Objectives　The objective of this study was to investigate the effect of a dietary supplement containing glucosamine hydrochloride, chondroitin sulfate, methylsulfonylmethane and guava leaf extract on quality of life of individuals with knee joint pain in stratified analysis based on Kellgren-Lawrence（K-L）grades.
Methods　A randomized double-blind placebo-controlled clinical trial was conducted in 38 subjects with knee joint pain. They were randomly assigned to two groups and administered with either a test supplement containing 1200 mg glucosamine hydrochloride, 80 mg chondroitin sulfate, 300 mg methylsulfonylmethane and 105 mg guava leaf extract per day or a placebo for 16 weeks. Stratified analysis was performed in subject with K-L grades≦�T or K-L grades≧�U for evaluating the quality of life（QOL）using Japanese Knee Osteoarthritis Measure（JKOM）criteria and C2C, a type�U collagen degradation marker.
Results　The results based on JKOM criteria indicated that the subscale score of“�W General activities”related to knee joint pain was significantly improved during the intervention（at week 4）in the test supplement group compared with the placebo group in the subject with K-L grades≦�T but not in the subject with K-L grades≧�U. Moreover, C2C was significantly suppressed during the intervention（at weeks 12 and 16）in the test supplement group compared with the placebo group in the subject with K-L grades≦�T but not in the subject with K-L grades≧�U.
Conclusions　These observations suggest that the daily administration of a test supplement is effective for improving QOL based on knee joint pain in healthy subjects with K-L grade≦�T possibly by suppressing type�U collagen degradation.