Adaptive Response of Humans to Changes in Dietary Calcium: Relationship Between Vitamin D Regulated Intestinal Function and Serum 1,25-Dihydroxyvitamin D Levels

We developed intestinal biopsy procedures in chicks that were extended to humans to study the role of vitamin D in regulating intestinal adaptation to dietary calcium. By comparing biopsy specimens from rachitic chicks (D–) to those from vitamin Dsupplemented chicks (D+) on otherwise identical diets, we observed that (a) the rates of calcium and phosphate accumulation by D+ duodenal or jejunal mucosa were ~50% greater than those by comparable D– mucosa, (b) alkaline phosphatase activity was three times greater in D+ duodenal mucosa brush border preparations than D- preparations, and (c) calcium binding activity was 10 times greater in the cytosol from D+ duodenal mucosa than from D– duodenal mucosa. We then evaluated the calcium and phosphate uptake and alkaline phosphatase activity of duodenal mucosal specimens obtained each week from 15 subjects ingesting, in successive weeks, 100 mg calcium per day (week 1) and 1000 mg calcium per day (week 2). Serum levels of 1,25-dihydroxyvitamin D, immunoreactive parathyroid hormone, calcium, and phosphorus were determined on the day the biopsy specimens were obtained. The subjects were prospectively selected to provide a range of basal 1,25-dihydroxyvitamin D levels from low to high, and included four osteoporotic, five control, and six hyperparathyroid subjects. The change from the 100-mg to 1000-mg calcium diet resulted in a fall of serum 1,25-dihydroxyvitamin D levels and duodenal calcium and phosphate uptake and alkaline phosphatase activity, with no change in serum calcium in the control subjects. Similar effects were observed in the osteoporotic subjects. The hyperparathyroid subjects experienced an increase in serum calcium and failed to reduce their serum 1,25-dihydroxyvitamin D levels on the high calcium diet. These hyperparathyroid subjects had the highest duodenal alkaline phosphatase activities and serum 1,25-dihydroxyvitamin D levels and the least consistent response of any intestinal function to the change in dietary calcium. We observed a strong correlation between duodenal alkaline phosphatase activity and serum 1,25-dihydroxyvitamin D levels on the low calcium diet (r = 0.777, P