A Combination of Whey Protein and Vitamin D Reduces Sarcopenia in Patients with Chronic Obstructive Pulmonary Disease. A Randomized Controlled Trial.

2026-06
Archives of medical research 57(4)
- Rizwan Qaisar
- Imran Ullah Khan
- Firdos Ahmad
- Asima Karim

PubMed: 41232427
DOI: 10.1016/j.arcmed.2025.103330

Study Design

Type: Randomized Controlled Trial (RCT)
Sample size: n = 83
Population: patients with COPD (n=163) and age-matched controls (n=75)
Methods: randomized, controlled, double-blind, single-center trial, 16 weeks of whey protein and vitamin D supplementation
Blinding: Double-blind
Duration: 16 weeks

Background and aims

Patients with chronic obstructive pulmonary disease (COPD) experience an accelerated decline in muscle strength, mass, and functional capacity, known as sarcopenia. The effects and relevant mechanisms of supplementing whey protein and vitamin D (whey-D) on sarcopenia are unclear.

Methods

We conducted a randomized, controlled, double-blind, single-center trial in patients with COPD, categorized as placebo (n = 83) and whey-D (n = 80), along with age-matched controls (n = 75) for 16 weeks. Handgrip strength (HGS), gait speed (GS), the short physical performance battery (SPPB), and plasma levels of c-terminal agrin-fragment-22 (CAF22, a marker of neuromuscular junction [NMJ] integrity), and neurofilament light chain (NfL, a marker of neurodegeneration) were measured before and after whey-D supplementation.

Results

At baseline, patients with COPD had lower HGS, GS, and SPPB scores, and higher plasma CAF22 and NfL levels than controls (all p <0.05). Whey-D supplements improved HGS, GS, and total SPPB scores in patients with COPD (all p <0.05), unlike the placebo group. Whey-D also reduced plasma CAF22 levels (p <0.05), suggesting NMJ repair, but did not alter plasma NfL. We also observed dynamic correlations of plasma CAF22 with HGS, GS, and total SPPB scores in the whey-D group. Lastly, whey-D also reduced plasma C-reactive protein and increased 25-OH vitamin D levels (both p <0.05).

Conclusion

Sixteen weeks of whey-D supplement improved muscle strength and functional capacity in patients with COPD, partly through NMJ repair. Our data show that targeted nutritional supplements may be relevant to treating sarcopenia and functional disability in patients with COPD.

Research Insights

Vitamin D→Improved Gait Speed
Whey-D supplements improved HGS, GS, and total SPPB scores in patients with COPD (all p <0.05), unlike the placebo group.
Effect
Beneficial
Effect size
Small
Vitamin D→Improved Handgrip Strength
Whey-D supplements improved HGS, GS, and total SPPB scores in patients with COPD (all p <0.05), unlike the placebo group.
Effect
Beneficial
Effect size
Small
Vitamin D→Improved Short Physical Performance Battery Score
Whey-D supplements improved HGS, GS, and total SPPB scores in patients with COPD (all p <0.05), unlike the placebo group.
Effect
Beneficial
Effect size
Small
Vitamin D→Increased 25-hydroxyvitamin D Level
whey-D also reduced plasma C-reactive protein and increased 25-OH vitamin D levels (both p <0.05)
Effect
Beneficial
Effect size
Small
Vitamin D→Reduced C-Reactive Protein Levels
whey-D also reduced plasma C-reactive protein and increased 25-OH vitamin D levels (both p <0.05)
Effect
Beneficial
Effect size
Small
Vitamin D→Reduced C-Terminal Agrin Fragment-22 Level
Whey-D also reduced plasma CAF22 levels (p <0.05), suggesting NMJ repair
Effect
Beneficial
Effect size
Small
Vitamin D→Reduced Neurofilament Light Chain Level
but did not alter plasma NfL
Effect
Neutral
Effect size
Small
Whey Protein→Improved Gait Speed
Whey-D supplements improved HGS, GS, and total SPPB scores in patients with COPD (all p <0.05), unlike the placebo group.
Effect
Beneficial
Effect size
Small
Whey Protein→Improved Handgrip Strength
Whey-D supplements improved HGS, GS, and total SPPB scores in patients with COPD (all p <0.05), unlike the placebo group.
Effect
Beneficial
Effect size
Small
Whey Protein→Improved Short Physical Performance Battery Score
Whey-D supplements improved HGS, GS, and total SPPB scores in patients with COPD (all p <0.05), unlike the placebo group.
Effect
Beneficial
Effect size
Small
Whey Protein→Increased 25-hydroxyvitamin D Level
whey-D also reduced plasma C-reactive protein and increased 25-OH vitamin D levels (both p <0.05)
Effect
Beneficial
Effect size
Small
Whey Protein→Reduced C-Reactive Protein Levels
whey-D also reduced plasma C-reactive protein and increased 25-OH vitamin D levels (both p <0.05)
Effect
Beneficial
Effect size
Small
Whey Protein→Reduced C-Terminal Agrin Fragment-22 Level
Whey-D also reduced plasma CAF22 levels (p <0.05), suggesting NMJ repair
Effect
Beneficial
Effect size
Small
Whey Protein→Reduced Neurofilament Light Chain Level
but did not alter plasma NfL
Effect
Neutral
Effect size
Small