The Birth of a Hybrid: Production of Scientific Knowledge on Glucosamine

Glucosamine is a natural substance. It is an amino sugar and component of cartilage, found in animal tissue and human joints. In both the food or pharma­ceutical industries, glucosamine can be manufactured by extraction from chitin in crustacean shells.

A debate on the effectiveness of Viartril-S and its generic equivalents per­sisted for years and played a key role in the social life of glucosamine sulfate. Two different scientific claims were declared and accepted in Europe and the United States: one recognized its medical benefits on managing osteoarthritis, while the other denied its effectiveness. The scientific evidence and food-drug boundary produced by the trials distinguished the regulation of glucosamine in these two regions.

Clinical trials published in the 1980s and 1990s explored the effectiveness of glucosamine sulfate in treating osteoarthritis. Most of the studies were only limited to European journals. According to a search of the PubMed database, the earliest of these investigations were two small clinical trials conducted by the Rotta Research Laboratorium that enrolled 30 and 20 patients with osteo­arthritis, respectively. Both trials were published in the same journal, Current

Medical Research and Opinion, in 1980.^[753] Improvements in joint pain, tender­ness, swelling, and restriction of movement following glucosamine consump­tion were reported.

By the 1990s, Viartril-S had gained popularity across Europe. In the United States, the regulation and circulation of this product were considerably dif­ferent. Rottapharm introduced glucosamine sulfate to the market under the brand name “Dona” no later than the 1990s; no details about the product in the United States before the 1990s can be found. Glucosamine products are regu­lated as dietary supplements in the United States according to the provisions of the Dietary Supplement Health and Education Act of 1994.^[755] Because glu­cosamine is produced by extraction from a food material, Dona and all other glucosamine-containing products are legally considered foods. Nevertheless, Rottapharm patented their glucosamine sulfate product in the early 1990s. To circumvent this patent, other pharmaceutical companies developed products using another form of glucosamine salt, glucosamine hydrochloride (HCL). Glucosamine HCL soon became another popular ingredient in glucosamine supplements.

Clinical trials conducted in the United States reached a different conclusion from those in Europe regarding the effectiveness of glucosamine.

Effective Health Foods, Ineffective Drugs 209 the glucosamine used in US studies is different. Specifically, they investigated glucosamine HCL, not glucosamine sulfate. The authors of a clinical trial pub­lished in Osteoarthritis and Cartilage in 2000 declared that their study was the first glucosamine clinical trial in the United States and that “the American literature is devoid of human clinical data while the data is copiously available from the European literature.” However, the therapeutic they examined was not glucosamine sulfate (as studied in the European evidence they cited) but rather glucosamine HCL combined with other components also intended to promote cartilage repair.^[756] Although their results revealed “effectiveness in the management of osteoarthritis of the knee,” most other trials yielded different conclusions. A notable trial published in the New England Journal of Medicine in 2006, sponsored by the US National Institutes of Health, recruited 1,583 patients with osteoarthritis.^[757] The researchers also examined glucosamine HCL instead of glucosamine sulfate.^[758] Although they found that glucosamine HCL “may have some efficacy in patients with moderate-to-severe symptoms,” their conclusion was more conservative: the overall results revealed no significant difference between glucosamine HCL and the placebo. Their findings support the regulatory status of glucosamine as a food in the United States. The results of this trial have been widely accepted and cited by medical professionals who deny the effectiveness of glucosamine, but few have mentioned the differences between the form of glucosamine investigated in the European and US trials. It depends on how you classify glucosamine (distinguish glucosamine HCL from sulfate form or lump them together) to regulate them as food or drugs.

Although clinical trials seem to conclude the debate on effectiveness, the testing material is problematic because of the same regulation dilemma.

This explains why the trials conducted in the United States tended to ignore positive outcomes associated with glucosamine. The history of glucosamine in the United States reveals how classificatory regulations limit the production and flow of medical knowledge.

Europe and the United States’ experiences with glucosamine provide differ­ent examples for understanding knowledge production, food-drug regulation, and their relationships. Although the European trials demonstrated the effec­tiveness of glucosamine sulfate, the design and conclusions of these trials have been criticized. Even after a series of clinical trials were conducted in the 1990s and 2000s, not all medical professionals were convinced. The US trials did not tarnish the perception of glucosamine sulfate in Europe because the exam­ined therapeutic was different. Rottapharm argued that its patented crystalline form of glucosamine sulfate has better bioavailability and is better absorbed in humans than are other forms of glucosamine sulfate. A 2015 Cochrane review of 20 randomized controlled trials determined that glucosamine sulfate was demonstrated to be effective in 10 trials specifically testing crystalline glucosa­mine sulfate.^[760] Therefore, from the viewpoint of Rottapharm, the distinction between glucosamine sulfate and HCL was not sufficiently clear.

Clinical trials on glucosamine have involved the governance frameworks of various countries and regions in a process of categorical coproduction, partially driven by pharmaceutical companies and partially consequent to local regula­tions. On the one hand, the trials produced scientific knowledge under the existing framework of food-drug regulation. On the other hand, this knowl­edge created new boundaries between forms of glucosamine, spurring a persis­tent debate on the status of glucosamine and further obscuring its category The history of glucosamine sulfate in Taiwan further reflects this process. Its social life involves the international flow of knowledge production from Europe and the United States as well as local regulations and Taiwan’s National Health Insurance (NHI) reimbursement scheme. The local experience also demon­strates how the Health Food Control Act failed to regulate such a hybrid in the food-drug borderland.

III.