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.