Glucosamine | AAFP

STEPHEN DAHMER, MD, AND ROBERT M. SCHILLER, MD

Am Fam Physician. 2008;78(4):471-476

Patient information: See related handout on glucosamine, written by the authors of this article.

Author disclosure: Nothing to disclose.

Glucosamine is one of the most popular dietary supplements sold in the United States. Most clinical trials have focused on its use in osteoarthritis of the knee. The reported adverse effects have been relatively well studied and are generally uncommon and minor. No significant supplement–drug interactions involving glucosamine have been reported. The National Institutes of Health–sponsored Glucosamine/chondroitin Arthritis Intervention Trial, the largest randomized, double-blind, placebo-controlled study involving the supplement, still has not confirmed whether glucosamine is effective in the treatment of osteoarthritis. Despite conflicting results in studies, there is no clear evidence to recommend against its use. If physicians have patients who wish to try glucosamine, it would be reasonable to support a 60-day trial of glucosamine sulfate, especially in those at high risk of secondary effects from other accepted treatments. The decision to continue therapy can then be left to patients on an individual basis, while the physician monitors for possible adverse effects. Glucosamine should be used with caution in patients who have shellfish allergies or asthma, and in those taking diabetes medications or warfarin.

Glucosamine and chondroitin sulfate are among the most popular dietary supplements sold in the United States.¹ The U.S. consumer market for glucosamine and chondroitin was estimated at $810 million in 2005.² Glucosamine is also one of the most studied supplements, with more than 20 randomized controlled trials involving over 2,500 patients. ³ Glucosamine sulfate attracted the attention of the scientific community after two long-term clinical trials showed that it could slow the progression of anatomic joint structure changes in knee osteoarthritis and control the progression of symptoms.^4,5 Subsequent trials have had conflicting results, including the largest study, the National Institutes of Health–funded Glucosamine/chondroitin Arthritis Intervention Trial (GAIT).⁶ Although most studies are of glucosamine alone, it is often sold in combination with chondroitin. It is not known if this combination is better than glucosamine alone, but animal studies suggest that this may be the case.^7,8 This article focuses on a literature review of glucosamine and its use in osteoarthritis.

Clinical recommendation	Evidence Rating	References
Treatment with glucosamine sulfate is a reasonable option in patients who wish to try it or in those who cannot tolerate traditional therapies for knee pain in osteoarthritis.	A	4, 5, 17, 18, 25
Caution is advised when using glucosamine in patients with an allergy to shellfish, patients with asthma, and those taking diabetes medications or warfarin (Coumadin).	C	34, 35, 37, 38

Pharmacology

Glucosamine (2-amino-2-deoxy-β-d-glucopyranose) is an endogenous aminomonosaccharide synthesized from glucose and utilized for biosynthesis of glycoproteins and glycosaminoglycans.⁹ Glucosamine is present in almost all human tissues, highly concentrated in connective tissues of the human body, and found at highest concentrations in the cartilage. In humans, about 90 percent of glucosamine is absorbed when administered as an oral dose of glucosamine sulfate, and is rapidly incorporated into articular cartilage.¹⁰ Glucosamine can be found in many forms, including sulfate, hydrochloride, N-acetyl-glucosamine, or chlorohydrate salt, and as a dextrorotatory isomer. There is some dispute over which form is most effective. Pooled findings from studies using a specific commercial glucosamine sulfate product called Dona suggest that this formulation reduces osteoarthritis pain, whereas other formulations do not.¹¹ Another study performed in China provides some evidence that glucosamine hydrochloride and glucosamine sulfate are equally effective.¹²

The sulfate salt of glucosamine forms one half of the disaccharide subunit of keratan sulfate, which decreases in patients with osteoarthritis. Hyaluronic acid (found in articular cartilage and synovial fluid) is composed of repeating dimeric units of glucuronic acid and N-acetylglucosamine.¹³ Possible mechanisms of action for the chondroprotective effect of glucosamine include direct stimulation of chondrocytes, incorporation of sulfur into cartilage, and protection against degradative processes within the body through altered gene expression.^10,14,15 The exact mechanism of action for the possible effect of glucosamine is unknown.

Uses and Effectiveness

Glucosamine has been studied for many uses, including treatment of temporomandibular joint disorder and rheumatoid arthritis, but most trials have focused on its use in osteoarthritis. Clinical trials have yielded conflicting results. Double-blind studies enrolling more than 400 persons found glucosamine and ibuprofen (Motrin) to be equally effective in reducing symptoms of knee and temporomandibular joint osteoarthritis.^16–18 In four studies involving more than 500 persons, glucosamine failed to provide any meaningful improvement in symptoms.^19–23 A recent study concluded that most of the trials with positive outcomes were funded by manufacturers of glucosamine products, whereas most trials performed by neutral researchers failed to find benefit.²⁴

Two of the largest placebo-controlled trials conducted before 2007 were in Europe and used the glucosamine sulfate formulation.^4,5 In the 2001 Belgian study, 212 persons with osteoarthritis of the knee were followed for three years, received either placebo or oral glucosamine sulfate in a dosage of 1,500 mg daily, and were evaluated using the Western Ontario and McMaster Universities (WOMAC) osteoarthritis index. ⁴ The WOMAC index is the most commonly employed questionnaire in clinical research to assess degree of pain and stiffness, as well as functional impairment caused by osteoarthritis. The study showed that patients taking glucosamine sulfate had modest pain reduction (average of 11.7 percent relative reduction in the WOMAC index compared with baseline) and reduced joint-space narrowing compared with placebo, as measured by weight-bearing anteroposterior view radiography (0.06 mm versus 0.31 mm). Both differences were statistically significant; however, there was no correlation between improvement in symptoms and radiographic findings.⁴

In a similar 2002 trial conducted in Prague, Czech Republic, 202 patients with osteoarthritis of the knee were given placebo or 1,500 mg of Dona and were followed for three years.⁵ Those receiving Dona showed statistically significant improvement in symptoms of pain and stiffness compared with placebo (26 percent versus 16 percent mean reduction in the WOMAC index) and radiographic evidence of decreased narrowing in the medial joint compartment (mean gain of 0. 04 mm versus 0.19 mm of joint-space narrowing).

The most recent meta-analysis of glucosamine was conducted in 2005 and included 20 randomized controlled trials with a total of 2,570 patients.¹¹ The investigators found that current evidence: (1) does not analyze the long-term effectiveness and toxicity of glucosamine; (2) does not differentiate which joints and which levels of severity of osteoarthritis warrant this therapy; (3) does not differentiate which dosage and route of administration are best; and (4) does not demonstrate whether glucosamine modifies the long-term progression of osteoarthritis. When restricting the analysis to eight studies with the highest-quality design, no overall improvement in pain or function was found.¹¹ The investigators concluded that there was high-quality evidence that glucosamine was not as useful for symptom improvement as had been previously thought.

The authors of the 2006 GAIT also were unable to conclude whether glucosamine is useful in the treatment of osteoarthritis. ⁶ GAIT was the first major clinical trial to directly compare glucosamine alone, chondroitin alone, combination glucosamine/chondroitin, a cyclooxygenase inhibitor, and placebo. It included more than 1,500 patients who were followed for six months. The WOMAC index was the primary outcome measure. Although radiographic data have yet to be published, the authors concluded that, compared with placebo, glucosamine alone or in combination with chondroitin did not reduce pain significantly after six months in patients with osteoarthritis of the knee. They did suggest that a combination of the two may be effective in a subgroup of patients with moderate to severe knee pain. An important finding in this study was a placebo effect of around 60 percent, suggesting that the sample size used was possibly inadequate.²⁵ Additional concerns about the study have been raised, including the attrition rate, limitations in data analysis, and the use of glucosamine hydrochloride preparation rather than the glucosamine sulfate preparation. ²⁶ A 2008 study of glucosamine sulfate in more than 200 patients with hip osteoarthritis showed no reduction in symptoms or progression of arthritis compared with placebo.²⁷

Glucosamine combined with chondroitin has been used in a topical form in a few small, randomized, double-blind, placebo-controlled trials with favorable results.^28,29 One study showed statistically significant improvement in pain reduction after eight weeks with a glucosamine/chondroitin preparation compared with placebo (visual analog scale measurements).²⁹ There have also been some initial studies suggesting that the addition of glucosamine to non-steroidal anti-inflammatory drugs (NSAIDs) could decrease NSAID use in those patients already taking them.³⁰ Because the anti-inflammatory ability of glucosamine is different from that of NSAIDs, it is possible the two might have a synergistic effect in alleviating some types of inflammation.³¹

Finally, a 2007 double-blind, placebocontrolled study of 51 Japanese patients with rheumatoid arthritis showed that glucosamine hydrochloride in a dosage of 1,500 mg daily significantly improved symptoms according to patients’ self-evaluation and physician global evaluation. ³² It did not, however, alter measures of inflammation as determined through blood tests.

Contraindications, Adverse Effects, and Interactions

The reported adverse effects have been generally uncommon and minor. Glucosamine is produced from the shells of lobster, crab, and shrimp. However, the antigen proteins associated with seafood allergies are not found in the shell, and there have been no reports of reactions in persons with shell-fish allergies who take glucosamine.³³ There also have been no significant supplement–drug interactions involving glucosamine. In one case report, the addition of glucosamine sulfate to a stable-dose regimen of warfarin (Coumadin) appeared to magnify the anticoagulant effects of warfarin in a 69-year-old man.³⁴ Only one person has been reported to have had an allergic reaction to oral glucosamine.³⁵

In a large open trial (n = 1,208), the most common adverse effects of oral glucosamine sulfate (1. 5 g daily) were epigastric pain or tenderness (3.5 percent), heartburn (2.7 percent), diarrhea (2.5 percent), and nausea (1 percent).³⁶ There was a single case report of a glucosamine-chondroitin sulfate compound triggering difficulty walking and climbing steps because of shortness of breath in a 52-year-old woman with longstanding intermittent asthma.³⁷ Finally, it has been hypothesized that glucosamine is associated with reducing the effectiveness of diabetes medications.³⁸ To date, this has been refuted, and the use of glucosamine in patients with diabetes has not been shown to affect insulin sensitivity or induce insulin resistance. Nonetheless, the Arthritis Foundation recommends that patients with diabetes monitor their blood glucose levels more often when taking glucosamine.³⁹ Scientific evidence for the safe use of glucosamine during pregnancy is not available.

Dosage

Glucosamine is supplied in tablets and capsules. The usual dosing schedule is 500 mg three times daily. In 2001, Consumer Reports evaluated 19 products and reported that most brands were reasonably well standardized, delivering at least 90 percent of the amount of glucosamine or chondroitin promised on the label. Only four products failed to meet that standard.⁴⁰ In 2001, one company recalled two products that were found to contain aristolochic acid, a substance that can cause kidney toxicity and cancer.⁴¹ Retail prices for a 30-day supply of glucosamine range from $9 to $35 (product quality may vary).³

Bottom Line

The use of glucosamine is widespread in the United States. Physicians should be encouraged to have open discussions with patients, as well as inform them about the controversy regarding the supplement’s effectiveness. Because of glucosamine’s potential for benefit, there is no reason to recommend against its use, especially in persons at high risk of secondary effects from other accepted treatments.

In trials that have found benefit with glucosamine, most focused on the glucosamine sulfate preparation, and most showed improvements after 30 to 90 days of therapy. Therefore, it would be reasonable to support a 60-day trial of glucosamine sulfate. The decision to continue therapy can then be left to patients on an individual basis, while the physician monitors for possible adverse effects. Caution is advised in patients with shellfish allergies or asthma, and in those taking diabetes medications or warfarin. If a patient chooses to try glucosamine therapy, the physician should recommend glucosamine sulfate (from a reputable source) in a dosage of 500 mg orally three times daily. Key points about glucosamine are summarized in Table 1.

Overview, Uses, Side Effects, Precautions, Interactions, Dosing and Reviews

Overview

Glucosamine is a chemical found in the body. Glucosamine supplements are sold as glucosamine sulfate, glucosamine hydrochloride, and N-acetyl glucosamine.

Glucosamine is used by the body to make other chemicals that build tendons, ligaments, cartilage, and the fluid that surrounds joints. Joints are cushioned by the fluid and cartilage around them. Taking glucosamine might increase the cartilage and fluid around joints and/or help prevent their breakdown.

People commonly use glucosamine sulfate and glucosamine hydrochloride for osteoarthritis. Glucosamine is also used for joint pain, rheumatoid arthritis, multiple sclerosis, and many other conditions, but there is no good scientific evidence to support these other uses.

Uses & Effectiveness ?

Likely Effective for

• Osteoarthritis. Taking glucosamine sulfate by mouth for at least 4 weeks can provide some pain relief and improve function for people with knee osteoarthritis. Products that contain glucosamine hydrochloride do not seem to work as well unless they are taken in combination with other ingredients. Taking glucosamine sulfate doesn’t seem to reduce the risk of getting osteoarthritis.

There is interest in using glucosamine for a number of other purposes, but there isn’t enough reliable information to say whether it might be helpful.

Side Effects

When taken by mouth: Glucosamine sulfate is likely safe in most adults when used for up to 3 years. Glucosamine hydrochloride is possibly safe for most adults when used for up to 2 years. N-acetyl glucosamine is also possibly safe when used for up to 6 months. Glucosamine can cause some mild side effects including bloating, nausea, diarrhea, and constipation.

When applied to the skin: N-acetyl glucosamine is possibly safe when used for up to 10 weeks.

When given as an enema (rectally): N-acetyl glucosamine is possibly safe when used in doses of 3-4 grams daily.

Special Precautions and Warnings

Pregnancy and breast-feeding: There isn’t enough reliable information to know if glucosamine sulfate, glucosamine hydrochloride, or N-acetyl glucosamine is safe to use when pregnant or breast-feeding. Stay on the safe side and avoid use.

Asthma: Glucosamine might make asthma worse. Until more is known, people with asthma should be cautious about taking products that contain glucosamine.

Diabetes: There used to be some concern that glucosamine might increase blood sugar levels. But most research shows that glucosamine doesn’t increase blood sugar levels in people with diabetes.

Glaucoma: Glucosamine might increase the pressure inside the eye and could worsen glaucoma. If you have glaucoma, talk to your healthcare provider before taking glucosamine.

High cholesterol: There used to be some concern that glucosamine might increase cholesterol levels. But most research shows that glucosamine doesn’t seem to increase cholesterol levels.

High blood pressure: There used to be some concern that glucosamine might increase blood pressure. But most research shows that glucosamine does not seem to increase blood pressure.

Shellfish allergy: Glucosamine is produced from the shells of shrimp, lobster, and crabs. If you have a shellfish allergy, talk to your healthcare provider before using glucosamine.

Interactions ?

Major Interaction

Do not take this combination

• Warfarin is used to slow blood clotting. Taking glucosamine with or without chondroitin increases the effects of warfarin. This can increase the risk for serious bruising and bleeding. Don’t take glucosamine if you are taking warfarin.

Moderate Interaction

Be cautious with this combination

• Some medications for cancer work by decreasing how fast cancer cells can copy themselves. Glucosamine might block these medications from working. Taking glucosamine along with some medications for cancer might decrease the effectiveness of these medications.

Minor Interaction

Be watchful with this combination

• Taking glucosamine SULFATE and acetaminophen together might affect how well each works. But more information is needed to know if this interaction is a big concern.

• Glucosamine might increase blood sugar levels. Taking glucosamine along with diabetes medications might reduce the effects of these medications. Monitor your blood sugar closely.

Dosing

Glucosamine sulfate and glucosamine hydrochloride have most often been used by adults in doses of 1500 mg by mouth daily for up to 3 years. Speak with a healthcare provider to find out what dose might be best for a specific condition.

Keep in mind that glucosamine used in supplements often comes from the shells of shellfish. Talk to your healthcare provider before taking these supplements if you have a shellfish allergy. Also, some glucosamine products aren’t labeled correctly. In some cases, the amount of glucosamine actually in the product has varied from none to over 100% of the amount stated on the product’s label. Some products have contained glucosamine hydrochloride when glucosamine sulfate was listed on the label.

View References

CONDITIONS OF USE AND IMPORTANT INFORMATION: This information is meant to supplement, not replace advice from your doctor or healthcare provider and is not meant to cover all possible uses, precautions, interactions or adverse effects. This information may not fit your specific health circumstances. Never delay or disregard seeking professional medical advice from your doctor or other qualified health care provider because of something you have read on WebMD. You should always speak with your doctor or health care professional before you start, stop, or change any prescribed part of your health care plan or treatment and to determine what course of therapy is right for you.

This copyrighted material is provided by Natural Medicines Comprehensive Database Consumer Version. Information from this source is evidence-based and objective, and without commercial influence. For professional medical information on natural medicines, see Natural Medicines Comprehensive Database Professional Version. © Therapeutic Research Faculty 2018.

Glucosamine instructions for use: indications, contraindications, side effects – description Glucosamine tab., cover. film coated, 750 mg: 10, 20, 30, 40, 50, 60 or 100 pcs.

(47775)

💊 The composition of the drug Glucosamine ✅ The use of the drug Glucosamine Keep for yourself Search for analogues Interaction Description of the active ingredients of the preparation Glucosamine (Glucosamine) The scientific information provided is general and cannot be used to make decisions. decisions about the use of a particular drug. Update date: 2022.03.21 Marketing authorization holder: ATOLL, OOO (Russia) Manufactured: OZON, OOO (Russia) ATX code: M01AX05 (Glucosamine) Active substance: glucosamine (glucosamine) Rec. INN WHO registered Dosage form Glucosamine Tab., coated film coated, 750 mg: 10, 20, 30, 40, 50, 60 or 100 pcs. reg. No.: LP-004619 dated 12/26/17 – Active Release form, packaging and composition drug Glucosamine Film-coated tablets white or off-white, oval, biconvex, scored on one side; two layers are visible on the fracture – the core is from white to white with a yellowish or brown tint and the film membrane. Excipients : microcrystalline cellulose – 320 mg, colloidal silicon dioxide – 10 mg, croscarmellose sodium – 44. 9 mg, purified water – 20 mg, povidone K25 – 49 mg, magnesium stearate – 14 mg. Excipients (shell): hypromellose – 22.8 mg, macrogol-4000 – 5.6 mg, titanium dioxide – 11.6 mg. 10 pcs. – cellular contour packings (1) – packs of cardboard. 10 pcs. – cellular contour packings (2) – packs of cardboard. 10 pcs. – cellular contour packings (3) – packs of cardboard. 10 pcs. – cellular contour packings (4) – packs of cardboard. 10 pcs. – cellular contour packings (5) – packs of cardboard. 10 pcs. – cellular contour packings (6) – packs of cardboard. 10 pcs. – cellular contour packings (10) – packs of cardboard. 10 pcs. – cans (1) – packs of cardboard. 20 pcs. – cans (1) – packs of cardboard. 30 pcs. – cans (1) – packs of cardboard. 40 pcs. – cans (1) – packs of cardboard. 50 pcs. – cans (1) – packs of cardboard. 60 pcs. – cans (1) – packs of cardboard. 100 pcs. – cans (1) – packs of cardboard. Clinical and pharmacological group: A drug that stimulates the process of cartilage tissue regeneration Pharmacotherapeutic group: Tissue repair stimulator Pharmacological action A drug that affects the metabolism in cartilage tissue. Replenishes the natural deficiency of glucosamine, stimulates the synthesis of proteoglycans and hyaluronic acid in the synovial fluid; increases the permeability of the joint capsule, restores enzymatic processes in the cells of the synovial membrane and articular cartilage. Promotes the fixation of sulfur in the process of synthesis of chondroitinsulfuric acid, facilitates the normal deposition of calcium in bone tissue, inhibits the development of degenerative processes in the joints, restores their function and reduces pain. Pharmacokinetics The oral bioavailability of glucosamine is 25% due to the “first pass” effect through the liver. The highest concentrations of glucosamine are found in the liver, kidneys and articular cartilage. It is excreted mainly in the urine unchanged; partially – with feces. T 1/2 is 68 hours Indications of the active substances of the drug Glucosamine Primary and secondary osteoarthritis, humeroscapular periarthritis, osteochondrosis, spondylosis, chondromalacia of the patella. Open list of ICD-10 codes M15 Polyarthrosis M22.4 Chondromalacia patella M42 Spinal osteochondrosis M47 Spondylosis M75. 0 Adhesive capsulitis of the shoulder Dosage regimen The method of administration and dosing regimen of a particular drug depends on its form of release and other factors. The optimal dosage regimen is determined by the doctor. Compliance of the dosage form of a particular drug with indications for use and dosing regimen should be strictly observed. Internal, intramuscular, external. The dose and duration of treatment is set individually. Side effects Possible: epigastric pain, nausea, flatulence, diarrhea, constipation, allergic reactions. Contraindications for use Hypersensitivity to glucosamine, phenylketonuria (if the drug contains aspartame), severe chronic renal failure, children under 12 years of age, pregnancy, breastfeeding. Use during pregnancy and lactation Use during pregnancy and lactation (breastfeeding) is contraindicated. Use in impaired renal function Contraindicated in severe chronic renal failure. Use in children Contraindicated in children under 12 years of age. Drug Interactions When used in combination, glucosamine increases the absorption of tetracyclines from the gastrointestinal tract and reduces that of penicillins and chloramphenicol. Glucosamine is compatible with NSAIDs, GCS. Keep If you want to place a link to the description of this drug – use this code Glucosamine . Description of the drug in the reference book Vidal.

Description GLUCOSAMINE indications, dosages, contraindications of the active substance GLUCOSAMINE