Do Joint Supplements Really Help?

Recently by Mark Sisson: You Want to Eat Like a Hunter-Gatherer

Today’s edition of Dear Mark is a relatively focused one, with just two topics. I spend the bulk of my time discussing the merits of glucosamine, chondroitin, and methylsulfonylmethane supplementation when it comes to treating osteoarthritis. This is a tough subject, because while these joint supplements are some of the most commonly taken, the evidence for their efficacy is mixed. It seems like people have one of three reactions to these particular supplements. Either they find them completely and utterly indispensable, completely and utterly useless, or kinda sorta helpful in a “but I’m not too sure” kind of way. Next, I discuss whether or not iodine supplementation is required on a Primal Blueprint eating plan.

Let’s get going, shall we?


I’ve searched through the site and surprisingly I’m hitting a wall while trying to find any information in regards to Glucosamine and Chondroitin, MSM. I did find a few bone health articles where you suggest using it, but do not go much further with details. Can you give us the ins and outs of these supplements? I’ve heard quite a bit about the benefits of each, however I’ve also heard quite a bit in regards to this being some kind of placebo effect that is doing nothing to improve joint function. I would love to hear your take on this.


Glucosamine, chondroitin, and MSM are all separate compounds, though they are grouped together in supplements so often that the names kind of blend together. Let’s go over each of them.

Glucosamine is a structural component of bone, exoskeletons, shells, and fungi cellular walls.

Chondroitin is a structural component of cartilage.

Methylsulfonylmethane (MSM) is an organosulfur compound (remember those?) found, in limited quantities, in certain plants.

Most of the studies are either inconclusive or indicate that neither glucosamine, chondroitin, nor MSM have much, if any, effect on humans with osteoarthritis. The latest one said as much. That’s it, then, right? It doesn’t work. And if it does work, it’s a placebo. Period. Throw away your supplements and start mainlining liquefied NSAIDs. How could anyone be so stupid as to use a supplement?

Eh, not so fast.

Some animal studies suggest that glucosamine, chondroitin, and MSM might work pretty well. And although animals are smarter than we often credit them, dogs, horses, and rats don’t get placebo effects. When I give Buddha a pill surrounded by raw ground beef, he’s just happy to eat some meat. He has no clue that I’m secretly giving him a glucosamine tablet, and even if he saw the tablet, he wouldn’t be affected by a “placebo” effect. For a placebo effect to occur, the patient must be aware of treatment. Dogs don’t really get the idea of treatment or medicine. They might enjoy and benefit from your hand rubbing their necks while they take a pill or get treated by the vet, but it’s not the same thing.

Let’s talk about humans, though. The main study cited in meta-analyses that conclude neither glucosamine nor chondroitin sulfate do anything for human osteoarthritis is the GAIT trial, a multicenter, placebo-controlled, double-blind study. Overall, the GAIT trial found that neither supplement, whether alone or in concert, performed better than placebo. However, in the “moderate-to-severe pain subgroup” of patients, a combination of glucosamine and chondroitin sulfate was far more effective than placebo at reducing osteoarthritis-related pain. But because the subgroup was relatively small, its results weren’t enough to affect the overall conclusion.

If glucosamine works, how does it work? The popular conception is that it, being a raw building block of bone, gets directly incorporated into damaged connective tissue. You eat the stuff and it somehow magically makes it to the afflicted areas. That’s how detractors eager to combat a strawman put it, but the funny thing is that the “strawman” might actually have some merit. A study found that 1500 mg of glucosamine sulfate crystalline powder taken orally appeared in the synovial fluid (a fluid found in joints that has a yolk-like consistency; scrambled synovia, anyone?) of osteoarthritic patients. Since synovial fluid provides lubrication and nutrients to and removes waste from articular cartilage, having higher levels of glucosamine (a precursor for the glycosaminoglycans which make up cartilage) could prove useful and even increase glycosaminoglycan production. Another interesting piece is that a later study found that glucosamine sulfate was more effective than glucosamine hydrochloride at showing up in synovial fluid after oral dosing. Perhaps if the GAIT trial had used glucosamine sulfate instead of glucosamine hydrochloride, the effects would been more pronounced.

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