Sep 17 2010

No Benefit from Glucosamine and Chondroitin

Just published in the British Medical Journal (BMJ), a meta-analysis of glucosamine and chondroitin for osteoarthritis involving 10 trials and 3803 subjects – showing no benefit for either, separately or in combination. These supplements, like so many that have gone before them, are little more than expensive placebos.

Glucosamine and chondroitin are among the most popular supplements, and the most popular for osteoarthritis. The theory is that these substances, which are made naturally in the body, are used to build cartilage, the smooth substance that lines joints and breaks down with age and wear and tear. This theory, however, has always been weak. It suffers from the same faulty assumptions of many supplements – that if little is good, more is better; that dietary sources of these substances are inadequate and that the biological processes that use them are limited by availability of this raw material. None of these assumptions are likely valid.

First, for many substances in the body (vitamins, minerals, etc.) there is likely an optimal range of intake, not a linear relationship where more is always better. This is generally what we find when we examine biological systems. So taking supplements to increase the amount of a nutrient is as likely to cause harm as good. This point may not be as relevant to building block nutrients like glucosamine and chondroitin as to cofactors like most vitamins, however.

More relevant, likely, are the latter two points, which both must be true in order for such a supplement to be helpful. In other words – in order for chondroitin or glucosamine to work as claimed – by providing more raw material for the repair of cartilage, then it must both be true that not enough of these materials is derived from the diet and the limiting factor to cartilage health and repair is the availability of these building blocks. But neither of these assumptions is proven, or perhaps even likely.

In developed nations these nutrients are unlikely to be lacking in the diet. Again – more is not necessarily better, and once as adequate supply is obtained from the diet supplementing would have no benefit. Further, break down of cartilage occurs with use. The ability to repair cartilage at a sufficient rate to balance wear and tear may not be limited by the availability of raw material. It may be limited by other biological factors. So supplements would not even be addressing the problem.

However, the supplement industry has built its market on the rather simplistic assumptions above. They are sometimes true, but such determinations should be based upon evidence, not assumptions. Salt is fortified with iodine and milk with calcium to address common nutrient insufficiencies. We may be facing a relative insufficiency of vitamin D that needs to be addressed. And there are many specific situations in which specific supplements are beneficial, like folate for pregnancy. But this should not lead to the casual assumption that supplements are always good, or that they can address any specific problem.

Getting back to this study, the authors found no statistical difference between glucosamine and chondroitin alone or in combination and placebo, either with subjective improvement or with objective findings, such as joint space narrowing. They also noted that supplement industry-sponsored studies showed a greater trend toward a positive result than did independent studies (the same effect has been found for pharmaceutical company-sponsored studies, so this should be no surprise).

They also found that there was no direct harm from the supplements, and so while they concluded that the NHS should not fund the supplement, they also said that if patients want to give it a try that was reasonable. I found that soft approach to be wanting, however. There may be no direct medical harm, but there is certainly financial harm and possible indirect harm from neglecting other interventions that may be more effective. The BBC notes that these supplements were a £1.3bn market in 2008. That is a lot of wasted resources. That is money that cannot be spent on other health care interventions that may be actually effective. People with limited resources who are deciding where to spend their limited health care dollars (or pounds) will be harmed if they are wasting their money on useless supplements.

Conclusion

The data has been coming back negative on glucosamine and chondroitin for years – this meta-analysis is just the capper. For example, the recent GAIT trial of glucosamine and chondroitin for knee arthritis found no benefit.

As a clinician, what to do with this evidence is clear. There is no benefit from these supplements, so I would recommend not to take them. Don’t waste your money and effort. But as a society the question is a bit trickier. What we largely have now is a situation where supplements can be marketed with implied health claims prior to evidence of actual efficacy. Over and over the public wastes billions of dollars on useless supplements, until the evidence comes in showing that they are ineffective, then the markets shrink but do not go away. Meanwhile, the supplement industry is on to the next miracle supplement. This does not seem like an effective system of regulation to me.

If the public wishes to err on the side of freedom vs quality control and consumer protection, so be it. But I don’t think this is a common popular choice. The public mostly believes that health products are regulated, and claims cannot be made without evidence, but in most countries this is simply not true. The supplement industry has successfully lobbied for relaxed regulations – to benefit them. Consumer protection advocates seem to be asleep at the switch.

Perhaps as we enter an era of greater attention to the cost of health care, more attention will be paid to this issue. We’ll have to wait and see.

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9 responses so far

9 Responses to “No Benefit from Glucosamine and Chondroitin”

  1. eeanon 17 Sep 2010 at 1:39 pm

    They add calcium to milk? Say it isn’t so.

  2. zenseion 22 Sep 2010 at 8:06 pm

    I had Bi-Lateral hip replacement in March of 2010, leading up to the time of the surgery my GP was suggesting Glucosamine and Chondroitin for “relief” leading up to the surgery, I declined, from talks I’ve had with her I believe that she knew it was useless and was hoping for a placebo effect, my surgeon Dr Richard Rothman on the other hand said no, don’t bother and after looking up his pub med contributions I absolutely believed him.

    I would love to see a Dr Novella consumer reports on modern hip and knee replacement systems, my guy helped design the Stryker system I received and I’m hoping it’s my last, recalls can be a bitch don’t you know :)

  3. HHCon 22 Sep 2010 at 9:02 pm

    I can appreciate the problems associated with hip and knee pain and the British study recommending against supplements. Many patients may require surgery. However, I was recommended to use an over-the-counter supplement for low back pain in 1998. According to MRIs, I healed all herniated discs in my low back without surgery.

    My physican gave me an official medical document in 1998 which I was required to show the pharmacist to receive the quality and quantity (dosing) recommended of glucosamine with chondroitin sulfate. He stated that numerous reports in the scientific literature suggest its benefit though no published prospective research studies demonstrated the effectiveness of the supplement. Side effects are very low; the body produces these micronutrients.

    My case results indicate drug effectiveness.

  4. eiskrystalon 29 Sep 2010 at 11:37 am

    Another issue with useless supplements that I haven’t seen mentioned before is that anything “new” on the market that does work is going up against a solidly marketed, probably well funded and already established, if useless placebo. This will have direct impacts on availability and recommendation of the newer drug in the market. Thus continuing unnecessary misery.

  5. zorrobanditoon 29 Sep 2010 at 12:33 pm

    Some of the ailments for which these supplements are recommended are intractable, and not all can be cured by joint replacement. (Luckily for me, what when wrong in my case was my knee. They sawed out the old one, popped in a new one made of titanium and plastic, and voila! condition cured.)

    But if what hurts cannot be summarily thus fixed, I see no harm in the placebo effect so long as the supplements do no other harm. If people feel better they feel better: is this such a terrible idea??

  6. zorrobanditoon 29 Sep 2010 at 1:09 pm

    Has any serious work been done on the placebo effect?

    Here we have a “treatment” which is cheap, has no side effects, and which seems to produce good results in a substantial proportion of the population (varying as to the disorder). How wonderful if we could harness this!

  7. tmac57on 29 Sep 2010 at 1:57 pm

    “Consumer protection advocates seem to be asleep at the switch.”

    The Sept. 2010 issue of Consumer Reports lists Glucosamine Sulfate as “Likely effective treatment for reducing symptoms of the knee.Might also help slow progression of osteoarthritis.”

    That was from a list of 11 supplements to consider that they published.

    I wished that they had referenced the study that led them to that conclusion.I usually trust their health advice,as they are fairly conservative and careful,but now I am conflicted.

  8. Calli Arcaleon 29 Sep 2010 at 2:21 pm

    zorrobandito: yes, studies have looked into the placebo effect. Aside from the ethical quandary (to knowingly prescribe a placebo, you pretty much have to lie about it to the patient), studies have found these effects:

    * placebo effects generally do not last a long time; for a chronic condition, within a few weeks it isn’t working as well

    * improvement is usually very modest

    * objective measures seldom improve, and when they do, they are things like better flexibility due to walking more which in turn comes from feeling that they’re going to get better soon; a placebo may not be the best way to achieve this

    * when mainstream physicians prescribe a placebo, it isn’t always an inactive drug; probably the most common one is antibiotics. These active drugs are sometimes prescribed by doctors who know they are useless for the condition and who know they have adverse side effects, but who are relying on the placebo effect to give the patient some peace of mind. This is definitely an abuse of patient trust, in my opinion.

    * most interesting of all, placebo effectiveness seems to correlate with the complexity and price of the procedure — this magnifies the ethical quandaries, because to make it work better, you have to jack up the price, and then you’re lying and profiting from it.

    Here’s my opinion: if a placebo effect helps somebody, that’s great. But if doctors knowingly prescribe them, they have embarked on a dangerously slippery slope with respect to medical ethics. We have to trust them to be truthful with us, and that pretty much rules out the use of placebos.

  9. zorrobanditoon 01 Oct 2010 at 11:17 am

    Thank you Calli, this is very interesting and helpful.

    We have an adult son who is mentally ill, and who is taking a cocktail of various psychoactive drugs. I belong to an on-line forum for parents of such children, and we have all noticed that when a new drug is prescribed the patient seems at first to improve, but this improvement typically lasts only a few weeks, and then the patient returns to his or her former condition, until yet another drug is added to the mix. Rinse and repeat. (That is one reason my son is taking so MANY drugs. I am not convinced that any of them are doing any good in his case.)

    We are not doctors or scientists on this parents’ forum, but we decided that what we had here at least in many cases is another example of the placebo effect. Your analysis supports that conclusion.

    There is some data that some of these psychiatric drugs do some good in some cases, but basically so far as I can figure out by reading journal articles, the science behind them – the details about just exactly why and how they work or don’t work – is iffy at best, and it seems likely to me that some or most of them don’t work very well at all. Nevertheless, these substances are what we have, until the working of the brain is understood a whole lot better than it is so far.

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