Glucosamine and Chondroitin are no help

From McDougall's newsletter Sept 2010:

Glucosamine and Chondroitin Do Not Help Arthritis

Effects of glucosamine, chondroitin, or placebo in patients with osteoarthritis of hip or knee: network meta-analysis by Simon Wandel, published in the September 22, 2010 issue of the British Medical Journal concluded, “Compared with placebo, glucosamine, chondroitin, and their combination do not reduce joint pain or have an impact on narrowing of joint space. Health authorities and health insurers should not cover the costs of these preparations, and new prescriptions to patients who have not received treatment should be discouraged.”¹ They went on to say, “Our network meta-analysis of all 10 available large scale patient blind randomised trials in 3803 patients with knee or hip osteoarthritis showed no clinically relevant effect of chondroitin, glucosamine, or their combination on perceived joint pain.”

Comment: The most common form of arthritis afflicting humans is osteoarthritis, often referred to as degenerative arthritis, because the joints slowly deteriorate as a result of “normal wear and tear associated with aging.” Doctors commonly advise people to lose weight, especially if they have disease of the joints of the lower extremities, and to avoid prolonged and strenuous use of the affected joints. Non-steroidal anti-inflammatory drugs (NSAIDs), such as Motrin and Advil, are commonly taken for pain relief. Paradoxically, these NSAIDs also accelerate the loss of cartilage in the joints and delay bone healing.^2,3 This then worsens the osteoarthritis.

Taking cartilage constituents, such as glucosamine and chondroitin, has been recommended for osteoarthritis, and many studies support its use. In my April 2004 newsletter I recommended glucosamine for arthritis based on the research I had available then. However, in the past six years I can recall no patients telling me of pain relief or improved mobility that they have achieved from taking this cartilage supplement. Therefore, I am changing my recommendation. Because of the low cost and few side effects, you may still wish to do your own personal trial with glucosamine, but I can no longer tell you that I believe it is beneficial. (I reserve the right to change my opinions on all medications and supplements because the research is always changing and most of it cannot be trusted as reliable in the first place. In case you are wondering, I will not be changing my opinion on the best diet for you.) I have never recommended chondroitin because it is derived from cow cartilage. This cow matter may contain infectious microbes, such as those that have been found to cause mad cow disease.⁴

The overall benefits of a healthier diet and weight loss for osteoarthritis are well established.⁵ Three-hundred and sixteen older, overweight or obese, sedentary men and women with x-ray evidence of knee osteoarthritis were randomly assigned to one of four 18-month treatments: healthy lifestyle control, diet-induced weight loss, exercise, and diet plus exercise. Those who lost weight due to an improved diet showed a decrease in inflammation measured by a variety of tests. Exercise did not seem to make a positive difference in this study.

I recommend people with osteoarthritis take very good care of their diseased joints. This means in many cases that they should avoid certain exercise. Someone with disease of their hips, knees, or ankles should not be running, and maybe should limit their walking. Instead, exercise for them should be bicycling, swimming, and/or rowing. The best diet for weight loss and overall joint health is the McDougall diet.

1) Wandel S, J¸ni P, Tendal B, N¸esch E, Villiger PM, Welton NJ, Reichenbach S, Trelle S. Effects of glucosamine, chondroitin, or placebo in patients with osteoarthritis of hip or knee: network meta-analysis.BMJ. 2010 Sep 16;341:c4675. doi: 10.1136/bmj.c4675.

2) Vuolteenaho K, Moilanen T, Moilanen E. Non-steroidal anti-inflammatory drugs, cyclooxygenase-2 and the bone healing process. Basic Clin Pharmacol Toxicol. 2008 Jan;102(1):10-4.

3) Ding C, Cicuttini F, Jones G. Do NSAIDs affect longitudinal changes in knee cartilage volume and knee cartilage defects in older adults? Am J Med. 2009 Sep;122(9):836-42.

4) Mad cow disease and chondroitin sulfate. Harv Health Lett. 2001 May;26(7):3.

5) Nicklas BJ. Diet-induced weight loss, exercise, and chronic inflammation in older, obese adults: a randomized controlled clinical trial. Am J Clin Nutr. 2004 Apr;79(4):544-51.

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The comments above are by Dr. McDougall. I notice that in his recommendations he says "exercise did not seem to have a positive effect in this study". Meaning exercise alone did not reduce pain. 

He goes on to recommend for and against certain types of exercise - swim, don't walk, for example. Take care of your joints.  And eat a low-fat vegan diet. I already eat a whole-foods vegan diet so do not believe that the inflammation in my joints comes from my food (I have done some limited tests). I do tend to stray from low-fat from time to time, sorry to say.

I think certain types of exercise can in fact reduce pain. But the exercises do need to be specific to the source of pain, which is the type that I am doing now. I have noticed some differences in the pain - both in the intensity and the length of time I am in pain, and I hope to find some specific changes when I go to the physical therapist tomorrow.

Another trip, another trial

I flew to Pensacola last Friday, from Burbank. I spent the weekend without my glucosamine (I forgot to pack it) and I didn't do the arthritis exercises (lazy lazy lazy!). But I did spend a fair amount of time in Pensacola standing and walking around. So the trip was a bit of a trial for my knees.

And I'm doing all right. I think the hardest thing for my knees is driving. Whenever I make long trips in the car I feel it that night. But it isn't awful.

Overall, the improvements in my knees seem to be holding, even when I fall off the routine.

Bike again

I took my bike out on the easy ride again, Orcutt-Tank Farm-Broad-Orcutt. This time I got off the bike three times - the first at the corner of my street and Orcutt, just to be safe turning the corner, the second when I slid into a gear that wasn't a gear and it froze up on me, the third when I walked it across Industrial Way to avoid traffic while getting back to Broad. I didn't stop for a drink or to buy anything.

My knee felt less pain this time than the last. I suspect the weather contributed, even though I have yet to find a real correlation, personally, between weather and how my knee feels. Yet it was hot and there was little wind, and those two factors might have meant less pressure on the knee joint. It was a nice feeling in any case. I even made the effort to use a little more muscle power. Just a wee bit. It's still a wimp's ride but I'm not proud and I don't care. It's working for me.

I think by this time I can say with near certainty that there has indeed been a change in my knee. It's as if the bottom level, the bad pain, the problem discomfort, has either gone altogether or shows itself very rarely now. This has been consistently so for at least two months. I suspect the glucosamine has done some work repairing the joint.

Glucosamine

The story from Wikipedia, admittedly not a perfect source but probably adequate for my purposes:

Oral glucosamine is commonly used for the treatment of osteoarthritis. Since glucosamine is a precursor for glycosaminoglycans, and glycosaminoglycans are a major component of joint cartilage, supplemental glucosamine may help to rebuild cartilage and treat arthritis. Its use as a therapy for osteoarthritis appears safe, but there is conflicting evidence as to its effectiveness.


Use
A typical dosage of glucosamine salt is 1,500 mg per day. Glucosamine contains an amino group that is positively charged at physiological pH. The anion included in the salt may vary. Commonly sold forms of glucosamine are glucosamine sulphate and glucosamine hydrochloride. The amount of glucosamine present in 1500 mg of glucosamine salt will depend on which anion is present and whether additional salts are included in the manufacturer's calculation. Glucosamine is often sold in combination with other supplements such as chondroitin sulfate and methylsulfonylmethane.

Glucosamine is a popular alternative medicine used by consumers for the treatment of osteoarthritis. Glucosamine is also extensively used in veterinary medicine as an unregulated but widely accepted supplement.


Safety
Clinical studies have consistently reported that glucosamine appears safe. Since glucosamine is usually derived from shellfish, those allergic to shellfish or who have kosher concerns may wish to avoid it. However, since glucosamine is derived from the shells of these animals while the allergen is within the flesh of the animals, it is probably safe even for those with shellfish allergy. Alternative sources using fungal fermentation of corn are available. Another concern has been that the extra glucosamine could contribute to diabetes by interfering with the normal regulation of the hexosamine biosynthesis pathway, but several investigations have found no evidence that this occurs. The U.S. National Institutes of Health is currently conducting a study of supplemental glucosamine in obese patients, since this population may be particularly sensitive to any effects of glucosamine on insulin resistance.

In the United States, glucosamine is not approved by the Food and Drug Administration for medical use in humans. Since glucosamine is classified as a dietary supplement, safety and formulation are solely the responsibility of the manufacturer; evidence of safety and efficacy is not required as long as it is not advertised as a treatment for a medical condition.

In Europe, glucosamine is approved as a medical drug and is sold in the form of glucosamine sulphate.

Clinical studies
There have been multiple clinical trials of glucosamine as a medical therapy for osteoarthritis, but results have been conflicting. The evidence both for and against glucosamine's efficacy has led to debate among physicians about whether to recommend glucosamine treatment to their patients.

Multiple clinical trials in the 1980s and 1990s, all sponsored by the European patent-holder, Rottapharm, demonstrated a benefit for glucosamine. However, these studies were of poor quality due to shortcomings in their methods, including small size, short duration, poor analysis of drop-outs, and unclear procedures for blinding. Rottapharm then sponsored two large (at least 100 patients per group), three-year-long, placebo-controlled clinical trials of the Rottapharm brand of glucosamine sulfate. These studies both demonstrated a clear benefit for glucosamine treatment. There was not only an improvement in symptoms but also an improvement in joint space narrowing on radiographs. This suggested that glucosamine, unlike pain relievers such as NSAIDs, can actually help prevent the destruction of cartilage that is the hallmark of osteoarthritis. On the other hand, several subsequent studies, independent of Rottapharm, but smaller and shorter, did not detect any benefit of glucosamine.

This situation led the National Institutes of Health to fund a large, multicenter clinical trial studying reported pain in osteoarthritis of the knee, comparing groups treated with chondroitin sulfate, glucosamine, and the combination, as well as both placebo and celecoxib. The results of this 6-month trial found that patients taking glucosamine HCl, chondroitin sulfate, or a combination of the two had no statistically significant improvement in their symptoms compared to patients taking a placebo. The group of patients who took celecoxib did have a statistically significant improvement in their symptoms. These results suggest that glucosamine and chondroitin did not effectively relieve pain in the overall group of osteoarthritis patients. However, exploratory analysis of a subgroup of patients suggested that the supplements may be effective in patients with pain classified as moderate to severe (see testing hypotheses suggested by the data).

In an accompanying editorial, Dr. Marc Hochberg also noted that "It is disappointing that the GAIT investigators did not use glucosamine sulfate ... since the results would then have provided important information that might have explained in part the heterogeneity in the studies reviewed by Towheed and colleagues[PMID 15846645]" But this concern is not shared by pharmacologists at the PDR who state, "The counter anion of the glucosamine salt (i.e. chloride or sulfate) is unlikely to play any role in the action or pharmacokinetics of glucosamine". Thus the question of glucosamine's efficacy will not be resolved without further updates or trials.

A subsequent meta-analysis of randomized controlled trials, including the NIH trial by Clegg, concluded that hydrochloride is not effective and that there was too much heterogeneity among trials of glucosamine sulfate to draw a conclusion.

From this it appears that the jury is still out.

34 Weeks

I finally went back to my calendar and counted up. This is my 34th week on the program. That's approximately eight months.

I have read that it takes six months or so for glucosamine to have an effect on joints. That is, for it to start rebuilding the joint, to some extent. Is this true? My memory is that there have been actual studies that show joint regeneration but is my memory wrong?

If it is true than what I have noticed in the last several weeks can probably be attributed to rebuilding. That would account for the lessening of pain overall, my ability to take on stairs without so much pain.

I'm going to hunt down the facts now.

Back on track

After weeks of missing exercises and supplements I am almost back on track entirely. This last week I did the Rx exercises M, W, F and did 30-min aerobic activities T, Th, S. I took glucosamine every day. I have, however, run out of ginger.

After those days of excruciating pain in the mornings I am back to more of a discomfort, a manageable pain in the morning. Perhaps it was good to go off for a bit to find that this program is helping. It is a little disconcerting to suspect that it is the regular maintenance of these activities that keeps it working. In other words, I doubt there have been any meaningful physical changes that are longer-term. I wish there were a way to test.

My 30-minute exercises tended to be less painful than before. Because I am just getting back into this, though, I can't count that as a done deal. I have to see if it keeps up. It is the roller-coaster nature of this condition that makes it hard for me to sift through what's working and what isn't. What I can tell right now is this: I have not lost weight and I have stopped taking ginger and still I am experiencing less pain. This suggests that there may actually be some longer-term effects or that the glucosamine and exercises alone are effective.

One more thing I am doing: I have been a vegetarian for almost 25 years. Most of that time I have not been vegan. In the last several months I have moved more toward veganism and right now am just about there. Very few exceptions. The occasional ice cream treat. I am wondering if the diminishing of pain might be related to the diminishing of high-fat dairy products, like cheese. I looked in the Arthritis Rx book and saw dairy products on the inflammatory foods list (except low-fat). So perhaps I am onto something here. Doing a better job on the diet can reap rewards.

testing, testing

Over the past several weeks I fell off the program. I was traveling and missed several days of exercises and then started missing days of glucosamine and ginger as well. Interestingly, the inflammation in my knee really kicked up and I have had some truly awful mornings. Waking up and putting my feet on the floor and standing up has been excruciating.

So on Monday I got back on track. Exercise and supplements both. And I am already starting to feel less pain.