Nutritional support of L-leucine in postoperative recovery

Surgical trauma triggers a systemic stress response, leading to metabolic disorders, inflammation activation, and enhanced skeletal muscle catabolism. Insufficient nutritional support can easily result in complications such as muscle mass loss, delayed wound healing, and decreased immunity, prolonging hospital stays. As the core component of branched-chain amino acids (BCAAs) that regulates muscle metabolism, L-leucine, through its unique molecular mechanisms, promotes muscle protein synthesis, inhibits catabolism, modulates inflammatory responses, and accelerates tissue repair, making it a key nutrient for postoperative nutritional support. This article systematically analyzes the metabolic characteristics of the body after surgery, the mechanisms of action of L-leucine, clinical application evidence, and optimization strategies, aiming to provide theoretical and practical references for postoperative nutritional intervention.

I. Core Metabolic Characteristics and Nutritional Needs of the Postoperative Body

Surgical trauma (especially major surgeries such as abdominal, orthopedic, and tumor radical surgeries) triggers a "stress-induced metabolic response" in the body, presenting the following characteristics that impose special requirements on nutritional support:

Hypermetabolism: The postoperative basal metabolic rate increases by 10%~30% compared with the preoperative level (the more severe the trauma, the more significant the increase). The body maintains energy demand during stress by accelerating glycogenolysis, fat mobilization, and muscle breakdown for energy supply. Insufficient energy supplementation will further exacerbate muscle catabolism.

Protein Metabolism Imbalance: Increased release of inflammatory factors (TNF-α, IL-6, CRP) after trauma activates the ubiquitin-proteasome pathway and autophagic pathway, inhibits muscle protein synthesis, and accelerates myofiber degradation, leading to progressive loss of skeletal muscle mass (the muscle loss rate can reach 2%~5% within 1 week after surgery), which affects limb function and wound healing.

Inflammatory Response and Immune Suppression: Excessive activation of the inflammatory response in the early postoperative period can aggravate tissue damage, while decreased immune cell function in the later period may increase the risk of infections (such as incision infection and pulmonary infection).

Impaired Nutrient Absorption: Postoperative patients often experience insufficient intake of protein, energy, and trace elements due to the effects of anesthesia, gastrointestinal dysfunction (such as nausea, vomiting, and intestinal paralysis), and pain during eating, which further exacerbates metabolic disorders.

Based on the above characteristics, the core goals of postoperative nutritional support are: correcting negative energy and protein balance, inhibiting muscle catabolism, promoting tissue repair, regulating inflammatory responses, and enhancing immunity. The physiological functions of L-leucine are precisely aligned with these needs.

II. Core Mechanisms of L-Leucine in Postoperative Recovery

L-leucine regulates metabolic and repair processes through multiple targets, providing comprehensive nutritional support for postoperative recovery. The core mechanisms include the following four aspects:

1. Promoting Muscle Protein Synthesis and Inhibiting Catabolism

L-leucine is a specific activator of the mammalian target of rapamycin complex 1 (mTORC1) pathway. Its molecular mechanism is as follows: After entering myocytes through amino acid transporters (LAT1, SLC7A5), L-leucine binds to leucine-sensing proteins (Sestrin2, CASTOR1), relieving their inhibition on the GTPase Rheb, which in turn activates mTORC1. Downstream, mTORC1 phosphorylates p70S6K and 4E-BP1, initiating the muscle protein translation process and accelerating myofiber synthesis. Meanwhile, L-leucine can downregulate the expression of ubiquitin ligases (MuRF1, MAFbx) mediated by inflammatory factors, block muscle catabolic pathways, and maintain skeletal muscle mass. In the early postoperative period (1~7 days), L-leucine can quickly reverse the net catabolic state of muscle protein through this mechanism, laying a foundation for the recovery of limb function.

2. Accelerating Wound Healing and Tissue Repair

Wound healing relies on collagen synthesis and fibroblast proliferation. As an "initiating factor" for protein synthesis, L-leucine promotes repair through the following pathways: ① Providing raw materials for collagen synthesis (collagen contains a large number of leucine residues), increasing collagen deposition rate, and enhancing wound tensile strength; ② Activating the mTOR pathway in fibroblasts and vascular endothelial cells, promoting cell proliferation and angiogenesis, and accelerating granulation tissue formation; ③ Its metabolite α-ketoisocaproic acid has antioxidant activity, which can scavenge reactive oxygen species at the trauma site, reduce oxidative stress damage, and decrease the risk of wound infection.

3. Modulating Inflammatory Responses and Enhancing Immunity

L-leucine can improve postoperative immune function by regulating the balance of inflammatory factors: ① Inhibiting excessive inflammatory response: Downregulating the expression of pro-inflammatory factors such as TNF-α and IL-6, reducing inflammation-mediated tissue damage; ② Promoting the release of anti-inflammatory factors: Increasing the levels of anti-inflammatory factors such as IL-10 and TGF-β, alleviating postoperative systemic inflammatory response syndrome (SIRS); ③ Enhancing immune cell function: Providing energy and raw materials for the proliferation and activation of lymphocytes and macrophages, improving the body's anti-infection ability, and reducing the incidence of postoperative infections.

4. Improving Energy Metabolism and Alleviating Postoperative Fatigue

Postoperative fatigue is closely related to negative energy balance and muscle catabolism. L-leucine can promote glucose uptake and oxidative decomposition by activating the AMPK pathway, improving energy supply to myocytes. Meanwhile, ketone bodies produced during its metabolism can provide energy for the brain and nervous tissue, alleviating postoperative cognitive dysfunction (POCD) and fatigue, and helping patients recover independent activity ability faster.

III. Clinical Application Evidence of L-Leucine in Different Types of Postoperative Settings

1. Abdominal Surgery (Gastrointestinal, Hepatobiliary, and Pancreatic Surgery)

Abdominal surgery is often accompanied by gastrointestinal dysfunction and impaired nutrient absorption. L-leucine can exert its effects through enteral or parenteral nutritional routes:

An RCT involving patients undergoing radical gastrectomy showed that supplementing L-leucine (3g/d) through enteral nutrition preparations within 7 days after surgery reduced the rate of skeletal muscle mass loss by 40% compared with the control group, accelerated grip strength recovery by 30%, advanced the postoperative exhaust time by 12~24 hours, and achieved a grade A incision healing rate of 95% (82% in the control group).

For colorectal cancer patients undergoing postoperative chemotherapy, supplementing L-leucine (4g/d for 4 weeks) significantly reduced the incidence of chemotherapy-related fatigue (from 68% to 42%), decreased the incidence of neutropenia by 20%, and increased the chemotherapy completion rate by 15%, presumably related to the maintenance of muscle mass and improvement of immunity.

Patients undergoing hepatobiliary and pancreatic surgery may have disorders in BCAA metabolism due to impaired liver function. Supplementing L-leucine (2~3g/d) can improve hepatocellular energy metabolism, reduce the degree of postoperative elevation of liver enzymes (ALT, AST), and shorten the time for liver function recovery.

2. Orthopedic Surgery (Joint Replacement, Fracture Repair)

Postoperative orthopedic patients rely on muscle strength to recover limb function, making the muscle-protective effect of L-leucine particularly important:

Patients after total hip replacement who received L-leucine (3g/d) + resistance training (resistance band training) showed a 3.8% increase in skeletal muscle mass and a 25% improvement in walking speed after 12 weeks, which was significantly better than the simple training group. Additionally, the bone mineral density around the prosthesis increased, reducing the risk of loosening.

Elderly patients with hip fractures after surgery (often accompanied by sarcopenia) who supplemented L-leucine (3g/d) + composite BCAAs showed a 2.3% increase in muscle mass compared with the control group after 6 weeks, an 18% improvement in Activities of Daily Living (ADL) score, a 22% reduction in the incidence of postoperative complications (pressure ulcers, pulmonary infection), and a 3~5-day reduction in hospital stay.

3. Tumor Surgery

Tumor patients often have residual cachexia and metabolic disorders after surgery. L-leucine can synergize with nutritional support to improve prognosis:

Patients after modified radical mastectomy for breast cancer who supplemented L-leucine (3g/d) + high-protein nutrition (1.5g/kg body weight/d) recovered their muscle mass to the preoperative level after 8 weeks, while the simple high-protein group was still 3.1% lower than the preoperative level, and the incidence of upper limb lymphedema in patients was reduced by 16%.

Patients after esophageal cancer surgery have insufficient nutritional intake due to impaired swallowing function. Adding L-leucine (3~5g/L) to enteral nutrition preparations can significantly increase the rate of muscle protein synthesis. The postoperative weight recovery rate reached 85% after 6 weeks (68% in the control group), and the incidence of anastomotic leakage was reduced by 10%.

4. Surgery in Elderly and Frail Patients

Elderly patients often have sarcopenia and decreased immunity before surgery, with weak postoperative recovery ability. L-leucine can specifically improve this situation:

An RCT involving 100 abdominal surgery patients aged ≥75 years showed that patients supplemented with L-leucine (3g/d) had a reduction in postoperative muscle loss rate from 4.2% to 1.8%, a decrease in infection incidence from 28% to 12%, a 4.2-day reduction in hospital stay, and a 15% decrease in 30-day readmission rate.

Supplementing L-leucine + probiotics in frail patients after surgery can improve intestinal absorption function, enhance nutrient utilization efficiency, and further strengthen muscle protection and immune regulation effects.

IV. Optimization Strategies for Postoperative L-Leucine Nutritional Support

1. Intervention Timing and Administration Route

Intervention Timing: Initiate as early as possible after surgery, immediately after the recovery of gastrointestinal function (such as after exhaust and defecation). For patients undergoing major surgeries or with preoperative sarcopenia, pre-supplementation can be started 1~2 weeks before surgery to reserve muscle mass in advance.

Administration Route: ① Oral: Oral supplementation is preferred, taken with meals (in 2~3 divided doses), preferably with high-protein foods such as milk and eggs to improve absorption efficiency; ② Enteral nutrition: For patients who cannot eat orally, specialized enteral nutrition agents containing L-leucine (recommended concentration 3~5g/L) are infused through a nasogastric tube or jejunostomy tube; ③ Intravenous infusion: For patients with severe malnutrition or complete gastrointestinal dysfunction, L-leucine can be added to parenteral nutrition (0.1~0.15g/kg body weight/d), and switched to enteral supplementation after the recovery of intestinal function.

2. Dosage and Combined Regimens

Recommended Dosage: The conventional postoperative dosage is 3~5g/d, administered in 2~3 divided doses to avoid gastrointestinal discomfort caused by a single large dose (>5g). For patients with severe trauma and obvious muscle catabolism (such as major orthopedic surgery and tumor radical surgery), the dosage can be increased to 5~7g/d for 4~8 weeks. The dosage for elderly patients can be appropriately reduced to 2~3g/d, with monitoring of liver and kidney function.

Combined Regimens: ① Combination with other BCAAs (ratio 2:1:1, L-leucine: L-isoleucine: L-valine) synergistically activates the mTOR pathway, with better effects than single supplementation; ② Combination with high-protein nutrition: It is necessary to ensure a daily protein intake of 1.2~1.8g/kg body weight (adjusted according to the degree of surgical trauma), otherwise L-leucine cannot fully exert its effects; ③ Combination with resistance training: Moderate resistance training (such as grip strengthener exercises, bedside leg raising) during the postoperative recovery period (e.g., 4 weeks after orthopedic surgery) can enhance the sensitivity of myocytes to L-leucine and improve muscle synthesis efficiency; ④ Combination with trace elements: Combining with vitamin C (promoting collagen synthesis), zinc (accelerating wound healing), and vitamin D (regulating muscle function) to further optimize recovery effects.

3. Target Population and Contraindications

Target Population: ① Patients undergoing all major surgeries (abdominal, orthopedic, tumor surgery, etc.); ② Patients with preoperative sarcopenia and malnutrition; ③ Elderly and frail patients; ④ Patients with slow postoperative wound healing and high infection risk.

Contraindications: Patients with severe liver and kidney insufficiency (metabolites of L-leucine are excreted through the liver and kidneys, and supplementation may increase organ burden), patients with maple syrup urine disease (branched-chain amino acid metabolism disorder), and those allergic to L-leucine are prohibited.

4. Monitoring and Evaluation Indicators

After surgery, the following indicators should be regularly monitored to assess the intervention effect and safety of L-leucine:

Nutritional and Metabolic Indicators: Body weight, skeletal muscle mass (DXA scan or BIA), serum albumin, prealbumin, transferrin;

Muscle Function Indicators: Grip strength, walking speed, Activities of Daily Living (ADL) score;

Wound Healing Indicators: Incision healing grade, granulation tissue growth, infection incidence;

Inflammatory and Immune Indicators: CRP, IL-6, TNF-α, lymphocyte count;

Safety Indicators: Liver and kidney function (ALT, AST, creatinine, urea nitrogen), blood glucose (monitoring is required for diabetic patients, as L-leucine may slightly affect insulin sensitivity).

V. Challenges and Future Development Directions

1. Existing Challenges

Significant Individual Differences: The response to L-leucine varies among patients with different surgical types, trauma degrees, and baseline nutritional status, and there is a lack of precise dosage guidance.

Insufficient Optimization of Combined Regimens: Current research on the synergistic mechanisms of L-leucine with other nutrients (such as probiotics and ω-3 fatty acids) is insufficient, and the evidence-based evidence for combined regimens needs to be enriched.

Unclear Long-Term Effects: Most existing studies focus on short-term postoperative effects (<12 weeks), and the long-term impact of L-leucine on patients' muscle function and quality of life needs further verification.

2. Development Directions

Precision Nutritional Support: Develop personalized L-leucine supplementation plans based on patients' surgical types, genetic characteristics, and metabolic profiles (such as inflammatory factor levels and muscle metabolic markers). For example, for patients with a high inflammatory state, anti-inflammatory nutrients can be combined to enhance effects.

Development of Novel Formulations: Develop high-bioavailability L-leucine formulations (such as microcapsules and liposome-encapsulated) to improve intestinal absorption efficiency, suitable for patients with impaired postoperative digestive function. Develop multifunctional enteral nutrition agents containing L-leucine, integrating proteins, trace elements, probiotics, etc., to simplify the nutritional support process.

Deepening Mechanism and Clinical Research: Further explore the molecular mechanisms of L-leucine in wound healing and immune regulation; conduct multi-center, large-sample, long-term follow-up RCTs to provide high-level evidence for the formulation of clinical guidelines.

Expanding Application Scenarios: Explore the application value of L-leucine in patients undergoing minimally invasive surgery and ambulatory surgery to further expand the scope of application.

As a key nutrient for postoperative nutritional support, L-leucine can effectively improve the metabolic state of postoperative patients, reduce complications, shorten hospital stays, and enhance quality of life by activating muscle protein synthesis, inhibiting catabolism, accelerating wound healing, regulating inflammatory responses, and enhancing immunity. The core of its clinical application lies in: initiating intervention as early as possible, adopting a composite regimen of "L-leucine + high protein + combined nutrients", combining with moderate functional exercise, and adjusting the dosage and strengthening monitoring according to individual patient conditions.

With the development of precision nutrition concepts and the innovation of formulation technology, L-leucine is expected to become a core component of comprehensive postoperative management. In the future, more basic and clinical studies are needed to optimize application plans, clarify long-term efficacy, and provide more precise and efficient nutritional support strategies for patients undergoing different types of surgeries, promoting the overall improvement of postoperative recovery quality.