Physiological role of chromium
The two types of the chromium element which are biologically important are the trivalent (3+) and the hexavalent (6+) forms. Chromium 6+ does not occur in nature and is quite toxic. The chromium found in food and in dietary supplements is all of the trivalent type. Whole grain products, such as bread (not white), legumes, nuts, and some spices contain low concentrations of chromium.
Trivalent chromium’s role in glucose metabolism has been known since the 1950s. The first studies were animal studies, which clearly showed that chromium is essential for a normal glucose metabolism.
A case report, published in 1977, discussed a woman, aged 40, who had to undergo a total enterectomy as the result of a mesenterial thrombosis. Following the procedure, she received total parenteral nutrition (TPN) through a subclavian catheter nightly. A little more than three years later, she lost more than five kilograms in a period of less than three months, and her plasma glucose concentration rose to values of manifest diabetes mellitus. To achieve a normoglycemic state, 45 units of zinc insulin were administered daily. Causes for the hyperglycemia were sought, because insulin resistance in a young woman who is not overweight is very rare. Chromium deficiency was considered as a possible cause after an article by Mertz from 1969 was discovered, in which the biological functions of chromium are discussed. The chromium concentration in her serum and hair was measured and found to be low (chromium in hair 154 ng/g (N > 500 ng/g), chromium in serum 0.55 ng/g (N 4.9 – 9.5 ng/g)). She was treated intravenously with 250 micrograms of chromium chloride daily for two weeks. This treatment resulted in a clear decrease in the amount of insulin required to treat her diabetes mellitus. After four months of chromium supplements, she no longer required insulin. She continued to receive 20 micrograms of chromium intravenously daily, and remained normoglycemic after a period of one year.
Since that time, many studies have been done on both humans and animals to study chromium’s effect on glycemic control. Healthy people require 25 to 35 μg of chromium in their daily diet. The average diet contains slightly less than 30 μg of chromium. A large proportion of healthy people therefore have enough chromium in their daily diet and probably would not benefit from supplements.
Vincent et al. have done extensive research investigating chromium’s mechanism of action at the cellular level. They discovered that the Apo-Low-Molecular-Weight-Chromium binding substance (also known as Apo-chromoduline), an oligopeptide described by them, plays an important role in potentiating the insulin response in cells sensitive to insulin (see figure 1).
Figure 1A = A cell sensitive to insulin. Figure 1B = Partial activation of the insulin receptor. Figure 1C = Apo-chromoduline loaded with chromium becomes Holochromoduline. Figure 1D = Complete activation of the insulin receptor. With permission: Kleefstra N, Bilo HJG, Bakker SJL, Houweling ST. Chroom en insulineresistentie. Ned Tijdschr Geneesk 2004;148(5):217-20.
Apo-chromoduline can bind four chromium ions when the insulin receptor is activated. This first activation takes place as soon as insulin binds to its receptor. This is how the chromium moves from the extracellular to the intracellular space (see figure 1B). Intracellularly, the Apo-chromoduline is loaded with a maximum of four chromium ions. This “loaded” Apo-chromoduline is now called Holo-chromoduline (see figure 1C). The Holo-chromoduline binds to the insulin receptor (see figure 1D), causing a stronger activation of the insulin receptor. When not enough chromium is available, the activation will be less. This could be one of the possible explanations for the insulin resistance seen with chromium deficiency.
Experiments using fat cells from rats showed that the activation of the insulin receptor (tyrosine kinase activation) is eight times stronger in the presence of chromium with equal concentrations of insulin.
^ Schwarz K, Mertz W. Chromium(III) and the glucose tolerance factor. Arch Biochem Biophys 2003;292-5
^ Jeejeebhoy KN, Chu RC, Marliss EB, Greenberg GR, Bruce-Robertson A. Chromium deficiency, glucose intolerance, and neuropathy reversed by chromium supplementation, in a patient receiving long-term total parenteral nutrition. Am J Clin Nutr 1977;30(4):531-8
^ Mertz W. Chromium occurrence and function in biological sytems. Physiol Rev 1969;49(2):163-239
^ Trumbo P, Yates AA, Schlicker S, Poos M. Dietary reference vitamin A, vitamin K, arsenic, boron, chromium, copper, iodine, iron, manganese, molybdenum, nickel, silicon, vanadium, and zinc. J Am Diet Assoc. 2001;101(3):294-301
^ Anderson RA. Chromium as an essential nutrient for humans. Regul Toxicol Pharmacol 1997;S35-41
^ Sun Y, Ramirez J, Woski SA, Vincent JB. The binding of trivalent chromium to low-molecular-weight chromium-binding substance (LMWCr) and the transfer of chromium from transferrin and chromium picolinate to LMWCr. J Biol Inorg Chem 2000;5(1):129-36
^ Kleefstra N, Bilo HJG, Bakker SJL, Houweling ST. Chroom en insulineresistentie. Ned Tijdschr Geneesk 2004;148(5):217-20
^ Davis CM, Vincent JB. Chromium oligopeptide activates insulin receptor tyrosine kinase activity. Biochemistry 1997;36(15):4382-5