Circulating concentrations of biomarkers and metabolites related to vitamin status, one-carbon and the kynurenine pathways in US, Nordic, Asian, and Australian populations.

Background: Circulating concentrations of biomarkers that are related to vitamin status vary by factors such as diet, fortification, and supplement use. Published biomarker concentrations have also been influenced by the variation across laboratories, which complicates a comparison of results from different studies.Objective: We robustly and comprehensively assessed differences in biomarkers that are related to vitamin status across geographic regions.Design: The trial was a cross-sectional study in which we investigated 38 biomarkers that are related to vitamin status and one-carbon and tryptophan metabolism in serum and plasma from 5314 healthy control subjects representing 20 cohorts recruited from the United States, Nordic countries, Asia, and Australia, participating in the Lung Cancer Cohort Consortium. All samples were analyzed in a centralized laboratory.Results: Circulating concentrations of riboflavin, pyridoxal 5'-phosphate, folate, vitamin B-12, all-trans retinol, 25-hydroxyvitamin D, and α-tocopherol as well as combined vitamin scores that were based on these nutrients showed that the general B-vitamin concentration was highest in the United States and that the B vitamins and lipid soluble vitamins were low in Asians. Conversely, circulating concentrations of metabolites that are inversely related to B vitamins involved in the one-carbon and kynurenine pathways were high in Asians. The high B-vitamin concentration in the United States appears to be driven mainly by multivitamin-supplement users.Conclusions: The observed differences likely reflect the variation in intake of vitamins and, in particular, the widespread multivitamin-supplement use in the United States. The results provide valuable information about the differences in biomarker concentrations in populations across continents.

Early calcifications in human coronary arteries as determined with a proton microprobe.

The current paradigm reads that calcifications characterize the advanced and complex lesions in the atherosclerotic process. To explore the possibility that coronary artery wall calcifications already commence at an early stage of atherosclerosis, a combination of proton beam techniques with a (sub-) micrometer resolution, i.e., micro-proton induced X-ray emission, backward and forward scattering spectroscopy, was applied on human coronary arteries with lesions preceding overt atheromas. The detection limits of phosphorus and calcium in each separate pixel, 0.88*0.88 microm2 in size, were approximately 150 and 80 microg/g dry weight, respectively. Calcium distributions of entire coronary artery cross section were obtained, and calcifications were demonstrated at a preatheroma stage of the atherosclerotic process. The size of the microcalcifications varied between 1 and 10 microm. The composition of the microcalcifications was deduced from the calcium-to-phosphorus ratio. In order to quantify this ratio, the thickness of the specific X-ray absorber used for PIXE had to be accurately determined. Also, thick target PIXE calculations were performed and the method was validated. The calcium-to-phosphorus ratios of the microcalcifications were assessed with good accuracy and varied from 1.62 to 2.79, which corresponds with amorphous calcium phosphate.

A model for carbon kinetics among plasma alanine, lactate, and glucose.

To account for the exchange of carbon atoms among alanine, lactate, and glucose in vivo, [2,3-3H]- and [U-14C]alanine or [3-3H]- and [U-14C]glucose were injected simultaneously to nonanesthetized normal dogs. The concentrations in plasma of 14C-labeled alanine, lactate, and glucose, and the injected 3H-labeled substrate were followed for 160 min after injection of the tracers. An integrated kinetic model describing the exchange of carbon atoms among substrates was developed from these data. The analysis suggests that there is a very rapid exchange of the carboxyl carbon of alanine with lactate in contrast to carbons 2 and 3. The model was used to calculate the fluxes of carbon atoms among the substrates in a steady state. In normal dogs plasma alanine and lactate contribute 14% of the carbon atoms released into the circulation as glucose.

Transfer of carbon atoms among circulating glucose, alanine, and lactate in pancreatectomized dogs.

The rates of transfer of carbon atoms (mg C . kg body wt-1 . min-1) among plasma glucose, alanine, and lactate have been calculated in pancreatectomized dogs from the tracer concentration versus time curves in the plasma after an intravenous injection of either [2,3-3H]- and [U-14C]alanine or [3-3H]- and [U-14C]glucose. The calculations were based on an integrated kinetic model derived earlier from experimental data. In comparison to normal dogs, in insulin-deprived pancreatectomized dogs, the rate of turnover of glucose (mg C . kg-1 . min-1) is increased about twofold, but the turnover rates of lactate and alanine are not changed significantly. About twice as much carbon is transferred from lactate to glucose, whereas the transfer of carbon from alanine is increased by 47%. Carbon transfer to glucose from unidentified sources is also doubled. In conclusion, in the pancreatectomized dog, gluconeogenesis is increased not by an increased production of alanine and lactate but by an increased diversion of their carbon atoms to glucose at the expense of other pathways.

Vitamin E protects mice against Diplococcus pneumoniae type I infection.

Vitamin E protects nonimmunized and immunized mice against fatal Diplococcus pneumoniae type I (DpI) infection. A dietary supplementation of 180 mg of dl-alpha-tocopheryl acetate per kg of diet increased survival of nonimmunized mice from 20 to 80% when challenged with 20 organisms, and of mice immunized with 0.5 ng of DpI polysaccharide from 15 to 70% when challenged with 20,000 organisms. The phagocytic index of immunized mice was four times higher in the 180-mg vitamin E group than in the control group. Both the survival and phagocytic index revealed a biphasic dose response, indicating a cause-effect relationship between phagocytosis and survival. Vitamin E also significantly increased the rate of carbon clearance from blood, indicating a general increase in phagocytic activity. The data indicated that increased macrophage activity probably aided by increased antibody production was the principal reason for increased protection.