FAQ’s on Alpha-2-Macroglobulin (A2M) Treatment for Arthritis

Alpha-2-macroglobulin (A2M) is a nonimmunoglobulin protein found in plasma protein. This substance can inactivate many proteinases that degrade chondrocytes (cartilage cells), which contribute to osteoarthritis (OA).

How does A2M work?

Through injection or administration of A2M protease, alpha-2-macroglobulin is inhibited. A2M can stop progression of OA by preventing the breakdown of cartilage and cartilage loss from the joint. When cartilage is preserved, joint function improves and pain decreases. A2M works by inhibiting cytokines, matrix metalloproteinases (MMPs), and a-disintegrin and metalloproteinase w/thrombospondin (ADAMTs). These three protein substances will degrade cartilage over time, and injections of A2M will protect the joint cartilage from catabolic reaction and inflammation.

Is alpha-2-macroglobulin effective for treating arthritis?

In a study where supplemental intra-articular alpha-2-macroglobulin was used in rat subjects, researchers evaluated the effects of the protein substance on cartilage and chondrocytes. The scientists found that in animals with OA and animals without OA, A2M inhibited the induction of certain protein activity in cartilage cells. As for rat subjects with OA, the A2M injections reduced damaging human MMP-13 in the synovial fluid. The researchers concluded that A2M offered chondral protection from arthritis.

How common is arthritis?

According to the Centers for Disease Control and Prevention (CDC), around 22% of U.S. adults have doctor-diagnosed arthritis. By 2014, researcher believe that 78 million Americans 18 years of age and older will have some form of arthritis.

What are the types of arthritis treated with A2M?

Osteoarthritis is the most common type of arthritis treated with alpha-2-macroglobulin. Other types of arthritis treated with A2M include rheumatoid arthritis, gouty arthritis, fibromyalgia, and lupus.

How is alpha-2-macroglobulin obtained and made?

A2M must be concentrated in the laboratory to be given by injection in to a joint. Alpha-2-macroglobulin is not a platelet product. Rather, A2M circulates in the plasma of the blood. The first process involves obtaining around 200 milliliters of blood from the patient via venipuncture. The blood is placed in special containers and concentrated by way of a filter concentrator device. Through multi-phase centrifugation and filtration, a concentrated solution of A2M is obtained. This solution can then be injected into a joint via a common joint injection procedure.

How do I prepare for the A2M injection?

Before the procedure, you will meet with the orthopedic specialist or pain management professional to go over your medical history. The doctor will ask you questions about your symptoms, take some imaging scans (x-rays or MRIs), and schedule your procedure. Because increased bleeding could occur, you must hold all medications and herbal products that thin the blood for a few days beforehand. These include Coumadin, Plavix, aspirin, and Ginkgo Biloba.

What can I expect during the A2M joint injection procedure?

When you arrive at the physician’s office, the knee, hip, or shoulder joint is cleaned with an antibacterial solution. The doctor will numb the skin and deeper tissues using a local anesthetic. Using fluoroscopy (x-ray guidance), a needle is inserted into the joint. Once the needle placement is confirmed, the A2M solution is injected. Once the A2M is inside the joint, the needle is withdrawn, and a bandage is applied to the injection site.

What can I expect after the joint injection with A2M?

After the alpha-2-macroglobulin is instilled, the knee or other joint will still feel a bit numb due to the local anesthetic. The injection site will be sore for 12-48 hours. In addition, the joint will experience an “exacerbation” period. During the next few days, the A2M solution will begin to work and cause slight inflammation of the joint. As the body’s normal immune defense mechanisms kicks in, the soreness will improve.

Dr. Zed with All Star Pain Management offers revolutionary A2M treatment for relieving arthritis pain and helping patients avoid the need for potentially risky surgery. Call us today!


Centers for Disease Control and Prevention (2017). Arthritis-related statistics. Retrieved from: https://www.cdc.gov/arthritis/data_statistics/arthritis-related-stats.htm

Wang S, Wei X, Zhou J, et al. (2014). Identification of α2-macroglobulin as a master inhibitor of cartilage-degrading factors that attenuates the progression of posttraumatic osteoarthritis. Arthritis Rheumatology, 66(7), 1843-1855.