Chondroitin and Glucosamine, Facts Only



By Mark Hopkins, M.D.

Board-Certified Orthopedic Surgeon

Flagstaff , Arizona


This article is both for the consumer and health care professional. I have no financial interest in any pharmaceutical company and am writing this in an attempt to tell the unbiased truth about these supplements.





Chondroitin Sulfate (CS) is a naturally produced polysaccharide molecule, a glycosaminoglycan (GAG). Chondroitin sulfate is a polymer composed of repeating disaccharide subunits of D-glucuronic acid and sulfated forms of N-acetylgalactosamine.


Glucosamine is an amino monosaccharide, also known as 2-amino-2-deoxyglucose. Glucosamine is a structural component of glycosaminoglycans such as hyaluronic acid and can be converted by chondrocytes to N-acetylgalactosamine found in chondroitin sulfate. The negatively charged ion of the glucosamine salt (hydrochloride or sulfate) has no function in the action or pharmacokinetics of glucosamine.




Low molecular weight (LMW) chondroitin sulfate and glucosamine have a positive effect on the structure and function of joint cartilage by promoting biosynthesis of the cartilage matrix and inhibiting degradative enzymes that break down the matrix.


Chondroitin sulfate:


•  Low molecular weight chondroitin sulfate has anti-catabolic (inhibitory) activity on enzymes which degrade articular cartilage and increases synthesis of hyaluronic acid.

•  In vitro studies indicate that LMW CS inhibits cytokine activity, responsible for generation of nitric oxide, pro-inflammatory prostaglandins and metalloproteinases, all agents that degrade cartilage matrix.




•  May be involved in the production of joint cartilage.

•  Stimulates the production of proteoglycans, glycosaminoglycans and synovial fluid.


Combined Chondroitin sulfate and Glucosamine:


•  Chondrocytes exposed to LMW CS and glucosamine are stimulated to synthesize new GAGs.

•  Data generated by metabolic studies and confirmed at the molecular (mRNA) level, suggest that these effects result from modulation of cellular gene expression that is responsible for the anabolic and anti-catabolic activity.

•  Research shows that a synergy exists between chondroitin sulfate and glucosamine, as both agents have greater anabolic effects when combined than when either agent is used separately.

•  Research shows that the combination may increase the ability of cartilage components to maintain and even improve articular cartilage under stress and may boost the natural protective response of cartilage and tissues under adverse environmental conditions.


Absorption and plasma levels:


There is an inverse relationship between the molecular size of CS and its permeability through cell membranes, with the lower molecular weight CS achieving greater permeability. Purified LMW CS has documented absorption and subsequent in vivo bioactivity. The differences in the absorption and bioavailability of the various CS formulations is strongly influenced by the structure and characteristics, such as molecular mass, charge density, and cluster of disulfated disaccharides, of the parental molecules. Ionized glucosamine, which is stabilized in a salt form as a hydrochloride, is of relatively low molecular weight (179.19) and readily absorbed from the gastrointestinal tract.


Total absorption in humans is variable with measured values of > 13% following oral administration amounts, increasing the level of circulating CS by as much as 200% over endogenous levels in as little as 2 hours after a single oral administration.


An increase in LMW CS plasma levels has been shown to occur after multiple-day administration.


Orally administered LMW CS and glucosamine have an affinity for cartilage tissues and joint structures.


In an animal study glucosamine hydrochloride was absorbed quickly (1.5 hours) but did not accumulate in the body with continuous administration like LMW CS does.


Research and Clinical Trials:


Research has demonstrated a significant enhancement of the bioactivity due to synergistic action of the specific combination used in Cosamin DS. Positive outcome studies have involved Cosamin DS combination of 95% TRH122 LMW CS, FCHG49 glucosamine hydrochloride and manganese ascorbate. Nearly all the positive outcome studies published have used the 95% LMW CS. Recommendations for use that can be made for this specific material may not be applicable to other grades of chondroitin sulfate.


A number of recently published, double blinded, placebo-controlled clinical studies as well as meta-analysis of a number of published trials have concluded that 95% LMW CS and glucosamine are significantly effective in improving joint function and reducing joint pain.


I have placed a copy of the research article from the National Institute of Health (NIH) in Bethesda , Maryland on this web site. The article is entitled “The Efficacy of Glucosamine and Chondroitin sulfate in Patients with Painful Knee Osteoarthritis (OA): The Glucosamine/Chondroitin Arthritis Intervention Trial (GAIT). The study used the same type of chondroitin sulfate and glcosamine found in Cosamin DS. There are also several references to validate this claim. Doses in the study were kept at a constant 1200/1500 mg dose of CS and glucosamine respectively. It is the preliminary findings, the full study to come later.


In experimental trials the combination of ingredients was more effective than either substance alone in inhibiting progression of cartilage lesions.


There are no known contraindications or drug interactions. Side effects are minimal and include rarely flatulence, nausea or changes in stool consistency.


The recommended dose is 1200 mg CS and 1500 mg glucosamine per day for the first 6-8 weeks, then the dose can be tapered to 800 mg CS and 1000 mg glucosamine per day when reading the label, but the NIH study above recommends continuing the dose at 1200/1500. Using the Cosamin DS brand this equates to 3 capsules per day.


One has to be very careful in analyzing the type of chondroitin sulfate and glucosamine to take. Make sure that the manufacturer can back up their product with their own clinical studies. Sometimes a manufacturer will say something like this, “Chondroitin sulfate and glucosamine used in combination have been shown by academic research to alleviate and even treat the symptoms of osteoarthritis.” They are very clever not to say that it is some other brand that was tested. Chondroitin sulfate and glucosamine are mentioned as if they are all the same. I've lately found that many manufacturers are now implying that the GAIT study applies to their brand, being careful not to include all details of the study. I have two articles representing two different methods of analysis, you be the judge.


A study published in 2000 analyzed different brands of chondroitin and glucosamine against manufacturer's specifications. A copy of the article is on this web site entitled “Analysis of Glucosamine and Chondroitin Sulfate in Marketed Products and the Caco-2 Permeability of Chondroitin Sulfate Raw Materials.” The amounts of glucosamine and chondroitin found after analysis were significantly different from the label claim in some products, with deviations from label claims ranging from as low as 0% to over 115%. Products with a retail price of less than or equal to one dollar per 1200 mg of CS were found to be seriously deficient in meeting the label claim (less than 10% of label claim). The permeability of the different molecular weight chondroitin sulfates was found to be significantly different (p<0.05), with the permeability coefficient increasing with decreasing molecular weight. This suggests that molecular weight of chondroitin sulfate could be a possible predictor of permeability. Incidently the two best brands in this study were Cosamin DS and Sundown.


I have listed references for you to check. Next to the references I have placed which brand the study used. It seems almost painful to be so careful what you buy and what you choose to take, but it is your health and unfortunately dietary supplements are not FDA regulated in the USA . I am not sure why but it probably has something to do with money. Dietary supplements are regulated in most of the European countries. I have written this article to help the average consumer and maybe even some of the doctors who desire more information. I have no affiliation with Nutramax (the manufacturer of Cosamin DS) other than taking the supplement myself. I just don't like it when a consumer walks in to a pharmacy (not to single any one out) and they are told, “Oh yeah, chondroitin, they are all the same, why don't you take this one, it's cheaper.” Sound familiar? I also don't like it when manufacturers ride the band wagon of someone else's product comparing it to their own when it is really different. Make your own choice and consult your physician before starting any new regimen or medicine.