A 12-week intervention with 1200 mg daily polyphenols (quercetin, EGCG, resveratrol, curcumin) preserved critical immune markers in 80 adolescent athletes during high-intensity training. The supplemented group maintained healthy CD4+/CD8+ ratios above 1.65 while controls dropped to 1.38, and salivary IgA declined only 6.5% versus 29.3% in placebo. Multi-omics analysis revealed 1,847 genes responding through NF-κB suppression and enhanced antioxidant pathways, while gut microbiome shifts doubled butyrate production. This represents a significant advance in sports immunology, addressing the well-documented phenomenon where intensive training paradoxically increases infection risk in young athletes. The mechanistic clarity through systems biology analysis strengthens confidence in polyphenol efficacy beyond previous observational studies. However, the relatively short 12-week timeframe and focus on adolescents limits broader applicability to adult populations or long-term training cycles. The 1200 mg daily dose is substantially higher than typical dietary intake, raising questions about optimal dosing and cost-effectiveness. While promising for competitive youth sports programs, the complex four-compound formula makes it difficult to identify which polyphenols drive the primary benefits.