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By Rick Swartzburg, D.C.
Updated 6/24/2009


Glucosamine and MSM (Methyl Sulfonyl Methane) are perhaps the most widely used natural supplements for those seeking alternative solutions for pain relief, inflammation and tissue repair.  This large scale interest was prompted from some early positive studies on these nutrients and has blossomed into a full spectrum of current and future planned scientific studies which preliminarily continue to validate supplemental use of these naturally occurring compounds for a variety of disorders.  Both of these supplements have been studied since the early 1980s, but with an increasing interest in alternative remedies that can perhaps offer a natural solution to a medical problem, the medical and scientific community has taken a much more active approach in researching these topics.  


Glucosamine, the precursor in the formation of Chondroitin, has been found to stimulate cartilage cells to synthesize glycosaminoglycans and proteoglycansore(1).  This essentially means that Glucosamine has the potential to rebuild the cartilage lost in a joint due to injury or osteoarthritis, also known as degenerative joint disease.  A very recent study, study discloses a possible new mechanism of action for Gluscosamine Sulphate that seems to be in keeping with a potential protective effect that it has on the stimulation of cartilage formuation(2).  With more than 30 million Americans suffering from this type of arthritis, it is no wonder that the American College of Rheumatology took a closer look at this supplement.  In a 1999 press release they proclaimed that Glucosamine reduces the signs and symptoms of osteoarthritis of the knee.  Lead investigator Jean-Yves Reginster, MD, PhD, of the University of Liege in Belgium added that "for the first time, we have shown that a compound may be able at least to slow down the progression of osteoarthritis." They based these findings on a three-year study where they compared disease symptoms and average joint space widths, as measured by X-rays, between patients taking a 1500 mg daily dose of Glucosamine sulfate and those taking a placebo. They found that joint space narrowed in patients taking a placebo, but showed no further narrowing in patients on Glucosamine sulfate. They also found that symptoms worsened for patients taking a placebo and improved for those on Glucosamine sulfate(3).  A study done over three years demonstrated virtually the same findings(4), further validating the use of Glucosamine for stimulating cartilage growth and joint pain.  In a 2008 study performed by the department of public health in Belgium, 340 Knee Osteoarthritis patients participating in two previous randomized, placebo-controlled, double-blind, 3-year trials of glucosamine sulphate and receiving treatment for at least 12 months, were systematically contacted to participate in a long-term follow-up retrospective assessment of the incidence of total knee replacement. This study concluded that Treatment of knee Osteoarthritis with glucosamine sulphate for at least 12 months and up to 3 years may prevent Total Joint Replacement in an average follow-up of 5 years after drug discontinuation(5)

Because  Glucosamine is a small molecule, it is easily absorbed and very permeable to cell linings.  According to the Encyclopedia of Nutritional Supplements, the absorption rate for Chondroitin Sulfate is estimated between 0 and 8 percent.  In contrast, studies show up to 98% of the orally administrated Glucosamine Sulfate is absorbed(6).   Following oral administration of a clinically recommended dose of glucosamine sulphate in equines, significantly higher synovial fluid concentrations of glucosamine are attained, when compared to an equivalent dose of glucosamine hydrochloride(6).  A long-term study demonstrated slightly higher side effects occurring with taking Glucosamine orally(4), while another demonstrated that only 1% of patients taking the Glucosamine had epigastric pain/tenderness, heartburn, diarrhea and nausea(7). Glucosamine can be taken in pill or liquid form, administered though intramuscular injections, and more recently can be found in topical formulas.  The effectiveness of a topical formula is dependent on the ability of the ingredients to penetrate the skin barrier. Creams and lotions usually lack this ability to penetrate, as they usually contain thick, non-absorbing, and often waxy ingredients.  Glucosamine Sulfate is currently sold over the counter in the United States as a supplement and therefore not currently evaluated by the FDA.


MSM (Methyl Sulfonyl Methane) was isolated by Robert Herschler and Dr. Stanley Jacob of the University of Oregon Medical School in the early 80's. Their research showed that MSM is a natural sulfur compound found in all living things.  It revealed that MSM one of the most prominent compounds in our bodies, just behind water and sodium.  In his research, Dr. Jacob found that the sulfur in MSM, called Sulfonyl, is as safe and is as important as vitamin C in our diet.  He observed that it is very different than the bad sulfurs like sulfite, often used to preserve certain foods.  MSM is a member of the sulfur family but should never be confused with sulfa drugs, to which some people are allergic.  MSM is a natural form of organic sulfur found in all living organisms, including human body fluids and tissues.  MSM originates in the ocean and reaches the human food chain through rainfall.  MSM is an odorless, water-soluble, white crystalline material that supplies a bio-available form of dietary sulfur.  While MSM is normally found in many common foods, including raw milk, meat, fish and a variety of fruits, vegetables, and grains, it is normally lost from our food by heating, storage, processing, drying, cooking and preserving and even washing.  MSM has been shown to add flexibility to cell walls while allowing fluids to pass through the tissue more easily.  MSM enhances tissue pliability and encourages the repair of damaged skin(8)  MSM levels in humans decline with age, resulting in symptoms of fatigue, tissue and organ malfunction, and increased susceptibility to disease(9). 

In a  study of 24 people with athletic injuries, MSM was shown to reduce symptoms by nearly twice as much as those taking placebos, and was able to reduce the average needed visits to the chiropractor by approximately 60%(10).  Another preliminary study compared 10 degenerative arthritis suffers taking MSM versus 6 who took a placebo.  Results indicate a better than 80 percent control of pain within six weeks for those patients using MSM, while only two patients showed a minimal improvement (less than 20 percent) on the placebo(11).  Dr. Lawrence, the medical doctor who headed up these studies, relates that he has treated more than one thousand patients with MSM and believes that it is safer than water.  He noted that it appears that the body uses what it requires and flushes out the rest within 12 hours.  According to a recent book by Lawrence, Jacob, and Zucker, entitled The Miracle of MSM, MSM can be a natural remedy for osteoarthritis, rheumatoid arthritis, Fibromyalgia, tendonitis and bursitis, muscular soreness and athletic injuries, carpal tunnel syndrome, post-traumatic inflammation and pain, heartburn and hyperacidity, headaches and back pain, and allergies.  It was also noted that people taking MSM may notice other benefits, including softer skin, harder nails, thicker hair, and softening of scar tissue.  An allotted time of 2 - 4 weeks may be needed before significant improvement is seen.  It was demonstrated that patients at the Oregon Health Sciences University who have received oral MSM as part of their treatment show no toxic build-up, even after years of ingesting more than 2,000mg of MSM each day(12).  In a more recent study, a randomized, double-blind, placebo-controlled trial was conducted with fifty men and women, 40-76 years of age with knee Osteoarthritis pain were enrolled in an outpatient medical center.  Each took 3 grams of MSM or a placebo twice a day.  Compared to placebo, MSM produced significant decreases in pain and physical function impairment, as well as demonstrating improvement in performing activities of daily living(13).  MSM can be taken orally in pill or liquid form, and is also found in topical formulas.  Topical creams with MSM may not offer much benefit, as the heating process may destroy the bio-availability of the MSM.  With MSM's ability to allow fluids to pass through the tissue more easily, it works well with other natural compounds to allow for better absorption.


The current scientific literature available supports the use of Glucosamine and MSM for the use of symptom reduction and tissue repair in damaged muscle and joints.  The low occurrence of mild side effects when taken internally far underscore the benefits demonstrated with the use of Glucosamine.  Topical formulas will not only avoid these mild side effects, but when combined with a good delivery system, will offer local transfer of ingredients directly to the site of irritation.  However, it will be beneficial to see future studies which compare outcomes using different formulations, dosages and musculoskeletal conditions to help better understand the limitations of these powerful nutritional supplements. 


1.  Basleer C and others. International Journal of Tissue Reaction 14:231, 1992.
2.  Valvason C, Musacchio E, Pozzuoli A, Ramonda R, Aldegheri R, Punzi L.  Influence of glucosamine
     sulphate on oxidative stress in human osteoarthritic chondrocytes: effects on HO-1, p22(Phox)
     and iNOS expression.  2008 Jan;47(1):31-5.  Rheumatology Unit, Department of Clinical and
     Experimental Medicine, University of Padova, Via Giustiniani, 2-35128 Padova, Italy. 
3.  American College of Rheumatology Specialists in Arthritis Care & Research
Monday Nov.15, press release from American College of Rheumatology Annual
     Scientific  Meeting Nov. 13-17 in Boston, Mass.
4.  JY Reginster et al. Long-term effects of glucosamine sulphate on osteoarthritis
     progression: a randomized, placebo-controlled clinical trial. Lancet 2001 357: 251-256.
5.  Bruyere O, Pavelka K, Rovati LC, Gatterová J, Giacovelli G, Olejarová M, Deroisy R, Reginster JY.
     Total joint replacement after glucosamine sulphate treatment in knee osteoarthritis:
     results of a mean 8-year observation of patients from two previous 3-year, randomised,
     placebo-controlled trials.  2008 Feb;16(2):254-60. Epub 2007 Jul 27.
     Encyclopedia of Nutritional Supplements, p.341
6.  Meulyzer M, Vachon P, Beaudry F, Vinardell T, Richard H, Beauchamp G, Laverty S.
    Comparison of pharmacokinetics of glucosamine and synovial fluid levels following administration
    of glucosamine sulphate or glucosamine hydrochloride. Département des sciences cliniques, Faculté
    de Médecine Vétérinaire, Université de Montréal, St. Hyacinthe, Québec, Canada
    2008 Sep;16(9):973-9. Epub 2008 Mar 4.

7.  MJ Tapadinhas, IC Rivera, AA Bignamini. Oral glucosamine sulphate in the
     management of arthrosis: report on a multi-centre open investigation in
     Portugal. Pharmacotherapeutica 1982 3: 157-68.
8.  Mindell EL. The MSM Miracle, Enhance your health with organic sulfur.
9.  M. Lawrence, M.D., Ph.D, Sanchez, D.C., C.C.S.P., Grossman, D.C. LIGNISUL MSM
10.  M. Lawrence, M.D., Ph.D. Assistant Clinical Professor, U.C.L.A.  LIGNISUL MSM
11.  ARTHRITIS(A Preliminary Correspondence) School of Medicine Los
     Angeles, California 4/10/01.
12. Jacob, S.W., Oregon Health Sciences University, Portland, Oregon, Personal
13. Kim LS, Axelrod LJ, Howard P, Buratovich N, Waters RF.  Efficacy of methylsulfonylmethane (MSM) in
     osteoarthritis pain of the knee: a pilot clinical trial.  Southwest College Research Institute2006
     Mar;14(3):286-94. Epub 2005 Nov 23.

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