A 2018 combined analysis of 29 studies in people with knee osteoarthritis (6,120 total participants) showed that global pain was significantly reduced by glucosamine or chondroitin taken separately but not by the combination of the two. The results of individual studies were inconsistent; some pointed to significant benefits, while others did not.

Glucosamine

A 2014 analysis of 25 studies of glucosamine taken alone for knee osteoarthritis (3,458 participants) showed a pattern in the results of individual studies: those who used the prescription drug formulation of glucosamine generally had more favorable results than those who did not. This pattern may reflect genuine differences in the effects of different products, but it could also be a result of bias. Most of the studies of the prescription drug formulation had a high risk of bias because of weaknesses in their study design, were published more than 20 years ago, and were funded by the pharmaceutical company.

Clinical practice guidelines issued by health professional organizations in the United States and other countries differ in their recommendations concerning glucosamine. The guideline published by the American College of Rheumatology (ACR) and the Arthritis Foundation (AF) in 2019 strongly recommended against the use of glucosamine alone or in combination with chondroitin for knee osteoarthritis, stating that the best data do not show any important benefits. Similarly, a 2019 guideline from Osteoarthritis Research Society International (OARSI) strongly recommends against the use of glucosamine for knee osteoarthritis on the grounds of lack of efficacy.

In contrast, the 2021 guideline from the American Academy of Orthopaedic Surgeons (AAOS) includes glucosamine in a list of dietary supplements that may be helpful in reducing pain and improving function in patients with mild-to-moderate knee osteoarthritis, although it cautions that the evidence is inconsistent. A 2019 statement from the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) strongly recommends prescription crystalline glucosamine sulfate for knee osteoarthritis but discourages the use of other glucosamine formulations.

Chondroitin

A 2019 analysis of 18 studies of chondroitin taken alone for osteoarthritis (3,791 participants), 16 of which were on knee osteoarthritis, showed a significant benefit of chondroitin, but with much inconsistency in the study results. When only studies with a low risk of bias were included in the analysis, there was a significant difference among brands of chondroitin, with a specific pharmaceutical grade preparation showing a greater reduction in pain.

Clinical practice guidelines differ in their recommendations about chondroitin. The 2019 ACR/AF guideline strongly recommends against the use of chondroitin alone or in combination with glucosamine for knee osteoarthritis, and the 2019 OARSI guideline strongly recommends against the use of chondroitin for knee osteoarthritis on the grounds that the evidence is of low quality. However, the 2021 AAOS guideline includes chondroitin in a list of dietary supplements that may be helpful in reducing pain and improving function in patients with mild-to-moderate knee osteoarthritis, although it cautions that the evidence is inconsistent, and the 2019 ESCEO statement strongly recommends prescription chondroitin sulfate for knee osteoarthritis and says that it should be distinguished from other chondroitin products.