Glucosamine

Experience From - Karl King#1 , Jay Hodde#1 , Karl King#2 , Karl King#3 , Doug Clark , Karl King#4 , Jay Hodde#2 , Karl King#5 , Damon ? , Kevin O'Neall , Jay Hodde#3 , Karl King#6 , Bill McDermott , Herb Hedgecock

NOTE: This information from Karl is also found in the Recovery section and is repeated here for assistance in cross reference purposes.

Put very simply, tendons are mostly protein with some "glue" based on carbohydrate structures. An analysis of the tissue shows that the amino acids which are the main building blocks are:

• hydroxy-Proline
• glycine ( about 1/3 of the total )
• lysine ( which forms cross-linked sites between individual fibers )

The "glue" is based on Glucosamine sulfate.

So, when I have tendon problems ( off and on over the years ) I take dairy products ( good source of L-Proline and lysine )

1 gram of Glycine
1 gram Glucosamine Sulfate
1 gram buffered vitamin C ( calcium ascorbate )

I'll take this at breakfast and bedtime. My personal experience is that the inclusion of the Glycine makes a big difference. All of these are inexpensive except for the Glucosamine. If a bottle of it gives you sticker shock, delete that from the list. The glycine seems to be a key element. If for some reason you avoid dairy products ( yogurt is my favorite ), you can get Proline from Knox Gelatin. The human body will make Glycine from other amino acids, so in theory one would not need a supplement. However, the rate at which it is made may not be fast enough to heal rapidly. A supplement gives the body more to work with.

Tendons have a paltry supply of blood, so to carry the nutrients into the tissues, you need to reduce inflammation and increase blood flow. The best way is the old standby - ICE.

If you have recurring tendon problems, try to figure out why. If you haven't upped your mileage a lot, maybe it is a mechanical problem that needs addressing. The nutrients will help one heal fast, but they won't remove a root cause ( unless your are severely nutritionally challenged ) so look for the root cause.

Doug Clark asked for references regarding Glucosamine. I am providing two review article abstracts for those interested. I am not very familiar with the therapeutic use of Glucosamine, but my research revolves around the role of proteoglycans, glycosaminoglycans (or mucopolysaccharides, as referenced below), and growth factors in the inflammatory process. I hope that others more familiar with the clinical use of Glucosamine can comment on it; I am only familiar with its role as a constituent of the extracellular matrix.

Article #1

Authors: McCarty MF.

Title: The neglect of Glucosamine as a treatment for osteoarthritis--a personal perspective. [Review]

Source: Medical Hypotheses. 42(5):323-7, 1994 May.

Abbreviated Source: Med Hypotheses. 42(5):323-7, 1994 May.

Abstract:
Osteoarthritis results from progressive catabolic loss of cartilage proteoglycans, owing to an imbalance between synthesis and degradation. Standard drug therapy is only of palliative benefit and may exacerbate loss of cartilage. Glucosamine is an intermediate in mucopolysaccharide synthesis, and its availability in cartilage tissue culture can be rate-limiting for proteoglycan production. A number of double-blind studies dating from the early 1980s demonstrate that oral Glucosamine decreases pain and improves mobility in osteoarthritis, without side effects. Nevertheless, medical researchers and physicians in the US have totally ignored this rational and safe therapeutic strategy. By mechanisms that are still unclear, the natural methyl donor S-adenosylmethionine also promotes production of cartilage proteoglycans, and is therapeutically beneficial in osteoarthritis in well-tolerated oral doses. These and other safe nutritional measures supporting proteoglycan synthesis, may offer a practical means of preventing or postponing the onset of osteoarthritis in older people or athletes. [References: 38]

Article #2

Authors: Spencer-Green G.

Institution: Dartmouth-Hitchcock Medical Center, Lebanon, NH 03756.

Title: Drug treatment of arthritis. Update on conventional and less conventional methods. [Review]

Source: Postgraduate Medicine. 93(7):129-40, 1993 May 15.

Abbreviated Source: Postgrad Med. 93(7):129-40, 1993 May 15.

Abstract
Nonsteroidal anti-inflammatory drugs comprise an important class of medications that reduce the signs and symptoms of osteoarthritis and rheumatoid arthritis. They bring relief to millions of people but do not eliminate underlying disease. Disease-modifying antirheumatic drugs also bring relief, but these drugs are often ineffective and not well tolerated. Failure to provide long-term benefits combined with the high toxicity of most of the disease-modifying agents has prompted a search for more effective treatments. New methods using modern technologies have generated much enthusiasm and hold promise for the future. In the meantime, administration of nonsteroidal anti-inflammatory drugs and judicious use of disease-modifying agents remain the cornerstone of therapy for arthritis. [References: 28]

Doug Clark asked about this. Jay Hodde listed references on the material.

Here's a little more. Glucosamine is a saccharide covalently bound to a peptide chain. The synthesis is done in the body from simpler components. The material than ends up in the matrix which holds the elastic parts of connective tissue. It breaks down over time and stress, and is replaced as needed - normally.

If the tissue is severely damaged, the matrix cannot be replaced faster than the body can make more. One way to speed up the process is to supply the chemicals that are further down the synthesis chain.

It is claimed that supplying Glucosamine preformed will speed healing. Anecdotal evidence from arthritis sufferers supports the claim. My personal experience with it for helping with tendinitis was initially not dramatic.

A non-running injury incurred prior to American River 50 spurred me to try Glucosamine in conjunction with glycine. About 1/3 of the elastic component of connective tissue is glycine. That combination, along with plenty of vitamin C gave me a very fast recovery which allowed me to run AR without serious problems.

Such self-treatment is generally not a good idea. I discontinued the combination as soon as the repairs seemed to be in place. Glucosamine has not had a long history of use in this country, so one should not self-medicate with it on a long-term basis unless prescribed by a physician. Taken for a few days after an injury to connective tissue it should be safe.

The biochemistry associated with Glucosamine is far too technical to post here. If you're interested, see the references list by Jay, along with a heavy-duty biochemistry text.

Troy Rondot asked about natural sources of Glucosamine.

Since it is found in connective tissue, that would be a natural source, but it may not survive cooking.

A relevant question is would a natural source provide effective amounts.

Your own body will do the biochemistry to synthesize Glucosamine sulfate provided you give it the right ingredients ( which is not hard to do ). It will however do that at a given rate, which may not be fast enough to repair the damage you do while exercising. The reason to take it orally is to provide it at a higher rate.

While it is an important component of body structures and fluids, please remember that it is not the only one. Endurance athletes need to maintain a strong level of nutritional competency so that the body can repair all the body tissues which get damaged while training. It is also important to realize that serious damage might be caused by bio-mechanical problems. Taking a nutrient can help in healing, but does not address the root cause of injury.

While Glucosamine sulfate can be useful, I'm hesitant to say that it is a "wonder drug". There are lots of tools in the toolbox, and that is just one of them.

Thanks for the tip about using glycine, lysine and vitamin C for the promotion of healing.

For several months I've taken the following, daily:

2 grams of glycine powder ( 1 g. at dawn, 1 g. at night)
0.5 gram of lysine (and, daily, I eat 8oz of yogurt & 6oz of tuna)
2 grams of Glucosamine sulfate ( 1 g. at dawn, 1 g. at night )
3 grams of vitamin C ( 1 g. at each meal )

My goal was to minimize the damage to joints (bone & tissue) from running. Additionally, I hoped Glucosamine sulfate would benefit osteoarthritis. At 6 feet, 185 pounds, I started running 3 years ago at age 50. I run 6 to 8 miles three times during the week & 15 to 20 on Sunday, usually at 10 min. per mile.

I am happy to report dramatic results. For years, I would have major (arthritic?) pain in my big toe after my runs. The longer the run, the more the pain. Arch supports have helped some. I continue to get a lot of toe pain after about 8 to 10 miles, but the good news is - it goes away when I stop running. It does not continue hurting for days as it used to.

Subject: Glucosamine Sulfate

Chemically, as the name implies, Glucosamine is a hybrid of carbohydrate and amino acid ( which tells you nothing about what it does ). Without delving too deeply into the biochemistry ( which Jay Hodde is more qualified to do than I am), it is a structural component of connective tissue.

Refer also to the post from Douglas Clark. Some time ago, he asked for nutritional advice on healing of connective tissue. At the time, I posted a note relating that connective tissue formed from glycine, proline, lysine (all amino acids ) and that Glucosamine sulfate was needed as a "glue" to hold the structures together. Vitamin C is part of the associated chemical reactions necessary for healing of damaged tissues.

Why would these supplements help? The body will go through the chemical reactions as needed, but my be limited in the rate at which connective tissue will be repaired by lack of raw materials. Adding the supplements basically makes sure those components are in supply.

Does it help to take such things? Generally, yes. Do they provide miracle cures for all sorts of ailments? No. Some supplement suppliers have useful products, but they promote them beyond reasonable expectation, and that is a disservice.

As a sidelight, a few days before the Glacial Trail 100K, I turned my right ankle. Desperate for a quick fix, I used the listed supplements to the hilt and iced according to the suggestions given me by Jay Hodde. The ankle responded and held up through the run. It has given me little problem in the weeks following. At 1 mile into the run, I turned the LEFT ankle. After 25 miles the pain got substantial and I dropped at 50K. It is rare to have the chance for a comparative study of turned ankles ( hard to get volunteers ) so I decided to let nature take its course with the left ankle. It took much longer to heal, and was sore for a month after the run.

That is only a sample of one, but I believe that glycine, lysine, C and Glucosamine can help speed the healing of damaged connective tissues. But I would not attribute any miracle cures to them beyond that use.

Karl King says:

"Chemically, as the name implies, Glucosamine is a hybrid of carbohydrate and amino acid (which tells you nothing about what it does ). Without delving too deeply into the biochemistry ( which Jay Hodde is more qualified to do than I am ), it is a structural component of connective tissue."

Glucosamine and galactosamine (hexosamine is a general term for the two substances) are important constituents of the class of "molecules" known as glycosaminoglycans (GAGs). An example of a GAG is heparin. GAGs are important structural components of another class of substances, the proteoglycans.

Proteoglycans are proteins that contain a GAG chain. They serve many different functions in the body. They may act as signaling molecules, adhesion molecules, or "storage" molecules -- essentially, they may be important in regulating many different cell functions. In addition to that, the structure of one particular proteoglycan, aggrecan, is such that it can act as a shock absorber. It is a principle component of articular cartilage.

It has been suggested that the availability of Glucosamine is the limiting factor in the biosynthesis of the GAG chain, and therefore, of the proteoglycan components of articular cartilage. If Glucosamine were readily available, it is thought, repair of cartilage would progress faster.

While I don't know of controlled studies that have looked into this, patients with osteoarthritis that have taken Glucosamine sulfate have reported less joint pain and stiffness. I'm not qualified to address clinical aspects, save one. It is my understanding that uptake studies performed comparing the body's utilization of Glucosamine to Glucosamine sulfate have indicated that Glucosamine sulfate can be utilized by the body, but that the free form (Glucosamine) is not absorbed. Something to watch if you decide supplementation is right for you.

After Jay's excellent note on the chemistry of glycosaminoglycans, here are a couple references on Glucosamine and arthritis. Note that neither of these studies used athletes.

1. Vaz,A.L., Double blind evaluation of the relative efficacy of Glucosamine sulfate in the management of osteoarthritis of the knee in out patients, Current Medical Research Opinion, 1982;8:145-149

68 patients were evaluated for pain reduction. Half got 1.5 gms Glucosamine per day, half got 1.2 gms Ibuprofen. The Glucosamine group had significantly less pain at the end of the study.

2. D'Ambrosio, E., et al, Glucosamine Sulfate: a controlled clinical investigation of arthrosis, Pharmatherapeutica, 1981;2(80):504-508

30 patients in a double blind were given either 0.5 gm per day or a placebo for 14 days. There was no change in the placebo group, but a 71% reduction in symptom scores ( pain, swelling, tenderness, loss of function ) in the Glucosamine group.

Glucosamine in the sulfate form was used in both studies.

Perhaps the only drawback of Glucosamine sulfate is that is darned expensive.

Based on some advice from some others on the list, and faced with running three ultras in 22 days in August while suffering Achilles problems, I tried Glucosamine Sulfate. I didn't do any ceteris parabus testing, as I also took amino acid supplements (including lysine), some PhosFuel, and my normal regimen of multi-vitamins, buffered C, and E.

I don't take most of these on a regular basis, but my Achilles problems that had plagued me for the last year or so have pretty much disappeared over the last few months. I have been taking the GS and Amino acid supplements a few times a week, and I use the PhosFuel just before and just after races, for a total of 5-7 days.

Be aware that Glucosamine Sulfate is rather expensive. I happened to get some at a 2-for-1 sale that brought the price down a lot.

Subject: Chindroitin

Jack Richardson wrote:

I have received information on two over the counter products that reportedly helped in the repair of cartilage.Glucosamine and Chondroitin are used by veterinarians for horses having shin splints and bone cartilage related problems. A local vet had her husband taking these over the counter products. He had experienced severe knee problems caused by competitive weight lifting. After using the two products he was able to compete again. Does anyone know of any clinical studies with these products? Has anyone tried them and what was the effect? Has anyone heard of them?

Glucosamine is a cofactor which helps repair cartilage and chondroitin is a cartilage protein. That's how it was explained to me.

I don't remember the title or author, but an MD wrote a recent best-seller on subject of arthritis treatments. Most of the book is a discussion of these two products. His bibliography would list any clinical trials that have been done.

Subject: Chindroitin

It was said:

Glucosamine is a cofactor which helps repair cartilage and chondroitin is a cartilage protein. That's how it was explained to me.

Glucosamine is a constituent of the chondroitin (more specifically, of ANY carbohydrate structure known as a glycosaminoglycan, of which chondroitin is a specific type. Heparin is an example of another glycosaminoglycan). It is thought that the limiting factor in proteoglycan synthesis is the availability of Glucosamine -- thus the clinical interest as a dietary supplement.

Glucosamine is sold in two forms: sulfate or hydrochloride.

To help some knee aches, I've tried both types and found that only the sulfate form works for me. After a few days on the hydrochloride form, my neck and shoulders get stiff and sore. My guess is that my spinal fluid is being affected by the hydrochloride form. A couple days off the hydrochloride form relieves the problem. The sulfate form does not cause that problem.

In general, my knees seem less achy when I use Glucosamine during "heavy" training. There may be some anti-inflammatory effect from Glucosamine, as well as aiding tissue repair.

I noticed that a Glucosamine-chondroitin over the counter formulation had the hydrochloride form ( it is cheaper ). Be sure to read labels if you purchase such a formulation.

From the biochemistry that I've read, the actual form used in tissues is the sulfate form. Given my reaction to the hydrochloride form, I have to wonder if the body is capable of replacing the chloride radicals with sulfate radicals.

Subject: Glucosamine and Chondroitin

The best selling book that Kevin O'Neall referred to is titled "The Arthritis Cure: The Medical Miracle That Can Halt, Reverse, and May Even Cure Osteoarthritis" and the principal author is Dr. Jason Theodosakis. The book includes a detailed discussion of how these two supplements can work to repair and regenerate cartilage. He also includes case studies.

The author says it is essential to use both Glucosamine and Chondroitin, not just one or the other, and he lists a number of the different products on the market.

I have been taking the supplements for about four months in an attempt to alleviate my problem with Chondromalacia in the knee. These are supplements, not drugs, and I am hoping for long term improvement rather than short term miracles. I am running reasonably well right now but I cannot make any conclusions yet on whether or not I have been helped by Glucosamine and Chondroitin.

Karl King wrote:

Glucosamine is sold in two forms: sulfate or hydrochloride

From the biochemistry that I've read, the actual form used in tissues is the sulfate form.