NSAIDs and Stem Cells: Naprosyn Messes Up Cartilage

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I highlighted a study recently that suggested that taking NSAID drugs long-term could cause more arthritis. However, the question is how that could happen. Now another recent study sheds light on a possible mechanism for how that could work—NSAIDs cause abnormal cartilage to be manufactured because of the interaction of NSAIDs and Stem Cells.

NSAIDs in the Water Supply

It’s amazing that every single guideline for treating an acute injury involves taking NSAID drugs. These are anti-inflammatory medications that include drugs like Motrin. Aleve, ibuprofen, Advil, Naprosyn, Celebrex, celecoxib, Mobic, and meloxicam (just to name a few). Doctors and the public seem to be under the bizarre illusion that these drugs are safe, when in fact they’re the most dangerous medications you can buy over the counter. Not only can they cause nasty stomach ulcers, but, more importantly, all NSAIDs increase your risk of having a fatal stroke or sudden-death heart attack. The lowest risk is Naprosyn, which more than doubles your risk of a stroke or heart attack, and the worst is Voltaren, which almost quintuples it!

We’ve told patients for years to get off NSAID drugs prior to a stem cell procedure, which can sometimes be quite difficult as many middle-aged and elderly patients take this stuff just to function normally. They begin to get aches and pains in middle age, and rather than managing them with diet, exercise, and natural supplements, like high-dose fish oil, curcumin, or glucosamine/chondroitin, they begin to pop Motrin pills like they’re scarfing M&M’s. The problem is the relationship between NSAIDs and Stem Cells as these little pills will mess up your stem cells. Let’s look at how that works…

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How Cartilage Is Made

New cartilage is made in your joints all the time. When you go for a run or even a walk, many cartilage cells and little bits of the matrix they produce are lost. This needs to be replaced, and that happens by local stem cells differentiating into cartilage cells to replace the dead ones. The new cartilage cells then lay down the stuff where they live, known as extracellular matrix, or ECM. In a joint, the cartilage cells plus the ECM are what we call “cartilage.”

The composition of the ECM is critical so it can resist force. In order for it to be strong enough, the right type of collagen has to be produced. Collagen is the stuff that makes up our skin, hair, bones, and many other tissues. It comes in many different flavors or types. Each organ or body part can be engineered to have certain properties, like more or less stretch or more or less firmness, just by altering the composition of the different collagen types. One of the things we know about bad cartilage (like the type found in arthritis) is that it has more collagen X (ten). This makes it too soft and unable to withstand normal forces.

The Dangerous Interaction Between NSAIDs and Stem Cells

The recent study looked at Naprosyn, also known as Aleve, as well as other NSAID drugs. The authors had found in a prior study that Naprosyn (but not other NSAID drugs) altered gene expression in stem cells for type-10 collagen (caused the cellular machinery that makes this protein to be stuck in overdrive). This study looked at stem cells from normal healthy patients and from patients with arthritis. The cells were then exposed to Naprosyn or not and then given clues to become cartilage cells. The cells exposed to Naprosyn made too much collagen X. Interestingly, this was happening because one of the inflammatory pathways that Naprosyn and other NSAIDs doesn’t block was also placed into overdrive. Also very interesting is that there are supplements, like high-dose fish oil and curcumin, that we know block this other inflammatory pathway (lipoxygenase).

So is Naprosyn the only bad actor? Not in the least. Here’s another study showing that Voltaren causes stem cells to turn into fatty pieces rather than turning into normal tendon cells. Other studies have shown that NSAIDs also mess with new bone formation and healing (although pharma has been working overtime to produce research reviews to block this one as this messes with orthopedic surgeons prescribing NSAIDs for postop patients).

The upshot? Normal inflammation is how we heal. So just from a 30,000-foot view, blocking it in a patient trying to heal or undergoing a treatment like stem cell therapy, where healing is the primary aim, just seems ill-advised. Now we have multiple studies that show that the interaction between NSAIDs and stem cells will mess with stem cells at multiple levels and through multiple mechanisms. So if you’re seeing a doctor who wants to perform a stem cell treatment, and he or she doesn’t provide advice to get off the NSAID sauce, find a new doctor!

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Chris Centeno, MD is a specialist in regenerative medicine and the new field of Interventional Orthopedics. Centeno pioneered orthopedic stem cell procedures in 2005 and is responsible for a large amount of the published research on stem cell use for orthopedic applications. View Profile

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