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.

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.

Eligibility Criteria:
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