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.

Do Flat Feet Cause Bad Knees?

This article would have you think so.

I was initially drawn to the story by the breathless tease on the top:

Having flat feet can destroy your knees: Many think wonky feet are a joke -- but the effects are often crippling.

Granted, this isn’t the New England Journal of Medicine. It’s Britain’s Daily Mail. Still, I was curious how flat feet could destroy a pair of perfectly good knees.

The story is that of Arti Godkhindi, 34, who describes her knees as “chronically bad.” The 5-foot-7-inch IT consultant weighed about 10 stone (140 lbs.) and got pregnant and gained two stone (28 lbs.) -- or 20 percent of her original weight. (For me, that would be like going from 175 lbs. to 210!)

During her pregnancy, she walked an hour a day to stay fit. After her daughter was born, she had trouble shedding her excess weight, so she joined a gym. “I started gently,” she says, then adds, “But as soon as I tried to do any running or stretching, I felt this excruciating pain on the inside of both knees.”

So she had an MRI done, which showed tears in the meniscus (pads of cartilage in the joint that absorb shock) in both knees. She was diagnosed with patellofemoral pain syndrome (which is pretty much a worthless diagnosis, I found: see here).

What’s the cause of her “permanent, disabling knee pain,” according to this article?

Her flat feet! Because, we are told, people like her (the quotes are from her doctor):

“... may have been living with faults in the way they walk, such as overpronation — also known as flat feet (which cause the feet to roll inwards) — or supination, where the feet roll outwards. They manage perfectly well until there is weight gain.”

Flat feet or other faults cause you to carry your weight through the wrong part of the foot, he [Dr. David Jones] explains, setting off a chain reaction upwards through the body.

“Where the knee cap connects with the thigh bone or femur, there is a V-shape groove, to help the knee cap glide up and down.

“If your feet roll inwards, the knee cap doesn’t move smoothly through this groove. We call this bad tracking and, over time, it leads to damage of the cartilage and pain.”

This is a conventional, structuralist sort of explanation for knee pain. However, as I’ve noted before, maltracking kneecaps may not be a significant predictor of knee pain (according to this study). And orthotics (which are recommended for flat feet sufferers later in the article), may be useless anyway, according to the New York Times ("The idea that they are supposed to correct mechanical-alignment problems does not hold up").

(Note: It is a good idea, of course, to wear proper-fitting shoes with good cushioning; that's common sense.) 

So, if I’m Arti’s flat feet, I’d start looking for a good defense attorney. After all, her Dad also has flat feet -- but no knee pain. What else may have caused her knee pain?

She gained a lot of weight during her pregnancy. Weight gain should always be a suspect in a knee pain whodunnit, whether you have flat feet or perfect arches.

Changes to her body during pregnancy (softening of muscles and ligaments, altering biomechanics, e.g.), as mentioned in the article, may have predisposed her to knee pain.

Her efforts to lose weight after the pregnancy should be strongly considered as possible culprits. Did she go from being fairly inactive to suddenly active? It wouldn’t need to take much either -- notice how a reference to running (“As soon as I tried to do any running or stretching, I felt this excruciating pain ...”) is quietly slipped into a quote.

But that’s huge! Running can be very hard on joints, especially if you’ve never done it before or are resuming the activity after a long layoff.

I’m not saying her flat feet are necessarily totally blameless. But I suspect their role in this misfortune has been much overstated.

The ‘Friend’ No Longer at My Side

First, to reassure you all: No, this isn’t a weepy or sentimental piece about the death of a loved one.

I’ve been on vacation this week. We had a quiet, family-oriented, stay-in-New-York vacation.

My wife, daughter and I went to the 9/11 Memorial, rode the Staten Island Ferry, visited the Metropolitan Museum, and stopped at about four playgrounds on the east side of Central Park.

And we walked. A lot. Sometimes, what’s more, I was carrying a tired three-year-old. I have no idea how many steps I took over the course of the last seven days.

There was a day, not so many years ago, when saying that would have been unthinkable. When I was battling knee pain, I never went anywhere without my pedometer. In fact, I remember on more than one occasion leaving my Hong Kong apartment without it, and rushing back, as if I had forgotten my wallet or keys.

Why?

Because I’d reached the conclusion that knee pain wasn’t random, as one of my doctors seemed to suggest when he shrugged and said, about my knees that he deemed beyond hope, “You’ll have good days and bad days.”

It made no sense to me that the rest of the physical world is governed by laws of cause and effect, but my knees existed within some strange Bermuda Triangle where “cause and effect” just went and vanished, without a trace.

In my attempts to decipher patterns in the apparent randomness, I knew I had to closely monitor how many steps I took. Gradually, it became an obsession. I seriously tracked and logged the steps I took outside, on shopping trips and walks and so on (note: I didn’t use the pedometer around the apartment, or if I was just going to say the post office.)

That blue clip-on pedometer really was a friend at my side. It told me when I had done enough walking and needed to rest (for a few minutes, or even for the day). It provided a sense of security, of structure. I was no longer free-floating in some nightmare world called “knee pain forever;” rather, there was a way to escape this place, but I had to be patient and get stronger, always conscious of my limits -- even though, I knew in my heart, they would be temporary.

Indeed they were. The last time I remember that pedometer getting a workout was when I came to New York to hunt for an apartment, in December of 2009. I remember too that my step total for one day was off the charts. Something like 20,000, or maybe 21,000 -- the equivalent of more than 10 miles of walking.

Wow. Even though by then I had been biking pretty hard, and was more than a year and a half into my recovery effort, I still thought, “Oh boy, you’re going to pay for this.”

And the next day ... I opened my eyes, climbed off my hotel bed ... and felt fine.

After that trip, I retired my pedometer.

When I needed it, it was invaluable. I would strongly recommend using one to others, because you don’t get better from knee pain just by crossing your fingers and hoping against hope. You need a plan. And ways to measure and monitor how well you’re doing within that plan.

But eventually, this is one friend at your side you’re going to outgrow, if all goes well. And that’s a good thing.

On Taking Nutritional Supplements for Knee Pain

A question came up recently in the comments section that went like this: I know you admire Doug Kelsey. What do you think of his recommendation that people with stiff joints take SAM-e and omega three supplements?

First, I do have tremendous respect for Kelsey. More than anyone, he helped put me on the right track to healing my bad knees -- and we don’t know each other and have never so much as exchanged a single word about knee pain or anything else for that matter.

However, I diverge from his thinking somewhat when it comes to supplements. To be fair, I haven’t done much research into supplements, with one notable exception: glucosamine. So the following is based on my own limited personal experience with supplements and my own reflections on how I healed. Take it for what it’s worth.

Here are four reasons I’m not a big believer in them:

(1) Glucosamine, the all-star of the bunch, is most likely a dud.

Sentiment in the medical community is starting to swing around on glucosamine, which in the early 2000s looked like it might be a wonder supplement to rebuild worn-out cartilage. Larger, better-run, more independent studies show that it’s probably just a placebo.

The fatal chink in the glucosamine story (as I observe in Saving My Knees) is that orally swallowed glucosamine is largely banged apart by your liver, leaving only inconsequential amounts to circulate intact through your bloodstream to your knee joints. This has been shown by at least two medical studies I’m aware of.

(2) I suspect the benefits of supplements are marginal, if anything.

I took several different types of “stop knee pain now!” and “rebuild your bad knees!” pills during my battle with chronic knee pain. I also ate a lot of garlic (touted as a natural anti-inflammatory). And of course I popped glucosamine for months, as I mention in Saving My Knees.

I experienced no discernible benefits from any of the above.

However, sticking to a good, sensible diet strikes me as a good idea. I do recall a few occasions when, after eating too much fatty, greasy, high-calorie food, I had more knee discomfort than normal.

(3) If you get the physical part right, I think the chemistry will follow.

Which means: A lot of these dietary supplements aim to reduce pain and inflammation. Certainly there is a biochemical basis for pain and inflammation. And you can choose to fight those problems on that level.

But in most cases, I suspect, the physical stuff (how you move, how often you move, what kind of load is on your joints when you move) greatly influences all of that biochemistry. In other words: If you want less inflammation in your knee, make sure you’re committed to a program of the right kind of motion, in the right amount. And the biochemical part will fix itself. (Note: this doesn’t apply, unfortunately, the same way to knee issues stemming from a systemic auto-immune disorder.)

(4) Focusing on healing through motion is simpler and cheaper.

Of course it’s not exactly simple -- you still have to figure out what activities, in what amounts, make your knees happy, and help restore them to good health.

But supplements, at least in my opinion, come with a difficult set of questions. Which supplements? How much of each? Does the brand matter? Do they interact with anything you’re already taking? Do they have side effects? And so on.

And the biggest question: How can you tell if they’re working and worth all the money you’re shelling out for them? Even if you’re certain that a particular one reduces pain and inflammation, is it really helping improve the strength of your knees? Because, ultimately, your goal isn’t just to be pain free, but to have stronger knees so you can hike up a mountain or bike to the shore without having problems.

Those are my thoughts on supplements. During my recovery, I did take extra protein, thinking my diet might not be providing enough, and my body needed more protein than normal anyway to assist in healing. But my (limited) experience with supplements was generally disappointing.

Anyone else want to share? Which ones worked or didn’t for you? Please chime in below!

Update: Readers, since posting this, I came across this New York Times piece about knee pain that suggests that SAM-e probably doesn't work:

Well-designed clinical studies have shown no significant relief of arthritic knee pain from supplements of glucosamine and chondroitin sulfate, taken alone or in combination, though Dr. Felson said that if people feel better taking them, he does not discourage the practice. Nor is there good evidence of benefit from methylsulfonylmethane, SAM-e or acupuncture.

A Note of Appreciation ... to All of You

I’ve been meaning to write this for a while.

Way back (well, closing in on two years now), I made Saving My Knees available as an electronic book on Amazon.com. I hoped the message would spread far and wide: that there really was hope for chronic knee pain, and the best kind of hope -- informed hope. I weaved that message through a telling of my own story, from the depths of despair to the joy of recovery.

I figured, though, I had to be realistic about sales. Amazon is choking on thousands of titles, on just about every conceivable subject. Worse-case scenario, I might move 10 to 20 copies, with Mom, Dad and acquaintances accounting for a handful of those. My middle scenario -- which I deemed most likely -- involved sales of 100 to 200 books.

My “home run” scenario was 500 to whatever. For a $10 electronic book, cast asea with tens of thousands of other electronic books (many with publicists and publishing houses behind them), that seemed pretty good.

Well, we’ve entered the “home run” scenario. The last two months, a steady stream of readers has been finding Saving My Knees. That’s gratifying.

Even more gratifying: the quality of comments on the blog has soared. That shows me that the book (and blog) are reaching the right audience: smart, open-minded, curious knee pain sufferers who still dare to be optimistic (even after many setbacks). That’s terrific.

I recently got an e-mail from a woman in Slovenia. I wanted to excerpt parts of it (anonymously), but she described herself as a private person, which I respect. Anyway, she’s in the thick of what I can tell will be a challenging struggle with knee pain. She was grateful for stumbling upon Saving My Knees.

She wrote, “It is like a revelation to me, it fills me with hope I’ve been searching for for so long.” Hearing those words from someone half a world away made my day.

So thanks to all of you for your support (and great questions and comments)! :)

How I Healed My Knees, In One Phrase

This blog, in aggregate, is a lot of words.

Me talking about stretching. About structuralists. About glucosamine. About hope, despair, and all sorts of feelings in between.

Sometimes I like to cut through the verbiage and get back to the simplest, most basic question a first-time visitor will have about my recovery from chronic knee pain.

How did you do it?

My shortest answer is that I followed this prescription:

The proper amount of appropriate motion.

Now here’s the unpack of that phrase, starting at the backend.

Motion means moving. It doesn’t necessarily mean exercising. “Exercising” is a loaded word that conjures up images of buff fitness freaks. It also suggests vigorous activities that may not be good for weak knees.

“Appropriate” is a significant modifier because there are lots of activities that I don’t think are suitable for people with weak knees. They include many low-repetition exercises aimed at strengthening the quadriceps muscles in the front of the thigh. My knees weren’t strong enough for such exercises (in some cases, where the knee pain isn’t too bad, your joints may be able to handle them).

To get enough “appropriate” motion, I considered three options: (1) something in the water (2) easy cycling (3) easy walking. Why those three in particular? They’re all gentle on the joints and good for doing high repetitions.

(1) was out -- water simply wasn’t convenient enough, plus I had some knee problems while moving about in a swimming pool. (2) didn’t work either -- I had messed up my knees cycling and they protested when I tried even easy spinning. That left (3). I built a recovery plan around appropriate motion that my knees liked: walking.

Now, what about those two words, “proper amount”? Why are they important?

Because there will be a sweet spot of the right amount of motion for your knees -- not so much that they get worse, but not so little that they fail to improve. Determining where that sweet spot is will be a difficult thing -- no sugarcoating here -- unless you’re working with a smart physical therapist who actually believes in measuring what kind of load your knee can tolerate (as Sports Center in Austin does) and who designs a program around that.

Warning: I’m aware of very, very few physical therapists that do such a measurement, in a scientific and quantitative manner. This is one reason why I think, for chronic knee pain, we’re still in the Dark Ages.

Further complicating matters, that “sweet spot” of motion is somewhat of a moving target. You must occasionally push your knees to meet more demanding tasks, to ensure they keep getting stronger. Figuring out how much, and how often, to push is yet another challenge.

All these challenges demand a sustained, concentrated effort at healing. Use tools that help you monitor progress and maintain consistency, such as a knee journal and pedometer. And be prepared to experiment, in a smart way. All of this I did -- and I got better, even after a doctor told me I never would.

A Reader Writes: Is It Best to Stay in a Completely “Pain-Free” Zone?

Someone posed these questions recently.

1. Did you try to stay in a completely "pain-free" zone for as long as you could? Or did you look for the point of little pain that marks the edge of your ability so that you push it further? (not sure if I wrote that clearly enough)
 2. Could you share some of the exercises you did that worked (beside walking)? 

I’ve answered these questions in places before, but from time to time, I like revisiting certain subjects, figuring some people have arrived at this blog for the first time.

On #1 -- Is there such a thing as good, or at least acceptable, pain? Should you expect to live with a certain amount of pain to “edge your training,” so to speak, in recovery? And how to figure out where to draw the lines?

Great, tough questions. What’s somewhat surprising: I’ve yet to find much in the way of answers either, in my wanderings on the Internet. What follows are my opinions, based on my own research and experience.

If you have a “pain-free” window each day, try to enlarge that window.

Which generally means: Stay in the “pain-free zone” as much as possible. So, very short bursts of walking may be better than long walks at first. Gradually re-introduce your bad knees to the rigors of daily living (long periods of sitting, climbing stairs).

What’s a pain-free window?

Well, if you’re lucky (as I was), you do wake up each morning with your knees feeling better. Someone once described this as “It’s like I wake up with a brand new set of knees each morning.”

But you really don’t because those knees wear down all too quickly -- in an hour, two hours, three -- because they’re not that strong.

Anyway, that pain-free window, of a few hours or however long it is, is what you want to try to enlarge, in my opinion.

If you don’t have a pain-free window, you want to work toward getting one.

If you’re always in pain, a good plan for recovery becomes more complicated (see here). In that case, if you’re too focused on avoiding all pain, your tendency is to move less -- which isn’t good. So you have to very very very slowly work on healing those knees: using some experimentation, quite possibly creativity -- and lots of patience.

Swelling is pretty much always bad.

That’s my opinion anyway. Swelling seems to me to be your angry joint screaming, “You overdid it, doofus. Now I hurt and can’t move through my normal range of motion!” If, however, the swelling isn’t mechanically induced, but caused by say an autoimmune disorder, the analysis about how to prevent it changes -- because it’s much less clear to me how you deal with that kind of problem, unfortunately.

You don’t necessarily need pain to “edge your training” when healing bad knees.

Again: my opinion. But joints aren’t muscles. After a hard run, during your preparation for the local 5k, maybe your muscles burn, in a good way that signifies you’re getting stronger. That same “burn” in your joints after a hard hike, because you’re trying to strengthen them, isn’t a good thing. In my opinion.

I got better by pushing my knees to do more, sure. But I pushed slowly, and carefully. To me, the ideal recovery is one in which you improve, and steadily push your knees to do more, while experiencing as little pain as possible.

As for that second question, about what other exercises I did: I have spent little time talking about them because, honestly, I don’t think they mattered much in my recovery. But here are my three favorites:

The “monster walk” (I call it the “crab walk,” which is think is more descriptive.) Knot the ends of a Theraband together, roll the loop up over your ankles, then walk side to side, against the band’s resistance. This exercise didn’t put much strain on my knees, I found.

Unloaded forward knee bends (Doug Kelsey describes these here.)

Unloaded squats (I invented one particular variety, using bungee cords and a rock-climbing harness -- more details here.)

UPDATE: There's a great comment below by "Knee Pain" that I urge everyone to read. It adds a lot to the discussion.