Efficacy Of A Six Nonessential Amino Acid Mixture In Mitigating Knee Joint Conditions In Adults

Knee joint issues impact exercise performance and daily life quality. Previously, we highlighted the beneficial effects of a mixture containing six nonessential amino acids abundant in collagens (alanine, aspartic acid, glutamic acid, glycine, proline, and serine; 6AA) on human tendons. However, the impact of 6AA on joint tissue remains unclear. PURPOSE: This study aimed to examine the effects of 6AA on knee joint problems in adults, with an investigation into its mode of action using a cell-based experiment. METHODS: A randomized, double-blind, placebo-controlled, parallel-group study was conducted, with 50 participants (20-64 years old; joint discomfort graded 0 or I on the K-L test) randomly and blindly assigned to the 6AA or placebo group. The 6AA group orally consumed 12 g of 6AA daily (4 g three times a day), whereas the placebo group received equivalent doses of a placebo for 12 weeks. Pain, stiffness, and discomfort on the knee joint were evaluated using the visual analogue scale (VAS), Japanese Knee Osteoarthritis Measure (JKOM), and Japanese Orthopedic Association score (JOA) at 0 (pre-experiment), 4, and 12 weeks. Human monocyte-derived macrophages (THP-1) were used to examine 6AA effects on inflammatory cytokine production. RESULTS: In the human study, the 6AA group exhibited significant reductions in all VAS scores at 4 weeks (group difference [mean and 95% confidence interval] in pain walking upstairs: −7.6, −11.1 to −4.2; p = 0.0001) and 12 weeks (−12.2, −21.6 to −2.8; p = 0.0123) compared with the placebo group. Additionally, JKOM (Week 4: −3.5, −5.6 to −1.4; p = 0.0014, Week 12: −4.4, −7.0 to −1.8; p = 0.0016) and JOA (Week 12: 1.7, −0.3 to 3.7; linear mixed model, p = 0.0210) scores significantly improved in the 6AA group. In vitro, 6AA significantly suppressed lipopolysaccharide (LPS)-stimulated inflammatory cytokine production, both genetically (100% LPS vs. LPS + 6AA: 48% suppression; p = 0.0007) and at the protein level (100% LPS vs. LPS + 6AA: 88%suppression; p = 0.0070). CONCLUSIONS: This study demonstrates that 6AA improves knee pain, stiffness, and discomfort symptoms. In vitro experiments also suggest that 6AA may improve knee joint conditions through inflammation inhibition.