Background

Commonly used for osteoarthritis, knee pain, and aging skin, but there is no strong evidence to support these uses.

Possibly safe when used orally at a total daily dose of 6 grams, when inserted into the rectum as a total daily dose of 8 grams, or when applied to the skin.

Taking products containing glucosamine and chondroitin sulfate in combination with warfarin has been reported to increase anticoagulant activity and the risk for bruising and bleeding.

People use this for...

Effectiveness Effectiveness definitions

INSUFFICIENT RELIABLE EVIDENCE TO RATE

Aging skin. Preliminary clinical research shows that topical application of a cream containing 2% N-acetyl glucosamine and 4% niacinamide to the face twice daily along with sunscreen for 10 weeks significantly decreases facial hyperpigmentation compared to sunscreen alone in women with skin hyperpigmentation and solar lentigines (liver spots) primarily due to aging and sun exposure (92721). The effect of N-acetyl glucosamine alone on aging skin is unclear.

Cardiovascular disease (CVD). Observational research of adults in the United Kingdom found that taking glucosamine is associated with an overall 15% reduced risk for fatal and non-fatal CVD events, including coronary heart disease and stroke (99682). However, this study did not clarify the form of glucosamine used, or the dose, frequency, or duration of use. Furthermore, the adults that reported glucosamine use also reported overall healthier lifestyle habits than those that were not taking glucosamine. Although this study attempted to control for these differences, higher quality, prospective research is needed to clarify the relationship, if any, between N-acetyl glucosamine and CVD risk.

Diabetes. Observational research in adults in the United Kingdom has found that glucosamine use is associated with a 17% lower risk of type 2 diabetes. The relationship between glucosamine use and diabetes appears to be even more pronounced in patients with high baseline levels of C-reactive protein, a marker of inflammation (103234). However, this study did not clarify the form of glucosamine used, or the dose, frequency, or duration of use. Furthermore, the adults that reported glucosamine use also reported overall healthier lifestyle habits than those that were not taking glucosamine. Although this study attempted to control for these differences, higher quality, prospective research is needed to clarify the relationship, if any, between N-acetyl glucosamine and the risk for diabetes.

Inflammatory bowel disease (IBD). There is preliminary evidence that oral or rectal N-acetyl glucosamine might decrease symptoms of IBD in children with Crohn's disease or ulcerative colitis (10234).

Knee pain. Preliminary clinical research shows that taking a specific supplement (Walker's Glucosamine, Kyowa) containing N-acetyl glucosamine 100 mg and chondroitin sulfate 180 mg daily for 24 weeks does not reduce pain or improve function of the knee compared to placebo in middle-aged and older Japanese patients with chronic knee pain (95795).

Stroke. Observational research of adults in the United Kingdom found that taking glucosamine is associated with a modest 9% reduced risk for overall stroke; however, sub-analyses show that glucosamine use is not associated with a reduced risk for fatal or non-fatal stroke, hemorrhagic stroke, or ischemic stroke (99682). This study did not clarify the form of glucosamine used, or the dose, frequency, or duration of use. Furthermore, the adults that reported glucosamine use also reported overall healthier lifestyle habits than those that were not taking glucosamine. Although this study attempted to control for these differences, higher quality, prospective research is needed to clarify the relationship, if any, between N-acetyl glucosamine and stroke risk. More evidence is needed to rate N-acetyl glucosamine for these uses.

Natural Medicines rates effectiveness based on scientific evidence according to the following scale: Effective, Likely Effective, Possibly Effective, Possibly Ineffective, Likely Ineffective, Ineffective, and Insufficient Evidence to Rate.

Dosing & administration

• AdultTopical:

  Aging skin A cream containing 2% N-acetyl glucosamine and 4% niacinamide, applied to the face twice daily along with sunscreen for 10 weeks, has been used (92721).

• ChildrenOral:

  Inflammatory bowel disease (IBD) N-acetyl glucosamine 1-2 grams three times daily has been used (10234).

  Rectal:

  Inflammatory bowel disease (IBD) N-acetyl glucosamine 3-4 grams daily in 2 divided doses has been used (10234).

• Standardization & formulationThere is insufficient reliable information available about the standardization of N-acetyl glucosamine.

Adverse effects

Endocrine: Elevated blood glucose levels in patients with diabetes have been reported with glucosamine (22). However, taking glucosamine for up to 3 months does not seem to affect hemoglobin A1C or blood glucose levels in healthy or obese people or patients with type 2 diabetes (10311,10317,12107,15111). It's unclear if taking N-acetyl glucosamine interferes with blood glucose control in diabetic patients.

Gastrointestinal: Orally, N-acetyl glucosamine might cause adverse effects similar to the effects seen with glucosamine. These might include mild gastrointestinal (GI) problems such as nausea, heartburn, diarrhea, and constipation (2608).

Immunologic: There is some concern that glucosamine products might cause allergic reactions in sensitive individuals. One review of glucosamine-related adverse events in Australia found that 72% of all reports involved hypersensitivity reactions. Of these reactions, 35% were mild, including pruritis, urticaria, and lip edema, 49% were moderate, including dyspnea, and 16% were severe, including gait disturbance, somnolence, and hypotension. Anaphylaxis was reported in 1.5% of cases (102115). Also, in one clinical trial, a single patient developed allergic dermatitis considered to be likely due to glucosamine hydrochloride (89516). Glucosamine is derived from the exoskeletons of shrimp, lobster, and crabs. However, it is unclear if these adverse reactions were due to a shellfish sensitivity or general atopy. Additionally, shellfish allergies are caused by IgE antibodies to antigens in the meat of shellfish, not to antigens in the exoskeleton. Regardless, it is possible that some glucosamine products might be contaminated by this allergen during production (102115).

Dermatologic: In some clinical research, skin reactions were reported in around 4% of patients applying a topical cream containing 2% N-acetyl glucosamine and 4% niacinamide to the skin (92721). Also, skin reactions have been reported for patients taking glucosamine orally (2608); theoretically N-acetyl glucosamine might cause similar effects.

Cardiovascular: There has been concern that glucosamine might increase the risk of metabolic disturbances resulting in increased cholesterol levels and blood pressure. However, glucosamine does not appear to increase the risk of these adverse effects. Taking glucosamine sulfate for up to 3 years does not significantly increase blood glucose or lipid levels, or cause any other disturbances in metabolism (7026,7075,8942,10311,10317). It's unclear if taking N-acetyl glucosamine is associated with metabolic disturbances.

General: Orally, N-acetyl glucosamine might cause adverse effects similar to the effects seen with other forms of glucosamine. These might include mild gastrointestinal problems such as nausea, heartburn, diarrhea, and constipation. Drowsiness, skin reactions, and headaches have also been reported with glucosamine (2608). Anecdotal reports have associated glucosamine with renal toxicity, but changes in renal function have not been reported in long-term studies (7026,8942,10408,10409). There is also concern that glucosamine products might cause allergic reactions (89516,102115). One review of glucosamine-related adverse reactions reported in Australia found that 72% of all reports involved hypersensitivity reactions. Glucosamine is derived from the exoskeletons of shrimp, lobster, and crabs. However, it is unclear if these reactions were due to shellfish sensitivity or general atopy (102115).

Neurologic/CNS: Drowsiness and headache have been reported with glucosamine (2608). Theoretically, due to its similarity to glucosamine, N-acetyl glucosamine use might cause drowsiness and/or headache in some patients.

Renal: Anecdotal reports have associated glucosamine with renal toxicity, but changes in renal function have not been reported in long-term studies (7026,8942,10408,10409).

Toxicology

Interactions with pharmaceuticals

WARFARIN (Coumadin)Interaction Rating: Major Do not take this combination.Severity: High Occurrence: Probable Level of evidence: DTaking glucosamine alone or in combination with chondroitin might increase the anticoagulant effects of warfarin (Coumadin) and increase the risk of bruising and bleeding. In one case, a 71 year-old man taking warfarin had his international normalized ratio (INR) increase from 2.3 to 4.7 after increasing the dose of a glucosamine-chondroitin supplement from glucosamine hydrochloride 500 mg and chondroitin sulfate 400 mg to glucosamine hydrochloride 1500 mg and chondroitin sulfate 1200 mg daily (16130). In another case, very high-dose glucosamine (3000 mg/day) plus high-dose chondroitin sulfate (2400 mg/day) combined with warfarin resulted in a significantly increased INR (11389). Additionally, 20 voluntary case reports to the U.S. Food & Drug Administration (FDA) have linked glucosamine plus chondroitin with increased INR, bruising, and bleeding events in patients who were also taking warfarin (16130). There have also been 20 additional case reports to the World Health Organization (WHO) that link glucosamine alone to increased INR in patients taking warfarin (16131).
Chondroitin is a small component of a heparinoid and might have weak anticoagulant activity. Glucosamine is also a small component of heparin, but is not thought to have anticoagulant activity; however, preliminary animal model research suggests that it might have antiplatelet activity (16131).
Patients taking warfarin should be advised to avoid or use glucosamine cautiously.

ANTIDIABETES DRUGSInteraction Rating: Moderate Be cautious with this combination.Severity: Moderate Occurrence: Possible Level of evidence: BIn vitro and animal research has shown that glucosamine might increase insulin resistance or decrease insulin production (371,372,3406). This has raised concerns that taking N-acetyl glucosamine, a specific form of glucosamine, might worsen diabetes and decrease the effectiveness of diabetes drugs. However, clinical research shows that taking glucosamine as glucosamine sulfate or glucosamine hydrochloride, two other forms of glucosamine, does not have adverse effects on blood glucose or hemoglobin A1c (HbA1c) in healthy, obese, or type 2 diabetes patients (7026,7075,8942,10311,10317,15111). It is unclear if N-acetyl glucosamine affects blood glucose or HbA1c in humans. Until more is known, use caution or avoid using N-acetyl glucosamine along with antidiabetes drugs. Some antidiabetes drugs include glimepiride (Amaryl), glyburide (DiaBeta, Glynase PresTab, Micronase), insulin, pioglitazone (Actos), rosiglitazone (Avandia), and others.

TOPOISOMERASE II INHIBITORSInteraction Rating: Moderate Be cautious with this combination.Severity: High Occurrence: Possible Level of evidence: DIn vitro research suggests that glucosamine might induce resistance to etoposide (VP16, VePesid) and doxorubicin (Adriamycin) by reducing the drugs' inhibition of topoisomerase II, an enzyme required for DNA replication in tumor cells (7639). N-acetyl glucosamine is one form of glucosamine. Theoretically N-acetyl glucosamine may induce resistance to other chemotherapeutic agents that work by inhibiting topoisomerase II. Some topoisomerase II inhibitors include etoposide (VP16, VePesid), teniposide (VM26), mitoxantrone, and anthracyclines such as doxorubicin (Adriamycin) and daunorubicin.

Interactions with herbs & supplements

None known.

Interactions with foods

None known.

Interactions with lab tests

None known.

Interactions with diseases

ASTHMA: Glucosamine might exacerbate asthma by an unidentified mechanism. Use N-acetyl glucosamine cautiously in patients with asthma (10002).

DIABETES: Some preliminary research raised concerns that glucosamine might increase insulin resistance or decrease insulin production, resulting in elevated blood glucose levels (5059,14810). There are also anecdotal reports of reduced blood glucose control in people with diabetes who take glucosamine (22,1203,1204,3405,3406). However, clinical studies show that glucosamine does not seem to adversely affect blood glucose control in people with type 2 diabetes, as measured by hemoglobin A1C (10311,10317,14808). It also does not seem to affect blood glucose in healthy or obese people who take glucosamine for up to 3 years (7026,8942,12107,15111).

HYPERLIPIDEMIA: There has been concern that glucosamine might cause metabolic disturbances that could results in increased cholesterol and triglyceride levels. Some preliminary research has suggested that glucosamine might increase insulin levels. Hyperinsulinemia is associated with elevated cholesterol and triglycerides (5059,7075). Animal model research has also shown that glucosamine might exacerbate hyperlipidemia (15110). But research in humans has not shown this effect. Glucosamine does not seem to increase lipid levels in people over age 45 who take glucosamine sulfate for up to 3 years (7026,8942).

HYPERTENSION: There has been concern that glucosamine might cause metabolic disturbances resulting in increased blood pressure. Some preliminary research has suggested that glucosamine might increase insulin levels. Hyperinsulinemia is associated with elevated blood pressure (5059,7075). But research in humans has not shown this effect. Glucosamine does not seem to increase blood pressure in people over age 45 who take glucosamine sulfate for up to 3 years (7026,8942).

SHELLFISH ALLERGY: There is concern that glucosamine products might cause reactions in people who are sensitive to shellfish. Glucosamine is derived from the exoskeletons of shrimp, lobster, and crab. But allergic reactions in people with shellfish allergy are caused by IgE antibodies to antigens in the meat of shellfish, not to the antigens in the exoskeleton. However, a review of glucosamine-related adverse events in Australia found that 72% of all reports involved hypersensitivity reactions. It is unclear from this report if these patients had a shellfish allergy; however, the reactions were similar to those seen in shellfish allergy. It is possible that allergen contamination can occur during the manufacture of some glucosamine products (102115).

SURGERY: Due to its similarity to glucosamine, N-acetyl glucosamine might affect blood glucose levels (22,1203,1204,3405,3406,5059,14810). Theoretically, N-acetyl glucosamine might interfere with blood glucose control during and after surgical procedures. Tell patients to discontinue N-acetyl glucosamine at least 2 weeks before elective surgical procedures.

Mechanism of action

General: N-acetyl glucosamine is the acetylated derivative of the amino sugar glucosamine, which is a constituent of cartilage proteoglycans. It is derived from marine exoskeletons or produced synthetically. Glucosamine is required for the synthesis of glycoproteins, glycolipids, and glycosaminoglycans (also known as mucopolysaccharides); these carbohydrate-containing compounds are found in tendons, ligaments, cartilage, synovial fluid, mucous membranes, blood vessels, heart valves, and structures in the eye. Glucosamine is also a component of biologically active compounds such as heparin, but it does not react with heparin-induced thrombocytopenia (HIT) antibodies (7640,7641,11831).

Analgesic effects: Glucosamine doesn't seem to directly affect cyclooxygenase, which is responsible for anti-inflammatory and analgesic effects of nonsteroidal anti-inflammatory drugs (NSAIDs), as well as adverse gastrointestinal (GI) effects (2604). In inflammatory bowel disease (IBD), N-acetylation of glucosamine is relatively deficient, possibly reducing the synthesis of the gastric and intestinal mucosa's protective glycoprotein cover (2609). Theoretically, supplementation with N-acetyl glucosamine could remedy this deficiency and restore the glycoprotein cover (2609). However, there aren't any human studies that have evaluated this claim.

Bone effects: In osteoarthritis, glucosamine stimulates metabolism of chondrocytes in the articular cartilage and synovial cells in the synovial tissues. There is some evidence that suggests that glucosamine might have a disease-modifying effect, therefore stopping or slowing the progression of osteoarthritis (7026).

Dermatologic effects: In vitro research shows that N-acetyl glucosamine decreases melanin production, which could explain its ability to decrease age spots when applied topically to women with skin hyperpigmentation. N-acetyl glucosamine is believed to inhibit the glycosylation of tyrosinase, an important step in the formation of melanin (92721).

Metabolic effects: There has been concern about potential adverse metabolic effects of glucosamine. Preliminary evidence suggests glucosamine might decrease glucose-induced insulin secretion by inhibiting pancreatic glucokinase in the beta cells of the islet of Langerhans (371,372,3406). Other preliminary research suggests that glucosamine might also impair insulin-mediated glucose uptake and metabolism in skeletal muscle (372,3406). Animal research suggests glucosamine might increase glucose metabolism through the hexosamine pathway, a pattern of change in glucose metabolism similar to that seen in type 2 diabetes (3405,3406). Animal models also suggest that glucosamine might exacerbate the hyperlipidemia caused by a high-fat Western diet (15110). However, animals may handle glucosamine differently than humans. Most of the research in humans suggests that glucosamine does not affect the pharmacokinetics of glucose. Research in people with normal glucose metabolism suggests glucosamine does not affect insulin sensitivity or plasma glucose (7637,7638). Clinical research in people with type 2 diabetes and people without diabetes suggests glucosamine doesn't have any significant effect on blood glucose or lipid levels when taken for up to 3 years (7026,8942,10311,10317,15111). Preliminary clinical research suggests that endogenous glucosamine and insulin levels are elevated in nondiabetic patients with ischemic heart disease (7640, 7641). Some researchers think that increased glucosamine production might contribute to endothelial cell dysfunction (8944).

Pharmacokinetics

Absorption: Glucosamine is absorbed 90% after oral administration. The bioavailability is approximately 26% after first pass metabolism (2608). The extent of N-acetyl glucosamine absorption following topical application is unclear.

Distribution: Glucosamine is incorporated into plasma proteins during first-pass metabolism, and unbound glucosamine is concentrated in the articular cartilage (2608). Free glucosamine is undetectable in the plasma (2607). The distribution of N-acetyl glucosamine is unclear.

References