The regulatory effect of L-isoleucine

I. Biological Characteristics of L-Isoleucine and Its Exercise-Induced Consumption

As one of the essential branched-chain amino acids (BCAAs, including leucine, isoleucine, and valine), L-isoleucine plays a critical role in skeletal muscle protein synthesis and energy metabolism. During high-intensity training, athletes experience increased BCAA oxidation for energy, leading to a 30%–50% decrease in plasma isoleucine concentration. Concomitantly, this triggers immune cell dysfunction (e.g., T cells, neutrophils), manifested as:

Reduced lymphocyte proliferation capacity;

Increased secretion of pro-inflammatory cytokines (e.g., TNF-α, IL-6);

Decreased activity of antioxidant enzymes (e.g., SOD) and enhanced oxidative stress.

II. Molecular Mechanisms of L-Isoleucine in Regulating Immune Function

1. Regulation of Immune Cell Energy Metabolism

Fuel Supply for T Cell Activation:

Isoleucine provides ATP for T cells via mitochondrial β-oxidation (1 molecule of isoleucine generates 11 ATP molecules upon complete oxidation). During the proliferation phase of CD8⁺ T cells (cytotoxic T cells), oxidative metabolism demand increases by 2–3 fold. Exogenous isoleucine supplementation maintains mitochondrial membrane potential, preventing energy depletion-induced cell apoptosis.

Regulation of Macrophage Polarization:

Isoleucine metabolite acetyl-CoA promotes macrophage differentiation into the anti-inflammatory M2 phenotype (increased CD206⁺ expression), reducing pro-inflammatory factor IL-1β secretion while enhancing phagocytic efficiency by 40%–60%.

2. Activation of Antioxidant and Anti-Inflammatory Signaling Pathways

Nrf2-ARE Pathway Activation:

Isoleucine activates AMP-activated protein kinase (AMPK), leading to phosphorylation and release of transcription factor Nrf2. This promotes expression of antioxidant genes (e.g., HO-1, NQO1), increasing glutathione (GSH) levels by 25%–30% and reducing exercise-induced oxidative stress (e.g., 15%–20% decrease in serum MDA levels).

NF-κB Pathway Inhibition:

Isoleucine competitively inhibits the binding of NF-κB subunit p65 to DNA, reducing mRNA transcription of pro-inflammatory factors (e.g., IL-6, TNF-α) by ~30%–40%. This significantly alleviates post-exercise muscle inflammation within 24 hours.

3. Protection of Intestinal Immune Barrier

Support for Intestinal Mucosa Cell Proliferation:

As an energy substrate for intestinal epithelial cells (IECs), isoleucine promotes synthesis of tight junction proteins (ZO-1, Occludin), maintaining intestinal barrier integrity. This reduces post-exercise endotoxin leakage (serum LPS levels decrease by 20%–25%), preventing systemic inflammation.

Regulation of Gut Microbiota:

Isoleucine selectively promotes the proliferation of probiotics (e.g., Bifidobacterium, Lactobacillus) by 1.5–2 fold. Their metabolic products, short-chain fatty acids (SCFAs), further enhance secretion of intestinal mucosal immunoglobulin A (sIgA) by 30%–40%, strengthening intestinal immune defense.

III. Application Value in Special Sports Scenarios

Immune Protection During High-Altitude Training:

At altitudes above 3,000 meters, isoleucine supplementation (4 g/d) improves mitochondrial function, reduces hypoxia-induced immune cell apoptosis (apoptosis rate decreases by 35%), and maintains T cell receptor (TCR) signaling efficiency.

Immune Maintenance During Weight Loss:

Under caloric restriction (500 kcal daily deficit), isoleucine supplementation (3 g/d) prevents atrophy of immune organs (thymus, spleen) (weight loss reduced by 40%) and maintains neutrophil phagocytic function.

Jet Lag Adjustment for Cross-Time Zone Competitions:

Isoleucine regulates the expression of circadian clock genes (e.g., Per2, Bmal1), shortening the immune dysfunction period caused by jet lag from 72 hours to 48 hours and reducing infection risk.

IV. Potential Risks and Precautions

Dosage Threshold:

Daily intake exceeding 6 g may cause:

Imbalance of gut microbiota (20% reduction in Bacteroidetes);

Central nervous system excitation (inhibited 5-hydroxytryptamine synthesis), affecting sleep quality.

Individual Variability:

Endurance athletes with high slow-twitch fiber ratios (e.g., long-distance runners) require higher isoleucine (recommended 5–6 g/d);

Caution is advised for individuals with renal insufficiency (isoleucine metabolite α-ketoisovalerate is excreted by the kidneys, potentially increasing burden).

V. Conclusion

L-isoleucine regulates athletes' immune function through multi-target mechanisms, extending beyond nutritional support to network regulation of energy metabolism–oxidative stress–intestinal immunity. Scientific supplementation serves as a key strategy for exercise-induced immune protection, especially during high-intensity training, weight loss, and environmental stress (high altitude, jet lag). However, dosage optimization should integrate sport type and individual characteristics.