The Effect of Protein on Calcium Absorption and Gastric Acid Production

Dietary Protein's Effect on Gastric pH and Calcium Absorption

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.

Study Overview

• Status: Completed
• Conditions: Osteoporosis
• Intervention / Treatment: Drug: esomeprazole; Drug: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale New Haven Hospital Hospital Research Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Yale University
• Investigators: Principal Investigator: Karl Insogna, MD, Yale University

Study record dates

Study Major Dates

• Study Start: January 1, 2005
• Primary Completion (Actual): May 1, 2008
• Study Completion (Actual): May 1, 2008

Study Registration Dates

• First Submitted: July 17, 2008
• First Submitted That Met QC Criteria: July 18, 2008
• First Posted (Estimate): July 21, 2008

Study Record Updates

• Last Update Posted (Actual): March 6, 2020
• Last Update Submitted That Met QC Criteria: March 4, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: Calcium sensing receptor; Calcium; Intestinal absorption; Dietary protein; Gastric acid
• Additional Relevant MeSH Terms: Metabolic Diseases; Musculoskeletal Diseases; Bone Diseases; Bone Diseases, Metabolic; Osteoporosis; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Gastrointestinal Agents; Anti-Ulcer Agents; Proton Pump Inhibitors; Esomeprazole
• Other Study ID Numbers: 0910005852; 129772 (Other Grant/Funding Number: Other Federal ID)