Is Chromium III a New Key To Effective Diabetes Management?

This nutritional supplement might be an inexpensive way to improve glycemic control for the 18 million Americans with diabetes
Thomas Morrow, MD

MANAGED CARE November 2005. ©MediMedia USA

This nutritional supplement might be an inexpensive way to improve glycemic control for the 18 million Americans with diabetes

Thomas Morrow, MD

Hardly a day goes by without seeing new information on the diabetes epidemic. With an estimated 18 million Americans suffering from this condition, diabetes is the sixth leading cause of death nationwide. Numerous medications including Byetta, Symlin, and Exubera have made managed care headlines over the past several months.

Intensive investigation has looked for a causal relationship in our lifestyle focusing on lack of exercise, poorly balanced diet, high stress jobs, and excessive intake of high fructose soft drinks, all leading to a controversial condition called the Metabolic Syndrome. Articles in Family Practice News (September 2005) and the Journal of Disease Management (August 2005), as well as presentations at the 2005 Scientific Sessions of the American Diabetes Association, Endocrine Society, and American Heart Association–Atherosclerosis, Thrombosis, and Vascular Biology have focused on the role of one particular form of the mineral chromium — chromium picolinate (CrP) — as well as a combination of chromium picolinate with biotin in diabetes treatment. These compounds are not drugs, but nutritional supplements.

Critical mineral

Chromium has long been studied as a critical mineral involved in glucose metabolism. In 1957, a “glucose tolerance factor” (GTF) found in brewer’s yeast was shown to prevent an age-related decline of glucose tolerance in rats. Chromium III (the number refers to a specific oxidative form of chromium) was found to be the active ingredient of GTF. Chromium was declared to be an essential nutrient by the USDA in 1977 after inadvertent elevations of blood glucose were discovered in a hospitalized patient receiving parenteral nutrition devoid of chromium. Blood glucose levels returned to normal when chromium was given to the patient. The USDA established guidelines for chromium use in 1996 and a quick check of the USDA Web site shows numerous studies discussing the need for chromium in the diet of Americans and its role in glucose metabolism.

Amplifying the action of insulin

It appears that chromium binds to an oligopeptide which then binds to the insulin receptor, increasing the activity of tyrosine kinase, and amplifying the action of insulin. Readers of this column will remember that tyrosine kinase is a cellular switch enabling many different processes to progress. Chromium is a cofactor that enhances insulin sensitivity. Interestingly, patients taking corticosteroids have an increased urinary excretion of chromium and studies have demonstrated normalization of corticosteroid-induced hyperglycemia with chromium supplementation.

There is no easy way to measure chromium in the human body. Studies have been difficult to do on humans as serum levels are not very useful. Most studies have focused on the use of toenail clippings to measure chromium stores in the human body.

Some investigators have established correlations between low levels of chromium and type 2 diabetes as well as increased risk of cardiovascular disease. Other studies have established that chromium supplementation can improve insulin sensitivity and hence blood glucose control. Past studies have not been uniformly successful.

One explanation is that there are numerous forms of chromium. One form, called chromium IV, which is used in industrial applications, is actually toxic. Chromium III is the non-toxic nutritional form, but it is poorly absorbed and is found in very low levels in most common American foods. Foods highest in natural chromium include whole grains, nuts, organ meats, and mushrooms. However, it is difficult to achieve recommended daily intakes of chromium simply by consuming these chromium-rich foods. In addition, food processing decreases the amount of chromium in the final food product.

A more absorbable form of chromium III, chromium picolinate (picolinate is a metabolite of tryptophan) appears to be much more metabolically active due to enhanced absorption.

Most of the studies demonstrating poor results with chromium did not use the picolinate form of chromium III.

Studies using chromium picolinate as the source of supplementation had a greater rate of success. In a study published in a 1997 issue of the journal Diabetes, improvements in fasting and two-hour blood glucose as well as fasting insulin and HbA1c levels were demonstrated with the addition of chromium picolinate to the treatment regimen of a patient with diabetes.

An article describing chromium titled: “Role of Chromium in Human Health and Diabetes,” published in Diabetes Care, November 2004, further describes this interesting mineral. Their conclusions: “A large body of literature in both experimental animals and humans indicates that chromium is an essential element involved in the action of insulin as demonstrated in the studies of chromium deficiency…. Growing evidence suggests that chromium supplementation, particularly at higher doses and in the form of CrP, may improve insulin sensitivity and glucose metabolism in patients with glucose intolerance and type 1, type 2, gestational and steroid-induced diabetes and in some individuals without diabetes.”

Chromium and biotin

Biotin, a safe, water-soluble B vitamin also known to play a role in glucose metabolism, has been studied in combination with chromium picolinate as a dietary supplement since the mid-1990s. Biotin stimulates glucokinase in the liver and improves pancreatic beta cell function. Skeletal cell culture studies using a combination of biotin and chromium picolinate demonstrated a synergistic effect on glucose uptake and glycogen synthesis.

Managed care’s response

Certainly, lifestyle changes in the modern world have contributed heavily to the dramatic increase in type 2 diabetes. The diet of the average American plus decrease in exercise, increase in weight, and many other changes have been implicated for years as the main causal forces.

Recent evidence points to the possibility that decreased dietary chromium may play a role. Supplementation with elemental chromium III in traditional multivitamins has not resulted in the desired outcome, with a reasonable explanation being the lack of bioavailability of the raw chromium III mineral as well as low dose levels in most multivitamin formulations (published literature has shown efficacy at ranges of 200 mcg to 1,000 mcg of chromium in the more bioavailable form of chromium picolinate).

Chromium picolinate has a better absorption profile than chromium alone. When the compound is added to biotin there is even more benefit. Several well designed randomized, controlled clinical trials have demonstrated improvement in most of the important measures used to monitor type 2 diabetes when chromium picolinate and biotin are added to the traditional oral diabetes therapy.

The cost of this combination, called Diachrome by the manufacturer, Nutrition 21, is minimal compared to most drugs. The retail price is approximately 35 cents per day. Safety appears to be a non-issue. Efficacy has been demonstrated on the most out-of-control population. But, how will managed care respond?

Should managed care organizations encourage even larger randomized studies? Should they encourage this supplement’s use through newsletters and disease management programs? Should they suggest that their providers encourage its use? Should they somehow manipulate benefits to provide this supplement via the pharmacy benefit? Or perhaps all of these? Should they encourage the American Dietetic Association to review this essential mineral or perhaps the specific form of chromium picolinate with biotin and include this in the national diabetes treatment guidelines?

A case for chromium

A number of relatively small open-label and randomized, double-blind, placebo-controlled multicenter trials published earlier this decade utilizing the combination of chromium picolinate and biotin verified improved glycemic control and lipid profiles in patients with type 2 diabetes.

More convincingly, Cesar Albarracin, MD, has presented results from a prospective, multicenter, randomized, double-blind placebo-controlled study involving 453 patients using chromium picolinate plus biotin who were already being treated with oral hypoglycemic drugs. This study was presented at the 2005 American Diabetes Association 65th Scientific Sessions. It demonstrated an overall decrease in mean HbA1c levels by 0.51.

Statistical significance

A sub-analysis of those with more elevated HbA1c levels at baseline demonstrated a significant decrease of 1.78 versus a placebo effect of -0.78 in those with baseline HbA1c levels above 10. In the most poorly controlled (starting HbA1c > 11.0), an even larger decrease of 1.96 versus placebo effect of -0.56 was demonstrated.

Statistical significance was demonstrated against placebo for the overall study as well as for those patients with a baseline HbA1c greater than 10.0 and greater than 11.0. A trend that was not significant was present for lesser baseline HbA1c level patients.

Additional similar randomized, double-blind, placebo-controlled, multi-center, prospective studies have confirmed these results. To put this into perspective, this overall decrease in HbA1c of about 0.5 is about the same as the reduction from the injectable 5mcg BID dose of Byetta, the latest entrant into the diabetic drug lineup.

Incidentally, dietary supplementation of chromium picolinate has been deemed safe by the FDA and has no known drug-to-supplement interactions.

Recently, an August 2005 paper in the journal Disease Management, written by Joseph Fuhr, PhD, and edited by David Nash, MD, from Thomas Jefferson University, suggested that billions of dollars could be saved in the United States if a combination of chromium picolinate and biotin were used in selected diabetic populations.

One thing is for sure: The review of the existing literature suggests that this vitamin-mineral combination offers people with diabetes hope for the future at a price that is less than what would be their copayment for a normal monthly generic drug.

Thomas Morrow, MD, is president of the National Association of Managed Care Physicians and vice president and medical director of Matria Health Care. He has 20 years of managed care experience at the payer or health plan level.
Dr. Morrow discloses that he has received honoraria or other financial benefit during the last three years from the following commercial companies: Amgen, Amylin Pharmaceuticals, AstraZeneca, Biogen Idec, Centocor, Galderma, Genentech, GlaxoSmithKline, Johnson & Johnson, Merck, Novartis, Novo Nordisk, Pfizer, Procter & Gamble, Q-Med, Sanofi-Aventis, Teva Pharmaceuticals Industries, UCB, and Wyeth.