Sunday, October 14, 2012

Glucosamine Sulfate and the Placebo Effect

I was doing some housekeeping recently on the computer, cleaning out old files, when I came upon this:
In a landmark meta-analysis of 10 placebo-controlled trials of glucosamine and chondroitin that researchers said should “close the book” on whether these popular supplements actually help arthritis sufferers, Peter Juni, MD, of the University of Bern in Switzerland, and colleagues concluded, ”Our findings indicate that glucosamine, chondroitin, and other combinations do not result in a relevant reduction of joint pain or affect joint-space narrowing compared with placebo … We believe it unlikely that further trials will show clinically relevant benefit of any of the evaluated preparations.”
The article isn’t that old (from last year), but it did manage to transport me back to the summer of 2007, and the early days of my struggle with knee pain.

My very first orthopedist introduced me to glucosamine. At the time, I was afraid I had some sort of damage inside my knee joints. I liked the idea of rebuilding my cartilage using natural supplements that supply a key ingredient for ensuring the tissue’s strength and elasticity.

By 2007, glucosamine had been the subject of a number of flattering books and articles. A decade earlier, in 1997, New York Times health columnist Jane Brody spurred sales after writing about how glucosamine and chondroitin supplements helped her arthritic dog. She then thought, “Hey, what if they can help my arthritic knees too?”

According to this Web site:
She limped, had difficulty with stairs, and with playing tennis ... After a year of taking glucosomine sulfate and chondroitin sulfate she is not totally pain free but neither is she disabled. Jane Brody now plays singles tennis two to four times a week, skates four or five times a week, and takes brisk 3 miles walks.
As for me, sadly, glucosamine had no perceivable effect on my knee health, as I note in Saving My Knees. After many months, I stopped taking it, convinced it was doing nothing. Eventually, I got around to investigating why it had done nothing for me.

That glucosamine is vital for ensuring healthy cartilage isn’t in dispute. Also, it’s been shown in studies to have a salutary effect, when additional amounts are introduced to cartilage sitting in petri dishes. But the glucosamine story goes awry at this point: in the real world, your knee cartilage isn’t conveniently lying in a petri dish -- you have to swallow tablets of the supplements, which unfortunately (as at least two studies have shown) get pretty well whacked apart by the liver.

An insignificant amount of glucosamine winds up making its way into your knee joints (here's one study that found that: "Low Levels of Human Serum Glucosamine After Ingestion of Glucosamine Sulphate Relative to Capability for Peripheral Efffectiveness," Annals of the Rheumatic Diseases 2006).

So why do so many people exult about the benefits of glucosamine? The closer you look, the more the answer appears to be the placebo effect. Still, what’s wrong with a placebo? Less pain is less pain, after all. I think this is a valid point, but a big caveat should accompany it.

The reason for that caveat I can illustrate with the story of my “Superman pill.”

A man seeks relief from chronic back pain. I give him a bottle of “Superman pills,” which (known only to me) are nothing more than super placebos. Anyone who ingests one feels a lessening of pain and believes he or she has a healed back as strong as Superman’s.

What happens next? Well, the back pain sufferer thinks he’s cured, decides to help his brother move a wood stove up three flights of steps (or something equally ambitious), and ends up really damaging his spine.

That, to me, is the big danger of the placebo effect: thinking you’re actually healed (or are healing) when you haven’t (or aren’t).

Which brings us back to Jane Brody. What the Web site I directed you to earlier doesn’t say (even though it claims to have been updated in 2011!) is that Brody had a double knee replacement, apparently in 2004 (which she discusses, in frank detail, here). Did taking glucosamine cause her to over-exert herself? Did she wrongly believe she could indulge freely in skating, tennis playing and brisk walking because the glucosamine supplements were busily repairing her bad cartilage?

I don’t know. But her story is certainly a cautionary tale for glucosamine enthusiasts.


  1. I agree. Also, another danger is that it gives you an easy answer to doing something for your knee. It can become a reflex to think of the pills as your way of action, to calm yourself psychologically that you're doing "all you can". That could actually hold you from doing what you really need (rest, walk etc.)

    I have 2 questions for you if you don't mind:
    1. When you walked the least (at your worst point), how many steps did you do a day?
    2. What do you think about cold/hot packs to help circulation. I know the cartilage has no blood, but do you think maybe extra circulation would help in some way?


    1. #1 When I walked the least, it appears from my journal that I did about 5,900 steps in two separate easy, flat-stage sessions of walking outside (plus bursts of very short walking around the apartment). I don't have an exact figure for the whole day (a lot of steps I didn't count). The big caveat is everyone's different of course: 5,900 was about where I started, but someone else may have to start at 4,000 or 2,000.
      #2 I'm not sure about cold/hot packs. I really haven't looked into it, but it sounds marginally beneficial, if anything. I think movement is a better way to improve circulation.

  2. The superman pill story is a good example of one possible peril of placebo, but on the other end of the spectrum might be the power of an optimistic disposition and of positive thinking in general, wedded to an adaptive, conservative and full spectrum approach to knee healing.

    I had a GP (of all people) tell me that he thought there was a relationship between depression and arthritis. Depending on who you talk to though, there are any number of possible candidates that can contribute to arthritis: Artificial sweeteners and mold exposure, to name a few. On the other end of the continuum, there are the usually structural and causal arguments by medicos: Congenital/genetic predispositions, mechanical issues, over-use, etc.

    So maybe placebo is one part of the healing process, but only when used with the "Richard" regime of knee healing- The paradigm where we progress intelligently and incrementally and try not to get too carried away on our good, superman days, so that we don't suffer huge, stove carrying set-backs.

    1. True, attitude is very, very important! A good outlook is a great ally when trying to beat something like this.

  3. I have been doing amazingly well...I had been able to bike up to 20 miles on flat orr 13 miles including hills. Been doing well for MONTHS and I thought I had beat this knee pain. But. Now I am having a huge flare up. This is the worst flare up since..... Probably February.

    I had been doing so well that I had stopped journaling about my knee activities. So, now I'm sort of scrambling and puzzling to think of WHAT did I do to cause this flare up. I know pain can have delayed on-set. But..... A week seems TOO extreme of a delay, right? But I had done a pretty hearty bike ride on 10/13 and I wonder if that is what caused this flare up which started coming on around 10/19.

  4. When something like this mystery flare up happens, It makes me feel afraid to try any activity because I don't know if I'm going to be hurting afterwards (a day later...a week later...) or not. Or maybe it wasn't the biking that did it. Maybe it was something else.

  5. Knee Pain,
    I know what you mean. I think the only way is to be patient and be kind to your knee. I find I get the best results when I don't try to "get" things from my knee but rather work with it together.

    Good luck.

  6. Thanks. I'm genuinely puzzled about this flare up. It was doing so well. Maybe I finally pushed it too hard on my Oct 13 bike ride? But a whole week delayed on-set of pain seems too long....doesn't it? I would think 24-48 hours delay. But.... A whole week? Especially when the pain is so severe? I know I've heard when someone is in a car accident sometimes they feel fine but then a week later they get back/neck pain. So, I wonder if this is similar.

    Well, as you say... The only thing to do now is rest and ice and recover. Then, back to gentle exercises. I wonder if I'll be reset to square zero or if I'll at least have a leg up this time (pun intended) and get to start at square 2.


    If anyone has insights into how long the pain delay onset can take, that would be interesting.

    1. Yes, a week "delayed effect" strikes me as far too long. I'd look for a more proximate cause. Even an activity like too much kneeling (or kneeling in the wrong way, just a couple of times) could conceivably cause problems. Anyway, if you had been making progress for a while, it's hard for me to believe you'd be knocked all the way back to where you were when you started ... or if you seem to be, maybe you'll only be stuck there for a few weeks. I know -- frustrating!

    2. Yes, very frustrating! How could I go from being able to bike 10 miles including hills to.... My same old stabbing pains when I bend my knee? I am very puzzled. But.... Ok, I won't blame my setback solely on my Oct 13 bike outing. And yet..... One would think a setback this big that I'd be able to remember SOMETHNG pretty major as the trigger.

      I've been making slow but steady progress since March 2012 .... So..... It's frustrating to now 7 months later have this mystery setback. :(

      I started journaling again so I can track how long it takes to recover. Hopefully a speedier recovery period.

    3. Try not to get too discouraged! Getting everything right, consistently, is very hard. And your setback may not have been caused by something major, in my opinion. See this bit of philosophizing about "breakdown points" and "discontinuities in healing":

  7. Ok, I've read the blog post and that's made me look back at my activities in October.

    I think you make some good points. It not just ONE thing that can cause a flare up but a series of things that all add up.

    In my case., I think my knee was getting grumpy even before the Oct 13th bike ride, but then I did the Oct 13th ride and instead of doing an easier route, I did a harder route with some challenging hills.

    Then... I didn't bother to ice because I'd gotten out of the habit of icing because there hadn't been a need.

    Then in Oct 17 played a game which called for some dashing about which I never do since I know that is bad for my knees. Then.... What else.....

    Knee was irritated On 19th & 20th......I laid low.

    . Feeling better Sunday 21. Rested. No walks.

    Monday 22 morrning was irritated in daytime but not at nighttime at night I walked 2 miles including a bill hill......

    Tuesdsy 23 knee was killing me.

    So... I can buy it that my knee was getting more n more irritated and then the 2 mike walk threw it into the abyss.

  8. I never thought glucosamine could have that kind of effect. And it is very dangerous. One might think he/she has been healed. But in reality, he/she is not.

  9. I had moderately good results from glucosamin/chondroitin.. Maybe it's placebo, but I don't care :)