The Nutritional Biochemistry of Chromium(III)

John Vincent

• Publisher: Elsevier
• Year: 2018
• ISBN:
  9780444641229
• Edition: 2
• Topic: Ciencias biológicas
• Subtopic: Biofísica

The Nutritional Biochemistry of Chromium(III), Second Edition, reviews the fields of chromium biochemistry and nutrition and how they have dramatically changed in the last decade. Editor John Vincent has lead much of the research that has resulted in new discoveries and reversals of previously held beliefs, such as health concerns surrounding the toxicity of chromium(III). New sections include a review of new evidence showing why chromium may not be an essential element, why national recommendations may need updating, and new data on the use of chromium supplementation in animal feeds.

Discussions on the controversial topic of the role of chromium(III) at the molecular level in insulin signaling and information on cell cultures and in vitro assays of chromium toxicity are also covered.

• Examines all of the significant research surrounding chromium, providing discussion on both sides of controversial issues
• Features new evidence that shows why chromium may not be an essential element
• Details why national recommendations may need updating
• Edited by leading expert in the field of chromium, with new contributions from leaders in different aspects of chromium research

Chapter 1

Introduction: A history of chromium studies (1955–2007)

John B. Vincent; Silas Brown Department of Chemistry, The University of Alabama, Tuscaloosa, AL, United States

Abstract

While chromium as the trivalent ion was proposed to be an essential element about sixty years ago, recent research as shown that the element can no longer be considered to be essential for animals or man. The element may be pharmacologically active, increasing insulin sensitivity in large, supranutritional doses. Glucose tolerance factor, proposed to be the biologically active form of chromium, is an artifact of its isolation. Chromium nutritional supplements have no effect on body mass or body composition. Chromium supplements have not been clearly demonstrated to have beneficial effects on diabetic subjects, although they appear to increase insulin sensitivity in rodent models of diabetes, potentially as humans have not received doses proportionally as large as those used in rodent studies.

Keywords

Chromium(III); Glucose tolerance factor; Chromium picolinate; Chromium nicotinate; Chromium propionate; Diabetes

Acknowledgments

Work on Cr(III) in the laboratory of J. B. V. has been funded by the NRICGP/USDA, NIH, NSF, American Diabetes Association, American Heart Association, and American Chemical Society/PRF. J. B. V. is also the inventor or coinventor of seven patents on the use of Cr-containing oligopeptides or synthetic Cr(III) compounds as nutritional supplements or therapeutic agents.

Introduction

With the 60th anniversary of the proposal that chromium (as the trivalent ion) is an essential trace element for mammals rapidly approaching, little progress has actually been made in establishing the nutritional requirement for and biochemistry of chromium over these six decades. In fact, Cr has been determined not to be an essential element for animals and humans. Cr in large doses may have a pharmacological effect, increasing insulin sensitivity. This is in stark contrast to the advances in knowledge of the nutritional role and biochemistry of the other essential trace elements. The transition metals in the third row of the period table from vanadium to zinc (V, Mn, Fe, Co, Ni, Cu, and Zn) and also molybdenum and tungsten are generally considered to be essential for some form of life. Currently for each of these transition elements except chromium, at least one metallobiomolecule has been well characterized in terms of its function, three-dimensional structure, and mode of action. In terms of its potential pharmacological, drug-like effect, its mode of action is unknown, despite several hypotheses being offered.

The fields of Cr nutrition and Cr biochemistry have had a problematic past. The purpose of this review is to lay out carefully this past with all of its skeletons exposed. Only from this starting point can the advances presented in the following chapters be put into a clearer perspective with the hope that answers to the many basic questions will soon appear. Ten years ago one of the authors wrote a major review of the field of Cr biochemistry which appeared in the first edition of this book (1); the current chapter represents a reappraisal of the field with 10 years of hindsight, including some appreciable reevaluation of some key issues.

Chromium(III)

The form of Cr proposed to be biologically important is the trivalent ion, Cr^{3 +}. The coordination chemistry of this ion is part of the problem in characterizing Cr-containing species in a biological environment. Cr^{3 +} possesses a d³ electron configuration and almost exclusively octahedral coordination. The cation is a hard acid and generally binds oxygen-based ligands, although nitrogen-based ligands are also common. With its three 3d electrons in half-occupied t_2g orbitals in an octahedral environment, its complexes are generally substitutionally inert, making a role for the ion in catalysis most unlikely and potential roles in biological systems probably limited to maintaining structural conformations. In aqueous solution with the type of ligands likely to be found in a biological environment (e.g., oxygen-based species such as carboxylates and phosphates), chromic complexes usually are electrochemically inactive. The electronic spectra of chromic complexes are usually devoid of intense features such as charge transfer bands; this prevents application of resonance Raman spectroscopy as a useful characterization tool. The visible spectra of its octahedral complexes are dominated by two bands, arising from d-d transitions, with extinction coefficients of 10² or less; the complexes of complexes with oxygen-based ligands are generally green or violet, depending on the relative intensity of the two bands. The paramagnetic nature of the spin 3/2 center makes nuclear magnetic resonance studies problematic. In fact, the three-dimensional structure is generally required to interpret the NMR spectra of Cr(III) complexes, rather than NMR being a useful aid in structural characterization. An appropriate source for use in Mossbauer spectroscopy of Cr does not exist. Thus these common bioinorganic probes are of limited utility. Cr levels in tissues and biological fluids are extremely low, generally within an order of magnitude of the detection limits of current analytical techniques, which was a major factor limiting studies of Cr in tissue and body fluids prior to 1980 (vide infra).

The Glucose Tolerance Factor (GTF) Story

The identification of GTF

The field of Cr biochemistry started in 1955 when Mertz and Schwarz fed rats a Torula yeast-based diet which resulted in the rats apparently developing impaired glucose tolerance in response to an intravenous glucose load (in addition to previously identified necrotic liver degeneration) (2). Shortly thereafter a dietary factor (selenium) was discovered which could reverse the liver disorder but not the glucose intolerance; thus the authors believed they had identified a new dietary requirement absent from the Torula yeast-based diet and responsible for the glucose intolerance, which they coined glucose tolerance factor or GTF (3).

These researchers (4) followed their report in 1959 by identifying the active ingredient of “GTF” as Cr^{3 +}. Inorganic compounds containing Li, Be, B, F, Ti, V, Mn, Co, Ni, Cu, Zn, Ge, As, Se, Br, Rb, Sr, Y, Zr, Mo, Ru, Rh, Pd, Ag, Cd, Sn, Sb, I, Cs, Ba, La, Ce, Ta, W, Os, Ir, Au, Hg, Tl, Bi, Th, and U (200–500 μg/kg body mass) could not restore glucose tolerance, while several inorganic Cr(III) complexes (200 μg Cr/kg body mass) restored glucose tolerance from a < 2.8% per minute rate of removal of intravenously injected glucose to the approximately 4% rate of control rats. Brewer’s yeast and acid-hydrolyzed porcine kidney powder were identified as natural sources of “GTF,” and the active (i.e., effective in reversing the inability to handle the glucose load) ingredient could be concentrated from these materials by physical and chemical means (4). When given by stomach tube (500–1000 μg/kg body mass), the intact materials and the concentrates could restore proper glucose metabolism in rats on the Torula yeast-based diet. Although the separation means to isolate “GTF” were not described in detail, “GTF” was found to be water soluble, extractable with phenol and isobutanol, and absorbable on charcoal and ion exchange resins.

From the benefit of over 50 years of hindsight, these studies are deeply flawed despite the success of similar studies in identifying other dietary requirements. Unfortunately, for example, the Cr content of the diet was not reported (although the experimental procedures at the time would not have likely produced the correct value). Additionally, the rats were maintained in wire mess cages, possibly with stainless steel components, allowing the rats to obtain chromium by chewing on these components. Consequently, the actual Cr intake of the rats in these studies is impossible to gauge, putting into great quest...

Table of contents

• Cover image
• Title page
• Table of Contents
• Copyright
• Contributors
• Preface to revised edition
• Chapter 1: Introduction: A history of chromium studies (1955–2007)
• Part I: Chromium as a Nutrient and Nutritional Supplement
• Part II: Biochemical Role(s) for Chromium(III)
• Part III: Chromium(III) as Therapeutic Agent
• Part IV: Toxicological Effects of Chromium(III)
• Index