Molecular mechanisms for regulation of intestinal calcium absorption by vitamin D and other factors

Abstract

Optimal intestinal calcium (Ca) absorption is necessary for the protection of bone and the prevention of osteoporosis. Ca absorption can be represented as the sum of a saturable pathway and a non-saturable pathway that is primarily dependent upon luminal Ca concentration. While models have been proposed to describe these transport components, significant gaps still exist in our understanding of these processes. Habitual low intake of Ca up-regulates the saturable transport pathway, a process mediated by increased renal production of 1,25 dihydroxyvitamin D (1,25(OH)2 D). Consistent with this, low vitamin D status as well as deletion/mutation of the vitamin D receptor (VDR) or 25 hydroxyvitamin D-1α hydroxylase (CYP27B1) genes limit Ca absorption by reducing the saturable pathway. There is some evidence that non-saturable Ca absorption in the ileum is also regulated by vitamin D status, but the mechanism is unclear. Treatment with a number of hormones can regulate Ca absorption in vivo [e.g. parathyroid hormone (PTH), thyroid hormone, growth hormone (GH)/insulin-like growth factor I (IGF-1), estrogen, testosterone]. However, some of these actions are indirect (i.e. mediated through the regulation of vitamin D metabolism or signaling), whereas only a few (e.g. estrogen, IGF-1) have been shown to persist in the absence of vitamin D signaling.

Effects of Inactive Vitamin D on Persistent Secondary Hyperparathyroidism in Patients on Hemodialysis

“…In dialysis patients, 25(OH) D, independent of 1, 25(OH)D3, could increase the absorption of calcium and phosphorus from the intestine and kidney (22). Also, 25(OH) D has a correlation with serum PTH level and indirect effect on bone absorption (23).…”

“…Multiple studies have examined the effect of vitamin D on serum PTH level in dialysis patients (22,23). In dialysis patients, 25(OH) D, independent of 1, 25(OH)D3, could increase the absorption of calcium and phosphorus from the intestine and kidney (22).…”

Recomendações da Sociedade Brasileira de Endocrinologia e Metabologia (SBEM) para o diagnóstico e tratamento da hipovitaminose D

“…However, there is evidence that the nonsaturable transport, which happens with part of calcium absorption in the human ileum is also vitamin D sensitive (25). According to He aney and cols., individuals with 35 ng/mL of 25(OH)D presented higher absorption than those with 25 ng/mL (26) (B).…”

Recalcitrant Hypocalcaemia in Autoimmune Enteropathy

“…8,12,14 The small intestine is primarily responsible for calcium absorption, predominantly the duodenum through active transport stimulated by 1,25-dihydroxyvitamin D. When this system is saturated (high calcium intake), passive absorption occurs in the jejunum and ileum. 19,20 Widely available calcium carbonate is best absorbed in a highly acidic environment. When administered with meals or other factors that increase stomach pH (proton pump inhibitors, pernicious anemia) absorption is reduced.…”

“…Calcium citrate absorption is not affected by acidity and therefore is preferable in autoimmune enteropathy. 20,21 Glucocorticoids reduce intestinal calcium absorption, renal calcium resorption, and bone remodelling 4 ; therefore, the need for stress dosing must be carefully assessed. In this case, recurrent diarrhea necessitated stress doses of hydrocortisone to prevent adrenal crisis and at times resulted in short-term improvement of diarrhea, suggesting immunosuppressive benefits.…”