Independent effects of whey protein and alkali supplementation on muscle health in healthy older adults: factorial randomized controlled trial.

2026-05
The American journal of clinical nutrition 123(5)
- Lisa Ceglia
- Elsa Konieczynski
- Elise Danico
- Ludovic Trinquart
- Benjamin Koethe
- Qingyan Xiang
- Roger A Fielding
- William J Evans
- Mahalakshmi Shankaran
- Bess Dawson-Hughes

PubMed: 41780731
DOI: 10.1016/j.ajcnut.2026.101257

Study Design

Type: Randomized Controlled Trial (RCT)
Sample size: n = 128
Population: healthy adults aged ≥65 years
Methods: randomized, 2 × 2 factorial, placebo-controlled study
Blinding: Double-blind
Duration: 24 weeks
Funding: Unclear

Large Human Trial

Background

Aging is accompanied by reduced muscle protein synthesis and increased circulating acid, both of which contribute to declines in muscle health.

Objectives

To determine the effects of whey protein (WP) and alkali (potassium bicarbonate, KHCO₃) supplementation on muscle performance and mass in healthy older adults.

Methods

In this randomized, 2 × 2 factorial, placebo-controlled study, healthy adults aged ≥65 years were assigned to either WP (1.5 g/kg/d) plus KHCO₃ (81 mmol/d), WP plus placebo-KHCO₃, placebo-WP plus KHCO₃, or double placebo. Double leg press muscle power (primary outcome), physical performance, lean mass by dual energy x-ray absorptiometry, muscle mass by D₃-creatine dilution, and serum insulin-like growth factor 1 (IGF-1) were measured at baseline and 24 weeks. Primary analyses estimated main effects of WP compared with placebo-WP and KHCO₃ compared with placebo-KHCO₃ using factorial comparisons "at-the-margins," following CONSORT/SPIRIT recommendations for factorial trials. Between-group differences in the 24-wk outcomes were estimated using analysis of covariance adjusted for baseline value, age, and sex.

Results

In the intention-to-treat sample (n = 128), 47.7% were female, mean ± SD age was 74 ± 6 y, and baseline protein intake was 0.85 ± 0.30 g/kg/d. Neither WP nor KHCO₃ affected muscle power compared with their respective placebo {WP to placebo-WP difference 4.7 watts [95% confidence interval (CI): -21.1,30.5; P = 0.72]; KHCO₃ to placebo-KHCO₃ difference -13.6 watts [95% CI: -39.6, 12.4; P = 0.30]}. No group differences were noted in physical performance or muscle mass. However, 24-wk mean IGF-1 level was higher in the WP and KHCO₃ groups compared with their respective placebo [WP to placebo-WP difference 14.2 ng/mL (95% CI: 7.5, 21.0; P < 0.01); KHCO₃ to placebo-KHCO₃ difference 7.2 ng/mL (95% CI: 0.4, 13.9; P = 0.04)].

Conclusions

In healthy free-living older adults reporting a protein intake at the current recommended daily allowance, neither increasing protein to 1.5 g/kg/d with WP nor adding a KHCO₃ supplement for 24 wk improved measures of muscle power, physical performance, or muscle mass despite achieving higher circulating IGF-1 levels.

Clinical trial registry number

This trial was registered as NCT04048616 at https://clinicaltrials.gov/study/NCT04048616?term=ceglia&rank=1.

Research Insights

Whey Protein→Improved Lean Mass
No group differences were noted in physical performance or muscle mass
Effect
Neutral
Effect size
Small
Dose
1.5 g/kg/d
Whey Protein→Improved Muscle Mass
No group differences were noted in physical performance or muscle mass
Effect
Neutral
Effect size
Small
Dose
1.5 g/kg/d
Whey Protein→Improved Muscle Power
Neither WP nor KHCO3 affected muscle power compared with their respective placebo {WP to placebo-WP difference 4.7 watts [95% confidence interval (CI): -21.1,30.5; P = 0.72]}
Effect
Neutral
Effect size
Small
Dose
1.5 g/kg/d
Whey Protein→Improved Physical Performance
No group differences were noted in physical performance
Effect
Neutral
Effect size
Small
Dose
1.5 g/kg/d
Whey Protein→Increased Insulin-like Growth Factor-1 Level
24-wk mean IGF-1 level was higher in the WP and KHCO3 groups compared with their respective placebo [WP to placebo-WP difference 14.2 ng/mL (95% CI: 7.5, 21.0; P < 0.01)]
Effect
Beneficial
Effect size
Small
Dose
1.5 g/kg/d