The Italian Drug Glucosamine (XICIL) In the Treatment Of Osteoarthritis

An excellent Belgian study appearing in the January 27, 2001 issue of the highly respected British medical journal The Lancet found that glucosamine (XICIL) was more effective than an inactive dummy pill, or placebo, in relieving the symptoms of osteoarthritis. Glucosamine may also have a positive effect in modifying the course of osteoarthritis compared to no treatment at all. The study was funded by the manufacturer of Xicil.

Glucosamine is a pure substance made in Italy that is synthesized from chitin and is a defined mixture of glucosamine, sulphate, and sodium chloride. Sodium and chloride together are table salt. Chitin is a long chain of glucosamine (a type of sugar) molecules linked together and referred to as a polymer. It is similar in chemical structure to cellulose or vegetable fiber. Chitin makes up the hard outer skeleton of beetles, crabs, and certain microorganisms. Glucosamine is also present in human cartilage and joint fluid.

The Belgian study involved 212 people with a diagnosis of osteoarthritis of the knee who were at least 50 years of age. Xicil powder was mixed and taken as an oral solution in a dose of 1,500 milligrams once daily by 106 patients, while the other 106 received an identical placebo. Only about two-thirds of the patients in each group completed the full three years of the study.

There were two primary outcome measures in the study. The first was joint structural changes which measured the average joint-space width using x-rays in order to determine if glucosamine would affect the course of joint damage seen in osteoarthritis. Increased narrowing of the joint-space over time is believed to indicate progressive damage to the joint from osteoarthritis.

The symptoms of osteoarthritis as perceived by the patients was the second outcome and was assessed using what is known as the Western Ontario and McMaster Universities questionnaire. This form, frequently used in osteoarthritis research, asks five questions about joint pain, two about stiffness, and 17 about limitations of physical function.

The 106 patients who received placebo treatment had progressive joint-space narrowing after three years while there was no significant narrowing in the Xicil group. The authors concluded that the glucosamine mixture in Xicil could modify the course of osteoarthritis. More on this later.

A positive effect was also seen on the symptoms of osteoarthritis in the Xicil group compared to those receiving the placebo. Based on the questionnaire used in the study, symptoms worsened slightly in patients receiving the placebo compared to the improvement seen in those taking Xicil.

The results of this study cannot be translated to the numerous unregulated glucosamine products sold in health food stores and pharmacies in this country. Because glucosamine can be sold as a dietary supplement under the Dietary Supplement Health and Education Act of 1994, manufacturers of glucosamine products and other dietary supplements are not required to follow pharmaceutical-type Good Manufacturing Practice (GMP) guidelines. Such GMPs ensure that what is listed on the label is in fact in the bottle and, among other things, tablets and capsules consistently disintegrate and dissolve rather than passing straight through the body without being absorbed.

The Council for Responsible Nutrition, a trade group representing largely unregulated dietary and herbal supplement producers in the U.S., is having a field day trying to piggyback results for Xicil, which is regulated as a drug in Italy, to the products sold by their members that are not required to adhere to pharmaceutical type GMP guidelines. Although the Council maintains that its members follow GMPs, they fail to mention that the GMPs that they follow are food GMPs that only require supplements to be produced in relatively clean facilities, not the more stringent pharmaceutical GMPs.

We have several caveats concerning the interpretation of the Belgian study. First, even though the glucosamine that was used in Xicil is regulated as a drug in Italy and some other European countries, not all drug regulatory authorities are equivalent to the FDA. In many European countries, Germany for example, the manufacturer and content of natural products is regulated but these products have never been reviewed for effectiveness. Since Europe has no Freedom of Information Act, the public has no way of knowing what the basis was for allowing glucosamine to be sold for osteoarthritis. There may be none.

Second, the boundaries between science and promotion have been blurred. It is no longer possible to accept at face value the veracity of data from published clinical trials—even those appearing in the most prestigious medical journals such as The Lancet. What is required is a rigorous review process that is open to the public, something that is lacking even in this country.

Third, the process by which osteoarthritis damages joints is not fully understood. In an editorial accompanying the study, it was suggested that imaging techniques other than x-rays of the joint-space may be more valid indicators of the progression of osteoarthritis. Right now, all that can be said is that Xicil may prevent the x-ray evidence of progression of osteoarthritis, which may be different than actually preventing the progression of the disease.

The National Institutes of Health is sponsoring a large study of glucosamine and chondroitin in the treatment of arthritis. This study will not be completed until March 2005. We strongly support this type of drug development research.

What You Can Do

You should avoid using dietary and herbal supplements until they are regulated by the FDA. Until then it is let the buyer beware.