Plasma Concentrations Of 25-hydroxyvitamin D3 Research Articles

VITMAIN D3 RESPONSE IN SHEEP TO ORAL VERSUS PARENTERAL ADMINISTRATION AND TO INTRAMUSCULAR DOSE LEVELS OF VITAMIN D3

Plasma vitamin D3 concentration changes were assessed in 10 crossbred wethers following oral or intramuscular administration of a single massive dose (5 × 106 IU) of vitamin D3. Blood plasma was taken at different times during a 3-wk experimental period. The intramuscular response was higher than the oral. In another experiment 15 ewes were administered 5 × 106 IU of vitamin D3 orally, intramuscularly, or intravenously. Blood plasma was taken at different times during a 3-wk experimental period for analyses of plasma vitamin D3 and 25-hydroxyvitamin D3. All animals were killed at the end of the experiment and vitamin D3 determinations were carried out on various tissues. Vitamin D3 given to ewes parenterally had a greater and more lasting effect on their plasma concentrations of vitamin D3 and 25-hydroxyvitamin D3 than did oral administration. While plasma vitamin D3 concentrations of the two parenteral groups were approximately equal, the plasma 25-hydroxyvitamin D3 concentrations were substantially higher in the intravenously treated group than in the intramuscularly treated group. Tissue vitamin D3 concentrations in the parenteral group were higher than in the oral group, and the adipose tissue contained higher concentrations of vitamin D3 than did other tissues. In a third experiment crossbred wethers were administered intramuscularly various amounts (5 × 106, 5 × 105, and 5 × 104 IU) of vitamin D3 in a single dose. Blood plasma was taken at different times during the subsequent 2-wk period. There was proportionality between the amount of vitamin D3 injected and plasma vitamin D3 concentration. The results suggest that parenteral administration induces both higher tissue levels and higher circulating levels of vitamin D3 than does oral administration, and that intravenous injection produces higher circulating levels of 25-hydroxyvitamin D3 than does intramuscular injection. Key words: Vitamin D3 status, sheep, oral, parenteral

Influence of Dietary Vitamin D3on the Circulating Concentration of its Active Metabolites in the Chick and Rat

Plasma concentrations of 25-hydroxyvitamin D3 (25-OHD3) and 1 alpha,25-dihydroxyvitamin D3 (1 alpha, 25-(OH)2D3) in growing chicks and weanling rats were measured by a new radioreceptor assay to determine the effects of varying dietary levels of vitamin D3. The plasma concentration of 25-OHD3 fell from 14.1 ng/ml in 1-day-old chicks to undetectable levels after 3 weeks on a rachitogenic diet. Circulating 1 alpha,25-(OH)2D3 hormone also decreased from 8.9 ng/100 ml to undetectable levels at 3 weeks in these chicks. Chicks receiving an optimal supplement of vitamin D3 (1.4 IU/g diet) for three to four weeks had plasma 25-OHD3 and 1 alpha,25-(OH)2D3 levels of 21-35 ng/ml and 5.1-7.5 ng/100 ml, respectively. Nutritional supplementation with a 50-fold excess of vitamin D3 (70 IU/g diet) elicited a substantial increase in plasma 25-OHD3 to 87-130 ng/ml, while plasma 1 alpha,25-(OH)2D3 was not increased. Increasing dietary calcium from 1.4 to 2.8% did not alter the circulating level of vitamin D3 metabolites in chicks fed 1.4 IU of vitamin D3/g diet. Direct measurement of the renal 25-OHD3-1 alpha-hydroxylase in vitro, showed that lowering dietary calcium or exclusion of vitamin D3 stimulated the biosynthesis of 1 alpha,25-(OH)2D3, but raising calcium did not alter the enzyme activity. It is concluded that the circulating concentration of the 1 alpha,25-(OH)2D3 hormone in the chick is unaffected by abnormally high intakes of vitamin D3 or calcium, but the renal production of the hormone increases during vitamin D3 or calcium deprivation. Additional studies in rats fed a diet supplemented with either 2 or 1000 IU of vitamin D3/g verify that the circulating concentration of 25-OHD3 is markedly increased when the dietary intake of vitamin D3 is elevated. Moreover, 1 alpha,25(OH)2D3 is not increased under these conditions, but actually falls significantly when the dietary level of vitamin D3 is raised from 2 to 1000 IU/g. These studies in both the chick and rat indicate that dietary vitamin D3 excess enhances circulating 25-OHD3, probably because the vitamin D3-25-hydroxylase enzyme is not strigently controlled. The fact that the circulating 1 alpha,25-(OH)2D3 is not concomitantly increased may reflect either decreased synthesis or increased utilization of the 1 alpha,25-(OH)2D3 sterol.