[Betsy Iole]

Dr. David Ramey is an equine veterinarian and a tireless advocate for evidence-based veterinary medicine. He is the author of numerous publications, including Complementary and Alternative Veterinary Medicine Considered (2004), Consumer's Guide to Alternative Therapies in the Horse, and the equine series of Concise Guides. The following is crossposted from the ALTVETSKEPT-L e-mail list, with permission from Dr. Ramey.

  I keep promising myself to write a summary of why I
think glucosamine is worthless, mostly because I find the
claims so inflated and aggravating.  Here goes (with
apologies to those who don't find the subject of interest).

    1.  At least in North America, glucosamine is an
over-the-counter dietary supplement and preparations made by different manufacturers have been shown to vary (including one study on horse products by your truly).  There may not be much glucosamine in your glucosamine.

    2.  The last four consecutive well-conducted clinical
trials have all shown no effect.  This is in contradistinction to the first 20-some, which suggested an anti-inflammatory and, in a few, a chondroprotective effect.  Curiously, the last four trials were independently funded, whereas the first 20-some were funded by the glucosamine industry.

    3.  Recent in vitro studies show that glucosamine does
not stimulate synthesis of chondroitin sulfate (Mroz and
Silbert, Biochem J 2003; 376:  511 - 515).  In fact, in
higher concentrations, it inhibits CS synthesis.

    4.  At the doses given, even if completely absorbed,
equally distributed and not metabolized, it is extremely
unlikely that relevant concentrations could reach the joint
(details of calculations in the Mroz paper).

    5.  It's questionable whether glucosamine even gets into
the systemic circulation following oral ingestion.  Most of
it gets taken to the liver where it gets metabolized or
incorporated into glycoproteins.  This is confirmed in
humans, dogs and rats (references available).

    6.Glucosamine is not ordinarily available in the
circulation as a source of components for synthesis of
cartilage matrix.  Cartilage uses glucose for this purpose.
Glucosamine is NOT essential for the biosynthesis of
cartilage molecules.

David Ramey, DVM

 

[TrudiRose]

Darn! You won't believe this, but I JUST spent $25 for a big bottle of glucosamine! TODAY!!! My basset Norton has been limping for the past few weeks, and the vet couldn't find anything wrong. Someone had posted that their basset was limping and the vet recommended Fortiflex, which is glucosamine. So that was in my mind. Then today at the dog run, a complete stranger said to me, "Your basset seems to be limping. You should give him glucosamine." So then I went to my local pet food store, and asked the owner about it, and she said yes, it was great for promoting healthy cartilage and bone.

So I paid $25 for this stuff, and gave it to my basset, and felt really good that I was doing something that would help his limp. Then I sign on here and find out it's a crock of you-know-what! Sigh..back to the drawing board... (But thanks for posting the info, Betsy!)

 

[Betsy Iole]

Has your vet mentioned the possibility of panosteitis (pano)? This condition produces lameness that may shift from limb to limb. It affects basset puppies, usually males. It's treated with crate rest and pain relievers, and may be exacerbated by vigorous activity.

Here are some links to more information about panosteitis.

Panosteitis, Eosinophilic Panosteitis (VetCentric.com)

Panosteitis (Dr. Nicholas Trout, PetPlace.com)

Panosteitis (Daniel A. Degner, DVM)

 

[biscuit]

I've been wondering if glucosamine's positive effects in people might be like a placebo effect.

I got some glucosamine a few months ago - I injured a hip when I was a kid and have developed bursitis in that hip and am having all kinds of crazy stuff going on as a result - including some arthritis kind of stuff.

But nada. Now I have positive effects from aspirin and yoga has been really helpful - and oddly, eating more fat seems t be helpful.

But not a thing from the glucosamine. Which makes me wonder if it's not a placebo effect for people.

 

[winnieslo]

I've never used it...for me or my arthritic dogs..asprin seems to do just fine. Because I'm a mom to a diabetic hound I have been very interested in the studies that suggest it somehow interfers with insulin action causing an increase in blood sugar

 

[biscuit]

 interfers with insulin action causing an increase in blood sugar  
 

Oh dear. I wonder if this is true.

I'm horribly hypoglycemic and have strong family history of diabetes. Coincidental to taking the glucosamine, my blood sugar shot up. Really freaked me out. I thought it shot up because I'd increased my carbs because I was quitting smoking (again) (I quit a lot, like every few weeks )

 

[Betsy Iole]

Good point about impaired glucose metabolism, Judy.

Biscuit, in medicine, there's the old saying that without treatment, 80% of complaints get better by themselves, 10% stay the same and 10% get worse. Or something like that. So, if someone (not naming names

[ January 15, 2004, 05:48 PM: Message edited by: Betsy Iole ]

 

[TrudiRose]

That's really odd, because my mother-in-law is a diabetic, and SHE takes glucosamine. Why would a diabetic be prescribed a medication that interferes with insulin.

 

[biscuit]

HOWEVER ... this is my very basic understanding. I'm hypoglycemic and always have been, which is sometimes but not always a precursor of diabetes. My sister, who was never gypoglycemic, is Type 2 diabetic, as were other relatives of mine. The Type 2s vary among themselves but tend to work differently than me.

I can't quite remember how it works, but I'm apparently even more sugar sensitive than my sister (who IS diabetic) but I'm not diabetic, I'm hypoglycemic.

So, long way around to say ... glucosamine may not be problematic for all people with blood sugar problems, but may be problematic for some.

 

[Mikey T]

gloucosomine in all it varied forms each touted as better than the next is general coupled with chondroitin sulfate in OTC supplements. Chondroitin Sulfate has been more extensively studied than gloucosomine and from the limited amount I have seen the results have been positive.

Results of a multicenter study of chondroitin sulfate (Condrosulf) use in arthroses of the finger, knee and hip joints"The decrease of pain was revealed to be statistically significant; serious side effects were not to be observed during the study. At the beginning of the observation period patients suffered from overall severe pain, and therefore the decrease of pain down to a level, which could not have been achieved by NSAID therapy alone to a greater extent, is of special interest. The results of this trial represent the first office based Austrian data on CS-therapy. In conclusion it could be demonstrated that a significant reduction of the daily NSAID consumption was possible by concomitant CS-therapy, without the risk of deterioration of the patients' symptoms. The 97% compliance does not give evidence for drop-out bias. Moreover, the results of this trial are comparable to other international double-blind, in part placebo-controlled studies, concerning CS-therapy, indicating beneficial results in the treatment of osteoarthritis."

Glucosamine, Chondroitin Sulfate Clinical Trials

Six of the 15 trials involved glucosamine and nine used chondroitin. The team used only trials of four or more weeks in duration because of evidence that it may take several weeks for the compounds to have a therapeutic benefit. Only one of the 15 trials was completely independent of manufacturer support.

The team's analysis of the trials had two key facets: a quality assessment to evaluate each of the clinical trials and a meta-analysis, which enabled them to integrate the data from different trials. The trials studied had many methodological flaws and biases, including those that tended to inflate the benefits of the compounds. The team was also concerned that trials having small or negative effects might not have been published, but after contacting study authors and other experts, they could locate no unpublished negative results.

Based on data from the trials, the researchers calculated an overall \"effect size\" for the two compounds: the figure 0.2 is considered a small effect; 0.5, moderate; and 0.8, large. The researchers calculated an effect size for glucosamine of 0.44 and for chondroitin sulfate of 0.78, but reported that these values \"were diminished when only high-quality or large trials were considered.\"

The study was published in the March 15, 2000, issue of the Journal of the American Medical Association (JAMA). Dr. McAlindon recommends that additional, rigorous, independent studies be done of these compounds to determine their true efficacy and usefulness.

Has any one seen any results from the NIH study

Effects of Oral Glucosamine on Insulin and Blood Vessel Activity in Normal and Obese People
"This study is currently recruiting patients."

 

[Betsy Iole]

Hardly inspires confidence, does it? Poorly designed studies, small samples, subjective endpoints. Studies that evaluate pain as an endpoint aren't all that useful--more objective endpoints such as functional and radiologic assessment are more informative. The meta-analysis is entertaining..."If we include the crappy studies, then we have something to report. If we include only the good studies, then we don't have anything to publish."
:roll:

 

[biscuit]

Only one of the 15 trials was completely independent of manufacturer support.
 

And of course, the manufacturers have no stake in the outcome, do they?

 

[shallhb]

Biscuit,
My husband claims eating more fat is helpful for most all his ills, , including feeling cold, feeling tired, feeling depressed...Of course, if the fat is embedded in a chocolate bar, all the better.

 

[Dean]

All I know is glucosamine helped me with my knees, and my old field basset Candy (11 1/2yrs) is much more active since she started on glucosamine. I would not hesitate to reccommend using it for any arthritis type problem and even as a supplement for older dogs before there is a problem

 

[murraysmom]

I have to weigh in on this one.Our 15 year old daschund Hansel was a mess last summer: his left hip joint, which was severly injured when he was a puppy, had deteriorated to the point where he didn't want to walk anymore. The vet put him on Cosequin, which combines chondroitin sulfate, glucosamine HCL and manganese ascorbate. He has been on it since July and we have seen steady improvement. He can get up our back steps again and even tries to play with Murray. I know this is just another piece of anecdotal evidence, but..I have to credit this stuff with really helping him.

[ January 16, 2004, 06:36 PM: Message edited by: murraysmom ]

 

[Mikey T]

"Studies that evaluate pain as an endpoint aren't all that useful--"

Aren't the most consumed and prescribed medications for osteoarthritis - pain relievers, without any possibility of joint repair? There are currently studies going on to see if Nsaid's while relieving pain actual contribute to joint degradation or the increased degradation associated with Nsaid's is because the joint is used more. A simple pain relief mechanism effective as Nsaids that does not have increased joint degradation, is a major advance in the treatment of arthritis and perhaps other causes of joint pain.


It is important to point out that Glucosamine has frequently become a generic term for A natural pain-reliever for joint pain. Most time any concoction referred to as Glucosamine also contains chondroitin Sulfate and some times MSM. It could be 1, some, all or none, of these products actual produces a scientifically verifiable result but when used in some combination new. This require quite extensive testing of all the permutations that won't be completed for some time.

Most of the studies have been of short duration also so other than pain it may not be possible to see measurable improvement or decline of the joint with use of the product. The NIH is conducting a phase three study of glucosamine, chondroitin sulfate both separately and combined against a placebo and celebrex as controls. When completed and published it should provide a clear understand of the value of these product

There are also various forms of Glucosamine such as Glucosamine HCL and Glucosamine Sulfate. Each with it's own proponents which just adds further confusion.

I have always found it curious the criticism of test/studies on alternative therapy's as flawed simply because they were conducted sponsored i.e. paid for by the manufacture of the product. Correct me if I'm wrong but isn't ever prescription drug ever OK'd by the FDA be done so either exclusively or mostly based on studied conducted, sponsored, paid for by the drug company? Yet we don't seem to have a problem with that.

 

[biscuit]

orrect me if I'm wrong but isn't ever prescription drug ever OK'd by the FDA be done so either exclusively or mostly based on studied conducted, sponsored, paid for by the drug company? Yet we don't seem to have a problem with that.
 

Um, you may not have a problem with it but I do.

Now, I believe in the efficacy of many pharmaceuticals --- but not all. My tendency is to be particularly suspicious of prescription drugs tested only by facilities and through grants provided by the producer of those drugs, and those which are heavily pushed but lack any particular track record.

In fact, it's my belief it's wise to be suspicious of any results from any testing on anything when that testing is associated in any way with vested interests.

I would comment further on the testing itself but I hate statistics, etc., just enough to get a headache even thinking about it.

Furthermore, it isn't a diametric opposition between natural approaches and medical approaches, except insofar as individuals make it so. For example, my own doctor has advised me to take specific vitamins and minerals because of their proven effects.

These things always become problematic when big $$$ is involved, however, no matter which side of the fence you sit on. So maybe the point is buyer beware, be smart about things and know what you're doing. Natural isn't always better - or natural, for that matter.

 

[Betsy Iole]

Not saying that pain relief isn't important, just that it's not possible to standardize and measure objectively, with instruments, for example. The perception of pain varies greatly among individuals and isn't uniform, and its characterization is imprecise. However, other parameters that are often correlated with pain relief, like improved joint function, range of motion, weight-bearing capacity, etc. can be measured objectively and precisely. Studies that measure these types of outcomes can be repeated and verified with greater confidence, and provide more useful information.

[ January 16, 2004, 08:24 PM: Message edited by: Betsy Iole ]

 

[Betsy Iole]

Biscuit writes

Furthermore, it isn't a diametric opposition between natural approaches and medical approaches, except insofar as individuals make it so. For example, my own doctor has advised me to take specific vitamins and minerals because of their proven effects.

That's exactly right! It's about what works, based upon sound evidence. Doesn't matter where or how it originated, if it's shown to be effective.

Edited to add a link to FDA's requirements for financial disclosure by clinical investigators, which reads, in part,

Sec. 54.1.b Purpose

...FDA may consider clinical studies inadequate and the data
inadequate if, among other things, appropriate steps have not been taken
in the design, conduct, reporting, and analysis of the studies to
minimize bias. One potential source of bias in clinical studies is a
financial interest of the clinical investigator in the outcome of the
study because of the way payment is arranged (e.g., a royalty) or
because the investigator has a proprietary interest in the product
(e.g., a patent) or because the investigator has an equity interest in
the sponsor of the covered study. This section and conforming
regulations require an applicant whose submission relies in part on
clinical data to disclose certain financial arrangements between
sponsor(s) of the covered studies and the clinical investigators and
certain interests of the clinical investigators in the product under
study or in the sponsor of the covered studies. FDA will use this
information, in conjunction with information about the design and
purpose of the study, as well as information obtained through on-site
inspections, in the agency's assessment of the reliability of the data.

No sure what, if any, effect this will have on your feelings on this subject.


[ January 16, 2004, 08:20 PM: Message edited by: Betsy Iole ]

 

[Mikey T]

for those interested links to studies on Glucosomine with other than pain as an endpoint
All done after 1998 and the meta-study by Timothy E. McAlindon, DM

Long-term effects of glucosamine sulphate on osteoarthritis progression: a randomised, placebo-controlled clinical trial.
J. Reginster, R. Deroisy, L. Rovati, et al. The Lancet;357:251-256 (January 27, 2001). [Correspondence: Dr. Jean-Yves Reginster, Bone and Cartilage Metabolism Research Unit (WHO Collaborating Center for Public Aspects of Osteoarticular Disorders), University of Liege, B-4020 Liege Belgium.

"FINDINGS: The 106 patients on placebo had a progressive joint-space narrowing, with a mean joint-space loss after 3 years of -0.31 mm (95% CI -0.48 to -0.13). There was no significant joint-space loss in the 106 patients on glucosamine sulphate: -0.06 mm (-0.22 to 0.09). Similar results were reported with minimum joint-space narrowing. As assessed by WOMAC scores, symptoms worsened slightly in patients on placebo compared with the improvement observed after treatment with glucosamine sulphate. There were no differences in safety or reasons for early withdrawal between the treatment and placebo groups."

Glucosamine Sulfate Use and Delay of Progression of Knee Osteoarthritis
A 3-Year, Randomized, Placebo-Controlled, Double-blind Study Karel Pavelká, MD, PhD; Jindriska Gatterová, MD; Marta Olejarová, MD; Stanislav Machacek, MD; Giampaolo Giacovelli, PhD; Lucio C. Rovati, MD Arch Intern Med. 2002;162:2113-2123.


And an explanation why glucosamine sulfate can work but not all glucosamines and some fators that might effect clinical trials of GS that have not been fully understood
Sulfate could mediate the therapeutic effect of glucosamine sulfate

These results do not prove that glucosamine sulfate improves osteoarthritis, but considered with other data, they do provide a plausible biochemical mechanism for its reported beneficial effects. This hypothesis is clinically relevant because it predicts that nonsulfate salts of glucosamine will be ineffective and that renal function, diet, and concurrent acetaminophen therapy could confound clinical trials of this therapy

[ January 16, 2004, 09:09 PM: Message edited by: Toughynutter ]