Saturday, February 11, 2017

With Glucosamine Studies, It Pays to Read the Fine Print

As many of you reading this know, I’m a skeptic when it comes to glucosamine supplements for treating knee pain. Of course my usual disclaimer applies: If it works for you, go ahead and keep taking it. I don’t think the supplements are actually harmful (unless you’re diabetic). For most people, the only damage will occur in the region of their wallet.

Occasionally a clinical study on glucosamine will catch my eye. Here’s one with an impressive headline: “Glucosamine-containing supplement improves locomotor functions in subjects with knee pain – a pilot study of gait analysis.”

First, let’s get right to the researchers’ exciting conclusion:
Our data based on gait analysis using a motion capture system suggest that supplements [containing glucosamine] can increase walking speed through increased stride length and increased force of kicking from the ground during steps, and these improvements may be associated mainly with alleviated knee pain and direct effects on muscle.
Well, this certainly sounds good. But one odd thing you’ll note if you look closely at this study. There didn’t seem to be a control group. In fact, the researchers make a damning admission near the end of their article:
There are some limitations to the present study. First, it was conducted as an open label study.
Hmm. An “open label study.” What the heck is that? Well, the gold standard would be a double-blind study. In such a clinical trial, the patients don't know whether they are receiving real glucosamine or a placebo. What’s more, the “double blind” means that the researchers don't know whether they are evaluating subjects who have taken glucosamine or a placebo.

So in other words, in a figurative sense, it’s like the subjects and the researchers are both wearing blindfolds until the very end. This ensures no placebo effect for patients and also that researchers won’t be swayed when they evaluate the results, because they happen to personally believe, or not believe, in the efficacy of glucosamine.

So what would be the opposite of a double-blind study? A study where both researchers and patients know who's taking the medicine that’s supposed to improve their joint health – thus fairly effectively polluting the integrity of the results? Well, that would be – you guessed it – an open label study.

Well, if the researchers weren’t at all conflicted, this still might work. Maybe. Maybe? Ah well so much for that. Four of the authors, it turns out, work for Suntory Wellness, which made the glucosamine supplement used in the trial.

Now you’re probably wondering: Who would publish such a conflicted study?

The article appeared in a publication of Dove Press, an “open-access” publisher that has taken some heat before for its business practices and has been tarred as a “predatory” open-access scholarly publisher. Such publishers “are predatory because their mission is not to promote, preserve, and make available scholarship; instead, their mission is to exploit the author-pays, open-access model for their own profit.”

I think the very fact this study includes FOUR authors who work for the company that makes the supplement being tested, and was “open label,” should be enough to send any smart knee-pain sufferer running in the other direction. Remember to read the fine print!


  1. Great advice, Richard! It's frightening how many people take the results of such studies at face value and neglect to question the methods and motivation behind them.

  2. Hi Richard, what you think about the integrity of this study?

    I haven't commented on a while, but six years ago I was diagnosed with a 6mm full thickness grade4 patellar articular cartilage defect. Since then, due to reading your hopeful book, I've been carefully bike and run commuting to work. The first few months my symptoms drastically improved but then finally plateaued to minimal pain and have remained there ever since.

    I'm hoping this study showing many grade4 defects improve is legit and explains why my symptoms improved. I'm going to follow up with another orthopedic appointment in hopes of another MRI to prove, stay tuned...

    Thanks, -Erik

    1. Glad you asked -- I love this study! It's cited in my book. You apparently discovered the same table that I did. That table shows that full-thickness (Grade 4) defects, after 2 years, stayed the same 20% of the time, improved to Grade 3 20% of the time, improved to Grade 2 40% of the time, and improved all the way to Grade 1 20% of the time (NOTE: sample size is VERY small for Grade 4 defects). However, if you look at other larger sample sizes in the table, you see a similar pattern -- some defects got worse, but many got better.

      What is another reason this study is so great? It's a NATURAL study. This is important. It means that the subjects didn't do anything special. They weren't in any particular knee-friendly regimen. Yet they still saw significant rates of improvement. This is a very, very hopeful kind of finding.

      Let us know what the MRI shows; it would be interesting. My theory is that there's a lot of positive and negative changes in knee joints, all the time. So maybe that Grade 4 defect in your knee is now Grade 2. However, prepare yourself: there may be another spot in there that's gotten worse.

      Anyway, I'd be interested to hear what you find. Cheers.

    2. Thanks sir. Had a follow-up appointment with one of the sports medicine doctors I originally saw five years ago (one year after my injury but before reading your book and beginning said commuting regimen). She said to let pain be my guide which I don't think any of us agree with, performed x-rays which thankfully and unsurprisingly showed nothing bad, and agreed to order the MRI. Unfortunately my insurance denied the MRI without PT (which was worthless the first time around) and injections (scary and no thanks). So I'm debating and leaning towards footing the MRI bill myself.

    3. FYI Richard, I've convinced my insurance to pay for the MRI. Appointment next week, stay tuned!

    4. Full report coming after I see results myself when they arrive in snail mail this week, but doctor called and reviewed preliminary over the phone. My knee achieved maximum results of microfracture surgery, without having the actual surgery! Unfortunately this means my pothole filled with scar tissue fibrocartilage and not the original desired hyaline cartilage. But if it's sustainable and I'm not in pain I don't care, risk is it contains a shorter life expectancy as you know.

      One interesting observation is there was no sign of healing in the nine months between my injury and when I received my first MRI and hadn't started commuting yet, I think this proves you don't need surgery if you're willing to put your knee in the correct environment. In my case I don't definitively know which variables contributed to my healing: random inconsistent supplements, some weight loss, or consistent motion. But I'm guessing the latter because I didn't start the former two until well after I began consistently and religiously bike commuting to work, and pain improved significantly before embarking on said former two a year or so later.

      One conclusion is I can never stop moving the rest of my life if I want to maintain my knee.

    5. Another interim update. Scheduled a doctor appointment 04/27/2018 to review the MRI results progression, and then would like to publish my full saga. But comparing the to MRI's myself, again I think the short of it is very consistent regular biking, plus inconsistently taking supplements off and on, resulted in my patellar grade 4 defect filling in with fibrocartilage. Like I said above, overall a good result I think considering most people require MFX to achieve this same desired outcome. Unfortunately the surrounding hyaline cartilage has thinned significantly over the past six years since my first MRI, so I'm unsure how long I'll remain pain free, also seems to correlate with short MFX lifespans.

      I regret waiting six years to request this second MRI and wish I had ordered more to better monitor over time and quantify the progression vs my activity levels. I've been running over the past year in addition to biking, and wonder if the running is causing the cartilage to thin.

    6. Hi Erik. Interesting story so far.
      How big was the grade 4 defect?
      Also, the pothole being filled with fibrocartilage is better than nothing at all, which is the result most people end up with!

      Running is pretty high impact on the knees. It's one of those things that readily depletes cartilage faster than cartilage can regrow.

      By the way, there are some pretty promising studies on oral collagen supplementation and showing actual cartilage thickness growth! the genacol company sponsored a few of these studies with x rays, but there are a few studies out there that are NOT sponsored. Give it a look.

      I have pretty severe knee and hip pain and i've started on hydrolyzed collagen myself ( great lakes brand ).

    7. Erik, definitely update us. Very interesting, and if true, correlates well with what I believe: changes in cartilage are dynamic and two-way.

    8. I'll post the full saga after my 04/27/2018 appointment, but until then you can view the MRI images here:

    9. A picture is worth 1,000 words! Quite interesting.

    10. Erik, can I post those images on this blog (I'll link back to your Strava)? They are interesting, and I was thinking of doing a post. Any details you want to share on what you did? (I know some details are scattered around the comment section.) Thanks.

    11. Thanks Richard. I'm completely all for you publishing my story and glad you ask, but I'd rather wait until after my appointment mentioned above. I have a LOT of details I plan on sharing with you, and I think it would be advantageous to wait and avoid unnecessary confusion and questions due to lacking context. Ultimately believe this stragedy will be more beneficial for your readers.

    12. No worries, that's fine. Glad things are looking good!

    13. FYI I've began typing up my saga, just don't want you to think I left you hanging!

      FWIW my doctor cleared me to exercise however I see fit and just let pain be my guide since whatever I'm doing is apparently working. That recommendation made me cringe, but I'm also not surprised given that's the possibly bad advice most doctors give.

    14. Ha, not surprising. Congrats on what you've achieved so far. It sounds pretty remarkable to me, and those MRIs validate the saying "seeing is believing."

    15. Thanks, sorry for continued delay. I'm a few hours into typing up my story, took a lot of research to go dig up all my old metrics and milestones. I'm probably about half complete but the timeline is coming together nicely. I'm excited to share with you all, I think you'll find it quite valuable. At this rate, please give me a couple more weeks or so. Thanks for your patience.

    16. No problem, Erik. Do it at your pace. People love success stories and it'd be great to have another to share. Cheers!

  3. Is your cartilage really thinning Erik? I am no expert in reading MRIs, but i went into photoshop and scaled and rotated the knee pictures, based on the black lines and the alignment of those two little lines on your patella... and noticed 3 things.

    1) Your patella is sitting at less of an angle.
    2) The spacing between your patella and the bone seems to be equal in distance. This is pretty impressive for someone who has been racing on a bike for 6 years after an injury!
    3) The area of bone pictured is very different here.

    As for what sport to do in the future? running is most likely higher impact.. how about commuting on an electric bike.. with the power set so low that it's only doing a fraction of the work?

    1. Thank you, but please wait for my full saga. It's not as simple as racing a bike for six years, in fact after reading Richard's book back then I took his approach and slowly started ramping biking until the pain subsided. Ultimately Richard had the most influence on my "healing", and I'd like to share that stragedy with you all after my follow up appointment end of this month.

      After reviewing the hundreds of MRI images, the cartilage has definitely thinned to the right of the original defect. And the defect itself is of different density consistent with fibrocartilage. But I completely hope your optimistic view is correct!

      Thank you again for taking the time to examine, I appreciate your insight. Please stay tuned, I've been hoping I could share this good news with this community for the past six years. I've never been satisfied with the lack of concrete data in this area, so hopefully my story will be valuable and provide hope.