Dear Mark: Glucosamine, Chondroitin, and MSM; Iodine for Thyroid

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.

Another idea is that glucosamine works by binding to free tissue transglutaminase (tTG) in the gut, thus preventing plant proteins (like gluten) from joining with tTG to form harmful inflammatory compounds that induce autoimmune disorders (like arthritis). This study seems to suggest that glucosamine can actually bind to lectins. Maybe it’s gut-mediated. Interesting stuff.

As for chondroitin sulfate, it’s usually paired with glucosamine, but there was a recent randomized, placebo-controlled, double-blind study that used only chondroitin sulfate. It found that patients with osteoarthritis of the knee experienced a reduction in cartilage loss and bone marrow lesions after just six months of chondroitin sulfate supplementation. They used 800 mg of chondroitin sulfate daily, and the results were confirmed via MRI. Pretty neat.

As for MSM, the evidence is mixed, but it appears at least mildly effective on knee osteoarthritis. It sounds like if it does work, it works best in conjunction with glucosamine.

In my experience, G/C/MSM (I’m getting tired of writing the full names) can work on humans, but not every one of them in every situation. People are unique. People’s contexts are unique. Their reasons for having knee pain are unique. Is it physical wear and tear from improper movement causing structural damage? Is it increased inflammation from grains and refined sugar? Is it a deficiency in micronutrients? How bad is it? Mild, moderate, severe? These all matter, but the studies won’t really tell you how.

Although the clinical evidence for G/C/MSM is equivocal, I still think it’s worth trying. I’ve seen it work for some but not for others. Since osteoarthritis really, really stinks, especially when it occurs in a joint attached to a prime mover, like the knee, located on a prime mover, like a Primal enthusiast, I say go for it – even if the evidence is mixed. And if you’d rather not spend money on more supplements, you could always eat connective tissue, make stock, and gnaw on joints. This “treatment” works for dogs, too.

I am new to the Primal lifestyle (2 weeks to the day) and have already obtained energy and lost weight. I’ve just started reading The Primal Blueprint and so far really enjoyed it. I was told by some others, who eat very similar, and they advised me to start taking Iodine for my thyroid to help metabolize the fats that I now consume. I just wanted to know what your take on take this was?

Your newest primate-


I’ve always wanted a pet primate.

Well, iodine is a vital component in the production of thyroid hormone, and thyroid hormone in part controls your metabolic rate as well as energy metabolism. So in a roundabout way, yes, iodine can support the metabolism of fats (as well as other forms of energy, like protein and carbohydrate) by providing the substrate for production of thyroid hormone. But just because you went Primal doesn’t mean you need to start popping iodine.

Of course, since you’re no longer eating processed food rich in iodized salt, which is where many people get their iodine, you may be missing out. And if you’ve switched from iodized table salt to unrefined sea salt – as many Primal eaters do – you’ve just removed another rich source of iodine in their diets. Instead of popping iodine or going back on the junk food, just eat foods rich in iodine. Seaweed, shellfish, and other seafood, seeing as how they spend most of their waking lives fully immersed in iodine-rich sea water, are excellent sources of iodine. Vegetables and the animals that eat them can also be good sources of iodine, but if the soil is iodine-depleted, so is the food that grows and eats there. The sea will most likely always be a good source.

Unless you’re actually hypothyroid and are working with a practitioner, I wouldn’t launch right into iodine supplementation. If you’re doing well on the Primal lifestyle, eating iodine-rich foods like seaweed, fish, shellfish, and pastured eggs, and you seem to be handling your dietary energy with grace and aplomb, I doubt you need to supplement. If you’re suffering and you don’t feel like your metabolism is able to handle the food you’re throwing its way, then it might be worth getting a thyroid panel done. While you’re at it, test for iodine deficiency.

And if you determine that iodine supplementation is right for you, make sure to get enough selenium before you begin supplementing, as selenium is also required for thyroid hormone synthesis. Get your selenium from foods like Brazil nuts (just one or two a day), wild salmon, kidneys, crimini and shiitake mushrooms, lamb, turkey, shrimp, cod, halibut, and egg yolks. For more info on selenium and thyroid health, check out Chris Kresser’s recent (and awesome) post on the subject.

Let me know how it goes, Mason!

Well, that’s it for this week’s installment of Dear Mark. Keep sending in the questions and I’ll do my best to get to them. Thanks for reading!

About the Author

Mark Sisson is the founder of Mark’s Daily Apple, godfather to the Primal food and lifestyle movement, and the New York Times bestselling author of The Keto Reset Diet. His latest book is Keto for Life, where he discusses how he combines the keto diet with a Primal lifestyle for optimal health and longevity. Mark is the author of numerous other books as well, including The Primal Blueprint, which was credited with turbocharging the growth of the primal/paleo movement back in 2009. After spending more than three decades educating folks on why food is the key component to achieving and maintaining optimal wellness, Mark launched Primal Kitchen, a real-food company that creates flavorful and delicious kitchen staples crafted with premium ingredients like avocado oil. With over 70 condiments, sauces, oils, and dressings in their lineup, Primal Kitchen makes it easy to prep mouthwatering meals that fit into your lifestyle.

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