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April 2001; Volume 4; 37-40
By Dónal P. O’Mathúna, PhD
Sales of chromium supplements generate more than $100 million annually.1 Chromium picolinate is promoted as a "fat burner" and "muscle builder" for losing weight and enhancing athletic performance. The supplement also allegedly increases energy, curbs addictions, cures acne, prevents insomnia, relieves depression, and increases life span.
Physicians have not yet warmed to prescription pharmacological approaches to dieting, after the 1997 withdrawals of fenfluramine and dexfenfluramine, both associated with valvular regurgitation and primary pulmonary hypertension. The November 2000 Food and Drug Administration (FDA) recommendation to withdraw phenylpropanolamine, present in popular over-the-counter weight-loss medications and associated with stroke, is a more recent reminder of the danger of these medications.2 Clinicians likely will receive more inquiries about the effectiveness and safety of chromium as a viable weight-loss alternative to the pharmaceuticals that remain, such as phentermine and sibutramine (Meridia®).
Chromium is an essential trace element and part of the insulin metabolic pathway.3 The USDA estimated safe and adequate daily dietary intake of chromium is 50-200 mcg for adults.3 The Institute of Medicine (IOM) 2001 report on Dietary Reference Intakes concluded there was insufficient evidence to set an Estimated Average Requirement or a Tolerable Upper Intake Level (UL) for chromium.4 In their place are Adequate Intake (AI) levels, which are the amounts expected to meet or exceed the daily requirements in essentially all healthy people. The AI level for chromium is 35 mcg/d for young men and 25 mcg/d for young women. A small number of studies have found little detriment from people consuming 15 or 25 mcg/d.4 Clinical research is hampered by the analytical challenges of accurately measuring chromium levels, since only 0.5-2% of chromium in dietary sources is absorbed, and urinary levels occur in parts per billion.4 There is no simple, reliable test for chromium deficiency.
Chromium deficiency was first reported in 1977 when patients on long-term total parenteral nutrition developed classic diabetic symptoms that were reversed with the addition of chromium to their diets.5 Research on the potentially beneficial role of chromium in treating type 2 diabetes in chromium-deficient patients was reviewed here previously.6 Because many overweight patients with type 2 diabetes can control their diabetes with effective weight management, and because chromium’s mechanism of action involves glucose and insulin metabolism, there is interest in chromium as a weight loss agent.
Mechanism of Action
Normally, receptors on the surfaces of insulin-sensitive cells bind insulin. This allows these cells to absorb chromium which then binds a small protein (chromodulin) inside the cell.1 The resulting complex then activates an enzyme called insulin receptor tyrosine kinase. This enzyme enhances glucose absorption and promotes fatty acid metabolism.
In contrast, "chromium deficiency" leaves cells desensitized to insulin (or "insulin resistant").7 Less glucose enters cells for energy production and instead is stored as fat. Insulin resistance also hinders the passage of amino acids into muscle cells, reducing protein synthesis.8 Chromium supplementation allegedly reverses these effects, leading to the "burning" of excess fat, weight loss, and increased muscle mass.
Clinical studies prior to 1998 were reviewed here previously;9 it should be noted that chromium doses are reported in mcg, where 1 mcg = 0.001 mg. The 1998 review found one 1969 study reporting increased fat-free body mass and decreased body fat after chromium supplementation, and five studies reporting no significant benefits. For this update, six more studies of chromium for weight loss were found: two with positive results, three with negative results, and one with mixed results. Additionally, four other studies focused primarily on diabetic outcomes and found no changes in body composition. These are reviewed elsewhere.6
Two randomized, double-blind trials found positive effects from chromium supplementation, yet both had methodologic flaws that call their results into question. In the first, 154 adults were divided into three groups and received 0 mcg, 200 mcg, or 400 mcg chromium picolinate daily.10 Subjects were instructed to consume "at least two servings" of a protein drink containing their assigned chromium dose. After 72 days, underwater displacement testing showed significantly reduced body fat in the chromium groups compared to placebo, but no significant difference between the two chromium groups. Amount of drink consumed, overall diet, and exercise frequency were not controlled.
In the second study, the same researchers randomly assigned 130 new subjects to groups taking capsules containing either 400 mcg chromium picolinate or placebo.8 After 90 days, body composition was measured using dual energy X-ray absorptiometry. Changes in actual weight, percent body fat, and fat-free mass did not differ between the two groups, but the chromium group showed significantly reduced fat mass (P = 0.023). After statistical adjustments to control for dietary and exercise differences, significant differences were calculated for actual weight (P < 0.001), percent body fat (P < 0.001), and fat mass (P < 0.001). However, the significant differences were found only in calculated estimates of weight and fat loss based on energy expenditure, not the measured values.
A recent randomized, double-blind study involved 18 older men (56-69 years) assigned to take either placebo or 924 mcg/d chromium picolinate in two capsules.11 Twice weekly all men participated in a supervised, resistance-training workout. Diet and urinary chromium levels were monitored. Although body composition and muscle strength changed during the study, no significant differences existed between the two groups.
Another randomized, double-blind study involved 19 healthy men and women aged 63-77 years.12 Subjects received either a placebo or 1,000 mcg/d chromium picolinate (divided equally between morning and evening). After eight weeks, no significant differences were found between the groups in body composition, insulin sensitivity, or serum lipids.
The third study with negative results examined 29 moderately obese patients at risk for developing type 2 diabetes.13 Subjects were given nutrition counseling in an effort to maintain their body weight and randomly assigned to either 1,000 mcg/d chromium picolinate or placebo for eight months. Significant improvements in insulin responses occurred in the chromium subjects, but no significant changes occurred in body weight, abdominal fat distribution, or body mass index.
One study examined the effect of both exercise and chromium supplementation in 43 mildly obese women.14 Those who took 400 mcg/d chromium picolinate for nine weeks but did not exercise had significant gains in body weight, fat-free mass, and fat mass. However, those who took 400 mcg/d chromium nicotinate and exercised aerobically had a small but statistically significant loss in body weight, and no significant change in fat-free mass or fat mass.
Chromium supplements are believed to be safe, with no clinical studies reporting adverse reactions. The IOM report found insufficient evidence to set a UL.4 Rats given several thousand times the equivalent of 200 mcg/d chromium in humans showed no adverse effects.15 However, four case reports of adverse effects exist, describing renal failure, liver dysfunction, short-lasting psychological changes, and acute generalized exanthematous pustulosis.6 The FDA has received more than 500 adverse event reports involving chromium supplements, though most involve dietary supplements containing numerous herbs and other agents.16
In vitro studies have demonstrated that chromium picolinate can produce chromosomal damage in hamster ovary cells17 and can cleave DNA in solution.18 Although the former study used doses vastly in excess of normal physiological levels, the latter occurred within physiological ranges. Chromium picolinate’s unique stability gives it good absorption, but also allows accumulation in body tissues, leading to concerns about long-term side effects.
No adverse drug interactions have been reported. However, ascorbic acid, aspirin, and indomethacin markedly increase chromium absorption, while antacids lower absorption.3 Diets high in complex carbohydrates, not simple sugars, increase chromium absorption.3 Potential interactions may occur with drugs affecting glucose or cholesterol levels, or with corticosteroids.19
Trivalent Cr3+ is the form found almost exclusively in foods, especially brewer’s yeast, liver, American cheese, cereals, and wheat germ. However, chromium content in foods is highly variable, and processing can either increase or decrease the level.4 The search for the biologically active form of chromium led to the extraction of glucose tolerance factor (GTF) from yeast.20 This complex contains chromium, nicotinate, and three amino acids. Various GTF formulations are marketed as the safer, more natural form of chromium.
However, GTF’s structure remains uncertain, and early conclusions about its role in glucose metabolism have been shown to be in error. While GTF makes chromium available to chromium-deficient animals, it inhibits insulin in animals with normal chromium levels.1 GTF is now regarded as an artifact of its harsh extraction conditions and its value as a dietary supplement is questionable.1
The identification of nicotinate in GTF led to interest in its closely related isomer, picolinate. Chromium(III) picolinate is now the most commonly used form, usually prepared in 200 mcg capsules. Many products contain smaller amounts of chromium picolinate along with numerous herbs and minerals.
Chromium’s essential role in insulin metabolism is well-established. Supplementation in chromium-deficient diabetics may offer some benefits, but not for those consuming adequate dietary chromium.6 However, most trials using chromium picolinate supplements, with or without exercise, found no significant benefit for weight loss or percent body fat reduction. The three trials finding some benefit had serious methodological weaknesses. Research is lacking on the long-term effects of consuming chromium picolinate.
Chromium supplementation offers little, if any, benefit to patients attempting to lose weight. While some controversy exists over the possibility of serious harmful effects, these have not been observed in clinical trials. Diabetic patients should not take chromium without first consulting their physicians and monitoring their blood glucose closely. For those attempting to lose weight, reducing caloric intake, increasing exercise, modifying eating behaviors, and enlisting others’ support remain the foundations for success.
Dr. O’Mathúna is Professor of Bioethics and Chemistry at Mount Carmel College of Nursing in Columbus, OH.
1. Vincent JB. Biological role for chromium at a molecular level. Accounts Chem Res 2000;33:503-510.
2. Food and Drug Administration. Letter to manufacturers of drug products containing phenylpropanolamine (PPA). November 3, 2000. Available at: www.fda.gov/ cder/drug/infopage/ppa/ppaltr.pdf. Accessed December 1, 2000.
3. Stoecker BJ. Chromium. In: Shils ME, et al., eds. Modern Nutrition in Health and Disease. 9th ed. Baltimore, MD: Lippincott, Williams & Wilkins; 1999: 277-282.
4. Institute of Medicine. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. Washington, DC: National Academy Press; 2001.
5. Jeejeebhoy KN. Chromium and parenteral nutrition. J Trace Elem Exp Med 1999;12:85-89.
6. O’Mathúna DP. Chromium supplementation in the treatment of type 2 diabetes mellitus. Altern Med Alert 2000;3:40-44.
7. Morris BW. Chromium action and glucose homeostasis. J Trace Elem Exp Med 1999;12:61-70.
8. Kaats GR, et al. A randomized, double-masked, placebo-controlled study of the effects of chromium picolinate supplementation of body composition: A replication and extension of a previous study. Curr Ther Res 1998;59:379-388.
9. McArdle WD, Moore BJ. Chromium shows little proof as weight loss supplement. Altern Med Alert 1998;1: 9-10.
10. Kaats GR, et al. Effects of chromium picolinate supplementation of body composition: A randomized, double-masked, placebo-controlled study. Curr Ther Res 1996;57:747-756.
11. 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.
12. Amato P, et al. Effects of chromium picolinate supplementation on insulin sensitivity, serum lipids, and body composition in healthy, nonobese, older men and women. J Gerontol A Biol Sci Med Sci 2000;55: M260-M263.
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. Grant KE, et al. Chromium and exercise training: Effect on obese women. Med Sci Sports Exerc 1997;29:992-998.
15. Ravina A, et al. Reversal of corticosteroid-induced diabetes mellitus with supplemental chromium. Diabetic Med 1999;16:164-167.
16. Porter DJ, et al. Chromium: Friend or foe? Arch Fam Med 1999;8:386-390.
17. Stearns DM, et al. Chromium(III) picolinate produces chromosome damage in Chinese hamster ovary cells. FASEB J 1995;9:1643-1648.
18. Speetjens JK, et al. The nutritional supplement chromium(III) tris(picolinate) cleaves DNA. Chem Res Toxicol 1999;12:483-487.
19. Jellin JM, et al. Pharmacist’s Letter/Prescriber’s Letter: Natural Medicines Comprehensive Database. Stockton, CA: Therapeutic Research Facility; 1999.
20. Mertz W. Chromium in human nutrition: A review. J Nutr 1993;123:626-633.