Fiber and Calcium Absorption in Older Men

Modulation of the Gut Microbiome by Dietary Fiber to Improve Calcium Absorption and Bone Health in Older Men

Osteoporotic fractures are a major but underrecognized problem in men. There is growing evidence that low dietary fiber intake is a modifiable risk factor for age-related bone loss in men. Preclinical and human studies in adolescents and postmenopausal women suggest that dietary fiber intake influences bone metabolism by modulating the gut microbiome to augment intestinal calcium absorption, but it is unclear through what molecular mechanism and whether dietary fiber has the same effects in older men. In this crossover intervention study, the investigators will enroll and follow 30 older male Veterans to evaluate the effects of soluble corn fiber on intestinal calcium absorption and explore the contribution of the gut microbiome.

Study Overview

• Status: Recruiting
• Conditions: Aging
• Intervention / Treatment: Dietary supplement: Soluble corn fiber

Detailed Description

Osteoporosis and associated fractures are a major problem in older men. One in four men over the age of 60 will sustain an osteoporotic fracture during his lifetime. Moreover, the mortality rate in men after fractures is nearly twice that in women. Despite the burden of fractures, little is understood about the pathogenesis of progressive bone loss in men. Studies point to dietary fiber as a potentially important mitigator of decline in bone mass, likely through increased intestinal calcium absorption and retention, as studied in adolescents, young men, and postmenopausal women. However, the effects of dietary fiber in older men have not been tested and the mechanism by which dietary fiber influences calcium absorption is unclear. The gut microbiome, which is crucial for host nutrient metabolism and hormone modulation, is a likely but underexplored mechanism.

The overall objective is to examine the effects of soluble corn fiber on intestinal calcium absorption with modulation of the gut microbiome in older men. The central hypothesis is that soluble corn fiber augments production of short-chain fatty acids by the gut microbiome, which modulates the production of systemic insulin-like growth factor 1 to increase calcium absorption and bone mass.

This study is a crossover intervention study on the effects of soluble corn fiber vs. placebo on intestinal calcium absorption and gut microbiome composition and function in 30 older male Veterans 60 years of age. Participants will be randomized 1:1 to sequential soluble corn fiber 20g/day vs. placebo for4 weeks each with a 4-week washout period. Individualized doses of calcium and vitamin D supplementation will also be provided through out the study period. Study measurements at the end of each intervention include intestinal calcium absorption via a dual stable isotope method, detailed gut microbiome characterization with metagenomics and metabolomics, dietary assessment, calciotropic hormones, and bone turnover marker levels. Baseline bone density and microstructure will also be obtained.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Karin C Wu, MD; Phone Number: (415) 221-4810; Email: karin.Wu@va.gov

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94121-1563
      • Recruiting
      • San Francisco VA Medical Center, San Francisco, CA
      • Contact: Karin C Wu, MD; Phone Number: 415-221-4810; Email: karin.Wu@va.gov
      • Principal Investigator: Karin C Wu, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Male Veterans 60 years of age

Exclusion Criteria:

• History of malabsorption
• Hypercalcemia (corrected Ca > 10.2 mg/dL)
• Vitamin D insufficiency (25OHD < 30 ng/mL)
• Chronic kidney disease stage 3B or worse (CrCl < 45 mL/min)
• Severe hypogonadism (AM fasting serum total testosterone < 150 ng/dL)
• Daily use of proton pump inhibitor
• Use of medication(s) known to affect calcium metabolism
• Use of medications or supplements that could impact gut microbiota in the previous 3 months (antibiotics or commercially available probiotics or prebiotics.
• Presence of a condition or abnormality that in the opinion of the Investigator that would compromise the safety of the patient or the quality of the data.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1; Soluble corn fiber 20g/day x 4 weeks, washout period for 4 weeks, and placebo (maltodextrin) x 4 weeks.	Dietary supplement: Soluble corn fiber; Soluble corn fiber, also referred to resistant maltodextrin, is a type of dietary fiber made from corn starch. Soluble corn fiber is typically used to thicken processed foods and has been marketed as a prebiotic to improve digestive health.
Experimental: Group 2; Placebo (maltodextrin) 20g/day x 4 weeks, washout period for 4 weeks, and soluble corn fiber x 4 weeks.	Dietary supplement: Soluble corn fiber; Soluble corn fiber, also referred to resistant maltodextrin, is a type of dietary fiber made from corn starch. Soluble corn fiber is typically used to thicken processed foods and has been marketed as a prebiotic to improve digestive health.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intestinal fractional calcium absorption	Dual stable calcium isotopic tracer method	At week 4 and week 12 of study participation (at the end of each treatment phase x2)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biochemical markers of bone turnover	Blood draw	At week 4 and week 12 of study participation (at the end of each treatment phase x2)
Calciotropic hormones	Blood draw	At week 4 and week 12 of study participation (at the end of each treatment phase x2)
Gut microbial profiling	Stool collection	At week 4 and week 12 of study participation (at the end of each treatment phase x2)
Adherence, tolerability, and acceptability	Questionnaire	Throughout study period, an average of 12 weeks

Collaborators and Investigators

• Sponsor: VA Office of Research and Development
• Collaborators: San Francisco VA Health Care System
• Investigators: Principal Investigator: Karin C Wu, MD, San Francisco VA Medical Center, San Francisco, CA

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2025
• Primary Completion (Estimated): January 1, 2029
• Study Completion (Estimated): January 1, 2029

Study Registration Dates

• First Submitted: June 20, 2024
• First Submitted That Met QC Criteria: July 19, 2024
• First Posted (Actual): July 25, 2024

Study Record Updates

• Last Update Posted (Actual): February 17, 2026
• Last Update Submitted That Met QC Criteria: February 11, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Other Study ID Numbers: ENDB-009-23F; 24-41270 (Other Identifier: San Francisco VA Health Care System)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No