Impact of Protein and Alkali Supplementation on Skeletal Muscle in Older Adults

Whether higher dietary protein benefits skeletal muscle health in older adults remains an ongoing area of investigation. This study will determine whether adding an alkaline salt supplement, potassium bicarbonate, to reduce the dietary acid load of a high protein diet can further enhance the beneficial impact of a high protein diet alone on muscle performance and mass in older underactive adults on baseline low protein diet.

Study Overview

• Status: Completed
• Conditions: Muscle Loss; Age-Related Sarcopenia
• Intervention / Treatment: Dietary supplement: whey protein isolate; Dietary supplement: potassium bicarbonate (KHCO3); Other: microcrystalline cellulose; Other: maltodextrin powder

Detailed Description

With aging, skeletal muscle mass and performance decline leading to an increased risk of falls and physical disability. There is ongoing research on whether increasing dietary protein intake in older adults improves indices of muscle health and thus translates to a reduction in physical disability. A main concern is that high protein results in a large dietary acid load from the breakdown of protein to acidogenic byproducts, which could in turn promote muscle degradation particularly in older adults with age-related declines in renal excretion of acid. The scientific premise of this project is that the balance between the amount of protein in the diet (anabolic component) and the net acid load of the diet (catabolic component) in part determines whether the diet as a whole has a net anabolic or catabolic effect on muscle. Preliminary data have suggested that a daily alkaline salt supplement (potassium bicarbonate, KHCO3) lowered the dietary acid load and improved lower extremity muscle power in postmenopausal women. The investigator's central hypothesis is that higher protein intake plus a neutralizing alkaline salt will have additive effects on muscle performance and mass in older adults to either intervention alone. To test the hypothesis, the investigators will conduct a randomized, double-blind, placebo-controlled, 2x2 factorial study in which underactive men and women age 65 and older on baseline lower protein diets will be enrolled. Participants will assigned to one of four groups: either a whey protein supplement (to raise protein intake to 1.5 g/kg/d) with or without KHCO3 81 mmol/d or an isocaloric placebo supplement with or without KHCO3 81 mmol/d for 24 wks. The primary outcome is lower extremity muscle power at 24 weeks. Secondary outcomes are lower extremity muscle power at 12 weeks, muscle endurance at 12 and 24 weeks, physical performance at 24 weeks, lean mass at 24 weeks, and 24-hr urinary nitrogen excretion adjusted for nitrogen intake at 24 weeks. Exploratory outcomes will include a measure of muscle mass - D3-creatine dilution - and how it correlates with lean mass. Changes in these outcomes will be compared in the 4 groups. If successful, this research would represent a meaningful step in defining the circumstances under which protein has its greatest anabolic benefit.

• Study Type: Interventional
• Enrollment (Actual): 141
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Lisa Ceglia, MD MS; Phone Number: 617-556-3085; Email: lisa.ceglia@tufts.edu
• Study Contact Backup: Name: Elise Reitshamer; Phone Number: 617-556-3265; Email: elise.reitshamer@tufts.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. ability to sign informed consent form
2. ambulatory community-dwelling men and women
3. age 65 years and over
4. habitual dietary intake of protein of ≤0.8 g/kg/d
5. underactive
6. estimated glomerular filtration rate ≥ 50 ml/min/1.73 m2

Exclusion Criteria:

1. participation in a diet or intensive exercise program during the study
2. vegetarian (no animal protein)
3. oral glucocorticoid use for > 10 days in the last 3 months
4. anabolic and gonadal hormones in the last 6 months
5. Tamoxifen/raloxifene in the last 6 months
6. regular use of alkali-producing antacids (> 3 times per week)
7. potassium-containing supplements or products
8. non-steroidal anti-inflammatory medications >3 times per week
9. antacids containing calcium carbonate, aluminum hydroxide, magnesium hydroxide, or calcium acetate
10. insulin
11. sulfonylureas
12. SGLT2 inhibitors
13. a lower extremity fracture in the last year
14. kidney stones in the past 5 years
15. hyperkalemia
16. elevated serum bicarbonate
17. hypercalcemia
18. uncontrolled diabetes mellitus defined as having fasting blood >150 or hemoglobin A1c >8%
19. untreated thyroid or parathyroid disease
20. significant immune disorder
21. current unstable heart disease
22. Crohn's disease
23. active malignancy or cancer therapy in the last year
24. alcohol use exceeding 2 drinks/day
25. current peptic ulcers or esophageal stricture
26. other condition or abnormality in screening labs, at discretion of the study physician

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: whey protein isolate + KHCO3; 1.5 gm/kg/day of whey protein and 81 mmol/day of KHCO3	Dietary supplement: whey protein isolate; one 15-25 gm (based on body weight) protein packet three times a day with each meal; Dietary supplement: potassium bicarbonate (KHCO3); two 13.5 mmol capsules three times a day with each meal
Active Comparator: whey protein isolate + microcrystalline cellulose; 1.5 gm/kg/day of whey protein and identical placebo microcrystalline cellulose capsules	Dietary supplement: whey protein isolate; one 15-25 gm (based on body weight) protein packet three times a day with each meal; Other: microcrystalline cellulose; identical placebo capsule
Active Comparator: maltodextrin powder + KHCO3; isocaloric placebo maltodextrin powder and 81 mmol/day of KHCO3	Dietary supplement: potassium bicarbonate (KHCO3); two 13.5 mmol capsules three times a day with each meal; Other: maltodextrin powder; isocaloric placebo powder
Placebo Comparator: maltodextrin powder + microcrystalline cellulose; isocaloric placebo maltodextrin powder and identical placebo microcrystalline cellulose capsules	Other: microcrystalline cellulose; identical placebo capsule; Other: maltodextrin powder; isocaloric placebo powder

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
lower extremity muscle power	measure of muscle power using a double leg press	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
lower extremity muscle power	measure muscle power using double leg press	12 weeks
isokinetic leg extension strength and endurance	measure knee extension strength, torque and fatigability using Biodex Isokinetic Dynamometer	12 and 24 weeks
handgrip strength	measure strength using grip strength dynamometer	24 weeks
appendicular lean body mass	Dual energy X-ray absorptiometry (DXA) lean mass of arms plus legs divided by height squared	24 weeks
physical performance battery	measure performance based on Health Aging and Body Composition-Physical Performance Battery	24 weeks
24 hour urinary nitrogen excretion to nitrogen intake	measure based on 24 hour urine and 24 hour diet recall	24 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
D3-creatine dilution (exploratory)	measure of total body muscle mass	24 weeks

Collaborators and Investigators

• Sponsor: Tufts University
• Collaborators: National Institute on Aging (NIA)
• Investigators: Principal Investigator: Lisa Ceglia, MD MS, Tufts Medical Center and Tufts University

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2019
• Primary Completion (Actual): December 21, 2023
• Study Completion (Actual): December 21, 2023

Study Registration Dates

• First Submitted: August 5, 2019
• First Submitted That Met QC Criteria: August 6, 2019
• First Posted (Actual): August 7, 2019

Study Record Updates

• Last Update Posted (Actual): January 10, 2024
• Last Update Submitted That Met QC Criteria: January 9, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Neuromuscular Manifestations; Pathological Conditions, Anatomical; Muscular Atrophy; Atrophy; Sarcopenia
• Other Study ID Numbers: 3010; 1R01AG055443-01A1 (U.S. NIH Grant/Contract)

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