Urinary chromium excretion in response to an insulin challenge is not a biomarker for chromium status.

Over 50 years ago, chromium (Cr) was proposed to be an essential trace element; however, recent studies indicate that this status should be removed as the effects of Cr supplementation appear to be pharmacological rather than nutritional. The pharmacological basis for Cr's effects can explain the inability of investigators to discover a biomarker for Cr status. One potential biomarker has not been examined to date. Cr is known to be mobilized in the body in response to insulin (or insulin release in response to a glucose challenge), resulting in an increase in urinary Cr excretion. The magnitude of increase in urinary Cr loss as a function of dietary Cr intake was tested as a potential biomarker for Cr. Zucker lean rats housed in carefully controlled metal-free conditions were provided a series of purified diets containing variable Cr contents (from 16 µg/kg diet to 2,000 µg/kg) for 23 weeks. The 16 µg/kg diet contained less Cr than any diet examined to date. Urine samples were collected before and after insulin and glucose challenges (0, 2, 6, and 12 h postinjection). Urinary Cr levels were analyzed by the standard method of addition using graphite furnace atomic absorption. The rate of urinary Cr loss after a glucose or insulin challenge was found to not be dependent on the Cr content of the rats' diets. Blood iron levels of the rats were also measured to determine if the addition of Cr to the diet altered iron status. The Cr content of the diet was found to have no affect on blood iron levels. Overall, the study demonstrated that insulin-stimulated urinary Cr excretion cannot be used as a biomarker for Cr status.

Potential of chromium(III) picolinate for reproductive or developmental toxicity following exposure of male CD-1 mice prior to mating.

Chromium(III) picolinate, [Cr(pic)(3)], is a commonly used nutritional supplement in humans, which has also been approved for use in animals. Health concerns have arisen over the use of [Cr(pic)(3)]. At high [Cr(pic)(3)] doses, developmental toxicity tests in female mice have shown a higher litter incidence of split cervical arch in exposed fetuses, but this was not consistently reproducible. In the current study, male CD-1 mice were used to further assess the potential for reproductive or developmental toxicity. Four weeks prior to mating, the males were fed a diet providing 200 mg/kg/day [Cr(pic)(3)] for comparison with untreated controls. Females were not treated. Each male was mated with two females, which were sacrificed on gestation day 17, and their litters were examined for adverse effects. Mating and fertility indices were not significantly altered by treatment. Male exposure to [Cr(pic)(3)] also had no effect on prenatal mortality, fetal weight, or gross or skeletal morphology. These results suggest that paternal dietary exposure to chromium(III) picolinate has little potential for adverse reproductive effects, even at exposure levels considerably higher than expected human exposures from nutritional supplements (1 mg of Cr per day or less).

Chromium is not an essential trace element for mammals: effects of a "low-chromium" diet.

Chromium was proposed to be an essential trace element over 50 years ago and has been accepted as an essential element for over 30 years. However, the studies on which chromium's status are based are methodologically flawed. Whether chromium is an essential element has been examined for the first time in carefully controlled metal-free conditions using a series of purified diets containing various chromium contents. Male Zucker lean rats were housed in specially designed metal-free cages for 6 months and fed the AIN-93G diet with no added chromium in the mineral mix component of the diet, the standard AIN-93G diet, the standard AIN-93G diet supplemented with 200 µg Cr/kg, or the standard AIN-93G diet supplemented with 1,000 µg Cr/kg. The chromium content of the diet had no effect on body mass or food intake. Similarly, the chromium content of the diet had no effect on glucose levels in glucose tolerance or insulin tolerance tests. However, a distinct trend toward lower insulin levels under the curve after a glucose challenge was observed with increasing chromium content in the diet; rats on the supplemented AIN-93G diets had significantly lower areas (P < 0.05) than rats on the low-chromium diet. The studies reveal that a diet with as little chromium as reasonably possible had no effect on body composition, glucose metabolism, or insulin sensitivity compared with a chromium-"sufficient" diet. Together with the results of other recent studies, these results clearly indicate that chromium can no longer be considered an essential element.

Urinary chromium loss associated with diabetes is offset by increases in absorption.

The results of the current study indicate that diabetic rats have increased urinary Cr loss as a result of their diabetes; however, this increased urinary Cr loss is offset by increased absorption of Cr. Insulin resistant, obese rats have alterations in the rates of Cr transport and distribution compared to lean rats but have similar levels of urinary Cr loss and Cr absorption. Thus, any increases in urinary Cr loss associated with insulin resistance or diabetes are offset by increased absorption. Given that dietary chromium is normally absorbed with only approximately 1% efficiency, suitable Cr exists in the diet so that a standard diet possesses sufficient chromium to allow for the increases in absorption associated with diabetes. Consequently, supplementing the diet with nutritionally relevant quantities of chromium is not anticipated to have any beneficial effects. Similarly, beneficial effects on plasma variables, such as cholesterol, triglycerides, and insulin concentrations, from supra-nutritional doses of Cr(III) complexes should not arise from alleviation of chromium deficiency. These beneficial effects must arise from pharmacological effects of high dose Cr(III) administration.

Stability of N18C6H6: triangular versus hexagonal structure.

Large nitrogen cage molecules Nx have been previously shown to prefer elongated, cylindrical structures with triangular caps versus more spherical structures composed entirely of pentagons and hexagons. It was argued that this preference derived from the electronic properties of the nitrogen atoms, including the lone pairs. In the current study, the same structural comparison is carried out, with the substitution of C-H-bonding groups for six of the nitrogens. Various substitution patterns on the cylindrical (triangular) and spherical (hexagonal) frameworks are examined. Isomers of N18C6H6 are studied by theoretical calculations to determine the relative stability of triangular versus hexagonal structures, as well as the stability effects of the substitution patterns on each framework. Hartree-Fock theory, density functional theory (PBE1PBE), and perturbation theory (MP2) are employed, in conjunction with the correlation-consistent basis sets of Dunning. Stability trends within each class of molecules and between the two classes of molecules are calculated and discussed.

Stability of N10C10H10 and N12C12H12 Cages and the Effects of Endohedral Atoms and Ions.

Cages of carbon and nitrogen have been studied by theoretical calculations to determine the potential of these molecules as high-energy density materials. Following previous theoretical studies of high-energy N6C6H6 and N8C8H8 cages, a series of calculations on several isomers of the larger N10C10H10 and N12C12H12 is carried out to determine relative stability among a variety of three-coordinate cage isomers with four-membered, five-membered, and/or six-membered rings. Additionally, calculations are carried out on the same molecules with atoms or ions inside the cage. Calculations are carried out with the B3LYP and PBE1PBE density functional (DFT) methods, with MP2 and MP4 calculations carried out to evaluate the accuracy of the DFT results. Trends in stability with respect to cage geometry and arrangements of atoms are calculated and discussed. Stability effects caused by the endohedral atoms and ions are also calculated and discussed.

Isomer stability and bond-breaking energies of N8C8H8 cages.

Molecules consisting entirely or predominantly of nitrogen have been extensively investigated for their potential as high-energy density materials (HEDM). Such molecules react to produce N2 and large amounts of energy, but many such molecules are too unstable for practical applications. In the present study, cage isomers of N8C8H8 are studied using theoretical calculations to determine the structural features that lead to the most stable cages and determine the energetics of dissociation for the various isomers. The isomers are evaluated for thermodynamic (isomer vs isomer) stability and kinetic (with respect to dissociation) stability. Density functional theory (B3LYP), perturbation theory (MP2), and coupled-cluster theory [CCSD(T)] are employed, in conjunction with the cc-pVDZ basis set of Dunning. Trends in isomer stability and dissociation energies are calculated and discussed.