# Synergistic Effects of Protein Intake and Exercise on Biomarkers of Sarcopenia: A Systematic Review

**Authors:** Stephanie Cruz-Pierard, Samuel Iñiguez-Jiménez

PMC · DOI: 10.3390/biom16020195 · Biomolecules · 2026-01-27

## TL;DR

Combining protein intake and exercise improves muscle-related biomarkers and function in older adults with sarcopenia.

## Contribution

Demonstrates synergistic effects of protein and resistance exercise on sarcopenia biomarkers through a systematic review.

## Key findings

- Protein plus exercise reduced myostatin, activin, and IL-6 while increasing IGF-1, follistatin, and IL-10.
- Functional improvements included gains in muscle strength and fat-free mass.
- The combined approach is promising for sarcopenia prevention and treatment despite study heterogeneity.

## Abstract

Sarcopenia, defined as the progressive decline of muscle mass, strength, and function, severely compromises autonomy and quality of life in older adults. This systematic review evaluated synergistic effects of protein supplementation combined with resistance exercise on biochemical and functional biomarkers of sarcopenia. The search for scientific evidence was conducted in PubMed, Scopus, ScienceDirect, and Cochrane databases (2019–2025), applying explicit inclusion and exclusion criteria, like only randomized controlled trials in humans, published in English, Spanish, or French, were included to ensure high-quality evidence. After selection, the risk of bias of the articles was assessed according to the Cochrane Handbook for Systematic Reviews of Interventions. Seven randomized controlled trials, with a total of 260 participants, met the eligibility criteria. Interventions combining resistance exercise three times per week at 60–80% of one-repetition maximum with daily protein supplementation of at least 15 g, mainly from dairy sources, showed synergistic effects. Improvements were observed in inflammatory and anabolic biomarkers, with reductions in myostatin, activin, and IL-6, and increases in IGF-1, follistatin, and IL-10. Functional outcomes included gains in muscle strength, fat-free mass, and muscle fiber cross-sectional area. Despite heterogeneity in duration and sample size, findings support this combined approach as a promising and clinically applicable strategy to prevent and treat sarcopenia. No external funding was received, and the review is registered in PROSPERO (CRD42025640989).

## Linked entities

- **Proteins:** LOC5521725 (growth/differentiation factor 8), Actbeta (Activin-beta), IGF1 (insulin like growth factor 1), LOC5564573 (agrin), IL6 (interleukin 6), IL10 (interleukin 10)

## Full-text entities

- **Genes:** INHBE (inhibin subunit beta E) [NCBI Gene 83729], IGF1 (insulin like growth factor 1) [NCBI Gene 3479] {aka IGF, IGF-I, IGFI, MGF}, TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}, INS (insulin) [NCBI Gene 3630] {aka IDDM, IDDM1, IDDM2, ILPR, IRDN, MODY10}, ALB (albumin) [NCBI Gene 213] {aka FDAHT, HSA, PRO0883, PRO0903, PRO1341}, GDF15 (growth differentiation factor 15) [NCBI Gene 9518] {aka GDF-15, HG, MIC-1, MIC1, NAG-1, PDF}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, IL10 (interleukin 10) [NCBI Gene 3586] {aka CSIF, GVHDS, IL-10, IL10A, TGIF}, MTOR (mechanistic target of rapamycin kinase) [NCBI Gene 2475] {aka FRAP, FRAP1, FRAP2, RAFT1, RAPT1, SKS}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, CRP (C-reactive protein) [NCBI Gene 1401] {aka PTX1}, GH1 (growth hormone 1) [NCBI Gene 2688] {aka GH, GH-N, GHB5, GHN, IGHD1A, IGHD1B}, FST (follistatin) [NCBI Gene 10468] {aka FS}, MSTN (myostatin) [NCBI Gene 2660] {aka GDF8, MSLHP}, IL2 (interleukin 2) [NCBI Gene 3558] {aka IL-2, TCGF, lymphokine}, RPS6 (ribosomal protein S6) [NCBI Gene 6194] {aka S6, eS6}, CXCL8 (C-X-C motif chemokine ligand 8) [NCBI Gene 3576] {aka GCP-1, GCP1, IL8, LECT, LUCT, LYNAP}
- **Diseases:** atrophy (MESH:D001284), osteoporosis (MESH:D010024), DM (MESH:D009223), chronic kidney disease (MESH:D051436), cancer (MESH:D009369), hypertrophy (MESH:D006984), diabetes (MESH:D003920), muscle weakness (MESH:D018908), cardiovascular (MESH:D002318), impaired regeneration (MESH:D060825), reduced strength (MESH:D001523), muscle hypertrophy (MESH:C536106), muscle (MESH:D019042), dyslipidemia (MESH:D050171), malnutrition (MESH:D044342), malabsorption (MESH:D008286), fractures (MESH:D050723), loss of power (MESH:D016388), hyperlipidemia (MESH:D006949), liver or kidney disease (MESH:D008107), Sarcopenia (MESH:D055948), Inflammatory (MESH:D007249), muscle wasting (MESH:D009133), catabolic diseases (MESH:D004194), injuries (MESH:D014947), skeletal muscle disease (MESH:D005207), chronic (MESH:D002908), decreased muscle mass (MESH:C536030), metabolic (MESH:D008659), glucose tolerance (MESH:D018149), muscle fiber damage (MESH:C563545), muscle loss (MESH:D009135), obese (MESH:D009765), impairment of neuromuscular innervation (MESH:D000093922), slow gait (MESH:D020234), type 2 diabetes (MESH:D003924)
- **Chemicals:** Ala (MESH:D000409), carbohydrate (MESH:D002241), phenylalanine (MESH:D010649), triglycerides (MESH:D014280), amino acid (MESH:D000596), DHEA-S (MESH:D019314), Cortisol (MESH:D006854), 2-butenedioic acid (MESH:C032005), estradiol (MESH:D004958), maltodextrin (MESH:C008315), L-[1-13C] leucine (-), 3-hydroxybutyric acid (MESH:D020155), Fat (MESH:D005223), reactive oxygen species (MESH:D017382), cholesterol (MESH:D002784), essential amino acids (MESH:D000601), lipid (MESH:D008055), testosterone (MESH:D013739), sucrose (MESH:D013395), Leu (MESH:D007930)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12937736/full.md

## References

55 references — full list in the complete paper: https://tomesphere.com/paper/PMC12937736/full.md

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Source: https://tomesphere.com/paper/PMC12937736