Can Chromium Supplementation Have An Impact For Patients With Diabetes?

We are encountering diabetes with increased frequency in daily practice. The disease is associated with obesity, dyslipidemia and cardiovascular abnormalities, and appears to be approaching epidemic proportions. Insulin resistance precedes the onset of overt type 2 diabetes. Many of the currently available drugs utilized for the treatment of insulin resistance are associated with significant adverse reactions. The utilization of supplements presents an attractive opportunity to reduce insulin resistance without adverse sequelae.

The administration of chromium can reverse manifestations of severe neuropathy, nerve conduction abnormalities and hyperglycemia in the patient. Chromium is an essential metal that plays a role in many metabolic processes and in homeostasis. Chromium, a trace metal element, has been implicated in diabetes and cardiovascular disease. As a trivalent ion, chromium has been proposed as a therapeutic agent to increase insulin sensitivity and improve lipid metabolism.

Research has also demonstrated chromium supplementation to be associated with an antidepressant effect as well as anti-diabetes effects.1 Hypochromia status is associated with lower glucose control and unfavorable lipid metabolism.1 Diminished chromium levels, as determined by scalp hair analysis utilizing spectrophotometry, can occur in patients with diabetes in comparison to patients without diabetes. In addition, Kolachi and colleagues have demonstrated decreased levels of magnesium, manganese and zinc in such patients.2 Authors suggest that lower levels of these essential metals may play a role in the pathogenesis of diabetes.

Recommendations for the utilization of chromium or supplementation in non-obese patients without diabetes are generally not supported. Although chromium is commonly recommended for the management of adverse sequelae associated with diabetes, non-obese patients with normal glycemia receiving chromium picolinate 500 mg bid do not demonstrate changes in the insulin sensitivity after 16 weeks of supplementation.3 Therefore, there is some evidence that chromium picolinate supplementation may not be effective in the prevention of diabetes.

A Closer Look At Laboratory Studies

Sundaram and colleagues have demonstrated the ability of chromium picolinate to attenuate hyperglycemia-induced oxygenated stress in streptozotocin-induced diabetic rats.4 The study authors utilized chromium picolinate at a 1 mg/kilogram body weight dosage daily over four weeks. This study demonstrated reduced activity of antioxidant enzymes such as superoxide dismutase, catalase and glutathione reductase. Furthermore, the administration of chromium picolinate normalized glucose levels and antioxidant status. This study suggests that chromium supplementation may be helpful for the management of diabetes associated ischemic pathology such as peripheral neuropathy or wound healing.

Additional laboratory studies have proven equally supportive of the utilization of chromium in the management of diabetes and its complications. Krol and co-workers examined the insulin sensitizing potential of chromium propionate complex combined with thiamine in rats who had a high fructose diet.5 The authors noted that chromium and thiamine supplemented Wistar rats demonstrated significant insulin sensitizing effects and moderate lipid lowering.

Increasingly, we recognize that depression is not uncommonly associated with diabetes mellitus. One common factor that may link diabetes and depression is oxidative stress. Komorowski and colleagues noted the potential usefulness of chromium picolinate in the management of these coexisting problems was suggested by the ability of chromium picolinate to modulate serotonergic properties and carbohydrate metabolism in Sprague-Dawley rats.6

What The Literature Reveals About Clinical Usage Of Chromium In Diabetes Mellitus

The use of chromium in the management of diabetes and its complications is well supported. Interestingly, certain medicinal plants classically utilized for the treatment of diabetes in traditional Sudanese medicine utilize optical emission spectrometry contain large amounts of chromium as well as zinc, manganese, selenium and magnesium.7

Several studies have evaluated the effectiveness of chromium picolinate or improving glycemic control in type 2 diabetes. In a randomized, double-blind, placebo-controlled clinical trial, Payami and colleagues administered 200 mcg chromium picolinate daily for three months.8 In comparison to placebo, researchers saw a significant decrease in hemoglobin A1c and the presence of fasting blood sugars in patients receiving chromium picolinate.

Utilizing scalp hair samples of the patients diagnosed with diabetes, Afridi and colleagues investigated the additional effects of smoking and excessive alcohol drinking in patients with diabetes.2 This investigation noted a deficiency of chromium, zinc and manganese in patients with diabetes who drank excessively and were smokers, pointing to the increased potential need for supplementation with chromium in such patients.

Basaki and colleagues had demonstrated deficiency in chromium concentrations as well as deficiencies in zinc, copper and iron in young patients with diabetes.9 This suggests that chromium deficiency occurs early in the course of the disease and that one should consider supplementation early in a potential effort to avoid complications associated with increased insulin sensitivity and diabetes.

Jain and coworkers have demonstrated the ability of chromium together with cysteine supplementation to improve glucose metabolism in patients with diabetes.10 This reduces oxidative stress and vascular inflammation, and improves glycemic control. The authors note that utilizing chromium dinicocysteinate supplementation for three months decreased insulin resistance and levels of protein oxidation.

Khosravi-Boroujeni and colleagues have demonstrated the reduction of cardiovascular risk factors in patients with type 2 diabetes, utilizing 300 mg tablets of brewer's yeast daily, each containing 1.2 g chromium.11 After eight weeks, cardiovascular risk factors such as LDL-C levels and plasma triglyceride levels were reduced while plasma HDL-C levels were significantly elevated from baseline. This study presented an interesting observation since brewer's yeast has been recommended for many years for the effective management of diabetic neuropathy. The utilization of yeast supplemented with chromium, selenium and zinc can be effective in reducing hyperglycemia, relieving oxidative stress and modulating disorders of lipid metabolism in diabetic mice.12 Liu and colleagues also demonstrated the ability of high chromium yeast in type 2 diabetic mice to improve histologic findings of pancreatic islet cells.13

Other research demonstrates that in the patient with high insulin resistance, greater urinary excretion of chromium occurs in comparison to those patients with diabetes who have a lesser degree of insulin resistance.14 This suggests that chromium deficiency may be associated with advancing renal dysfunction and chromium loss.

Ahmed and coworkers demonstrated an overall significant lower chromium level in patients with diabetes and a negative correlation between serum levels and hemoglobin A1c independent of renal function evaluation.15 Sharma and colleagues noted //that fasting blood glucose level was significantly reduced in the subjects consuming yeast supplemented with chromium.16 Selcuk and colleagues described the effects of chromium picolinate as well as chromium histidinate on renal dysfunction in the laboratory utilizing a rat kidney model.17 The authors demonstrated that the administration of chromium may be of benefit in reducing renal disease in the patient with diabetes by modulation of nuclear factor-kappa B pathways.

In Summary

As noted earlier, the administration of chromium picolinate has generally proven to be helpful in the management of diabetes. One meta-analysis demonstrated that supplementation with chromium picolinate lowers hemoglobin A1c, fasting blood sugar and two-hour postprandial blood sugars.18 This study was consistent with an earlier systematic review demonstrating the effectiveness of chromium supplementation to significantly improve hyperglycemia in patients with diabetes.19

Authors have suggested for some time that tissue chromium levels in a patient with diabetes are lower than those of normal controls and a relationship has existed between the incidence of type 2 diabetes and chromium levels.20 Diabetes is generally regarded as a disease of aging and it does appear that chromium deficiency develops with aging with or without diabetes. This suggests that chromium supplementation may be important to consider in the older patient with diabetes.21

Considerable research exists to suggest the benefit of chromium in the management of diabetes and complications associated with diabetes including neuropathy, cataracts and renal disease. It appears that chromium is helpful for reduction of insulin resistance and provides improved glycemic control as evidenced by lowering of fasting glucose levels and hemoglobin A1c.

It does not appear that there is a specific definition of "chromium deficiency" but rather a general relationship between lower chromium levels and increased incidence of diabetes and its complications.

Recommended dosages for chromium supplementation range from 100 up to 3,000 mcg per day in various studies. Administering dosages greater than 200 mcg per day for greater than two months appears to provide the most effective intervention or diabetes and its complications. Generally, higher dosages of chromium supplementation appear to be associated with improved responses.

References

1. Cieslak W, Pap K, Bunch DR, et al. Highly sensitive measurement of whole blood chromium by inductively coupled plasma mass spectrometry. Clin Biochem. 2013; 46(3):266-70.

2. Afridi HI, Kazi TG, Brabazon D, et al. Comparative metal distribution in scalp hair of Pakistani and Irish referents and diabetes mellitus patients. Clin Chim Acta. 2013; 415:207-14.

3. Masharani U, Gjerde C, McCoy S, et al. Chromium supplementation in non-obese non-diabetic subjects is associated with a decline in insulin sensitivity. BMC Endocrine Disorders. 2012; 12:31.

4.Sundaram B, Aggarwal A, Sandhir R. Chromium picolinate attenuates hyperglycemia-induced oxidative stress in streptozotocin-induced diabetic rats. J Trace Elem Med Biol. 2013; 27(2):117-21.

5. Krol E, Krejpcio Z, Michalak S, et al. Effects of combined dietary chromium(III) propionate complex and thiamine supplementation on insulin sensitivity, blood biochemical indices, and mineral levels in high-fructose-fed rats. Biol Trace Elem Res. 2012; 150(1-3):350-9.

6. Komorowski JR, Tuzcu M, Sahin N, et al. Chromium picolinate modulates serotonergic properties and carbohydrate metabolism in a rat model of diabetes. Biol Trace Elem Res. 2012; 149(1):50-6.

7. Ebrahim AM, Eltayeb MH, Khalid H, et al. Study on selected trace elements and heavy metals in some popular medicinal plants from Sudan. J Nat Med. 2012; 66(4):671-9.

8. Payami P, Saffarian S, Hasanzadeh, A. Effects of chromium supplementation on glycemic control in patients with type 2 diabetes. Iran J Endocrinol Metab. 2012; 14(3):215-21.

9. Basaki M, Saeb M, Nazifi S, Shamsaei HA. Zinc, copper, iron, and chromium concentrations in young patients with type 2 diabetes mellitus. Biol Trace Elem Res. 2012; 148(2):161-4.

10. Jain SK, Kahlon G, Morehead L, et al. Effect of chromium dinicocysteinate supplementation on circulating levels of insulin, TNF-α, oxidative stress, and insulin resistance in type 2 diabetic subjects: randomized, double-blind, placebo-controlled study. Mol Nutr Food Res. 2012; 56(8):1333-41.

11. Khosravi-Boroujeni H, Rostami A, Ravanshad S, Esmalilzadeh A. Favorable effects on metabolic risk factors with daily brewer's yeast in type 2 diabetic patients with hypercholesterolemia: a semi-experimental study. J Diabetes. 2012; 4(2):153-8.

12. Liu J, Bao W, Jiang, et al. Chromium, selenium, and zinc multimineral enriched yeast supplementation ameliorates diabetes symptom in streptozocin-induced mice. Biol Trace Elem Res. 2012; 146(2):236-45.

13. Liu L, Jin W, Lu JP. Effect of high chromium yeast on blood lipids and pancreatic islets in type 2 diabetic mice model. Chin J Clin Nutr. 2012; 20(2):93-98.

14. Bahijri SM, Alissa EM. Increased insulin resistance is associated with increased urinary excretion of chromium in non-diabetic, normotensive Saudi adults. J Clin Biochem. 2011; 49(3):164-8.

15. Ahmed HI, Helal, MM. Serum chromium levels in Egyptian diabetic patients. Compar Clin Pathol. 2012; 21(6):1373-77.

16. Sharma S, Agrawal RP, Choudhary M, et al. Beneficial effect of chromium supplementation on glucose, HbA1C and lipid variables in individuals with newly onset type-2 diabetes. J Trace Elem Med Biol. 2011; 25(3):149-53.

17. Selcuk MY, Aygen B, Dogukan A, et al. Chromium picolinate and chromium histidinate protects against renal dysfunction by modulation of NF-κB pathway in high-fat diet fed and Streptozotocin-induced diabetic rats. Nutr Metab (London). 2012; 9:30.

18. Patal PC, Cardino MT, Jimeno CA. A meta-analysis on the effect of chromium picolinate on glucose and lipid profiles among patients with type 2 diabetes mellitus. Philippine J Int Med. 2010; 48(1):32-37.

19. Balk EM, Tatsioni A, Lichtenstein AH, Lau J, Pittas AG. Effect of chromium supplementation on glucose metabolism and lipids: a systematic review of randomized controlled trials. Diabetes Care. 2007; 30(8):2154-63.

20. Hummel M, Standl E, Schnell O. Chromium in metabolic and cardiovascular disease. Horm Metab Res. 2007; 39(10):743-51.

21. Preuss HG, Echard B, Perricone NV, et al. Comparing metabolic effects of six different commercial trivalent chromium compounds. J Inorg Biochem. 2008; 102(11):1986-90.



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