New Study Finds PeptiStrong® Outperforms Leucine and HMB in Aging Muscle, and Works Even Better in Combination

Nuritas, the biotech company that discovers and clinically validates bioactive peptides from whole food sources announced the publication of new peer-reviewed research comparing its Vicia faba–derived peptide ingredient PeptiStrong® (VFH) against leucine and HMB (β-hydroxy-β-methylbutyrate), two of the most widely used studied ingredients for supporting muscle protein synthesis (MPS). The study, “A comparison of the effects of leucine, HMB, and Vicia faba hydrolysate on activation of ERK1/2 and protein synthesis signalling in a young and aged muscle model,” was published in NFS Journal (DOI: 10.1016/j.nfs.2026.100285) and is available open access under a Creative Commons license.

The paper introduces a novel doxycycline-inducible model of human skeletal muscle (DIMs) developed by Nuritas, designed to capture muscle-specific changes that occur through replicative aging addressing a long-standing gap in muscle research, where reliable human cell models for studying aging muscle have been scarce. A full characterization paper on the model is forthcoming.

Key findings:

• PeptiStrong® drove significantly greater activation of mps signaling than either leucine or HMB, increasing phosphorylation of ribosomal S6 (a key marker of mTORC1 activation) by 5.82-fold in young muscle cells and 3.39-fold in aged muscle cells.
• PeptiStrong® also significantly increased phosphorylation of 4EBP1, another key protein synthesis marker, by 2.53-fold in young cells and 1.92-fold in aged cells.
• Using a kinase array and pathway inhibitors, the researchers identified the MAPK/ERK pathway as a key driver of PeptiStrong®’s activity, with ERK1/2 phosphorylation increasing by up to 2.25-fold following treatment.
• Aged muscle cells showed a marked reduction in LAT1 transporter expression (the pathway leucine relies on to enter cells), which appeared to impair leucine’s ability to activate anabolic signaling — a possible explanation for the inconsistent clinical results leucine has shown in older adults. PeptiStrong® retained its anabolic activity even when this transporter was blocked, confirming its effects are independent of leucine.
• Combining PeptiStrong® with leucine or HMB further boosted signaling beyond either ingredient alone — S6 phosphorylation increased by up to 2.89-fold with leucine and 4.40-fold with HMB in aged cells.

Leucine and HMB are foundational ingredients in sports nutrition and healthy-aging formulations, but clinical results, particularly for leucine in older adults, have been inconsistent. This study offers a possible mechanistic explanation: reduced expression of the LAT1 transporter in aging muscle appears to blunt leucine’s effects. Because PeptiStrong® activates muscle protein synthesis through the MAPK/ERK pathway independently of LAT1 and leucine, it can address this age-related gap directly and, this research shows, meaningfully amplify the effects of leucine- or HMB-based formulations rather than compete with them. That makes PeptiStrong® a differentiated addition for brands formulating next-generation muscle health products for aging populations.

“Understanding how skeletal muscle responds to nutrition during aging is essential for developing more effective interventions. This study demonstrates that Vicia faba hydrolysate (PeptiStrong®) works partly through a distinct biological pathway and complements established ingredients such as leucine and HMB, offering a promising approach to enhancing protein synthesis signaling that may ultimately support healthy muscle aging.” says Owen Connolly, Senior Scientist – Molecular Biology at Nuritas

About the study: Researchers compared leucine, HMB, and PeptiStrong® (VFH) in C2C12 myotubes and in a newly developed model of aging muscle (DIMs).[OC1]  Using Western blotting, a human phospho-kinase array, and pathway inhibitor studies, the team assessed activation phosphorylation of mTORC1-linked protein synthesis markers (S6, 4EBP1) and traced PeptiStrong®’s mechanism to MAPK/ERK signaling, independent of the LAT1 amino acid transporter used by leucine. The study was authored by Owen Connolly, Robert Radford, Emily Hart, Stephen Kenny, Nora Khaldi, Andy Franklyn-Miller, and Brian Keogh, all of Nuritas.

About PeptiStrong® PeptiStrong® is Nuritas clinically validated, food-derived bioactive peptide ingredient, discovered using the company’s AI platform and developed from Vicia faba (fava bean) protein. Backed by multiple human clinical trials, it is designed to support muscle strength, recovery, and physical function and, per this latest research, to do so through mechanisms distinct from, and complementary to, traditional amino acid–based ingredients like leucine and HMB.