Quickie of the Week: Glucosamine = Joint Savior or Expensive Urine?

Megan A. from Jazzercise Los Altos asks:

Do you think glucosamine and chondroitin really help joints (even for people without arthritis) and if so, how much and which one?

GangnumStyleJoints

Great question, Megan! Glucosamine is being jammed into our faces as the magical cure for joint pain, so much so that some of my supp-worshiper friends are taking it prophylactically, as if popping Glucosamine-coated maltballs is going to prevent them from any skeletal issues they might incur from repetitively playing rugby with guys the size of sofas.

What’s the sitch?

First off: Arthritis sucks.  Or, it rubs. Osteoarthritis is basically a breakdown of cartilage, so instead of a bouncy cushion in

Kick Arthritis' Ass

Kick Arthritis’ Ass

between your bones, you get the bones rubbing up against each other. Not everyone gets it, it’s NOT a natural part of aging, but a lot of people suffer from it, so it’s extensively researched.

Before we get into the glucosamine question, just know that you’re already doing something HUGE: physical activity.  Exercise keeps the joints moving and lubricated, and all that strength work at the end of your Jazzercise class builds up the muscles around the culprit joints to support them! Also, exercise leads to good weight maintenance, so here’s another bonus for you; every pound a person is overweight, there is an additional 4 pounds of force on the knee joints, and 6 pounds for hip joints. So Jazzercise, or any regular exercise program, helps arthritis in lots of ways.

Jazzercise is an hour. A pill takes 2 seconds. Tell me about glucosamine!?

Glucosamine is a naturally occurring compound in lots of our organs (1); most of it in our body is used to make the non-collagen portion of our cartilage.  So, somewhat naturally, people thought hey, why not eat some of the stuff that is breaking down so that we have more of it?

zombieseatbrains

Nice idea! Too bad it doesn’t always workout that way (else I guess we’d be nomming on brains more often!) (2).

Also, in addition to just being part of what’s missing in the joints, it turns out that glucosamine actually has other effects, like stopping the breakdown of tissue.

Why do you always give me information I don’t care about? Does. It. Work.

First of all, form matters. There are two commonly available forms of glucosamine: Glucosamine hydrochloride and Glucosamine sulfate.  Glucosamine hydrochloride has not panned out so well (3). There is strong evidence that glucosamine sulfate is effective at slowing degeneration and alleviating pain. Newer studies have shown yet another form of glucosamine, called NAG, or N-acetyl-glucosamine, may be the most effective.

That being said, the strongest evidence for this supplement comes from studies sponsored by the pharm company that makes the product (Rotta, a company in Italy).

What? Can we trust them? Maybe they spiked their supplements with morphine to make it work!

It’s always sketch to see evidence from companies who sponsor their own research, but there are other studies supporting the effectiveness of glucosamine in cells and humans to alleviate pain and slow degenerative changes in joints, so I’m not willing to toss the evidence into a Porta-potty.

What about chondroitin?

Chondroitin sulfate has been shown to reduce joint pain, and may help restore the integrity of the joint, but the evidence is mixed (meaning significant help is not consistently found) (4).

Overdose

NOM NOM!! GLUCOSAMINE!!

So should we all start adding glucosamine and chondroitin to our cereal?

Glucosamine and chondroitin may not work for everyone. Some people report noticeable changes while others might not. If you don’t notice a difference after 6 months, maybe stop and wait for the next research-based form / dose recommendation and try again.

Also, people with diabetes, bleeding disorders, or shellfish allergies (for chondroitin) should check with their Dr. before taking these guys. To my knowledge, it’s never been researched in people without arthritic pain, so it’s not clear if you should just start bathing in it without any clinical evidence of having a joint degenerative condition.  If it ain’t broke, I think the best prophylaxis is strength and exercise and keeping that range of motion in the joint.

Ok, if I WERE to add it to my cereal, how much should I add?

The “recommended” dose, at least in Europe, seems to be 1500 mg once a day.  Some people think this “barely reaches” the amount you need to make a difference in plasma and tissue. Turns out glucosamine is popular in your body, so there is intense competition for its attention; usually the liver, the intestine, and the kidney steal the glucosamine, leaving little leftover for the cartilage-starved joint.  Therefore, we might see better effects as forms and methods of administering the glucosamine improve.

My puppy (Acting! She's really happy inside.)

My puppy (Acting! She’s really happy inside…)

What about my dog? There are lots of dog foods that scream about glucosamine. Should I spend the money?

Funny you should ask!! Because it turns out glucosamine and chondroitin have been studied in dogs! When you can show something is effective in dogs, you can really diminish the possibility of a placebo effect, or people feeling better just because they strongly believe in the pill they are taking. Even still, this study had a placebo condition, so that all dogs got the same number of “treats.” Yay!

There were four groups:

  1. Group 1 had a placebo
  2. Group 2 had UC-II (an un-denatured collagen from chicken sternum that is used for dogs with arthritis),
  3. Group 3 got Glucosamine hydrochloride (the kind not shown to help humans) + Chondroitin sulfate,
  4. Group 4 had all three: UC-II  + Glucosamine + Chondroitin.

How did they measure dog’s pain?

If you own a dog, you know they are tough cookies. They don’t ever cry or whine when in chronic pain, only if it’s an acute pain (or, in my dog’s case, a plane flies overhead or it rains too hard).

SO to measure pain, they had three observational measures, where researchers blind to treatment condition would evaluate dogs’ favoring of the limb / vocalization / reluctance to squat, etc. after a period of rest, after joint manipulation, and after 5 minutes of exercise.  They also had an objective measure using the ground force plate where they could actually detect how much weight or force the dog put on the arthritic limb.

After 150 days, groups 2, 3, and 4 ALL had a significant reduction in pain based on observations.

ChickenCartoon

For some reason, however, only group 2 showed a significant improvement when using the ground force plate. So, grab some chicken sternum...!

Wait… Why did they use the glucosamine hydrochloride form? I thought sulfate was the winner?!

My question exactly! But, then again, there is some evidence that form works really well in other animals.

I actually didn’t ask that question, you just wrote it in there like I did…

Right. OK. Anyway, best bet for arthritis (aside from medications):

  1. Exercise—both cardio and strength training (for you and your dog!)
  2. Eat 2-3 servings of fatty fish per week (more on how this helps another day).
  3. If you want to try glucosamine, first ask your Dr. if you have any conditions that would interact with glucosamine sulfate. If not, then you can give it a go for 6 months and see what happens! 1500 mgs per day is the most commonly used dosage.  And remember! Don’t just buy any supplement, as they aren’t regulated (see this blog post for more info!) Use Consumer Reports or find a USP regulated glucosamine supplement if you go this route.

This post wasn’t as fun as your last one. And it’s been so long in between posts!

Ask me a question you care about! And I’ve had the flu, so cut me some slack.

Marily O.

MS, RD, PhD

Fun Footnotes:

1. Actually, it’s an amino sugar…glucose (sugar) amine (amino, part of an amino acid, or specifically here, glutamine). Ok, I thought that was cool…

2. The problems are that first you have to somehow absorb it; with our great digestive system breaking stuff down all the time, it’s hard to absorb things in the form you’d like in this case. Secondly, if it gets in, you have to hope it will be actually USED instead of just broken down for parts. PS- this is main mistake body builders make with protein consumption; they often consume muscle (or meat) imagining that this will get used to make more muscle. The problem is—well, this is a topic for another day!

3. Of note- a lot of the huge effects seen “in vitro” or in a test tube with human bone and cartilage tissue, had doses of glucosamine that were insanely higher (up to 2000 times more!) than the amount you can actually get going on after taking 1500 mgs of glucosamine.

4. There’s recently been some pretty awesome in-vitro (test tube) studies that show, in human cartilage cells essentially injected with inflammation, chondroitin sulphate has an anti-inflammatory effect that is different than glucosamine, and also that it may prevent the breakdown of tissue. Yay! Does it work in us? Maybe!  Stay tuned.

 

The SOURCES:

A clear and objective review of  recent evidence for glucosamine, in-vitro, in-vivo, plus meta-analyses:

Henrotin, Y., Mobasheri, A., & Marty, M. (2012). Is there any scientific evidence for the use of glucosamine in the management of human osteoarthritis? Arthritis Research and Therapy, 14, 201.

Study at Rotta Pharmaceuticals showing (surprise!) their drug works. But like I said, there is other evidence apart from their stuff that makes this not as sketch.

Rovati, L.C., Girolami, F., & Persiani, S. (2012). Crystalline glucosamine sulfate in the management of knee osteoarthritis: efficacy, safety, and pharmacokinetic properties. Therapeutic Advances in Musculoskeletal Disease, 4(3), 167-180.

Wandel et al. (below) found significant benefit with glucosamine in general compared to placebo. However, when just glucosamine hydrochloride studies were analyzed there was no statistically significant benefit. When just glucosamine sulfate studies were analyzed, there was statistically significant benefit

Wandel S, Juni P, Tendal B, Nuesch E, Villiger PM, Welton NJ, et al. (2010). Effects of glucosamine, 
chondroitin, or placebo in patients with osteoarthritis of hip or knee: network meta-analysis. BMJ, 341, c4675.

In-vitro study on Glucosamine Sulfate. Again, this only is a good reason to TRY real-life studies. It doesn’t mean it will work. But the test tube studies can also help illuminate mechanism, which is very powerful, both for understanding how other drugs may be useful as well for suggesting as what form and mode of administration glucosamine might be most efficacious.

Kapoor, M., Mineau, F., Fahmi, H., Pelletier, J.P., & Martel-Pelletier, J. (2012). Glucosamine sulfate reduces prostaglandin E(2) production in osteoarthritic chondrocytes through inhibition of microsomal PGE synthase-1. Journal of Rheumatology, 39(3), 635-644.

An in-vitro study of chondroitin sulfate. You know the deal. Test tubes=helpful! Not necessarily translatable.

Calamia, V., Lourido, L, Fernandez-Puente, P., Mateos, J., Rocha, B., Montell, E. Verges, J., Ruiz-Romero, C., & Blanco, F. (2012). Secretome analysis of chondroitin sulfate-treated chondrocytes reveals anti-angiogenic, anti-inflammatory and anti-catabolic properties. Arthritis Research and Therapy, 14, R202.

An INJECTION in-vivo study—a nice and exciting pilot that suggests a better mode of administration for these drugs (compared to swallowing pills).

Henrotin, Y., Hauzeur, J, Bruel, P, & Appelboom, T. (2012). Intra-articular use of a medical device composed of hyaluronic acid and chondroitin sulfate (Structovial CS): effects on clinical, ultrasonographic, and biological parameters. BMC Research Notes, 5, 407.

These guys’ own words on their conclusions in the review below: Eight primary trials were included with a duration of at least 12 months. There was evidence of statistically significant improvements in joint space loss, pain and function for glucosamine sulphate; however, the clinical importance of these differences was less clear. In two studies of glucosamine sulphate, both funded by the manufacturer (Rotta, Italy) of an oral powder product, the need for knee arthroplasty was reduced from 14.5% to 6.3% at 8 years’ follow-up. For other preparations of glucosamine, chondroitin and combination therapy, there was less evidence to support a clinical effect. There was evidence from biological studies to support the potential clinical impact of glucosamine sulphate. For other preparations, the evidence base was less consistent (chondroitin) or absent (glucosamine hydrochloride).

Black C, Clar C, Henderson R, MacEachern C, McNamee P, Quayyum Z, Royle, P., & Thomas, S. (2009). The clinical effectiveness of glucosamine and chondroitin supplements in slowing or arresting progression of osteoarthritis of the knee: a systematic review and economic evaluation. Health Technology Assessment, 13(52), DOI: 10.3310/hta13520.

The dog study I talked about. A cool read!

RidiculousGupta, R.C., Canerdy, T.D., Lindley, J., Konemann, M., Minniear, J. Carroll, B.A., Hendrick, C., Goad, J.T., Rohde, K., Doss, R., Bagchi, M., & Bagchi, D. (2012). Comparative therapeutic efficacy and safety of type-II collagen (uc-ii), glucosamine and chondroitin in arthritic dogs: pain evaluation by ground force plate. Journal of Animal Physiology and Animal Nutrition, 96(5), 770-777.

A VERY small dog study (only 3 beagles!) but it showed some cool pilot results implying that glucosamine HCL could promote cartilage regeneration. WAY too small and short to assume anything. But cool cuz it’s about 3 beagles.

Osaki, T., Azuma, K., Kurozumi, S., Takamori, Y., Tsuka, T., Imagawa, T., Okamoto, Y., & Minami, S. (2012). Metabolomic Analyses of Blood Plasma after Oral Administration of D-Glucosamine Hydrochloride to Dogs. Marine Drugs, 10, 1873-1882.

 

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5 responses

  1. OK, so this is a sample of n=1 but in my personal experience when I was doing a lot of long distance running I found glucosamine + chondroitin felt liked it worked for cranky knees. However, I wasn’t eating ANY fat in those days (misguided, I know) and these days I have a slightly higher fat diet (avos, eggs, seeds, nuts, olive oil and even a bit of butter and coconut oil) and my knees are fine without supplementation. (Although I’m not running the miles I used to). Anecdotal evidence I know, but that’s been my personal experience on sore knees!

    • Awesome, Sarah! Thanks so much for sharing! Interesting that your change in diet (or fewer miles) allowed your knees to be happy without the supps. So glad that your knees are doing well, now!

  2. Glucosamine and Chondroitine are well known supplement for different purpose, mostly for arthritis patients. I am impressed of your way of representation on the topic but every medicine in market has their own negative points. Most of the time these two things works with most people and sometime fails with few people that doesn’t mean this is not a good curing process. It’s all depends upon percentage of ingredients packed in right amount and patient is taking it with right amount.

    Ruth

    • Excellent point, Ruth! You are so right in that something does not have to work for everyone for it to be legitimately effective. Thank you for your insight, it’s an important perspective.

      Marily

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