25-Hydroxyvitamin D3: Evidence of an Enterohepatic Circulation in Man

Abstract

AND VAY L. W. G O Mayo Clinic and Mayo Foundation, Rochester, Minnesota 5590125-Hydroxyvitamin D3 (25-OH-D3) is a metabolite of vitamin D3 that has greater biologic potency than D3 (1) and is the predominant form of vitamin D in plasma (2), where it circulates bound to specific carrier proteins (3). The physiologic role of 25-OH-D3 is not entirely understood, but it is a precursor of more polar and biologically active forms of vitamin D in deficient animals (4, 5). Physiologic quantities may not be directly involved in biologic effects of vitamin D but pharmacologic doses of 25-OH-D3 have direct effects on calcium transport in tissue culture (6), induce calciumbinding proteins in vitro (7), and mobilize calcium from bone in the anephric animalIn the course of studies on the distribution and excretion of small doses (5 p g ) of intravenously administered [26, 27-3H]-25-hydroxyvitamin D3 (25-OH-D3), we discovered that, in addition to a role in the 25-hydroxylation of vitamin D3 (9), the liver participates in the secretion of this metabolite into the intestine. Subsequent reabsorption of intestinal radioactivity suggests that 25-OH-D3 undergoes an enterohepatic circulation similar to that of other constituents of bile, such as bile acids (10).Methods and Materials. In order to quantify the intestinal and plasma distribution of intravenously administered 25-OH-D3 simultaneously, normal adults (two men and one woman) were prepared for study by an overnight fast and by intubation a few hours before the study. A triple-lumen nasoduodenal tube was positioned so that the first aperture was located proximal to the ampulla of Vater, the second was distal to it at the ligament of Treitz, and the third was located 30 cm distal to the second (11). The lumen ending most proximally was perfused (8).570 at a rate of 2 ml/min with polyethylene glycol (PEG), 5 g/liter, a nonabsorbable marker used for quantification of duodenal contents. From the second lumen, duodenal aspirates were collected every hour, for 30-36 hr, into a chilled beaker, and the volume was measured; 10-ml samples were taken and the remainder was reinfused through the third lumen.Meals were given in liquid form while the tube was in place (11). Oral administration of a fecal marker (chromium sesquioxide, 0.5 g three times daily) was started just prior to the intravenous bolus injection of 8-10 pCi of [26, 27-3H]-25-OH-D31 (New England Nuclear, 1.2 Ci/mmole) dissolved in 1 ml of propylene glycol. Serial blood specimens and all the urine and feces excreted for 12 days after injection were collected for analysis.Total ?H in homogenized stool samples (1-2 g) and duodenal aspirates (0.3-0.5 ml) was determined by liquid scintillation counting after combustion in an oxidizer; values were corrected for volume and for recovery of isotope added to the samples. The volume and bile acid content of duodenal contents were determined by previously validated methods (12). Because of variable delays in passage of intestinal contents from duodenum to colon, fecal data were correct...

1,25-dihydroxyvitamin D3 and its receptor inhibit the chenodeoxycholic acid-dependent transactivation by farnesoid X receptor

“…Thus, D3 and VDR have a profound effect on the signal transduction mediated by bile acid/FXR. Since the reduction in the expression of BSEP and I-BABP may inhibit the enterohepatic circulation of bile acid, D3 may affect the intestinal absorption of D3 itself (Arnaud et al 1975) as well as lipophilic molecules, including T 3 /T 4 (DiStefano et al 1993), RA (Thompson & Strautnieks 2001), TZD (Kawai et al 2000), and 22(R)-HC. Our results also suggest that D3/VDR downregulates SHP expression (Fig.…”

Determinants of vitamin D status in adult Crohn's disease patients, with particular emphasis on supplemental vitamin D use

“…A reduced efficiency of intestinal absorption of vitamin D, as a consequence of ileopathy (Haderslev et al, 2003), a disrupted enterohepatic circulation of vitamin D (Arnaud et al, 1975) and/or renal insufficiency (Freaney et al, 1993) have been suggested as possible contributory factors to the lower vitamin D status in CD patients. Disease activity (Harries et al, 1985;Tajika et al, 2004) has also been suggested to influence vitamin D status in CD.…”

Vitamin D absorption: consequences of gastric bypass surgery

“…The hypothesis on entero-hepatic circulation of vitamin D was generated in the seventies based on observations in humans showing that considerable amounts of i.v. administered H 3 -labelled cholecalciferol or 25-OHD derivates appeared in the bile (20). Subsequent studies, however, revealed that vitamin D was mainly excreted as biologically inactive polar degradation products and that the amount of intact cholecalciferol or 25-OHD was negligible (21,22).…”