Natural Standard® Patient Monograph, Copyright © 2014 (www.naturalstandard.com). All Rights Reserved. Commercial distribution prohibited. This monograph is intended for informational purposes only, and should not be interpreted as specific medical advice. You should consult with a qualified healthcare provider before making decisions about therapies and/or health conditions.

Background

Glucosamine is a compound that is naturally made in humans. It is involved in the creation of molecules that form cartilage.

Evidence supports the use of glucosamine sulfate in the treatment of knee osteoarthritis. It is believed that the sulfate portion may help strengthen cartilage. If this is confirmed, it would mean that the glucosamine sulfate form is more effective than glucosamine without sulfate.

Glucosamine is often taken together with chondroitin, which comes from cartilage. The use of integrative therapies like glucosamine is often seen in people with osteoarthritis. These treatments may help reduce doses of drugs such as nonsteroidal anti-inflammatory agents (NSAIDs).

Glucosamine has also been studied for possible benefits on wound healing, skin conditions such as psoriasis, and the prevention of migraine. More research is needed in these areas.

Research shows that glucosamine is well tolerated for up to three years. However, people who are allergic to shellfish should avoid using it.

There have been concerns about the effects of glucosamine on insulin and blood sugar. However, some recent studies suggest that glucosamine may not affect these measures. This remains an area of controversy.

Dosing

The below doses are based on scientific research, publications, traditional use, or expert opinion. Many herbs and supplements have not been thoroughly tested, and safety and effectiveness may not be proven. Brands may be made differently, with variable ingredients, even within the same brand. The below doses may not apply to all products. You should read product labels, and discuss doses with a qualified healthcare provider before starting therapy.

Adults (18 years and older)

Note: Full benefit of glucosamine may take up to one month in some people. Glucosamine hydrochloride may provide more glucosamine than the glucosamine sulfate salt form.

To treat bone diseases (Kashin-Beck disease), 480 milligrams of glucosamine hydrochloride has been taken by mouth three times daily for six months, as well as 750 milligrams of glucosamine hydrochloride by mouth twice daily for six weeks.

To treat circulation problems (chronic venous insufficiency), Perclar® has been taken by mouth at doses of 48 milligrams, 72 milligrams, or 96 milligrams.

To treat high cholesterol, 1,500 milligrams of glucosamine, 1,527 milligrams of glucosamine sulfate (equivalent to 1,200 milligrams glucosamine), or 750 milligrams glucosamine hydrochloride (equal to 625 milligrams glucosamine) has been taken by mouth daily for up to 14 weeks.

To treat knee osteoarthritis, 300-500 milligrams of glucosamine sulfate or 480 milligrams of glucosamine hydrochloride has been taken by mouth three times daily for up to 12 weeks.

To treat low back pain, 1500 milligrams of glucosamine has been taken by mouth daily for six months. Additionally, 3 milliliters of glucosamine sulfate cream or 3 milliliters of glucosamine sulfate have been given through the skin via iontophoresis (using electricity to deliver the drug) or massaged into the skin for 15 minutes, three times weekly for four weeks.

To treat multiple sclerosis, 1000 milligrams daily of glucosamine sulfate has been taken by mouth for six months.

To treat osteoarthritis (general), 1000-2000 milligrams daily of glucosamine, glucosamine sulfate, or glucosamine hydrochloride in the form of tablets, capsules, or crystalline powder has been taken by mouth for up to 18 months. Up to 400 milligrams of glucosamine has also been injected into the joint, vein, or muscle for varying durations.

To treat rheumatoid arthritis, 420 milligrams of Teoremac® has been taken by mouth daily for 14 days.

Children (under 18 years old)

Glucosamine is not suggested in children, due to lack of data. Research suggests that there may be a link between autism and methylsulfonylmethane (MSM), which is often marketed with glucosamine. However, there is still a lack of information. Doses of 3-6 grams of N-acetyl-glucosamine have been used to treat inflammatory bowel disease in children.

Evidence

These uses have been tested in humans or animals.  Safety and effectiveness have not always been proven.  Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider.

Key to grades

A
Strong scientific evidence for this use
B
Good scientific evidence for this use
C
Unclear scientific evidence for this use
D
Fair scientific evidence against this use (it may not work)
F
Strong scientific evidence against this use (it likely does not work)

Grading rationale

Evidence gradeCondition to which grade level applies
B

Knee osteoarthritis

Evidence supports the use of glucosamine sulfate taken by mouth to treat knee osteoarthritis. Nearly all studies have used glucosamine sulfate supplied by Rotta Research Laboratorium, a manufacturer in Europe. It is unclear if glucosamine sold by other manufacturers are equally effective. Studies demonstrating a lack of efficacy have included people with severe osteoarthritis or used formulas other than glucosamine sulfate.
B

Osteoarthritis (general)

Several studies have found that glucosamine may benefit osteoarthritis in other body parts, aside from the knee. However, there is less evidence to support this compared to knee osteoarthritis. Knee osteoarthritis appears to respond better than other joints to any treatment. Overall, high-quality studies are lacking. More research is needed in this area.
C

Bone diseases (Kashin-Beck disease)

Preliminary evidence suggests that glucosamine with and without chondroitin sulfate may preserve articular cartilage, decrease pain, increase physical function, and enhance self-care activities in people with Kashin-Beck disease (KBD). Further research is needed.
C

Circulation problems

Glucosamine has been studied for chronic venous insufficiency, a disease in which there are problems sending blood back to the heart from the legs. Currently, there is a lack of evidence supporting the use of glucosamine for this disorder. More research is needed in this area.
C

Diabetes

There is controversy regarding the effects of glucosamine on insulin and blood sugar. Despite concerns about the use of glucosamine in people with diabetes, some studies suggest that it may lack significant effects on insulin or blood sugar. Further research is needed in this area.
C

Inflammatory bowel disease (Crohn's disease, ulcerative colitis)

Early research suggests a lack of evidence to support the use of glucosamine in the treatment of inflammatory bowel disease. More research is needed in this area.
C

Interstitial cystitis (bladder wall inflammation)

Early study suggests that a product containing both glucosamine sulfate and chondroitin sulfate may benefit interstitial cystitis symptoms. More research is needed in this area.
C

Knee pain

A few studies have found improvement in knee pain with the use of glucosamine. Although promising, further research is needed before conclusions may be made.
C

Lumbar pain (lower back pain)

Glucosamine sulfate has been studied in the treatment of lumbar pain (pain near the lower spine). Treatment with glucosamine sulfate alone or in combination with potassium may help reduce pain. Another study reported a lack of effect on low back pain. Additional studies are needed in this area.
C

Multiple sclerosis

Early evidence suggests that the use of glucosamine may lack an effect in people who have multiple sclerosis. More research is needed in this area.
C

Rheumatoid arthritis

Early evidence suggests that there is a lack of evidence to support glucosamine use for rheumatoid arthritis. More research is needed in this area.
C

Sexual disorders

A glucosamine combination product has been shown to improve sexual dysfunction in men. Further studies are required before firm conclusions can be made.
C

Temporomandibular joint (TMJ) disorders

Early evidence suggests a lack of evidence to support glucosamine alone or in combination with chondroitin for TMJ disorders (jaw and face pain). More research is needed in this area.
D

High cholesterol

Glucosamine has been studied for its possible benefits in lowering low-density lipoprotein (LDL or "bad") cholesterol. It has also been studied for increasing high-density lipoprotein (HDL or "good") cholesterol. Results from these studies show that glucosamine lacked significant benefits. Additional study is needed in this area.

Uses based on tradition or theory

The below uses are based on tradition or scientific theories. They often have not been thoroughly tested in humans, and safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider.

AIDS, ankylosing spondylitis (spine arthritis), athletic injuries, bleeding esophageal varices (blood vessels in the esophagus), cancer, congestive heart failure, depression, diabetic complications, fibromyalgia (pain disorder), immune system function, joint problems, kidney stones, metabolic abnormalities (Fabry's disease), migraine headache, migraine headache prevention, osteoporosis, psoriasis (skin disorder), skin pigmentation disorders, skin rejuvenation, wound healing.

Interactions

Interactions with Drugs

Glucosamine may increase the risk of bleeding when taken with drugs that increase the risk of bleeding. Some examples include aspirin, anticoagulants ("blood thinners") such as vitamin K antagonists (warfarin, Coumadin®) or heparin, anti-platelet drugs such as clopidogrel (Plavix®), and non-steroidal anti-inflammatory drugs such as ibuprofen (Motrin®, Advil®) or naproxen (Naprosyn®, Aleve®).

Glucosamine may affect insulin and blood sugar levels. Caution is advised when using medications that may affect blood sugar. People taking drugs for diabetes by mouth or insulin should be monitored closely by a qualified healthcare professional, including a pharmacist. Medication adjustments may be necessary.

Glucosamine may interfere with the way the body processes certain drugs using the liver's "cytochrome P450" enzyme system. As a result, the levels of these drugs may be increased in the blood, and may cause increased effects or potentially serious adverse reactions. People using any medications should check the package insert, and speak with a qualified healthcare professional, including a pharmacist, about possible interactions.

Glucosamine may also interact with acetaminophen; agents applied to the skin; agents eliminated by the kidneys; agents for the stomach or intestines; agents that increase sun sensitivity; agents that may increase urine flow; alcohol; anticancer agents; antidepressants; anti-hemorrhage agents; caffeine; chitosan; doxorubicin; etoposide; nicotine; nonsteroidal anti-inflammatory drugs (NSAIDs); pain relievers; rosiglitazone; teniposide; thiazolidinediones.

Interactions with Herbs and Dietary Supplements

Glucosamine may increase the risk of bleeding when taken with herbs and supplements that are believed to increase the risk of bleeding. Multiple cases of bleeding have been reported with the use of Ginkgo biloba, and fewer cases with garlic and saw palmetto. Numerous other agents may theoretically increase the risk of bleeding, although this has not been proven in most cases.

Glucosamine may interfere with the way the body processes certain herbs or supplements using the liver's "cytochrome P450" enzyme system. As a result, the levels of other herbs or supplements may become too high in the blood. It may also alter the effects that other herbs or supplements possibly have on the P450 system.

Glucosamine may affect insulin and blood sugar levels. Caution is advised when using herbs or supplements that may affect blood sugar. Blood glucose levels may require monitoring, and doses may need adjustment.

Glucosamine may also interact with anticancer herbs and supplements; antidepressants; anti-hemorrhage herbs and supplements; antioxidants; avocado or soybean oils or extracts; bromelain; celadrin; Chinese skullcap; chondroitin sulfate; fish oil; ginger; green-lipped mussel extract; herbs and supplements applied to the skin; herbs and supplements eliminated by the kidneys; herbs and supplements for the stomach or intestines; herbs and supplements that increase sun sensitivity; herbs and supplements that may increase urine flow; Lindera aggregata; manganese; pain relievers; potassium; vitamin C.

Methodology

This information is based on a systematic review of scientific literature, and was peer-reviewed and edited by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

Monograph methodology

Related terms

2-Acetamido-2-deoxyglucose, acetylglucosamine, aminoglycoside, Arth-X Plus®, Artrox®, chitosamine, chitosan, D-glucosamine, D-glucosaminic acid, enhanced glucosamine sulfate, Flexi-Factors®, GlcN, GlcN-HCl, GlcN-S, glucosamine chlorohydrate, Glucosamine Complex®, glucosamine hydrochloride, glucosamine hydroiodide, Glucosamine Mega®, glucosamine N-acetyl, glucosamine sulfate, glucosamine sulphate, glucosamine-hydrochloride, glutamate, glutathione, Joint Factors®, N-acetylated low-molecular-weight chitosan, N-acetyl-D-glucosamine (NAG, N-A-G), N-acetylglucosamine, Nutri-Joint®, poly-N-acetyl glucosamine, poly-NAG, Teoremac®, Ultra Maximum Strength Glucosamine Sulfate®.

Note: Move Free® Advanced (glucosamine, chondroitin, hyaluronic acid, Uniflex proprietary extract), Tradamixina (Alga Ecklonia Bicyclis, Tribulus Terrestris, D-Glucosamine, and N-Acetyl-D-Glucosamine).

Safety

The U.S. Food and Drug Administration does not strictly regulate herbs and supplements. There is no guarantee of strength, purity or safety of products, and effects may vary. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy. Consult a healthcare provider immediately if you experience side effects.

Allergies

Allergic reactions, such as worsened asthma and swelling under the skin, have been reported with glucosamine use. Avoid in people with asthma.

Avoid in people with a known allergy or sensitivity to glucosamine sulfate or its parts. Glucosamine comes from shrimp, crab, and other shellfish, and should be avoided if allergic or sensitive to shellfish or iodine. Some glucosamine from specific manufacturers (Schiff®, Weider Nutrition Group, Salt Lake City, UT; Cargill Acidulants Regenasure®, Eddyville, Iowa Falls, IA) may have low levels of shrimp allergen and may be safe for allergic people.

Side Effects and Warnings

Glucosamine is likely safe when taken by mouth in studied doses (500 milligrams three times daily up to 90 days or 1,500 milligrams once daily up to six months) for a short time by healthy adults. Glucosamine sulfate is likely safe when injected into the joint at recommended doses for up to six weeks (not available in the United States).

Glucosamine is possibly safe when taken by mouth in recommended doses for up to three years. Doses of up to 3 grams daily and higher have been used in people with osteoarthritis.

Use cautiously in women who are, or plan to become, pregnant, or are breastfeeding. Use cautiously in children under 18 years old.

Drowsiness or sedation may occur. Glucosamine may also cause insomnia. Use caution if driving or operating heavy machinery.

Use cautiously when taking recommended doses over a long time period or if injected into the muscle. Use cautiously if using doses higher than those recommended. Use cautiously in people with low blood platelet counts, as glucosamine may interact with antibodies.

Use cautiously in people who have asthma, kidney disorders, active peptic ulcer disease, depression, skin conditions, or in people who need to restrict potassium intake.

Use cautiously in people who are at risk for cataracts, or in older people who have dry eyes. Glucosamine may cause increased cataract risk or dry eyes.

Use cautiously in people taking agents that increase the flow of urine.

Glucosamine may increase the risk of bleeding. Caution is advised in people with bleeding disorders or taking drugs that may increase the risk of bleeding, such as vitamin K antagonists (warfarin). Dosing adjustments may be necessary.

Glucosamine may affect blood pressure. Caution is advised in people with high blood pressure or heart conditions, or those taking drugs or herbs and supplements that affect blood pressure. Glucosamine may cause abnormal heart rate and palpitations.

Glucosamine may affect insulin resistance and/or blood sugar levels. Caution is advised in people with diabetes or low blood sugar, and in those taking drugs, herbs, or supplements that affect blood sugar. Blood sugar levels may need to be monitored by a qualified healthcare professional, including a pharmacist, and medication adjustments may be necessary.

Avoid using glucosamine-chondroitin supplements that contain Chinese skullcap. Liver damage has been reported with use of the Chinese skullcap contained in the Move Free® Advanced dietary supplement.

Avoid use with methylsulfonylmethane in children due to a potential link with autisim.

Avoid in people with a known allergy or sensitivity to glucosamine sulfate or its parts. Glucosamine comes from shrimp, crab, and other shellfish, and should be avoided if allergic or sensitive to shellfish or iodine.

Glucosamine may also cause anorexia, back or neck pain, changes in levels of creatine phosphokinase (enzyme found in heart, brain, and skeletal muscle), blood urea nitrogen, or creatine levels, constipation, coughing, diarrhea, dizziness, dry mouth, ear inflammation, a feeling of heaviness in the stomach, fluid accumulation, gas, headache, heartburn, increased blood lipids, increased growth rate of fingernails, indigestion, liver problems, muscle problems, nausea, stomach pain, toughened nails, upper abdominal tenderness, and vomiting.

Pregnancy and Breastfeeding

Use cautiously in women who are or plan to become pregnant, or those who are breastfeeding, due to lack of evidence.

Selected references

  1. Chopra A, Saluja M, Tillu G, et al. A Randomized Controlled Exploratory Evaluation of Standardized Ayurvedic Formulations in Symptomatic Osteoarthritis Knees: A Government of India NMITLI Project. Evid.Based.Complement Alternat.Med 2011;2011:724291.
  2. de Souza, R. F., Lovato da Silva, C. H., Nasser, M., Fedorowicz, Z., and Al-Muharraqi, M. A. Interventions for the management of temporomandibular joint osteoarthritis. Cochrane Database Syst.Rev 2012;4:CD007261.
  3. Dostrovsky NR, Towheed TE, Hudson RW, et al. The effect of glucosamine on glucose metabolism in humans: a systematic review of the literature. Osteoarthritis.Cartilage. 2011;19(4):375-380.
  4. Eggertsen, R., Andreasson, A., and Andren, L. No changes of cholesterol levels with a commercially available glucosamine product in patients treated with lipid lowering drugs: a controlled, randomised, open cross-over trial. BMC.Pharmacol Toxicol. 2012;13(1):10.
  5. Kanzaki, N., Saito, K., Maeda, A., Kitagawa, Y., Kiso, Y., Watanabe, K., Tomonaga, A., Nagaoka, I., and Yamaguchi, H. Effect of a dietary supplement containing glucosamine hydrochloride, chondroitin sulfate and quercetin glycosides on symptomatic knee osteoarthritis: a randomized, double-blind, placebo-controlled study. J Sci Food Agric. 3-15-2012;92(4):862-869.
  6. Liu, W., Liu, G., Pei, F., Liu, Y., Zhou, Z., Li, J., Shen, B., Kang, P., Xie, Q., and Ma, X. Kashin-Beck disease in Sichuan, China: report of a pilot open therapeutic trial. J Clin Rheumatol. 2012;18(1):8-14.
  7. Murphy, R. K., Ketzler, L., Rice, R. D., Johnson, S. M., Doss, M. S., and Jaccoma, E. H. Oral glucosamine supplements as a possible ocular hypertensive agent. JAMA Ophthalmol. 7-1-2013;131(7):955-957.
  8. Roemer, F. W., Kwoh, C. K., Hannon, M. J., Green, S. M., Jakicic, J. M., Boudreau, R., Crema, M. D., Moore, C. E., and Guermazi, A. Risk factors for magnetic resonance imaging-detected patellofemoral and tibiofemoral cartilage loss during a six-month period: the joints on glucosamine study. Arthritis Rheum. 2012;64(6):1888-1898.
  9. Selvan, T., Rajiah, K., Nainar, M. S., and Mathew, E. M. A clinical study on glucosamine sulfate versus combination of glucosamine sulfate and NSAIDs in mild to moderate knee osteoarthritis. ScientificWorldJournal. 2012;2012:902676.
  10. Simon RR, Marks V, Leeds AR, et al. A comprehensive review of oral glucosamine use and effects on glucose metabolism in normal and diabetic individuals. Diabetes Metab Res Rev. 2011;27(1):14-27.
  11. Smidt D, Torpet LA, Nauntofte B, et al. Associations between oral and ocular dryness, labial and whole salivary flow rates, systemic diseases and medications in a sample of older people. Community Dent.Oral Epidemiol 2011;39(3):276-288.
  12. Trc T and Bohmova J. Efficacy and tolerance of enzymatic hydrolysed collagen (EHC) vs. glucosamine sulphate (GS) in the treatment of knee osteoarthritis (KOA). Int.Orthop. 2011;35(3):341-348.
  13. Van Vijven, J. P., Luijsterburg, P. A., Verhagen, A. P., van Osch, G. J., Kloppenburg, M., and Bierma-Zeinstra, S. M. Symptomatic and chondroprotective treatment with collagen derivatives in osteoarthritis: a systematic review. Osteoarthritis.Cartilage. 2012;20(8):809-821.
  14. Wu, H., Liu, M., Wang, S., Zhao, H., Yao, W., Feng, W., Yan, M., Tang, Y., and Wei, M. Comparative fasting bioavailability and pharmacokinetic properties of 2 formulations of glucosamine hydrochloride in healthy Chinese adult male volunteers. Arzneimittelforschung. 2012;62(8):367-371.
  15. Yue, J., Yang, M., Yi, S., Dong, B., Li, W., Yang, Z., Lu, J., Zhang, R., and Yong, J. Chondroitin sulfate and/or glucosamine hydrochloride for Kashin-Beck disease: a cluster-randomized, placebo-controlled study. Osteoarthritis.Cartilage. 2012;20(7):622-629.

This evidence-based monograph was prepared by The Natural Standard Research Collaboration

www.naturalstandard.com