Although high-protein diets induce hypercalciuria in humans, the source of the additional urinary calcium remains unclear. One hypothesis is that the high endogenous acid load of a high-protein diet is partially buffered by bone, leading to increased skeletal resorption and hypercalciuria. We used dual stable calcium isotopes to quantify the effect of a high-protein diet on calcium kinetics in women. The study consisted of 2 wk of a lead-in, well-balanced diet followed by 10 d of an experimental diet containing either moderate (1.0 g/kg) or high (2.1 g/kg) protein. Thirteen healthy women received both levels of protein in random order. Intestinal calcium absorption increased during the high-protein diet in comparison with the moderate (26.2 +/- 1.9% vs. 18.5 +/- 1.6%, P < 0.0001, mean +/- sem) as did urinary calcium (5.23 +/- 0.37 vs. 3.57 +/- 0.35 mmol/d, P < 0.0001, mean +/- sem). The high-protein diet caused a significant reduction in the fraction of urinary calcium of bone origin and a nonsignificant trend toward a reduction in the rate of bone turnover. There were no protein-induced effects on net bone balance. These data directly demonstrate that, at least in the short term, high-protein diets are not detrimental to bone.

Increasing dietary protein induces hypercalciuria and a negative calcium balance. Despite this, the influence of dietary protein on the parathyroid hormone (PTH) I-a-hydroxylase axis is not well understood. We therefore examined the effect of three amounts of dietary protein: low (0.7 g/kg), medium (1.0 g/kg), and high (2.1 g/kg) on mineral metabolism and the PTH-1-alpha-hydroxylase axis in 16 healthy women aged 26.7 +/- 1.3 y. By day 4, urinary calcium decreased significantly with the low-protein diet and increased significantly with the high-protein diet compared with the medium-protein diet (control). Also by day 4, there were striking elevations in serum PTH and calcitriol [1,25-dihydroxyvitamin D] in subjects consuming the low-protein diet. Serum PTH, by two different assays, was 1.5-2.4 times higher and by day 14 1.6-2.7 times higher during the low-protein diet compared with the medium-protein diet. This was accompanied by a significant increase in both nephrogenous cyclic adenosine monophosphate (cAMP), a sensitive and specific indicator of PTH bioactivity, and serum calcitriol by day 14. In comparison, there were relatively minor changes in the calcitropic hormones with the medium- and high-protein diets. The stimulus for the elevation in PTH induced by protein restriction is unclear, but probably does not involve a simple renal mechanism and could reflect either a decline in intestinal calcium absorption, a reduction of bone turn-over, or both. Our data indicate that dietary protein is a powerful regulator of calcium metabolism. Further study is needed to both clarify the mechanisms by which these changes are induced and to better define the amount of dietary protein that will optimize skeletal health in young women.

Proton pump inhibitors (PPIs) are the most potent gastric acid suppressing drugs available, and their use is widespread. An emerging concern about chronic PPI therapy is whether these drugs impair intestinal calcium absorption, resulting in a negative calcium balance and thereby potentially causing bone loss. The objective of this study was to evaluate the acute effect of the PPI esomeprazole or placebo on intestinal calcium absorption in healthy adults. Twelve young adults participated in a placebo-controlled, double-blind, crossover study. There were two 3-week interventions that included a 14-day adjustment period (designed to stabilize calcium homeostasis) followed by 6 days of a diet containing 800 mg of calcium and 2.1 g/kg of protein (intervention). During the last 3 days of the adjustment period and throughout the intervention period, subjects consumed esomeprazole or placebo. Half the subjects underwent 24-hour continuous gastric acid pH monitoring. Intestinal calcium absorption was measured using dual-stable calcium isotopes at the end of each intervention. Treatment with esomprazole significantly increased gastric pH (mean pH on PPI 5.38 AE 0.13, mean pH on placebo 2.70 AE 0.44, p ¼ .005). Neither calcium absorption (PPI 34.2% AE 2.4%, placebo 31.5% AE 2.1%, p ¼ .24) nor urinary calcium (PPI 321 AE 38 mg/34 hours, placebo 355 AE 37 mg/34 hours, p ¼ .07) differed between the PPI and placebo groups. It is concluded that short-term gastric acid suppression by PPIs does not attenuate intestinal calcium absorption in healthy young adults. ß

Background:We reported previously that lowering dietary protein intake in young healthy women to 0.7 g/kg depressed intestinal calcium absorption and was accompanied by elevations in parathyroid hormone (PTH). Moderate amounts of dietary protein (1.0 g/kg) did not appear to perturb calcium homeostasis. Objective: The purpose of this study was to evaluate the effect of graded intakes of dietary protein (0.7, 0.8, 0.9, and 1.0 g/kg) on calcium homeostasis. Design: The experiment consisted of 2 wk of a well-balanced diet containing moderate amounts of calcium, sodium, and protein followed by 4 d of an experimental diet containing 1 of 4 amounts of protein. Eight young healthy women received the 4 amounts of protein in random order. The average age of the subjects was 23.1 ± 2.3 y, their weight was 64 ± 3 kg, and their body mass index (in kg/m 2 ) was 24.3 ± 0.9. Results: Elevations in PTH developed by day 4 of the diets containing 0.7 and 0.8 g protein/kg but not during the diets containing 0.9 or 1.0 g protein/kg. By day 4 of the 0.7-and 0.8-g/kg diets, midmolecule PTH, calcitriol, and nephrogenous cyclic adenosine monophosphate were 1.5-3.5-fold higher than on day 0. Calcitropic hormones on day 4 of the diets containing 0.8 and 0.9 g protein/kg were within the normal range and 23-57% lower than values observed with the 0.7-and 0.8-g/kg diets (P < 0.005). Mean 24-h urinary calcium was 3.29 ± 0.35 mmol with the diet containing 0.7 g protein/kg and 3.54 ± 0.46 mmol with the diet containing 1.0 g protein/kg. Conclusions: Our data suggest that in young healthy women consuming a well-balanced diet, the current recommended dietary allowance for protein (0.8 g/kg) results in short-term perturbations in calcium homeostasis.Am J Clin Nutr 2000;72:168-73. KEY WORDSDietary protein, calcium metabolism, calcitropic hormones, vitamin D, parathyroid hormone, young healthy women, recommended dietary allowance INTRODUCTIONThe effect of dietary protein on calcium metabolism in humans was first documented nearly 80 y ago (1). There has been considerable investigative interest in the potential negative effects of a high-protein diet on mineral and skeletal homeostasis. For example, increasing dietary protein induces urinary calcium loss, negatively affects calcium balance (2), increases bone turnover (3), and may be associated with an increased risk of fracture (4). However, the effect of low-protein diets on calcium and bone homeostasis has received considerably less attention.We reported that in 16 young healthy women, 4 d of a lowprotein diet decreased urinary calcium excretion and was accompanied by elevations in calcitropic hormones; 1.5-3-fold increases were observed in concentrations of serum parathyroid hormone (PTH), 1,25(OH) 2 vitamin D (calcitriol), and urinary nephrogenous cyclic adenosine monophosphate (NcAMP; a bioindex of PTH action). The low-protein diet contained an average of 45 g protein (0.7 g/kg), including both animal and vegetable sources of protein; 20 mmol calcium; and 100 mmol sodium and was otherwi...