The distribution of vitamin D between the blood and the liver in the pig, and observations on the pathology of vitamin D toxicity

Abstract

The distribution of vitamin D in the body has not been studied thoroughly because of its normally very low concentration and difficulty of assay. Most estimations have been made on blood but, if vitamin D is concentrated in the liver in the same way as the fat-soluble vitamins A and E, estimation of the level in blood cannot give an indication of the total amount of the vitamin in the body. That such concentration of vitamin D can occur under certain circumstances has been shown in rats by Kodicek (1958). He gave rats I mg ergocalciferol by mouth and found, 24 h later, 5-7 % of the dose as biologically active vitamin D in the liver and 1-2 % in the blood. The vitamin D content of the bones and intestines was similar to that of the blood. A similar distribution was found when the rats were given only 10 pg (400 i.u.) of the vitamin (Kodicek & Ashby, 1960). Earlier work from the same laboratory (Cruickshank & Kodicek, 1953) showed that the recovery of vitamin D from liver and intestinal tissue decreased considerably during the first 2 days after the dose was given but the recovery from the rest of the body remained more constant. Thus the percentage of the dose recovered from the liver after each of the first 4 days was 3.7, 1.2, 1-0 and 1.0, that from intestinal tissue was 0.6, 0.2, 0.2 and 0.1, and that from the rest of the body was 1-7, 1.6, 1-9 and 1.3. A similar distribution of vitamin D among the tissues 24 h after a relatively large dose had been given to rats and Rhesus monkeys was found by Blumberg, Aebi, Hurni & Schonholzer (1960). It is possible that in these experiments the relatively higher levels of vitamin D found initially in liver and intestinal tissue may have been a consequence of a relatively large dose of the vitamin or a transitory result independent of the dose. Evidence with other animals is scanty, but it has been shown in calves that were given vitamin D supplements, or whose dams were given supplements before parturition, that the liver levels of the vitamin were always about the same as or lower than the blood levels (Eaton, Spielman, Loosli, Thomas, Norton & Turk, 1947a, b ; Guerrant, Morck, Bechdel & Hilston, 1938). Guerrant et al. (1938) estimate that the total amount of vitamin D in the blood is about four times that in the liver. The antirachitic activity in brain, heart and kidney was too small to estimate. Other investigations of the problem of vitamin D distribution in sheep (New Zealand Department of Agriculture, 1949-50) failed to reveal any concentration of the vitamin in any of thirty-five organs or eight fat depots at I and 4 months after a subcutaneous injection. These tissues contained only traces of vitamin D compared with the blood.

Assessment of Plasma 25-Hydroxyvitamin D Response to Ultraviolet Irradiation over a Controlled Area in Young and Elderly Subjects

“…This suggests that the deficit may be constituted by cholecalciferol, and preliminary work measuring this metabolite directly suggests that'this is the case (unpublished data). The capacity of plasma, compared with other organs, to hold vitamin D activity [as 25-(OH)Dl has been repeatedly observed (Quarterman, Dalgarno, Adam, Fell & Boyne, 1964;Rosenstreich, Rich I% Volwiler, 1971).…”

The Distribution and Storage of Vitamin D and its Metabolites in Human Tissues

“…Earlier, unsuccessful attempts to define a site of storage in animals were based on biological assays of tissues (Quarterman, Dalgarno, Adams, Fell & Boyne, 1964), which were usually sampled within 2-3 days of giving a single massive dose of the vitamin (Heymann, 1937;Morgan & Shimatori, 1943 ;Cruickshank, Kodicek & Armitage, 1954). Subsequent investigations using radioactive cholecalciferol have shown that the concentration of the tracer within individual tissues varies continually during the first 48 h after its administration (Norman & DeLuca, 1962;Neville & DeLuca, 1966;.…”

Absorption of vitamin D3-3H in control subjects and patients with intestinal malabsorption.

“…The subsequent distribution of vitamin D after absorption in man is unknown. In the rat, vitamin D is initially deposited mainly in the liver (22), but in pigs it has been reported that blood is the main storage site (23). Vitamin D does not appear to have been excreted by the kidney to any significant degree, since only 1% of the urinary radioactivity was lipid soluble.…”