB, Li T, et al. Lower toenail chromium in men with diabetes and cardiovascular disease compared with healthy men. Diabetes Care 2004;27:2211-6)
28 (Anderson RA, Polansky MM, Bryden NA, Roginski EE, Mertz W, Glinsmann W: Chromium supplementation of human subjects: effects on glucose, insulin, and lipid variables. Metabolism 32:894–899,1983; Anderson RA, Polansky MM, Bryden NA, Canary JJ: Supplemental-chromium effects on glucose, insulin, glucagon, and urinary chromium losses in subjects consuming controlled low-chromium diets. Am J Clin Nutr 54:909–916, 1991)
29 (Uusitupa MI, Mykkanen L, Siitonen O, et al. Chromium supplementation in impaired glucose tolerance of elderly: effects on blood glucose, plasma insulin, C-peptide and lipid levels. Br J Nutr 1992;68:209-16)
30 (Grant AP, McMullen JK: The effect of brewer's yeast containing glucose tolerance factor on the response to treatment in type 2 diabetics: a short controlled study. Ulster Med J 51:110–114, 1982; Bahijiri 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 21:831–837, 2000)
31 (Lee NA, Reasner CA. Beneficial effect of Chromium supplementation on serum triglyceride levels in NIDDM. Diabetes Care 1994;17:1449-52.; Anderson RA, Cheng N, Bryden NA, et al. Elevated intakes of supplemental chromium improve glucose and insulin variables in individuals with type 2 diabetes. Diabetes 1997;46:1786-91; Rabinovitz H, Friedensohn A, Leibovitz A, et al. Effect of chromium supplementation on blood glucose and lipid levels in type 2 diabetes mellitus elderly patients. Int J Vitam Nutr Res 2004;74:178-82; 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;41:768-71.)
32 (Roeback JR, Hla KM, Chambless LE, Fletcher RH. Effects of Chromium supplementation on serum high-density lipoprotein cholesterol levels in men taking beta-blockers. Annals Int Med 1991;115:917-24.)
33 (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;41:768-71.)
34 (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;41:768-71.)
35 (Martin J, Wang ZQ, Zhang XH, et al. (2006) Chromium picolinate supplementation attenuates body weight gain and increases insulin sensitivity in subjects with type 2 diabetes. Diabetes Care 29:1826-32).
36 (Martin J, Wang ZQ, Zhang XH, et al. (2006) Chromium picolinate supplementation attenuates body weight gain and increases insulin sensitivity in subjects with type 2 diabetes. Diabetes Care 29:1826-32).
37 (Kaats GR, Blum K, Fisher JA, Adelman JA. Effects of chromium picolinate supplementation on body composition: a randomized, double-masked, placebo-controlled study. Curr Ther Res 1996;57:747-56; Gilbert R. Kaats, Kenneth Blum, Dennis Pullin, Samuel C. Keith and Robert Wood. "A randomized, double-masked, placebo-controlled study of the effects of chromium picolinate supplementation on body composition: a replication and extension of a previous study," Current Therapeutic Research 59(6):379-388, 1998.; Martin J, Wang ZQ, Zhang XH, et al. (2006) Chromium picolinate supplementation attenuates body weight gain and increases insulin sensitivity in subjects with type 2 diabetes. Diabetes Care 29:1826-32; Pittler MH, Stevinson C, Ernst E. Chromium picolinate for reducing body weight: meta-analysis of randomized trials. Int J Obes Relat Metab Disord 2003;27:522-9; )
38 (Hallmark MA, Reynolds TH, DeSouza CA, et al. Effects of chromium and resistive training on muscle strength and body composition. Med Sci Sports Exerc 1996;28:139-44.; Lukaski HC, Bolonchuk WW, Siders WA, Milne DB. Chromium supplementation and resistance training: effects on body composition, strength, and trace element status of men. Am J Clin Nutr 1996;63:954-65. Trent LK, Thieding-Cancel D. Effects of chromium picolinate on body composition. J Sports Med Phys Fitness 1995;35:273-80; Vincent JB. The potential value and toxicity of chromium picolinate as a nutritional supplement, weight loss agent and muscle development agent. Sports Med . 2003, 33:213-230; Jenkinson DM, Harbert AJ. Supplements and sports. Am Fam Physician . 2008;78(9):1039-1046; Kleefstra N, Houweling ST, Bakker SJ, et al. Chromium treatment has no effect in patients with type 2 diabetes in a Western population: a randomized, double-blind, placebo-controlled trial. Diabetes Care . 2007;30(5):1092-1096.)
39 (Drug Alcohol Depend. 2009 Jun 1;102(1-3):116-22. A proof of concept randomised placebo controlled factorial trial to examine the efficacy of St John's wort for smoking cessation and chromium to prevent weight gain on smoking cessation. Parsons A, Ingram J, Inglis J, Aveyard P, Johnstone E, Brown K, Franklin M, Bermudez I.)
40 (Fisher J. The Chromium Program. New York, NY: Harper and Row; 1990.; McCarthy MG. Hypothesis: Sensitization of insulin-dependent hypothalamic glucoreceptors may account for the fat-reducing effects of Chromium Picolinate. J Optimal Nutr 1993;21:36-53.; Evans GW, Pouchnik DJ. Composition and biological activity of chromium-pyridine carbosylate complexes. J Inorgranic Biochemistry 1993;49:177-87.; Katts GR, Ficher JA, Blum K. The effects of Chromium Picolinate supplementation on body composition in different age groups. Age 1991;14(4):138 (Abstract #40))
41 (Davidson JR, Abraham K, Connor KM, McLeod MN. Effectiveness of chromium in atypical depression: a placebo-controlled trial. Biol Psychiatry. 2003 Feb 1;53(3):261-4.).
42 (Docherty JP, Sack DA, Roffman M, Finch M, Komorowski JR. A double-blind, placebo-controlled, exploratory trial of chromium picolinate in atypical depression: effect on carbohydrate craving. J Psychiatr Pract. 2005 Sep;11(5):302-14.)
43 (McLeod MN, Gaynes BN, Golden RN. Chromium potentiation of antidepressant pharmacotherapy for dysthymic disorder in 5 patients. J Clin Psychiatry. 1999 Apr;60(4):237-40.)
44 (Anderson RA, Polansky MM, Bryden NA, Bhathena SJ, Canary JJ. Effects of supplemental chromium on patients with symptoms of reactive hypoglycemia. Metabolism. 1987 Apr;36(4):351-5.)
45 (Sahin K, Tuzcu M, Orhan C, Ali S, Sahin N, Gencoglu H, Ozkan Y, Hayirli A, Gozel N, Komorowski JR.Chromium modulates expressions of neuronal plasticity markers and glial fibrillary acidic proteins in hypoglycemia-induced brain injury. Life Sci. 2013 Dec 18;93(25-26):1039-48.)
46 (Shabana Valiji Bharmal, Veronica Moyes, Sahid Ahmed, Ashley Grossman . Hypoglycaemia: Possible mediation by chromium salt medication. HORMONES 2010, 9(2):181-183)
47 (Chakraborty P, Ghosh S, Goswami SK, Kabir SN, Chakravarty B, Jana K.Altered trace mineral milieu might play an aetiological role in the pathogenesis of polycystic ovary syndrome. Biol Trace Elem Res. 2013 Apr;152(1):9-15. doi: 10.1007/s12011-012-9592-5. Epub 2013 Jan 16.)
48 (Lydic ML, McNurlan M, Bembo S, Mitchell L, Komaroff E, Gelato M. Chromium picolinate improves insulin sensitivity in obese subjects with polycystic ovary syndrome. Fertil Steril. 2006 Jul;86(1):243-6. Epub 2006 May 30.)
49 (Saner G, Yüzbaşiyan V, Neyzi O, Günöz H, Saka N, Ciğdem S. Alterations of chromium metabolism and effect of chromium supplementation in Turner's syndrome patients. Am J Clin Nutr. 1983 Oct;38(4):574-8).)