Chromium Supplementation in the Treatment of Type 2 Diabetes Mellitus
Chromium Supplementation in the Treatment of Type 2 Diabetes Mellitus
April 2000; Volume 3; 40-44
By Dónal P. O’Mathúna, PhD
Diabetes mellitus is 90% type 2 (non-insulin dependent) diabetes mellitus.1 Numerous supplements are alleged to prevent or treat it, especially chromium, the sales of which are second only to calcium among minerals.2 Chromium picolinate, it is also claimed, enhances weight loss, increases energy, improves sports performance, curbs addictions, cures acne, prevents insomnia, relieves depression, and increases life span. But improved control of diabetes mellitus would be enough for clinicians to consider chromium’s use.
Biochemistry
Chromium was identified as an essential trace element in 1959, and plays a role in insulin action.2 Many ionic forms of chromium exist. Only 0.5-2% of dietary chromium is absorbed, leading to daily absorption of 1-200 nanograms. Urinary excretion levels are measured in parts per billion. Clinical research is hampered by the analytical challenges of accurately measuring such low concentrations, coupled with the lack of a simple, reliable test for chromium deficiency.
Pharmacology
Chromium deficiency was first reported in 1977. Some patients on long-term total parenteral nutrition developed classic diabetic symptoms that were reversed by chromium.3
Plasma chromium levels in diabetic patients are 40% lower and urinary excretion levels three times higher than in healthy patients.4 Normal plasma levels are ~0.1 µg/L. Chromium is widely distributed in tissues, at levels 10-100 times plasma levels. However, plasma, urine, and tissue levels do not correlate well. High plasma chromium levels can exist with symptoms of deficiency and a negative chromium balance.
Mechanism of Action
Biochemical studies show that chromium increases insulin sensitivity and the number of insulin receptors on insulin-sensitive tissues. Chromium binds to an undetermined compound which both activates enzymes that enhance insulin’s activity and inhibits enzymes that inactivate insulin receptors.5 The currently accepted model is that chromium normally leaves the plasma in response to hyperinsulinemia, which sensitizes the tissue to insulin.4 Chromium deficiency leaves cells desensitized to insulin, or resistant to insulin, a condition present in some patients with type 2 diabetes.
The picolinic acid found in chromium picolinate is an isomer of nicotinic acid (or niacin), which enhances chromium’s absorption.
Clinical Studies
Mertz reviewed clinical studies using chromium for diabetes between 1966 and 1992.6 Twelve of the 15 trials using clearly defined compounds and proper controls showed sugar or lipid improvements, but 11 of these had between six and 28 subjects. The largest and most recent trial was a randomized, double-blind, placebo-controlled trial (RDBPCT) involving 76 subjects with established atherosclerotic disease.7 Twenty-five patients had stable type 2 diabetes while 51 were non-diabetic. Each group was randomized to receive either 250 µg chromium chloride or placebo in 5 ml syrup. While serum chromium levels were fivefold higher after one month of supplementation (P < 0.005) and remained elevated (mean duration, 11.1 months), fasting blood glucose levels were unchanged.
In contrast, U.S. investigators conducted a RDBPCT in China with three groups of 60 patients each receiving either placebo, 100 µg chromium picolinate bid, or 500 µg bid for four months.8 Medications, diet, and exercise routines were unchanged. Fasting and two-hour postprandial blood glucose levels were significantly lower in the 1,000-µg group after two and four months (P < 0.05), but not in the 200-µg group or placebo. Fasting and
two-hour postprandial blood insulin levels were significantly lower in both the 200-µg and 1,000-µg groups
(P < 0.0001), but not the placebo group. HbA1c values were significantly lower in both chromium groups at four months, but in only the 1,000-µg group at two months (P not reported).
These researchers then invited Chinese type 2 diabetic patients to chromium supplement seminars.1 Those purchasing supplements were randomly asked to volunteer for an uncontrolled study where fasting and postprandial blood glucose were measured monthly for 10 months. The 833 participants took 500 µg chromium picolinate daily. Fasting blood glucose levels dropped significantly after one month (10.0 to 8.0 mmol/L;
P < 0.05), and were slightly lower after 10 months. Postprandial glucose levels decreased significantly after one month (12.0 to 9.9 mmol/L; P < 0.05) and were 8.0 mmol/L after 10 months. Participants completed a questionnaire before supplementation and after one month. Those reporting excessive thirst decreased from 334 to 47; those reporting excessive urination decreased from 322 to 40; and those reporting excessive fatigue decreased from 443 to 52 (P < 0.001).
Another observational study recruited 162 patients, 114 with type 2 diabetes and 48 with type 1.9 All patients took 200 µg chromium picolinate every morning for three months, and halved their dose of hypoglycemic agents. Blood sugar levels in 74% of type 2 diabetic patients did not increase despite reduced medication
(P < 0.001); 71% of the type 1 patients similarly responded positively (P < 0.05). Positive response correlated well with reduced HbA1c values (11.13 to 9.36; P < 0.001).
Chromium excretion during pregnancy and chromium supplementation for gestational diabetes have also been examined.10 Twenty pregnant women with gestational diabetes were randomized to receive either 4 µg/kg/d chromium picolinate or placebo. Later, 10 more women with gestational diabetes were matched to the placebo group and received 8 µg/kg/d chromium. After eight weeks, significantly lower levels were found for fasting insulin and one-hour postprandial glucose, insulin, and C-peptide (P < 0.05 for all results in this study). HbA1c levels were reduced significantly in the 4-µg group only. No group changed in fasting glucose or C-peptide levels. Women with severe glucose intolerance still required insulin therapy: one taking 8 µg, three taking 4 µg, and four taking placebo. Uncontrolled observational studies with corticosteroid-induced diabetes (n = 13 and n = 50) also produced encouraging results.11,12
A RDBPCT examined moderately obese patients at risk for developing type 2 diabetes (> 125% optimal body weight and a first-degree relative with the disease).13 After nutrition counseling designed to maintain body weight, 29 subjects took either 1,000 µg chromium picolinate daily or placebo for eight months. An insulin sensitivity test examined the ability of injected insulin to enhance intravenous glucose disappearance and inhibit hepatic glucose production. Those taking chromium showed significantly increased insulin sensitivity at four months (P < 0.05) and eight months (P < 0.005). No significant changes occurred in body weight, abdominal fat distribution, fasting insulin levels, HbA1c levels, or 24-hour insulin profiles.
Adverse Effects
Chromium supplements are believed to be safe, with no clinical studies reporting adverse reactions. The U.S. EPA safe exposure dose is 350 times the upper limit of the USDA adult estimated safe and adequate daily dietary intake.5 Rats given several thousand times the equivalent of 200 µg chromium showed no adverse effects.11
One case of chronic renal failure was attributed to 600 µg chromium picolinate taken daily for six weeks.14 Others disagreed with this diagnosis, including the research vice president of Nutrition 21, the company that holds the exclusive patent rights for manufacturing chromium picolinate.15 Another case reported renal failure, liver dysfunction, and other problems after 1,200-2,400 µg chromium picolinate was taken daily for 4-5 months.16 Acute, short-lasting cognitive, perceptual, and motor changes were reported an hour after another patient took 200-400 µg chromium picolinate.17 Acute generalized exanthematous pustulosis was reported after 1,000 µg.18 The FDA has received more than 500 adverse events involving chromium supplements, though most involve dietary supplements containing numerous herbs and other agents.19
More seriously, two in vitro studies demonstrated that chromium picolinate, and not other Cr3+ complexes, causes cleavage of DNA strands.20 Industrial chromium toxicity is unrelated, because industrial chromium is Cr6+.19 Chromium picolinate’s unique stability gives greater absorption, but therefore may have long-term side effects.
Drug Interactions
No adverse drug interactions have been reported. However, ascorbic acid, aspirin, and indomethacin markedly increase chromium absorption, while antacids lower absorption.2 Diets high in complex carbohydrates, not simple sugars, increase chromium absorption.2
Chromium picolinate supplements appear to be generally safe, although:
a. no long-term studies have been conducted.
b. there is some concern about potential mutagenic effects.
c. cases of renal failure have been reported.
d. All of the above.
e. None of the above.
Formulation
Trivalent Cr3+ is the form of chromium found almost exclusively in foods, especially brewer’s yeast, liver, American cheese, cereals, and wheat germ. The estimated safe and adequate daily dietary intake is 50-200 µg for adults.2 About 90% of Americans consume less than this, but several studies found no detrimental effects from diets containing less than 25 µg daily.2
Brewer’s yeast and the saltbush plant (Atriplex halimus) are traditional chromium sources, but the most common supplement is chromium picolinate salt. Almost all chromium supplements contain chromium picolinate, usually 200 µg in capsules. Some studies used 1,000 µg/d, but optimal doses have not been determined. Numerous herbal combination products include smaller amounts of chromium picolinate. (See Tables 1 and 2 for chromium supplement formulations and dietary sources.)
| Table 1-Chromium formulation and price comparison | |||
| Manufacturer | Formulation Manufacturer's | Recommended Dose | Price/Quantity |
| Nutritional Dynamics | Two tablets contain 500 mg citrimax (Garcinia cambogia fruit | 2 tablets/d | $19.95/ |
| Sugar Control Ultra | standardized to 50% hydroxycitrate), 400 mg Rehmannia glutinosa root (naturally rich in in beta-sitosterol and aucubin), 250 mg L-glutamine, 250 mg L-alanine, 200 mg Gymnema sylvestre leaf (standardized to 75% gymnemic acids), and 500 µg chromium (polynicotinate) | 60 tablets | |
| Rainbow Light | One tablet provides 200 µg Gtf chromium (Chromemate® | 1-3 tablets/d | $16.95/ |
| Gtf Chromium Complex | polynicotinate), 75 mg Hawaiian spirulina, 75 mg Chlorella (grown under heterotrophic conditions), 40 mg apple pectin, 1.5 mg L-glutathione, 328 mg custom herbal extract blend (Siberian ginseng, fenugreek seed, Chinese cinnamon bark, alfalfa leaf, Gymnema sylvestre leaf, reishi, artichoke leaf, licorice root) | 90 tablets | |
| The Vitamin Shoppe | One capsule contains 4 mg Chromax ii (compound of trivalent | 1 capsule/d | $13.95/ |
| Ultra Chromium Picolinate | chromium and picolinic acid) supplying 500 µg trivalent chromium | 100 capsules | |
| Twinlab | One hard gelatin capsule contains 1.67 mg pure crystalline chromium | 1 capsule/d | $10.50/ |
| Chromium Picolinate | picolinate supplying 200 µg trivalent chromium | 100 capsules | |
| Futurebiotics | One capsule contains 200 µg trivalent chromium from chromium picolinate | 1 capsule/d | $9.95/ |
| Chromium Picolinate | (a patented form of biologically active, yeast-free, organically bound, glucose | 100 capsules | |
| tolerance factor chromium) | |||
| Source Naturals | One tablet contains 200 µg chromium gtf (Chromemate® [chromium | 1 tablet/d | $7.75/ |
| Gtf Chromium Yeast Free | polynicotinate]), 1.8 mg niacin (nicotinate) | 120 tablets | |
| Solgar Co. | One vegicap provides 200 µg chromium (niacin-bound, yeast-free | 1 vegicap/d | $6.80/ |
| Chromium Polynicotinate chromium) | 50 vegicaps | ||
| Source: Online mail-order companies | |||
| Table 2-Selected dietary sources of chromium | ||
| Food | Serving Size | Chromium Content |
| American cheese | 1 oz | 48 µg |
| Peanut butter | 1 tablespoon | 41 µg |
| Cooked spinach | 1 cup | 36 µg |
| Chicken breast | 3 oz | 22 µg |
| Mushrooms | 1 cup | 20 µg |
| Wheat bread | 1 slice | 16 µg |
| Apple | 1 medium | 15 µg |
| Adapted from: Chromium. Mediconsult.com, Inc. Available at: http://www.cyberdiet.com/foodfact/ffarticles/1999. Accessed March 6, 2000. | ||
The estimated safe and adequate daily dietary allowance of chromium for adults is:
a. 250 µg.
b. 50-200 µg.
c. 10-25 µg.
d. 50-200 mg.
Conclusion
Chromium’s contribution to insulin resistance and diabetes is well-established biochemically. Supplements overcome deficiencies, but those already consuming adequate chromium would not be expected to show improvements, which likely explains much of the variability found in clinical trials. The U.S.-sponsored studies conducted in China are especially encouraging, but may not be applicable to other populations where dietary chromium levels are higher.
Chromium supplementation shows promise as an adjunct to conventional therapy in treating cases of type 2 diabetes mellitus involving chromium deficiency. However, there is currently no reliable diagnostic test to determine which patients are chromium deficient. Chromium picolinate gives better chromium absorption than other chromium salts, and appears to be safe. However, research on its long-term effects has not been conducted.
Recommendation
Chromium supplementation may benefit patients with type 2 diabetes mellitus who are chromium deficient. Without an accurate diagnostic test, a therapeutic trial with chromium picolinate is a reasonable way to assess benefit. Close monitoring of blood glucose is essential, with adjustment of other medications as necessary. Monitoring renal status is also important, especially if renal damage from diabetes is already suspected or documented. Although chromium may allow certain diabetic patients to reduce other medications, adherence to dietary and exercise guidelines remains a top priority. Patients should be encouraged to use reputable brands, since all products sold as dietary supplements are likely to vary widely in quality and concentration.
The best way to establish chromium deficiency is to order:
a. commercially available blood tests.
b. special hair analysis tests.
c. careful observations of diabetic patients’ responses to chromium supplements.
d. nutritional analysis of patients’ diet.
Dr. O’Mathúna is Professor of Bioethics and Chemistry at Mount Carmel College of Nursing, Columbus, OH.
References
1. Cheng N, et al. Follow-up survey of people in China with type 2 diabetes mellitus consuming supplemental chromium. J Trace Elem Exp Med 1999;12:55-60.
2. Stoecker BJ. Chromium. In: Shils ME, et al, eds. Modern Nutrition in Health and Disease. 9th ed. Baltimore, MD: Williams & Wilkins; 1999:277-282.
3. Jeejeebhoy KN. Chromium and parenteral nutrition.
J Trace Elem Exp Med 1999;12:85-89.
4. Morris BW. Chromium action and glucose homeostasis. J Trace Elem Exp Med 1999;12:61-70.
5. Anderson RA. Chromium and diabetes. Nutrition 1999;15:720-722.
6. Mertz W. Chromium in human nutrition: A review.
J Nutr 1993;123:626-633.
7. Abraham AS, et al. The effects of chromium supplementation on serum glucose and lipids in patients with and without non-insulin-dependent diabetics. Metabolism 1992;41:768-771.
8. Anderson RA, et al. Elevated intakes of supplemental chromium improve glucose and insulin variables in individuals with type 2 diabetes. Diabetes 1997;46:1786-1791. Also abstracted as: Anderson R, et al. Beneficial effects of chromium for people with type II diabetes [abstract]. Diabetes 1996;45(suppl):124A.
9. Ravina A, et al. Clinical use of the trace element chromium (III) in the treatment of diabetes mellitus.
J Trace Elem Exp Med 1995;8:183-190.
10. Jovanovic L, et al. Chromium supplementation for women with gestational diabetes mellitus. J Trace Elem Exp Med 1999;12:91-97. Also abstracted as: Jovanovic-Peterson L, et al. Chromium supplementation for gestational diabetic women improves glucose tolerance and decreases hyperinsulinemia [abstract]. Diabetes 1996;45(suppl):337A.
11. Ravina A, et al. Reversal of corticosteroid-induced diabetes mellitus with supplemental chromium. Diabetic Med 1999;16:164-167.
12. Ravina A, et al. Control of steroid-induced diabetes with supplemental chromium. J Trace Elem Exp Med 1999;12:375-378.
13. Cefalu WT, et al. Effect of chromium picolinate on insulin sensitivity in vivo. J Trace Elem Exp Med 1999;12:71-83. Also abstracted as: Cefalu WT, et al. The effect of chromium supplementation on carbohydrate metabolism and body fat distribution [abstract]. Diabetes 1997;46(suppl):55A.
14. Wasser WG, et al. Chronic renal failure after ingestion of over-the-counter chromium picolinate. Ann Intern Med 1997;126:410.
15. Over-the-counter chromium and renal failure [letters]. Ann Intern Med 1997;127:654-656.
16. Cerulli J, et al. Chromium picolinate toxicity. Ann Pharmacotherapy 1998;32:428-431.
17. Huszonek J. Over-the-counter chromium picolinate. Am J Psychiatry 1993;150:1560-1561.
18. Young PC, et al. Acute generalized exanthematous pustulosis induced by chromium picolinate. J Am Acad Dermatol 1999;41:820-823.
19. Porter DJ, et al. Chromium: Friend or foe? Arch Fam Med 1999;8:386-390.
20. Speetjens JK, et al. The nutritional supplement chromium(III) tris(picolinate) cleaves DNA. Chem Res Toxicol 1999;12:483-487.
April 2000; Volume 3; 40-44
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