Glucosamine - Side Effects

What is glucosamine ?


Glucosamine is an amino sugar naturally occurring. It is a simple substance, composed of a glucose molecule of which a hydroxyl group has been replaced by an amino group (NH2 group) at the 2-position. It is the main building block for the biosynthesis of macromolecules as glycosaminoglycans (for example, hyaluronan), glycolipids, and glycoproteins. In humans and animals, these biopolymers in virtually all body tissues, but the highest concentrations are found in cartilage (cartilage matrix and synovial fluid), tendons and ligaments.

Glucosamine is sometimes used as a treatment for osteoarthritis because in vitro studies and animal studies show glucosamine sulfate able to normalize cartilage metabolism, to repair damaged cartilage and also appears to have mild anti-inflammatory properties. Intervention studies in humans the effects of glucosamine in osteoarthritis but delivers varying results. For this reason, it is not a generally accepted treatment method and it is mainly in the complementary medicine popular. Glucosamine sulfate is present in more than 56 countries (including 22 EU countries) registered as a drug.

Glucosamine is usually administered orally, in the form of a tablet or capsule, although it is also injected locally.

Naming and shapes

The scientific name of glucosamine is 2-amino-2-deoxy-alpha and -beta-D-glucopyranose. Although both the alpha and the beta form occur, the beta form is most common in nature. Glucosamine is a derivative of glucose, where it only differs by substitution of the hydroxyl group (at the second carbon atom) with an amino group. This amino group is positively charged at physiological pH. The anion in the salt may vary:

-D-Glucosamine Sulfate: This compound is rather unstable (in contact with water or air), which is why this type of glucosamine should be stabilized before use. There, sodium chloride (from glucosamine Rottapharm) or potassium chloride (most other glucosamine preparations) used for. These stabilizers may constitute up to one third of the weight of this raw material. This form of glucosamine since the early 80s of last century, available as a pharmaceutical preparation (Rottapharm) and these form the vast majority of clinical studies of glucosamine in the 80s and 90s.
-D-Glucosamine hydrochloride (glucosamine-HCl, sometimes incorrectly referred to as "glucosamine chloride"): This compound is more stable and better shelf life than glucosamine sulfate, and glucosamine supplies percentage more per gram of raw material. A number of large intervention studies from the first decade of the 21st century, where glucosamine proved ineffective, was conducted with glucosamine hydrochloride.
-N-acetyl-D-glucosamine (GlcNAc): This group of nitrogen to the acetylated form of the form in which glucosamine is glucosamine in a variety of biological macromolecules, such as in cartilage and synovial fluid, is built in.
-D-Glucosamine hydroiodide: This form is usually only used in injectable preparations.

The hydrochloride, and the sulfate form of glucosamine are most commonly used.
A major form in which glucosamine active in the body is glucosamine-6-phosphate.
Virtually all commercially available glucosamine is isolated from chitin, which in most cases from the exoskeleton of crustaceans (usually shrimp) is derived. For people with a shellfish allergy is glucosamine (hydrochloride) from plant material (fermented corn) available.

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Absorption and pharmacokinetics

Glucosamine is a small molecule which is easily absorbed, approximately 90% of orally administered glucosamine hydrochloride and glucosamine sulfate is absorbed intact from the gastrointestinal tract. The bioavailability of glucosamine hydrochloride (oral) in horses is between 3% and 6%, about 12% in dogs and 21% in rats. In humans, the bioavailability is probably higher than 20%. Absorbed glucosamine achieved through the joint synovial fluid, whence by cartilage cells (chondrocytes) will be drawn and incorporated as a component of the glycosaminoglycan in cartilage and the synovial fluid. Estimates of the half-life in humans range between approximately 15 hours and 70 hours.
Glucosamine is mainly excreted in the urine, only small amounts are found in the stool. Significant volumes today also be converted to carbon dioxide and excreted in exhaled air.

Legal Situation

Glucosamine sulfate is registered in more than 56 countries as a medicine, of which 22 countries of the European Union. In the Netherlands in 2005, the first glucosamine product registered as a non-prescription medicine for relief of symptoms in mild to moderate osteoarthritis of the knee. In 2012, in the Netherlands there are five glucosamine products (in all cases, glucosamine sulfate) with such a drug registration.

The other glucosamine products on the Dutch market classified as a food supplement and should therefore carry no medical claims. In the United States, glucosamine only sold as a dietary supplement. There are large differences in quality between various commercially available glucosamine sulfate products

Safety

In all meta-analyzes and reviews concluded that glucosamine has a favorable safety profile. Side effects of glucosamine, if they occur, are limited to mild gastrointestinal symptoms such as stomach upset and nausea, actually only in people with peptic ulcer. There are never any statistical or clinically significant differences were found between the occurrence of adverse events between glucosamine sulfate and placebo.

Despite attempts of glucosamine could never be identified a lethal dose.

Allergy
Glucosamine may contain shellfish allergens. In the literature, one hypersensitivity reaction following use of glucosamine described (angioedema). Products with glucosamine derived from shellfish is, therefore, an allergen entry mandatory. For vegetable glucosamine does not apply this requirement.
When produced according to pharmaceutical quality glucosamine total protein fraction is removed and the final product contains no allergens. Such glucosamine is well tolerated by people with shellfish allergy.

Diabetes
After an enhancement of insulin resistance in rats was found after intravenous administration of very high doses of glucosamine sulfate, it is further investigated whether a similar effect also occurs in humans. Although it was concluded initially that such an effect in humans would not occur, even not when also were administered intravenously in humans high doses, there are Also studies have been in which it was found that glucosamine indeed would have an effect on glucose metabolism, in particular in people with an already disordered glucose metabolism. Use of glucosamine would potentially interfere with the normal regulation of the hexosamine biosynthesis pathway. On the conclusions to be drawn for (pre) diabetes differ experts believe. Nevertheless, it may be advisable in such patients to monitor blood glucose levels during the treatment with glucosamine.

Cholesterol
Glucosamine can infrequently result in an increase in cholesterol, so it is recommended to check this during treatment.

Use during pregnancy and lactation
About possible risks from the use of glucosamine during pregnancy or lactation is insufficient reliable information available. A number of suppliers of glucosamine containing preparations recommend the use of glucosamine during pregnancy or lactation off.

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