Clinical application of L-leucine in the treatment of malnutrition

As the core component of branched-chain amino acids (BCAAs), L-leucine occupies an important position in malnutrition treatment due to its characteristics such as "high bioavailability, specific activation of muscle protein synthesis, and efficient energy supply." It is particularly suitable for populations with insufficient nutrient intake or metabolic disorders caused by senile sarcopenia, postoperative recovery, chronic consumptive diseases, etc. Its clinical applications focus on "correcting amino acid imbalance, promoting muscle synthesis, improving nutritional status, and enhancing clinical outcomes." The specific application scenarios, mechanisms, and practice guidelines are as follows:

I. Core Clinical Application Scenarios and Target Populations

1. Malnutrition Related to Senile Sarcopenia

Elderly individuals are prone to sarcopenia (reduced muscle mass and strength) and associated malnutrition risks due to declined digestive absorption function, insufficient protein intake, and decreased physical activity. L-leucine is a key intervention nutrient:

Target Population: Elderly aged 65 years and above, especially sarcopenia patients with BMI < 20 kg/m², grip strength < 26 kg (males)/< 16 kg (females), and walking speed < 0.8 m/s.

Clinical Value: Supplementing L-leucine directly activates the mTOR signaling pathway, promotes muscle protein synthesis, delays muscle loss, and improves appetite and nutrient intake. Clinical studies show that daily supplementation of 3–5g L-leucine combined with high-quality protein increases muscle mass by 8%–12%, grip strength by over 15% in elderly patients after 12 weeks, and improves the Mini Nutritional Assessment (MNA) score from "at risk" to "normal."

Application Characteristics: Synergistic supplementation with isoleucine, valine (2:1:1 ratio), vitamin D, and calcium is required to enhance muscle synthesis efficiency and avoid metabolic imbalance of a single amino acid.

2. Postoperative Malnutrition (Especially After Abdominal and Orthopedic Surgeries)

Surgical trauma triggers stress responses, leading to accelerated muscle protein breakdown and increased energy consumption. Postoperative patients often experience malnutrition due to decreased appetite and inhibited digestive function, which impairs wound healing and rehabilitation:

Target Population: Patients with malnutrition or high risk after abdominal surgeries (gastrointestinal resection, hepatobiliary surgery) or major orthopedic surgeries (joint replacement, spinal surgery), with serum albumin < 35 g/L and prealbumin < 200 mg/L.

Clinical Value: L-leucine is rapidly absorbed through the intestines (without first-pass metabolism in the liver), providing substrates for muscle protein synthesis, reducing muscle protein breakdown under stress, and accelerating wound healing and physical recovery. Studies indicate that starting L-leucine supplementation (4–6g/day) on the first postoperative day shortens wound healing time by 20%–30%, reduces postoperative hospital stay by 3–5 days, and decreases infection rate by 40%.

Application Characteristics: Oral supplementation is preferred in the early postoperative period (after intestinal function recovery), which can be mixed into enteral nutrition preparations or liquid foods. High-dose single supplementation (>6g/day) should be avoided to prevent gastrointestinal discomfort.

3. Malnutrition Related to Chronic Consumptive Diseases

Diseases such as chronic obstructive pulmonary disease (COPD), chronic kidney disease (CKD), and tumors cause increased energy consumption and impaired nutrient absorption, leading to "cachexia" or malnutrition and exacerbating disease progression:

Target Population:

COPD patients: BMI < 18.5 kg/m², 6-minute walking distance < 300 m;

CKD stage 3–5 patients: Serum albumin < 30 g/L, muscle mass loss > 10%;

Tumor patients: Weight loss > 5% within 1 month after chemotherapy, visual analog scale (VAS) appetite score < 5.

Clinical Value:

For COPD patients: L-leucine enhances respiratory muscle strength, improves lung function, boosts immunity, and reduces the frequency of acute exacerbations;

For CKD patients: A low-protein diet (0.6g/kg/day) combined with L-leucine (3g/day) maintains muscle mass while controlling nitrogen load, avoiding the dual risks of malnutrition and renal function deterioration;

For tumor patients: L-leucine alleviates chemotherapy-induced muscle loss and appetite loss, improves quality of life, and provides nutritional support for subsequent treatment.

Application Characteristics: Dosage should be adjusted according to disease characteristics. For example, CKD patients need to control total BCAA intake to avoid increasing renal burden; tumor patients can be combined with glutamine and ω-3 fatty acids to enhance anti-cachexia effects.

4. Protein-Energy Malnutrition (PEM) in Children and Adolescents

PEM in children and adolescents caused by unbalanced diet or digestive absorption disorders (e.g., irritable bowel syndrome, short bowel syndrome) affects growth and development. L-leucine can be used as a nutritional fortifier:

Target Population: Children under 5 years old with weight below the 3rd percentile for age and gender, and serum albumin < 32 g/L.

Clinical Value: As an essential amino acid for children's growth and development, L-leucine promotes skeletal muscle and bone growth, improves intestinal absorption function, and enhances overall nutrient utilization efficiency. Studies show that adding L-leucine (1–2g/day, 20–40mg/kg body weight) to conventional nutritional support increases children's weight growth rate by 30%–50%, height growth by 1–2cm, and reduces anemia incidence by 25% after 6 months.

Application Characteristics: Dosage must be strictly calculated by body weight to avoid excessive supplementation. It can be combined with whey protein and carbohydrates into special nutritional preparations for children to improve taste and acceptance.

II. Core Mechanisms of Clinical Application

1. Activate Muscle Protein Synthesis and Reverse Muscle Loss

L-leucine is a specific activator of the mammalian target of rapamycin (mTOR) signaling pathway. It can directly bind to the mTOR complex, upregulate the phosphorylation levels of ribosomal protein S6 kinase (p70S6K) and eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1), and initiate muscle protein synthesis. This mechanism is particularly critical in malnutrition, reversing "synthesis-degradation imbalance" and maintaining muscle mass and strength.

2. Regulate Energy Metabolism and Improve Nutrient Utilization Efficiency

Populations with malnutrition often suffer from insufficient energy supply and metabolic disorders. L-leucine regulates energy metabolism in two ways: first, it is transaminated in skeletal muscle to form α-ketoisocaproate, which enters the tricarboxylic acid cycle for energy supply, 1.5 times faster than glucose; second, it inhibits hepatic gluconeogenesis, reduces muscle protein breakdown for energy, and promotes insulin secretion to enhance glucose and amino acid absorption and utilization efficiency.

3. Improve Appetite and Digestive Absorption Function

Most people with malnutrition are accompanied by decreased appetite. L-leucine improves appetite by regulating central neurotransmitters (e.g., promoting dopamine synthesis and inhibiting 5-hydroxytryptamine secretion). Its small molecular structure reduces gastrointestinal digestive burden, making it suitable for people with weak digestive function. In addition, L-leucine promotes the proliferation of intestinal mucosal cells, repairs the intestinal barrier, and improves the absorption efficiency of nutrients.

4. Enhance Immunity and Reduce Complication Risks

Malnutrition leads to decreased immune function and increased infection risk. L-leucine promotes the proliferation of T lymphocytes and macrophages, enhances the secretion of immune cytokines (IL-2, TNF-α), and improves the activity of antioxidant enzymes (SOD, GSH-Px), reducing oxidative stress damage to immune cells and lowering the risk of complications such as postoperative infections and acute exacerbations of chronic diseases.

III. Clinical Application Guidelines and Precautions

1. Supplementation Dosage and Methods

Dosage:

Preventive (high-risk population for malnutrition): 1–3g/day;

Therapeutic (confirmed malnutrition patients): 3–6g/day, up to 6–8g/day for severe cases (taken in 2–3 divided doses);

Pediatric dosage: 20–40mg/kg body weight/day, taken in 2 divided doses.

Methods:

Oral supplementation: Can be taken alone (dissolved in warm water or juice) or mixed into enteral nutrition preparations, porridge, milk, etc. Avoid taking on an empty stomach;

Addition to enteral nutrition preparations: Add 1–2g L-leucine per 100g standard enteral nutrition powder;

Intravenous supplementation: Suitable for critically ill patients who cannot take orally. Infuse compound amino acid injections containing L-leucine (e.g., BCAA injections) through central or peripheral veins, with a daily dosage of 0.1–0.2g/kg.

2. Combined Supplementation Strategies

The effect of L-leucine alone is limited, and combined supplementation is mostly used clinically to improve efficacy:

Combined with other BCAAs (isoleucine, valine) in a 2:1:1 ratio to avoid metabolic imbalance caused by excess of a single amino acid;

Combined with high-quality protein (whey protein, soy protein) with a protein intake of 1.2–1.5g/kg/day to provide sufficient substrates for muscle protein synthesis;

Synergistic with vitamin D, calcium, ω-3 fatty acids, etc., to enhance muscle synthesis, bone health, and immune regulation effects;

Combined with probiotics to improve intestinal flora balance and enhance the absorption efficiency of L-leucine and nutrients.

3. Contraindications and Precautions for Special Populations

Contraindicated Populations: Patients allergic to L-leucine, patients with severe liver insufficiency (decompensated cirrhosis) (BCAA metabolic disorders may induce hepatic encephalopathy);

Populations Requiring Caution:

End-stage chronic kidney disease (dialysis patients): Dosage must be controlled under medical guidance to avoid excessive nitrogen load;

Diabetic patients: L-leucine may promote insulin secretion, requiring blood glucose monitoring to avoid hypoglycemia;

Pregnant and lactating women: Insufficient safety research, use only after medical evaluation.

4. Clinical Monitoring Indicators

The following indicators should be regularly monitored during application to evaluate efficacy and safety:

Nutritional Status Indicators: Serum albumin, prealbumin, hemoglobin, BMI, muscle mass (measured by DEXA or bioelectrical impedance analysis);

Functional Indicators: Muscle strength (measured by dynamometer), walking distance, activities of daily living (ADL score);

Safety Indicators: Liver and kidney function, blood glucose, electrolytes, to avoid metabolic disorders.

IV. Clinical Evidence and Guideline Recommendations

Expert Consensus on Diagnosis and Treatment of Senile Sarcopenia in China (2023) recommends that sarcopenia patients supplement BCAAs (containing 3–5g/day L-leucine) on the basis of ensuring protein intake (1.0–1.2g/kg/day) to effectively improve muscle mass and strength;

Expert Consensus on Nutritional Treatment of Chronic Obstructive Pulmonary Disease suggests that COPD patients with malnutrition can add L-leucine (2–4g/day) to improve respiratory muscle function and quality of life;

Guidelines from the International Society of Renal Nutrition and Metabolism (ISRNM) recommend that CKD stage 3–5 patients on a low-protein diet supplement L-leucine (2–3g/day) to maintain muscle mass and nutritional status.

The clinical application of L-leucine in malnutrition treatment mainly addresses nutritional imbalance in different populations through four core mechanisms: "activating muscle protein synthesis, regulating energy metabolism, improving nutrient absorption, and enhancing immunity." Its application scenarios cover senile sarcopenia, postoperative recovery, chronic disease consumption, pediatric PEM, etc. Individualized supplementation plans (dosage, method, combined strategy) must be formulated according to population characteristics and disease status. In clinical practice, it is necessary to strictly follow guideline recommendations and strengthen monitoring to ensure efficacy and safety, ultimately achieving the goals of improving nutritional status, enhancing clinical outcomes, and improving quality of life. Future research should further conduct large-sample, long-term follow-up studies to explore the application value of L-leucine in special populations (e.g., rare disease patients, intensive care unit patients) and optimize clinical application plans.