Ebook Tracing the Fate of Chromium Nutritional Supplements in the Body
The element chromium (Cr) in the +3 oxidation state has been proposed to be an essential trace element for mammals [14]. The National Academy of Sciences of the United States has set the adequate intake (AI) of chromium at 35 µg daily for men and 25 µg daily for women [13]. Even though the typical American diet provides an adequate amount of chromium, chromium supplements are currently on the market and include chromium chloride, chromium picolinate, and chromium nicotinate. However, a consensus exists among researchers that chromium supplementation of healthy rats does not provide any therapeutic effects except for the compound Cr3 [10, 8, 15, 1]. Several reasons may explain this difference among Cr chloride, Cr nicotinate, Cr picolinate and the cation Cr3.
Olin et al. [9] and Anderson et al. [2] have shown that Cr chloride, Cr nicotinate, and Cr picolinate are absorbed with efficiencies between 0.5-1.3 % of the gavaged dose after 24 hours. However, for Cr3, 40% of the Cr at a pharmacological dose and 60% of the Cr at a nutritionally relevant dose are absorbed over a 24 hour period. (The nutritional dose was 3 µg Cr/kg body mass while the pharmacological dose was 3 mg Cr/kg body mass). The better absorption efficiency of Cr3 may explain its better effectiveness as a therapeutic agent.
Cr chloride used in nutritional supplements is not actually the simple salt CrCl3 with waters of hydration but is actually the compound trans-[CrCl2(H2O)4]Cl. Oligomerization, the chemical process of forming a degree of polymerization from a monomer, commonly occurs, especially at basic pHs, and results in the formation of multinuclear hydroxo-bridged chromic species. This diminishes the therapeutic value of the CrCl3 since the solubility of the oligomerized and polymerized species is limited, especially while passing through the basic pH levels of the intestines [4]. Chromium chloride is commonly used as a model for dietary chromium.
The chemical structure of chromium nicotinate has not yet been fully characterized, but the compound is known to have only limited solubility in water (i.e., it is essentially insoluble in water). The ligands of the chromium nicotinate tend to allow creation of other Cr forms that can bind to various biomolecules and undergo olation due to their relative lability. Thus the nicotinate species degenerate in the gastrointestinal tract of the rats [7].
Chromium picolinate has poor solubility in water [6] and other common solvents and also lacks strong degree of lipophilicity [3]. Its solubility actually decreases as pH is lowered until the hydrogen ion concentration is so high that the compound decomposes. This pH is approximately that of the stomach lining. However, Cr3 is extremely soluble in water and stable in dilute mineral acid and is thus better able to maintain its chemical structure under physiological conditions, such as conditions in the stomach [11]. Cr3 has been proposed to act as a biomimetic of chromodulin, a naturally present oligopeptide that stimulates tyrosine kinase activity of the insulin receptor. Thus, Cr3 has been shown in healthy and type 2 diabetic model rats to increase insulin sensitivity while also decreasing plasma triglycerides and total cholesterol and low-density lipoprotein (LDL) cholesterol concentrations [4]. After a period of three months, the daily intravenous administration of Cr3 at a concentration of 20 µg Cr/kg body mass lowered plasma triglycerides and total and LDL cholesterol levels in healthy rats [12]. Another study also demonstrated that six months of intravenous administration of Cr3 at the pharmacological doses of 5-20 µg Cr/kg body mass resulted in a reduction in plasma triglycerides, total and LDL cholesterol, insulin concentrations and an increase in insulin sensitivity for both healthy and type 2 diabetic model rats.
Since the fate of these nutritional supplements in the body has not been well established, the use of liquid chromatography mass spectrometry (LCMS) could allow the fate of chromium from these chromium supplements to be followed better inside the body than with previously utilized techniques. Prior studies primarily relied on the use of radioactive Cr-51, which yielded liquid chromatography column elution profiles which provided approximate molecular weights of the radiolabeled chromium containing species, not the identity of compounds.
The purpose of this project is to elucidate the speciation of chromium from chromium supplements provided by gavage administration within the body tissues of rats as a function of time. The four chromium species that were utilized were CrCl3, Cr picolinate, Cr nicotinate, and triaqua-µ3-oxo-µ-hexapropionatotrichromium(III) cation, also known as Cr3. Only non-radioactive chromium was utilized to gavage the rats. Blood samples and body tissues were harvested for investigation and include liver, spleen, heart, kidney, testes, fat, pancreas, skeletal muscle, and femur. The significance of this research is that it may be possible to determine the fate of Cr from the supplements in body organs of the rat. This was not previously possible with other techniques; now, however, the fate of the chromium might be followed better throughout the body. This knowledge could be utilized to better understand the mode of action by which chromium can potentially be used to treat type 2 diabetes.
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