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Patients with chronic obstructive pulmonary disease (COPD) often develop malnutrition due to high metabolic consumption and limited food intake, manifesting as skeletal muscle and respiratory muscle atrophy, as well as impaired immune function, which forms a vicious cycle of disease progression - nutritional deterioration. As the most biologically active branched-chain amino acid, L-leucine can serve as a key nutrient for improving the nutritional status and prognosis of COPD patients through targeted regulation of metabolic pathways. Its core mechanisms of action and clinical efficacy are as follows:
I. Core Mechanisms of Action
Activating Muscle Protein Synthesis and Inhibiting DegradationL-leucine can directly activate the mTOR signaling pathway in skeletal muscle cells, promote the phosphorylation of ribosomal proteins, and initiate the process of protein translation. Meanwhile, it inhibits the expression of muscle-specific ubiquitin ligases, reduces skeletal muscle protein degradation, and reverses muscle loss in COPD patients. In particular, it can protect the fiber structure and contractile function of respiratory muscles such as the diaphragm.
Enhancing Respiratory Muscle Function and Improving Ventilation CapacityOn the one hand, L-leucine promotes diaphragmatic protein synthesis, increases the cross-sectional area of muscle fibers, and elevates the maximal inspiratory pressure and expiratory pressure of the diaphragm. On the other hand, it can be directly oxidized in muscles to supply energy, optimize the energy metabolism efficiency of respiratory muscles, extend the exercise endurance time of patients, and alleviate dyspnea symptoms.
Regulating Immune Function and Reducing Infection RiskL-leucine provides raw materials for the proliferation and activation of immune cells, promotes lymphocyte differentiation and cytokine synthesis, and enhances the antigen-presenting ability of dendritic cells. It improves the imbalance of CD4⁺/CD8⁺ T cell subsets in COPD patients, thereby reducing the incidence of pulmonary infections and acute exacerbations of the disease.
Alleviating Oxidative Stress and Improving Energy Metabolismα-Ketoisocaproic acid, a metabolite of L-leucine, can activate the activity of antioxidant enzymes such as superoxide dismutase (SOD) and reduce the serum malondialdehyde (MDA) level. Meanwhile, it promotes mitochondrial biogenesis, improves the energy utilization efficiency of muscle cells, reduces the production of reactive oxygen species (ROS), and mitigates the oxidative stress damage to lung tissues and muscles.
II. Clinical Nutritional Efficacy
Improving Nutritional Indicators and Reversing Muscle LossSupplementing L-leucine on the basis of routine nutritional support can significantly increase the body mass index (BMI), appendicular skeletal muscle mass, and serum albumin level of patients. For mechanically ventilated patients, adding L-leucine to enteral nutrition preparations can reduce muscle catabolism and improve the success rate of weaning from mechanical ventilation.
Enhancing Exercise Endurance and Improving Quality of LifePatients supplemented with L-leucine show an increase in the 6-minute walk distance, improved grip strength, reduced dyspnea scores, and a significant decrease in the St. George’s Respiratory Questionnaire (SGRQ) score, with improvements in daily activity ability and sleep quality.
Reducing the Risk of Acute Exacerbations and Lowering Hospitalization RatesLong-term supplementation with L-leucine can reduce the incidence of acute exacerbations in COPD patients by 35%, decrease the hospitalization rate due to infection by 40%, and shorten the length of hospital stay. The prognostic improvement effect is particularly significant in elderly patients.
III. Key Application Points
Dosage and Administration MethodFor stable-phase patients, the recommended daily dosage is 2–3 g; for patients in acute exacerbation or severe stage, the dosage can be increased to 3–5 g. Oral administration is preferred—L-leucine can be dissolved in liquid food or taken as a dedicated nutritional preparation, and divided into 2–3 doses daily to improve absorption efficiency.
Combined SupportIt should be combined with a nutritional plan containing high protein (1.2–1.5 g/kg body weight per day) and sufficient energy. Meanwhile, supplementation with nutrients such as vitamin D and zinc can be added to exert a synergistic effect and enhance efficacy.
Safety PrecautionsAvoid excessive single supplementation (no more than 10 g per day). For patients with complicated liver and renal insufficiency or diabetes, the dosage should be adjusted individually and close monitoring should be strengthened.