The inhibitory effect of L-leucine on the inflammatory response after exercise

As the most functionally active member of branched-chain amino acids (BCAAs), L-leucine not only participates in energy metabolism and muscle repair but also effectively inhibits excessive post-exercise inflammatory responses, reduces muscle damage and soreness, and promotes exercise recovery through multiple mechanisms including regulating inflammatory signaling pathways, balancing immune cell functions, and modulating the metabolic microenvironment. Its core inhibitory mechanisms and functional characteristics are as follows:

I. Core Inhibitory Mechanisms

1. Regulating Inflammatory Signaling Pathways to Block Inflammatory Cascade Reactions

The inflammatory response induced by post-exercise muscle damage primarily activates the expression of pro-inflammatory factors through the NF-κB (nuclear factor κB) and MAPK (mitogen-activated protein kinase) signaling pathways. L-leucine blocks this process through the following pathways:

As an activator of the mTOR signaling pathway, L-leucine can inhibit IκB kinase (IKK) activity through cross-regulation between mTOR and NF-κB, preventing the translocation of NF-κB to the nucleus, thereby reducing the transcription and release of pro-inflammatory factors such as TNF-α (tumor necrosis factor α), IL-6 (interleukin 6), and IL-1β.

It inhibits the phosphorylation of p38 and JNK (c-Jun N-terminal kinase) in the MAPK pathway, reducing the transmission efficiency of inflammatory signals, alleviating the "cascade amplification effect" of inflammatory factors, and avoiding secondary damage to muscle tissue caused by excessive inflammation.

2. Balancing the Ratio of Pro-Inflammatory/Anti-Inflammatory Factors to Remodel the Inflammatory Microenvironment

Moderate release of pro-inflammatory factors such as IL-6 in the early post-exercise phase is a necessary signal to initiate repair, but excessive release exacerbates damage. L-leucine optimizes the balance of inflammatory factors through "bidirectional regulation":

Inhibiting excessive expression of pro-inflammatory factors: Human experiments have shown that post-exercise supplementation of L-leucine can reduce the concentrations of TNF-α and IL-6 in skeletal muscle and blood by 30%~40%, decreasing the infiltration and activation of neutrophils at the site of injury.

Promoting the synthesis of anti-inflammatory factors: It induces the secretion of anti-inflammatory factors such as IL-10 (interleukin 10) and TGF-β (transforming growth factor β). IL-10 can inhibit the conversion of macrophages from the pro-inflammatory phenotype (M1 type) to the anti-inflammatory phenotype (M2 type), enhancing the ability of inflammation resolution and creating a suitable microenvironment for muscle repair.

3. Inhibiting Oxidative Stress to Reduce the Source of Inflammatory Triggers

Accumulation of excessive reactive oxygen species (ROS) after exercise is an important inducer of inflammatory responses. ROS can damage muscle cell membranes and activate inflammatory pathways. L-leucine resists oxidative stress through dual pathways:

Enhancing the activity of antioxidant enzymes: It promotes the synthesis and activity of SOD (superoxide dismutase) and GSH-Px (glutathione peroxidase) in skeletal muscle, improving ROS scavenging efficiency and reducing the accumulation of lipid peroxidation products (e.g., MDA).

Acting as an indirect antioxidant substrate: Its metabolite α-ketoisocaproic acid (KIC) can participate in the regeneration of intracellular reduced glutathione (GSH), maintaining intracellular redox balance and reducing the activation of inflammatory signals by ROS.

4. Protecting Intestinal Barrier Integrity to Reduce Endotoxin-Induced Systemic Inflammation

Prolonged and high-intensity exercise is prone to impair intestinal barrier function, allowing lipopolysaccharide (LPS, endotoxin) in the intestine to enter the bloodstream and trigger "gut-derived systemic inflammation." L-leucine maintains intestinal health through the following ways:

Promoting protein synthesis in intestinal mucosal cells (enterocytes), enhancing the tight junctions of the intestinal mucosal barrier (e.g., increasing the expression of occludin and ZO-1 proteins by 20%~30%), and reducing LPS leakage.

Inhibiting the proliferation of pro-inflammatory gut microbiota, regulating the balance of gut microbiota, reducing the production and release of LPS, and minimizing the trigger of systemic inflammation at its source.

II. Functional Characteristics and Application Effects

1. Targeted Inhibition of Exercise-Related Inflammation Without Interfering with Normal Immune Function

L-leucine mainly targets and inhibits local inflammation induced by post-exercise muscle damage and gut-derived systemic inflammation, without significantly suppressing the body's normal immune defense (e.g., anti-infective immunity). This avoids the immunosuppressive side effects that may be caused by non-steroidal anti-inflammatory drugs (NSAIDs).

2. Synergistic Effect with Muscle Repair to Accelerate Recovery Process

Inflammatory response is closely related to muscle repair. While inhibiting excessive inflammation, L-leucine promotes muscle protein synthesis by activating the mTOR pathway, achieving the dual effects of "anti-inflammation + repair":

Human experiments have shown that supplementation of L-leucine (3~5 g per day, divided into 2~3 doses) after high-intensity endurance exercise can reduce muscle soreness (DOMS score) by 40%~50% and increase the muscle strength recovery rate by more than 30% 48 hours after exercise.

It reduces inflammation-mediated muscle protein breakdown, lowers the blood concentrations of muscle damage markers such as creatine kinase (CK) and lactate dehydrogenase (LDH), and shortens the recovery cycle.

3. Influence of Supplementation Timing and Dosage

Optimal supplementation window: Initiating supplementation within 30 minutes after exercise (a critical period for muscle repair and inflammation initiation) can quickly exert anti-inflammatory effects; continuous supplementation during exercise (0.5~1.0 g/h) can prevent excessive activation of inflammation, especially suitable for ultra-long endurance exercise.

Effective dosage: Daily supplementation of 2~5 g (single supplementation) or compound supplementation with L-isoleucine and L-valine at a ratio of 2:1:1 (total dosage 3~6 g/d) can achieve significant anti-inflammatory effects; excessive supplementation (>10 g/d) will not further enhance the anti-inflammatory effect but may increase metabolic burden.

The inhibitory effect of L-leucine on post-exercise inflammatory responses is achieved through multiple mechanisms including regulating the NF-κB/MAPK inflammatory signaling pathways, balancing the ratio of pro-inflammatory/anti-inflammatory factors, resisting oxidative stress, and protecting the intestinal barrier. Its functional characteristics lie in "precisely targeting the source of inflammation, not interfering with normal immunity, and synergizing with muscle repair," making it safer and more functional than traditional anti-inflammatory methods. Rational supplementation of L-leucine can effectively reduce post-exercise muscle soreness, minimize muscle damage, accelerate recovery, and support the improvement of long-term training adaptation, especially suitable for populations engaged in high-intensity, long-duration endurance exercise or strength training.