Amino acid supplementation accelerates resolution of exercise-induced phagocyte infiltration in human skeletal muscle

Background: Amino acids activate neutrophil phagocytosis and free radical release in vitro. Aim: We examined the effects of amino acid supplementation on post-exercise accumulation of myeloperoxidase-positive (MPO⁺) cells in human skeletal muscle using a randomized, double-blind, placebo-controlled crossover design. Methods: Ten young men (22 ± 2.8 years) consumed either amino acids (15 g) or an isocaloric placebo before resistance exercise. Biopsies of the vastus lateralis muscle were collected at baseline, immediately after exercise (0 h), and 24 h post-exercise. Results: Resistance exercise increased MPO⁺ cell infiltration (+161%, p = 0.02) and 8-hydroxy−2-deoxyguanosine (8-OHdG) levels (+66%, p = 0.02) at 24 h. Amino acid supplementation accelerated MPO⁺ cell infiltration to 0 h (+100%, p = 0.03), which diminished by 24 h post-exercise (+53%, p = 0.06). Immunofluorescence co-staining revealed that MPO⁺ cells exhibited markedly higher mitochondrial density (TOM20-labeled) and integrated with the injured regions of adjacent myofibers showing lower mitochondria. Other infiltrating MPO-negative cells also contributed mitochondria to exercised muscle tissue, resulting in an overall ~2-fold increase in mitochondrial content during 24-h recovery (p < 0.001), similar under both supplementation conditions. Cellular senescence marker p16Ink4a mRNA decreased by 58% at 24 h post-exercise, with an earlier reduction observed under amino acid treatment (0 h: –49%, p = 0.05). Conclusion: These findings indicate that amino acid supplementation accelerates the resolution of inflammation in exercised human skeletal muscle. Immunofluorescence evidence further suggests that infiltrating bone marrow-derived cells contribute to fast mitochondrial gains as part of the muscle damage-response following exercise.