The Effect of Protein on Calcium Absorption and Gastric Acid Production

Study Overview
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Brief Summary
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We have established that dietary protein is an important regulator of intestinal calcium absorption in humans. However, we do not understand the mechanism by which dietary protein is affecting calcium absorption. Therefore, the purpose of this research is to evaluate whether dietary protein-induced changes in gastric acid secretion explain the observed changes in intestinal calcium absorption.

Detailed Description
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We have established that dietary protein is an important regulator of intestinal calcium absorption in humans. However, we do not understand the mechanism by which dietary protein is affecting calcium absorption. Therefore, the purpose of this research is to evaluate whether dietary protein-induced changes in gastric acid secretion explain the observed changes in intestinal calcium absorption. We have compelling in vitro data that amino acids can stimulate gastric acid secretion. We have found that this occurs via allosteric activation of the calcium sensing receptor expressed on the gastric acid-secreting parietal cells. At a fixed concentration of extracellular calcium, addition of L but not D isomers of specific amino acids activates the calcium sensing receptor and stimulates parietal cell acid production. We hypothesize that dietary protein induced gastric acid production increases calcium solubility and bioavailability thereby increasing its absorption. We will test this hypothesis in humans by quantifying the impact of dietary protein on intestinal calcium absorption in subjects who cannot make gastric acid. We will measure intestinal calcium absorption in healthy adults as they consume either a high protein diet with concomitant administration of a proton pump inhibiting (PPI) drug or the same high protein diet with a placebo instead of a PPI. The order of the 2 interventions will be randomized, and study will be double-blind and placebo controlled. If our hypothesis is correct, then intestinal calcium absorption will be highest during the high protein diet with placebo, and lowest during the drug intervention.

Official Title
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Dietary Protein's Effect on Gastric pH and Calcium Absorption

Conditions
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Osteoporosis

Intervention / Treatment
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* Drug: esomeprazole
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy men and women age 18-45 years Caucasian or Asian descent due to increased risk of Osteoporosis Exclusion Criteria: gastrointestinal diseases osteoporosis diabetes hypertension liver disease thyroid disorders kidney disease kidney stones cancer heart disease eating disorders obesity hypogonadism amenorrhea oligomenorrhea abnormal serum FSH or estradiol levels birth control medication or other hormone-altering medications pregnancy Lifestyle factors such as: smoking excessive exercise (although moderate exercise is allowed) prescription medications known to influence vitamin D or calcium metabolism or gastric acid excessive body weight change during the past 6 months food allergies unusual eating habits or medically prescribed diets

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Esomeprazole<br> | Drug: esomeprazole<br>* 2 Interventions with esomeprazole 20 mg twice a day for 9 days vs. a placebo for 9 days while on a high protein diet<br>Drug: Placebo<br>* Placebo 20 mg twice a day for 9 days<br>|
| Active Comparator: Placebo<br> | Drug: esomeprazole<br>* 2 Interventions with esomeprazole 20 mg twice a day for 9 days vs. a placebo for 9 days while on a high protein diet<br>Drug: Placebo<br>* Placebo 20 mg twice a day for 9 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change in Intestinal Calcium Absorption | This is completed by measuring the amount of calcium absorbed by utilizing dual stable calcium isotopes. It was hypothesized that we would see a percent decrease as a result of the proton pump inhibitor. Previous published data indicated a decline in calcium absorption of 6.6 +/- 5.5% when gastric pH is blocked. | Day 5 of a high protein diet | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gastric pH | The American Heritage Dictionary defines pH as a measure of the acidity or alkalinity of a solution, numerically equal to 7 for neutral solutions, increasing with increasing alkalinity and decreasing with increasing acidity. The pH scale commonly in use ranges from 0 to 14. The normal pH range for stomach acid is between 1.5 and 3.5. | Day 5 of a high protein diet | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gastric acid, Dietary protein, Calcium, Intestinal absorption, Calcium sensing receptor