The safety and efficacy of high-dose chromium - High-Dose Chromium

Alternative Medicine Review, June, 2002 by Davis W. Lamson, Steven M. Plaza

Abstract

The data on the standards for chromium requirements and the safety of various chromium compounds and doses are reviewed. The 350-fold difference between the acceptable daily intake and the calculated reference dose for humans of 70 mg per day seems without precedent with respect to other nutritional minerals. Previous claims of mutagenic effects of chromium are of questionable relevance. While studies have found DNA fragmentation (clastogenic effects) by chromium picolinate, anecdotal reports of high-dose chromium picolinate toxicity are few and ambiguous. The beneficial effects of chromium on serum glucose and lipids and insulin resistance occur even in the healthy. Serum glucose can be improved by chromium supplementation in both types 1 and 2 diabetes, and the effect appears dose dependent. Relative absorption of various chromium compounds is summarized and the mechanism of low molecular weight chromium binding substance (LMWCr) in up-regulating the insulin effect eight-fold is discussed. There is evidence of hormonal effects of supplemental chromium besides the effect on insulin. Chromium supplementation does result in tissue retention, especially in the kidney, although no pathogenic effect has been demonstrated despite considerable study.

Introduction

Chromium, an essential nutrient for human life, has been used at dosages higher than the minimum nutritional level to offset problems of malabsorption or to pharmacologically influence the chemistry of blood sugar control in diabetics. Questions have arisen as to whether chromium at higher dosages can cause DNA fragmentation (clastogenic effect), which is separate from any issue of biochemical toxicity. While evidence for this concern is sparse, the question deserves to be examined along with potential benefits of higher chromium doses.

Chromium compounds (along with other higher-than-divalent minerals) are not readily absorbed. Along with the question of chromium dosage level, there is also the question of potential variation in absorption or utilization with different chromium compounds. The data on chromium surveyed below includes historical background of biological effects, as well as results of chromium supplementation on hypoglycemia, diabetes, serum cholesterol, serum dehydroepiandrosterone (DHEA), and calcium excretion. The safety of various oral chromium doses is discussed. The phenomenon of glucose tolerance factor (GTF) and the mechanism of low molecular weight chromium-binding substance (LMWCr) on the insulin receptor are reviewed. This presentation is intended to demonstrate important concepts with respect to high dose chromium, not be a comprehensive survey of chromium biochemistry.

Historical Background

In 1929 Glaser et al (1) discovered brewer's yeast exhibited a potentiating effect on the hypoglycemic action of insulin. In 1958 the potentiating effect was rediscovered when rats fed a Torula yeast-based diet began to show signs of glucose intolerance, which was reversed by a diet of brewers yeast? This discovery led to the isolation of a "glucose tolerance factor" or GTF. (2,3) Trivalent chromium (CrIII) was found to be the active component of GTF. The biological activity of chromium was found to be contingent on the valence, Cr III being the only biologically active form.

Chromium is now recognized as one of 15 trace elements critical for proper physiological functioning of lipid and carbohydrate metabolism. Deficiency of chromium has been linked to a number of disorders, including symptoms of type 2 diabetes, such as decreased glucose tolerance, (4-7) increased serum insulin levels, (8) and decreased number of insulin receptors. (9) Chromium deficiency can also mimic many signs of cardiovascular disease, such as elevated serum cholesterol and triglycerides, as well as decreased high-density lipoprotein cholesterol (HDL). (10)

The most dramatic examples of clinical syndromes due to chromium deficiency have been seen in long-term total parenteral nutrition (TPN). Although chromium had been previously found in animal studies to be essential in glucose control, it was not until 1977 that the first definitive human case of glucose intolerance with neuropathy and weight loss was reported in a patient receiving long-term TPN. (11) The administration of 200 mcg/ day of chromium chloride corrected all symptoms, and in three weeks the patient was able to discontinue all insulin medication. This patient was the first documented case that showed humans could have similar clinical presentations of glucose intolerance as test animals, and that the clinical syndrome could be reversed by the administration of Cr III. Similar dramatic reversals of high blood glucose have since been reported with the supplementation of chromium in TPN patients, although these cases did not include neurological deficits. (12-14) Another case, involving not only hyperglycemia and insulin resistance, but also peripheral neuropathy, ataxia, postural tremor, and muscle weakness, was treated successfully by the administration of 250 mcg/day of Cr III, and resulted in normalized blood glucose, as well as improved insulin resistance and nerve conduction. (15)