Problems with joints can be caused by an injury, excess effort or degenerative changes. Such disorders of the musculoskeletal system affect the quality of life and make it difficult to complete everyday tasks. An effective way to get rid of joint pains is through supplementation with glycosaminoglycans (GAG) and collagen. GAGs are active substances that are usually added to products recommended for enhancing the proper functioning of joints. What are the mechanisms of action of GAGs and why are they so effective in the treatment and prevention of arthritis? The answer is presented below.


1. When your joints fail you

Articular cartilage is mainly composed of glycosaminoglycans (including, among others, chondroitin sulfate, glucosamine sulfate and hyaluronic acid). The biomechanics of cartilage is determined by the physicochemical properties of these macro-molecules. For this reason, disturbed biosynthesis and homeostasis of the glycosaminoglycan environment weakens the structure of articular cartilage, which may lead to arthritis.

Arthritis is a popular ailment of developed countries, which involves joint inflammation with the accompanying pain, swelling and stiffness. There are two types of arthritis:

  • osteoarthritis, caused by degeneration of overly strained articular cartilage,
  • rheumatoid arthritis, the most common consequence of joint damage or fracture.

2. Arthritis. Treatment methods.

Currently, arthritis treatment focuses on alleviating the ailments through palliative procedures encompassing pharmacology and surgeries. The medicines used in the ailment have a pain-killing and anti-inflammatory effect (nonsteroidal anti-inflammatory drugs NSAIDs). In osteoarthritis, the treatment is supplemented by slow-acting medicines (SYSADOA). The active ingredients of this group of medications produce a delayed effect and relieve ailments caused by osteoarthritis after c.a. one month of use, with the effect persisting for up to several weeks after withdrawal. Such active ingredients include, among others, chondroitin sulfate and glucosamine sulfate, which proved to be highly effective in the treatment of osteoarthritis, additionally producing an anti-inflammatory effect. Let us now have a closer look at the efficiency of the most popular compounds recommended for problems with joints.

3. Chondroitin sulfate (CS)

Chondroitin Sulfate (Bovine) is one of the best clinically tested compounds when it comes to its bioavailability after oral administration. Research (Volpi, 2002 and 2003) shows that blood concentration of chondroitin sulfate grows significantly within 1 to 6 hours after administered, with peak concentration in the second hour after taking the supplement. Serum concentration of this macromolecular compound remains significantly high (over 200% of base concentration) for up to 4 hours, and drops afterwards. Supplementation with bovine and shark cartilage chondroitin sulfate has been confirmed to effectively raise the blood concentration of the compounds. Thus, it has been proved that macro-molecules with high-density loads can be transported by the mucosa of the small intestine.


The positive effects of oral administration of chondroitin sulfate in osteoarthritis treatment have been broadly confirmed in clinical trials. Chondroitin sulfate obtained from several different sources (bovine, shark, bird) and used in different doses (500 to 1,200 mg/day) and for different periods (3-24 months) was tested. The manner of administration differed, too (every day throughout the test period or twice, in 3-month cycles). Nevertheless, all tests showed that long-term oral administration of chondroitin sulfate is safe, well tolerated and highly effective in alleviating osteoarthritis-related pain and in enhancing the mobility of the affected knee joint.

4. Glucosamine sulfate (GS)

Glucosamine sulfate belongs to the most popular supplements used in osteoarthritis prevention and alleviation of symptoms of the disease. The effectiveness of glucosamine has stirred controversies for years, being the subject of numerous disputes and experiments. The negative opinions on the effects of glucosamine on the joints were based mainly on observations of a single chemical form of the substance (glucosamine hydrochloride), the absorbability of which is restricted to dozen or so percent only. Another problem was the lack of knowledge on the substance’s pharmacokinetics when administered orally or injected. The methods used were not sensitive enough to allow exact evaluation of the concentration of the ingredient in biological fluids. Plus, the quality of the glucosamine sulfate used left a lot to be desired, which significantly reduced its efficiency in the experiments. The situation is different now. Long-term clinical research on patients suffering from arthritis of the knee shows that glucosamine sulfate is effective in reducing the negative symptoms of the disease.


Glucosamine sulfate is characterised by a very high bioavailability. When administered orally, the substance is quickly absorbed from the alimentary tract and is available in the circulatory system. After 3 to 4 hours after administration, the blood concentration of glucosamine sulfate slowly drops, but remains above the average base level for the next 48 hours, irrespective of the dose. Another characteristic feature of glucosamine is that after a sudden growth of its blood level as a result of absorption of the substance from intestines, the concentration of the substance drops multi-exponentially. This shows that glucosamine is distributed in considerable amounts to non-vascular organs of the human body (joints and articular cartilages). It has also been observed that the maximum average concentration of glucosamine sulfate after its administration depends on the dose, with the half-life of c.a. 15 hours. The differences in pharmacokinetic distribution of the compound are sex-specific.

Dosage Рthe recommended daily dose is 1,500 mg per day. Higher doses disturb the absorption and distribution of glucosamine sulfate, while lower doses proportionally lower the glucosamine blood concentration and, thus, produce weaker physiological and therapeutic effect.

5. Hyaluronic acid (HA)

Hyaluronic acid is the main ingredient of the synovial fluid, which helps maintain its proper biomechanics. Hyaluronic acid is frequently added to supplements for problems with joints or to supplements aimed to keep the skin healthy. The most popular and the best source of hyaluronic acid is rooster combs and bacterial fermentation processes. However, some producers use powdered or hydrolysed cartilage, which is not a source of high-quality cartilage. Products like this should be avoided.

Hyaluronic acid is broadly used in medicine, to heal degenerative changes in joints (injections) and alleviate the symptoms of cartilage damage (oral administration). Both forms of supplementation have been proved effective.

How hyaluronic acid gets to the joints

How come a compound with such a high molecular weight is transported from the alimentary tract to the body’s connective tissues, all the more that it is effectively decomposed in the liver? The answer is that hyaluronic acid is transported through the lymphatic system and not by the blood. What is more, owing to its strong adhesive properties, the substance penetrates through the peritoneal mucosa to the blood (the same mechanism is used for its uptake from the alimentary tract). Nevertheless, high molecular weight and low fat solubility make the effectiveness of absorption of high molecular hyaluronic acid from the alimentary tract range from 5 to 20%. The effectiveness of hyaluronic acid absorption from the intestines can be increased (by more than 20%) by simultaneous administration of phospholipids, which naturally occur in cell membranes.

Dosage. The most effective molecular mass of hyaluronic acid used in joint ailment prevention equals c.a. 1 MDa.

6. Collagen

Next to glucosamine sulfate, collagen remains among the most popular and most frequently used supplements to treat ailments in the musculoskeletal system including, in particular, joint problems. Collagen is the main protein occurring in the connective tissue of mammals. It is used in dietary supplements as hydrolysate obtained through enzymatic digestion of animal-derived gelatine. A number of studies carried out have shown that collagen hydrolysates are absorbed by the body from the alimentary tract and transported with blood to the articular cartilage, where they stimulate the activity of chondrocytes (cells of the cartilage) and enhance the synthesis of new collagen molecules. All this makes the joints, and the entire musculoskeletal system, function better.