From the Guidelines
Alpha-2-macroglobulin (A2M) is not recommended as a primary treatment for joint arthritis due to limited and inconsistent evidence supporting its efficacy. Current research suggests A2M may help reduce inflammation and protect cartilage by inhibiting destructive enzymes like matrix metalloproteinases that break down joint tissue 1. However, the most recent and highest quality study on the management of osteoarthritis, published in 2020, does not mention A2M as a recommended treatment option 1.
Established Treatments
The 2019 American College of Rheumatology/Arthritis Foundation guideline for the management of osteoarthritis of the hand, hip, and knee recommends established treatments such as:
- Exercise
- Weight loss in patients with knee and/or hip OA who are overweight or obese
- Self-efficacy and self-management programs
- Tai chi
- Cane use
- Hand orthoses for first carpometacarpal (CMC) joint OA
- Tibiofemoral bracing for tibiofemoral knee OA
- Topical nonsteroidal antiinflammatory drugs (NSAIDs) for knee OA
- Oral NSAIDs
- Intraarticular glucocorticoid injections for knee OA
Considerations for A2M Therapy
A2M therapy typically involves injecting concentrated A2M derived from the patient's own blood plasma directly into affected joints, similar to platelet-rich plasma injections. While some clinical studies and case reports indicate improvements in pain and function, A2M therapy is still considered experimental with inconsistent results across studies. Patients may experience mild injection site pain or swelling, but serious side effects appear rare. Insurance typically doesn't cover this treatment, with out-of-pocket costs ranging from $500-2000 per injection.
Recommendation
Patients should consider established treatments like physical therapy, anti-inflammatory medications, and lifestyle modifications as the primary approach for managing joint arthritis. A2M therapy may be considered as a complementary approach, but patients should be aware of the limited and inconsistent evidence supporting its efficacy, as well as the potential costs and side effects.
From the Research
Efficacy of Alpha-2 Macroglobulin (A2M) in Treating Joint Arthritis
- A2M has been shown to have anti-inflammatory properties and inhibit cartilage degeneration in osteoarthritic joints 2, 3.
- Studies have found increased concentrations of A2M in the synovial fluid of patients with rheumatoid arthritis, which is significantly related to acute phase reactants, local inflammatory parameters, and joint damage 4.
- A2M has been proposed as a potential treatment for cartilage-based pathology and inflammatory arthritides, with autologous concentrated A2M from plasma being used to successfully treat various painful arthritides 3.
- The unique method by which A2M inhibits the associated inflammatory cascade and disrupts the catabolic process of cartilage degeneration makes it a promising treatment option 3.
- However, the relationship between A2M concentrations and inflammation activity in the joints of patients with rheumatoid arthritis and osteoarthritis is unclear, with some studies finding no correlation 5.
- Neutrophils have been shown to play a predominant role in the inactivation of A2M in arthritic joints, with the release of reactive oxygen species and lysosomal proteinases contributing to this inactivation 6.