“My veterinarian gave my horse (or dog) glucosamine, and the animal stopped limping, so I started taking it and I feel less stiff. But I sure hate those big horse pills!”
That’s what I heard from patients in the mid-1990s. Veterinarians already knew that animals responded remarkably well to these oral supplements, with no apparent downsides. The science of why they worked was largely suppressed by the pharmaceutical community, as supplements did not represent a profitable pathway for them.
Over the last few decades, though, basic science clarified the mechanism of action, and clinical trials in the most arthritic subgroups demonstrated equal pain relief between glucosamine and chondroitin and expensive anti-inflammatory drugs.
The supplements worked by increasing the production of charged sugars in the articular cartilage matrix of joints. These sugars attracted water, hydrating the cartilage and surrounding tissues. Glucosamine and chondroitin were the key building blocks to produce the normal lubricants of the joint called hyaluronic acid. And glucosamine and chondroitin affected the genes, upregulating specific genetic activity involved in maintaining the health of joint tissues. But they were not effective enough to stop arthritis, or restore damaged cartilage to health. And damaged cartilage leads to inflammation and pain.
Until recently, few other supplements showed adequate benefits. But this is about to change, as leading-edge science shows that modifications of inflammation itself may actually permit cartilage regeneration. This is a completely novel concept, as traditional orthopaedic science taught that articular cartilage had no healing potential.
There is now emerging evidence that some other supplements affect inflammation in novel ways. Some may clear away dead cells (called senolytic cells). These cells, in the process of dying, release degradative enzymes into the joint tissues. In arthritic tissues (as well as in other diseases), the natural process that allows new cells to build restorative tissues is overwhelmed by these toxins. This causes damage to the surrounding tissue as well as irritation, leading to painful inflammation. Pioneering work, led by Jonny Huard Ph.D., is demonstrating that if senolytic cells are cleared away with certain anti-inflammatory supplements the tissues can rebuild themselves — even the articular cartilage of joints.
Various medications used for blood pressure control, infection, and other problems may also have a role in conditioning the tissues to be receptive to anti-inflammation supplements. Again, this is a novel concept: Who would have thought that a blood pressure medication, or an antibiotic, could affect musculoskeletal tissues in unexpected and helpful ways?
The confusing part of the puzzle is that inflammation has both good and bad features. Inflammatory cells kill cancer cells, which pop up in our bodies every day. They control harmful bacteria that escape from our gut or mouth into our bloodstream. Inflammation is a normal part of wound healing. It is becoming clear that inflammation has a wide range of features, is far more complex than we thought, and can be viewed as good or bad depending on its specific locations and situations.
Overloading ourselves with anti-inflammatory diets, supplements, and drugs is probably not the best strategy for longevity. But selectively targeting specific tissues with just the right combination of supplements and drugs may make our joints happier, lives longer, and surgeons less busy.
Dr. Kevin R. Stone is an orthopedic surgeon at The Stone Clinic and chairman of the Stone Research Foundation in San Francisco.