Plasma Ca influences vitamin D metabolite levels as rats develop vitamin D deficiency

Abstract

The hypocalcemia that accompanies vitamin D deficiency is a major obstacle to proper interpretation of the role(s) of vitamin D metabolites in Ca-sensitive tissues. This paper describes the development and complete characterization of a dietary regimen with which normocalcemia was maintained in rats throughout the development of vitamin D deficiency. Normal weanling rats were fed diets containing 0.8% Ca, 0.5% P, and vitamin D3 (group A), or vitamin D-deficient diets containing 0.8% Ca and 0.5% P (group B); 2.0% Ca and 1.25% P (group C); or 2.0% Ca, 1.25% P, and 20% lactose (group D) for 19 wk. Group D rats were normocalcemic and normophosphatemic with normal parathyroid hormone (PTH) levels throughout the study. In contrast, from 4-19 diet wk, groups B and C were hypocalcemic with elevated PTH. Initially, plasma 25-hydroxyvitamin D3 [25(OH)D3] levels decreased most rapidly, and 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] levels decreased least rapidly in group B rats, such that plasma 25(OH)D3 levels were reduced to 200-300 pg/ml before a decrease in 1,25(OH)2D3 levels was observed. However, vitamin D metabolite levels were similar in groups B, C, and D from 4-19 wk. Duodenal active Ca transport mirrored changes in plasma 1,25(OH)2D3 levels and was abolished after 10 wk. The results also suggested that vitamin D may not be necessary for normal bone mineralization since tibia mineral content and plasma alkaline phosphatase levels were similar in normocalcemic groups A and D throughout the study.

Chemopreventive and chemotherapeutic effects of dietary supplementation of vitamin D on cholangiocarcinoma in a Chemical-Induced animal model

“…2a, b, &c). Since the vitamin D content in the regular rat chows which contain 2.2 IU/g vitamin D [33] is comparable to our special 2 IU/g diet, apparently, the normal level of vitamin D in the diet or normal circulating level [33] of 25(OH)D may not be sufficient for preventing ICC tumor initiation and progression (Fig. 2a, b, &c).…”

“…1b and 1c). This observation, showing no adverse effects on body weight and serum calcium, indeed indicates that supplementation with 6 IU/g of vitamin D 3 did not cause unwanted side-effects even though they had serum 25(OH)D higher than the normal range [33]. Furthermore, the lack of increase in serum calcium in 6 IU/g group demonstrates that any anti-ICC effects observed in this group are most likely a direct consequence of vitamin D supplementation, and not a secondary effect attributable to calcium [34, 35].…”

The Effects of a Vitamin D–deficient Diet on Chronic Cadmium Exposure in Rats

“…The active metabolite has many functions related to Ca regulation and bone metabolism, including intestinal Ca and P absorption, Ca mobilization in the bone, and resorption of P and Ca in the renal tubular cells (Deluca 2004;Jones et al 1998;Lips 2006). Although vitamin D interacts with PTH (Deluca 2004;Jones et al 1998), hypovitaminosis D does not influence PTH under sufficient serum levels of Ca (Dabbagh et al 1989;Kollenkirchen et al 1991), and many researchers (Fox 1992;Lee et al 1991;Masuyama et al 2003) have reported a vitamin D-independent Ca homeostasis system. Therefore, hypovitaminosis D alone might not affect Ca homeostasis and bone remodeling owing to the vitamin D-independent system in the present experiment.…”

1,25-Dihydroxyvitamin D-stimulated calmodulin binding proteins: a sustained effect on distal tubules

“…This dietary regimen results in ϪD with normocalcemia after 6-8 wk, which is sustained for at least 4-5 mo (26,27). In these studies, rats were maintained on the ϪD diet for 7 wk-5 mo before hor-…”