Explore the Optimal Treatment Regimen Across Combinations of Variate Protein Sources and Exercise Modalities and Its Associated Factors in Older Adults: A Network Meta-Analysis and Meta-Regression of Randomized Controlled Trials.

2026-04-29
Nutrients 18(9)
- Che-Li Lin
- Shih-Wei Huang
- Hung-Chou Chen
- Mao-Hua Huang
- Tsan-Hon Liou
- Chun-De Liao

PubMed: 42124009
DOI: 10.3390/nu18091409

Study Design

Type: Meta-Analysis
Sample size: n = 980
Population: untrained older adults
Methods: Systematic review and network meta-analysis of RCTs

Rigorous Journal

Background/Objectives: Aging is closely associated with sarcopenia, which has a significant impact on muscle mass and its function. Protein supplementation (PS) brings benefits such as lean mass and strength gains during exercise training. This paper determined the optimal regimen among the composites of variate protein sources and training modalities for older individuals. Methods: We comprehensively searched the electronic databases, namely MEDLINE Complete, PEDro, the Cochrane Library, Google Scholar, EMBASE, and the China National Knowledge Infrastructure, from its inception until December 2025. We included randomized controlled trials (RCTs) that examined the effectiveness of any type of PS combined with one of three exercise types-resistance, aerobic, or multicomponent training-in untrained older adults. The main outcomes used to identify sarcopenia were assessed, including lean mass, handgrip and leg strength, and physical mobility measures. Network meta-analysis (NMA) was performed by a frequentist method using random-effects models. The estimated treatment effect was expressed as the standard mean difference (SMD) with a 95% confidence interval (CI). Any potential factor moderating the treatment effect was determined by the meta-regression analyses, including participant characteristics and methodological factors. Certainty of evidence (CoE) was assessed by the GRADE framework. Results: In total, we included 235 RCTs (20,980 participants) for analyses. A total of 10 protein sources (whey, soy, casein, milk, and the others) were identified, corresponding to 24 monotherapy and combined regimens of PS and exercise. Among the treatment arms, whey plus resistance training was ranked as the most effective treatment for muscle mass (large SMD, 1.29; CoE, moderate) and leg strength (large SMD, 1.16; CoE, moderate); additionally, whey plus multicomponent exercise training achieved the most promising effects on such sarcopenia-related physical indicators such as chair rise (large effect, SMD = 1.09; CoE: high), timed up and go (medium SMD, 0.70; CoE, high), and global mobility score (large SMD, 1.02; CoE, high). Conclusions: The treatment efficacy appears to be moderated by the participant's conditions, PS resource, and PS dose, particularly the outcome of muscle mass and strength. The present NMA results indicate that whey protein incorporated with resistance training is the optimal program to help combat sarcopenia in older adults.

Research Insights

Casein Protein→Increased Lean Mass
This paper determined the optimal regimen among the composites of variate protein sources ... (milk was among the 10 sources analyzed; network meta-analysis includes all sources and the conclusion singled out whey, implying milk did not show a significant large effect).
Effect
Neutral
Effect size
Small
Milk Protein→Increased Lean Mass
This paper determined the optimal regimen among the composites of variate protein sources ... (milk was among the 10 sources analyzed; network meta-analysis includes all sources and the conclusion singled out whey, implying milk did not show a significant large effect).
Effect
Neutral
Effect size
Small
Soy Protein→Improved Leg Strength
Among the treatment arms, whey plus resistance training was ranked as the most effective treatment for ... leg strength ... (other protein sources did not reach that level of effectiveness in the NMA).
Effect
Neutral
Effect size
Small
Soy Protein→Increased Lean Mass
This paper determined the optimal regimen among the composites of variate protein sources ... (milk was among the 10 sources analyzed; network meta-analysis includes all sources and the conclusion singled out whey, implying milk did not show a significant large effect).
Effect
Neutral
Effect size
Small
Whey Protein→Improved Chair Rise Performance
whey plus multicomponent exercise training achieved the most promising effects on such sarcopenia-related physical indicators such as chair rise (large effect, SMD = 1.09; CoE: high)
Effect
Beneficial
Effect size
Large
Whey Protein→Improved Handgrip Strength
The main outcomes used to identify sarcopenia were assessed, including ... handgrip ... (the abstract does not report a significant finding for handgrip strength for any specific regimen; it only highlights leg strength and physical mobility outcomes, implying no significant effect on handgrip or it was not among the top-ranked outcomes).
Effect
Neutral
Effect size
Small
Whey Protein→Improved Leg Strength
Among the treatment arms, whey plus resistance training was ranked as the most effective treatment for ... leg strength ... (other protein sources did not reach that level of effectiveness in the NMA).
Effect
Neutral
Effect size
Small
Whey Protein→Improved Mobility Score
whey plus multicomponent exercise training achieved the most promising effects on such sarcopenia-related physical indicators such as ... global mobility score (large SMD, 1.02; CoE, high)
Effect
Beneficial
Effect size
Large
Whey Protein→Improved Timed Up and Go
whey plus multicomponent exercise training achieved the most promising effects on such sarcopenia-related physical indicators such as ... timed up and go (medium SMD, 0.70; CoE, high)
Effect
Beneficial
Effect size
Moderate
Whey Protein→Increased Lean Mass
This paper determined the optimal regimen among the composites of variate protein sources ... (milk was among the 10 sources analyzed; network meta-analysis includes all sources and the conclusion singled out whey, implying milk did not show a significant large effect).
Effect
Neutral
Effect size
Small