Serum 1 H‐NMR Metabolomic Profiling of Full‐Thickness Rotator Cuff Tears: A Hypothesis‐Generating Case–Control Pilot Study

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Abstract
Rotator cuff (RC) tears are a prevalent source of shoulder pain that restrict everyday activities and diminish quality of life. While MRI reveals structural damage in the tendon, it is uncertain if RC illness is also indicated in the body's circulating metabolites. The establishment of systemic signals may guide the future creation of blood‐based biomarker panels; however, existing evidence is currently insufficient. This exploratory, hypothesis‐generating case–control study investigated serum metabolites via proton nuclear magnetic resonance ( 1 H‐NMR) in persons with full‐thickness RC injuries and age‐ and sex‐matched healthy controls (50 cases, 50 controls). Spectra underwent meticulous quality assessments, and predetermined statistical analyses were conducted with management of false discoveries. We also examined how well different metabolites discriminated RC tears from controls and explored which metabolic pathways were most represented. Numerous metabolites exhibited variations between the groups. Concentrations of N‐carbamoyl‐β‐alanine, taurine, erythritol, and N‐acetylaspartate were elevated in RC tears, but levels of 3‐methylhistidine and proline were diminished. Pathway enrichment revealed pyrimidine metabolism, bile‐acid biosynthesis, taurine/hypotaurine metabolism, β‐alanine metabolism, and histidine metabolism, indicating coordinated perturbations at the pathway level rather than isolated alterations. These data must be regarded as preliminary and hypothesis‐generating, lacking the establishment of causation or immediate clinical applicability. Although preliminary, these findings are scientifically significant because they suggest that full‐thickness RC tears may be associated with a coordinated systemic metabolic signature rather than only a focal tendon abnormality. This systems‐level perspective adds to the current understanding of RC pathology by generating biologically plausible hypotheses related to tissue remodeling, oxidative stress adaptation, and energy metabolism. Prospective longitudinal investigations with targeted quantification, external validation, and integration with imaging and clinical outcomes are required before clinical translation.

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