Author
CEGLIA, LISA - Jean Mayer Human Nutrition Research Center On Aging At Tufts University | |
HARRIS, SUSAN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University | |
RASMUSSEN, HELEN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University | |
DAWSON-HUGHES, BESS - Jean Mayer Human Nutrition Research Center On Aging At Tufts University |
Submitted to: Osteoporosis International
Publication Type: Peer Reviewed Journal Publication Acceptance Date: 3/11/2008 Publication Date: 3/1/2009 Citation: Ceglia, L., Harris, S.S., Rasmussen, H.M., Dawson-Hughes, B. 2009. Activation of the calcium sensing receptor stimulates gastrin and gastric acid secretion in healthy participants. Osteoporosis International. 20:71-78. Interpretive Summary: It has long been known that increasing calcium intake leads to increased gastric acid but the mechanism for this effect is not known. In the last decade, the calcium sensing receptor was discovered on parathyroid and kidney cells, where it regulates the handling of calcium. Recent animal studies have identified this receptor on the acid-producing cells in the stomach. We conducted an 18-day double-blind, placebo-controlled study to determine whether treatment with an agent that stimulates the calcium sensing receptor, cinacalcet, would stimulate gastric acid secretion in healthy adults. Seventeen subjects had gastric acid measurements before and after treatment with cinacalcet or placebo. We found that stimulating the calcium sensing receptor with cinacalcet significantly increased gastric acid production. In conclusion, this study provides the first evidence that activation of the calcium sensing receptor promotes gastric acid production in humans. The increase in gastric acid secretion may promote calcium absorption, but this remains to be demonstrated. Technical Abstract: Gastric acid secretion is a complex process regulated by neuronal and hormonal pathways. Ex vivo studies in human gastric tissues indicate that the calcium sensing receptor (CaR), expressed on the surface of G and parietal cells, may be involved in this regulation. We sought to determine whether cinacalcet, a CaR allosteric agonist, increases serum gastrin levels and gastric acid secretion. This 18-day randomized placebo-controlled double-blind study with a fixed metabolic diet was conducted in 17 healthy subjects age 45-70 with normal gastric acid output. Exclusion criteria included diseases and medications known to affect gastric acid and calcium balance. On day 8 (baseline), subjects were given cinacalcet (15 then 30 mg daily) or placebo for 11 days. Basal and maximal gastric acid output and serum gastrin levels were measured on days 8 and 18. Baseline basal and maximal gastric acid output and serum gastrin levels were similar between groups. However, changes in serum gastrin and basal acid output (adjusted for baseline weight) were significantly more positive in the cinacalcet group compared to placebo (P=0.004 and P=0.039, respectively). Change in maximal acid output was similar in the 2 groups (P=0.995). As expected, cinacalcet produced significant decreases in serum PTH (P<0.001) and ionized calcium levels (P=0.032), and increases in serum phosphorus levels (P=0.001) and urinary calcium excretion (P=0.023). In conclusion, this study provides in vivo evidence that activation of the CaR increases serum gastrin levels and basal gastric acid secretion in healthy adults. |