Metabolism of Vitamin D3-3H in Human Subjects: Distribution in Blood, Bile, Feces, and Urine*

Abstract

Summary. Vitamin D8-3H has been administered intravenously to seven normal subjects, three patients with biliary fistulas, and four patients with cirrhosis. Plasma D3-3H half-times normally ranged from 20 to 30 hours. in vivo evidence that a metabolic transformation of vitamin D occurs was obtained, and a polar biologically active vitamin D metabolite was isolated from plasma.Urinary radioactivity averaged 2.4% of the administered dose for the 48-hour period after infusion, and all the excreted radioactivity represented chemically altered metabolites of vitamin D. The metabolites in urine were mainly water-soluble, with 26% in conjugated form.From 3 to 6% of the injected radioactivity was excreted in the bile of subjects with T-tube drainage and 5% in the feces of patients having no T-tube. The pattern of fecal and biliary radioactivity suggested that the passage of vitamin D and its metabolites from bile into the intestine represents an essential stage for the fecal excretion of vitamin D metabolites in man.Abnormally slow plasma disappearance of vitamin D3-3H in patients with cirrhosis was associated with a significant decrease in the quantity and rate of glucuronide metabolite excretion in the urine.

Vitamin D supplementation during pregnancy: safety considerations in the design and interpretation of clinical trials

“…74 Absorbed vitamin D3, transported in serum primarily by the DBP, can be considered to have four possible fates: (1) hepatic uptake of vitamin D3 for 25-hydroxylation to its major circulating intermediate metabolite, 25(OH)D, and subsequent metabolism to various 25-hydroxylated derivatives, including 1,25(OH)2D; (2) metabolism of circulating D3 via alternative pathways not involving 25-hydroxylation; (3) circulation or deposition of D3 into tissues in the nonhydroxylated state (primarily in adipose tissue and skeletal muscle); 75 or (4) direct excretion in urine or feces. 76 Although 25-hydroxylation is not known to be regulated by endocrine feedback inhibition, a constraint on hepatic 25-hydroxylation has been observed, whereby excess circulating D3 is shunted into tissue stores or metabolized when the capacity of the hepatic 25-hydroxylases is exceeded. 77,78 Vitamin D entering the blood via the gastrointestinal route reaches the liver faster than vitamin D endogenously produced in the skin, 79 suggesting a higher risk that 25-hydroxylase function will be overwhelmed and alternative metabolites will be formed following oral vitamin D ingestion in comparison with D3 generated by sun exposure.…”

“Activation” of vitamin D by the liver

“…Investigations in man (6) and in rats (7) have shown that the disappearance of 'H from the plasma after an intravenous dose of tritiated vitamin D3 is interrupted by a very characteristic rebound of radioactivity after 2-4 hr. It has been possible to show that the liver is responsible for this transient increase in plasma radioactivity by quickly releasing into the blood a large porReceived for publication 25 February 1969 and in revised form 22 May 1969. tion of the dose which had been initially cleared from the plasma and accumulated in the liver.…”

Assay of Vitamin D and its Metabolites

“…Studies of intestinal absorption showed that peak plasma radioactivity occurred 3-6 hours after oral administration (Thomson et al, 1967). Biliary excretion of vitamin D and its metabolites was shown to be of major importance (Avioli et al, 1967), and metabolism of the isotope, in terms of its fractional rate of conversion to 3H,25-0HD3 and more polar metabolites, was found to be determined mainly by the state of vitamin D nutrition . Distribution of isotopic metabolites in human tissues and the formation in man of 3H,1,25(OHhD and 3H,24,25(OHhD have been further studied by this group (Mawer et al, 1972;Mawer et al, 1975 (Haddad and Chyu, 1971). over shown that at physiological serum concentrations of 25-0HD (5 x 10-8 mol/litre) only 2-3 %of serum 25-0HD binding sites are occupied.…”