N-acetyl D-glucosamine

Glucosamine/Drug Interactions:

  • GeneralGeneral: According to expert opinion, significant supplement-drug interactions involving glucosamine are lacking from current reports (80).
  • AcetaminophenAcetaminophen: In clinical research, decreased analgesic effect of acetaminophen was reported after using glucosamine (195).
  • AlcoholAlcohol: According to expert opinion, alcohol may affect the way glucosamine works (79).
  • AnalgesicsAnalgesics: According to data from the Norwegian Prescription Database, patients who started taking glucosamine did not reduce use of codeine-containing analgesics, and there was a positive correlation between use of glucosamine and use of nonsteroidal anti-inflammatory drugs (NSAIDs) (196). However, in clinical research, analgesic use decreased in the glucosamine group vs. the placebo group (130). Additionally, the combination of NSAIDs and glucosamine sulfate had a greater effect on pain reduction than glucosamine sulfate alone in individuals with mild-to-moderate osteoarthritis, suggesting that prolonged use may decrease dependence on NSAIDs (197).
  • Anticoagulants and antiplateletsAnticoagulants and antiplatelets: In clinical research, glucosamine-chondroitin products have been shown to elevate the international normalized ratio (INR) and potentiate the anticoagulant effects of warfarin (198; 199; 119). The exact mechanism for the interaction is unclear.
  • AntidepressantsAntidepressants: In human research, depressed mood was reported by 9% of participants receiving glucosamine, although the link to treatment was unclear (129).
  • Antidiabetic agentsAntidiabetic agents: The effect of glucosamine on glucose levels or insulin resistance has been controversial, and it remains unclear if interactions with agents possessing glycemic properties may occur. Despite initial concerns about use in diabetic patients based largely on cell, animal, and preliminary clinical research, which noted insulin resistance and possible glycemic effects (100; 101; 102; 103; 104; 105; 106; 107), more recent human research reports a lack of statistically significant effects (including on hemoglobin A1C levels in patients with type 2 diabetes after 90 days of therapy) (108; 109). Clinically relevant effects on blood sugars have been lacking in clinical research (108; 189; 95; 99). In ambulatory elderly persons, the use of drugs for diabetes mellitus was negatively associated with the use of supplements in general, with most of this attributed to low use in those taking glucosamine, chondroitin, multivitamins, and echinacea (200). In human research, glucosamine levels and glucose concentrations were negatively associated, suggesting that direct effects of glucose on glucosamine are lacking, and that normalized insulin through antidiabetic drugs may lower glucosamine-induced peripheral resistance (111).
  • Antihemorrhage agentsAntihemorrhage agents: In animal research, poly-N-acetyl glucosamine gel, administered intravariceally and paravariceally to dogs with bleeding esophageal varices, was an effective and safe method for stopping the hemorrhage and inducing permanent varix obliteration (10). Theoretically, glucosamine may interact with other antihemorrhagic agents.
  • Antineoplastic agentsAntineoplastic agents: In vitro, glucosamine reduced the effectiveness of antineoplastic topoisomerase inhibitors by decreasing the drug's inhibition of topoisomerase II (201).
  • CaffeineCaffeine: According to expert opinion, caffeine may affect the way glucosamine works (79).
  • ChitosanChitosan: According to a review, chitosan as a pharmaceutical excipient is not well absorbed, but any that is absorbed may undergo enzyme degradation to glucosamine and N-acetylglucosamine (202).
  • CYP450 inhibitorsCYP450 inhibitors: In human research, clinically significant CYP2C inhibition was lacking with glucosamine (203). In cell research, glucosamine lacked an inhibitory effect on cytochrome P450 isoforms (204).
  • DiureticsDiuretics: In clinical research, concomitant therapy of glucosamine and a diuretic was associated with an increased risk of side effects (113).
  • DoxorubicinDoxorubicin: In vitro, glucosamine reduced the effectiveness of doxorubicin by decreasing the drug's inhibition of topoisomerase II (201).
  • EtoposideEtoposide: In vitro, glucosamine reduced the effectiveness of etoposide by decreasing the drug's inhibition of topoisomerase II (201).
  • Gastrointestinal agentsGastrointestinal agents: In human research, constipation and mild heartburn have been reported (146). There have been other instances of digestive problems associated with glucosamine, including epigastric pain and tenderness, heartburn, diarrhea, nausea, dyspepsia, vomiting, constipation, gastric heaviness, anorexia, abdominal pain, and flatulence (113; 109; 154; 130; 191; 131; 167; 114; 124; 33; 125; 115; 116; 126; 127).
  • NicotineNicotine: According to expert opinion, smoking may affect the way glucosamine works (79).
  • Nonsteroidal anti-inflammatory drugs (NSAIDs)Nonsteroidal anti-inflammatory drugs (NSAIDs): According to data from the Norwegian Prescription Database, patients who started taking glucosamine did not reduce use of codeine-containing analgesics, and there was a positive correlation between use of glucosamine and use of NSAIDs (196). In human research, the combination of NSAIDs and glucosamine sulfate had a greater effect on pain reduction than glucosamine sulfate alone in individuals with mild-to-moderate osteoarthritis, suggesting that prolonged use may decrease dependence on NSAIDs (197).
  • PhotosensitizersPhotosensitizers: In human research, photosensitization has been reported with glucosamine use (121).
  • Renally eliminated agentsRenally eliminated agents: In human research, hindered renal excretion of glucosamine hydrochloride occurred (120).
  • RosiglitazoneRosiglitazone: In cell research, concurrent use of rosiglitazone and glucosamine prevented glucosamine-induced islet beta-cell apoptosis and dysfunction (205).
  • TeniposideTeniposide: In cell research, glucosamine reduced the effectiveness of teniposide by decreasing the drug's inhibition of topoisomerase II (201).
  • ThiazolidinedionesThiazolidinediones: In cell research, concurrent use of rosiglitazone and glucosamine prevented glucosamine-induced islet beta-cell apoptosis and dysfunction (205).
  • Topical agentsTopical agents: Several studies have reported skin reactions, including itch, with the use of glucosamine (112; 113; 130; 131; 116).
  • Vitamin K antagonistsVitamin K antagonists: According to expert opinion, use of glucosamine and vitamin K antagonists may increase the risk of bleeding (80; 118).
  • WarfarinWarfarin: According to expert opinion, use of glucosamine and vitamin K antagonists, particularly warfarin, may increase the risk of bleeding (80; 118). In case reports, glucosamine-chondroitin products have been shown to elevate INR and potentiate the anticoagulant effects of warfarin (198; 199; 198). In the WHO-ADR database, a total of 19 cases of coagulating disorders were reported, with the interaction of glucosamine and warfarin as a suspected cause (119). The effect was usualy observed within three weeks to nine months of beginning glucosamine supplementation with stable INR levels and long-term warfarin use. INR levels were normalized after discontinuation of glucosamine in 16 of the 19 cases.

    • Glucosamine/Herb/Supplement Interactions:

  • AnalgesicsAnalgesics: According to data from the Norwegian Prescription Database, patients who started taking glucosamine did not reduce use of codeine-containing analgesics, and there was a positive correlation between use of glucosamine and use of NSAIDs (196). However, in clinical research, analgesic use decreased in the glucosamine group vs. the placebo group (130). Additionally, the combination of NSAIDs and glucosamine sulfate had a greater effect on pain reduction than glucosamine sulfate alone in individuals with mild-to-moderate osteoarthritis, suggesting that prolonged use may decrease dependence on NSAIDs (197).
  • Anticoagulants and antiplateletsAnticoagulants and antiplatelets: In clinical research, glucosamine-chondroitin products have been shown to elevate INR and potentiate the anticoagulant effects of warfarin (198; 199; 119). In human research, a combination of glucosamine and celadrin (esterified fatty acids) reduced platelet aggregation when stimulated ex vivo (206). It is unclear whether glucosamine, the fatty acids, or both play a role.
  • AntidepressantsAntidepressants: In human research, depressed mood was reported by 9% of participants receiving glucosamine, although the link to treatment was unclear (129).
  • Antihemorrhage agentsAntihemorrhage agents: In animal research, poly-N-acetyl glucosamine gel, administered intravariceally and paravariceally to dogs with bleeding esophageal varices was an effective and safe method for stopping the hemorrhage and inducing permanent varix obliteration (10). Theoretically, glucosamine may interact with other antihemorrhagic agents.
  • AntineoplasticsAntineoplastics: In cell research, glucosamine reduced the effectiveness of antineoplastic topoisomerase inhibitors by decreasing the agent's inhibition of topoisomerase II (201).
  • AntioxidantsAntioxidants: In cell research, glucosamine sulfate, as well as the combination of glucosamine sulfate and chondroitin sulfate, inhibited MMP3 secretion (207). Theoretically, this may have additive effects when used with other antioxidants.
  • Avocado unsaponifiablesAvocado unsaponifiables: According to clinical research and meta-analysis, avocado and soybean unsaponifiables, with or without glucosamine and chondroitin, appear to be beneficial in patients with osteoarthritis (208).
  • BromelainBromelain: According to anecdotal reports, the concomitant use of bromelain and glucosamine may result in synergistic effects. It is unclear if a specific form of glucosamine has been implicated in this interaction.
  • CeladrinCeladrin: In human research, a combination of glucosamine and celadrin (esterified fatty acids) reduced platelet aggregation when stimulated ex vivo (206). It is unclear whether glucosamine, the fatty acids, or both play a role.
  • Chinese skullcapChinese skullcap: Two patients have developed hepatotoxicity associated with Chinese skullcap contained in the Move Free? Advanced dietary supplement, a supplement that also contains glucosamine (137).
  • Chondroitin sulfateChondroitin sulfate: There are numerous studies evaluating the concomitant use of glucosamine and chondroitin sulfate (209; 210; 211; 212), suggesting that they may work synergistically.
  • CYP450 inhibitorsCYP450 inhibitors: In human research, clinically significant CYP2C inhibition was lacking with glucosamine (203). In cell research, glucosamine lacked an inhibitory effect on cytochrome P450 isoforms (204).
  • DiureticsDiuretics: In clinical research, concomitant therapy of glucosamine and a diuretic was associated with an increased risk of side effects (113).
  • Fish oilFish oil: In clinical research, concomitant use of glucosamine and fish oil may have additive effects as a treatment for psoriasis (7). When used in combination, glucosamine and omega-3 fatty acids were superior to glucosamine only in osteoarthritis patients (213). In cats with joint disease, a diet high in EPA, DHA, green-lipped mussel extract, and glucosamine-chondroitin improved mobility (214).
  • Gastrointestinal agentsGastrointestinal agents: In human research, constipation and mild heartburn have been reported (146). There have been other instances of digestive problems associated with glucosamine, including epigastric pain and tenderness, heartburn, diarrhea, nausea, dyspepsia, vomiting, constipation, gastric heaviness, anorexia, abdominal pain, and flatulence (113; 109; 154; 130; 191; 131; 167; 114; 124; 33; 125; 115; 116; 126; 127).
  • GingerGinger: In human research, the daily use of ginger combined with 1,000mg of glucosamine effectively treated osteoarthritis and lacked the adverse effects on stomach mucosa seen with diclofenac treatment (215).
  • Green-lipped muscle extractGreen-lipped muscle extract: In cats with joint disease, a diet high in EPA, DHA, green-lipped mussel extract, and glucosamine-chondroitin improved mobility (214).
  • HypoglycemicsHypoglycemics: The effect of glucosamine on glucose levels or insulin resistance has been controversial, and it remains unclear if interactions with agents possessing glycemic properties may occur. Despite initial concerns about use in diabetic patients based largely on cell, animal, and preliminary clinical research, which noted insulin resistance and possible glycemic effects (100; 101; 102; 103; 104; 105; 106; 107), more recent human research reports a lack of statistically significant effects (including on hemoglobin A1C levels in patients with type 2 diabetes after 90 days of therapy) (108; 109). Clinically relevant effects on blood sugars have been lacking in clinical research (108; 189; 95; 99). In ambulatory elderly persons, the use of drugs for diabetes mellitus was negatively associated with the use of supplements in general, with most of this attributed to low use in those taking glucosamine, chondroitin, multivitamins, and echinacea (200). In human research, glucosamine levels and glucose concentrations were negatively associated, suggesting that direct effects of glucose on glucosamine are lacking (111).
  • Lindera aggregataLindera aggregata: In cell research, constituents of Lindera aggregata showed activity against glucosamine-induced insulin resistance (216; 217).
  • ManganeseManganese: There are anecdotal reports of beneficial effects of concomitant use of glucosamine with manganese, due to the role of manganese as an essential cofactor for bone and joint formation. Manganese is thought to improve glucosamine utilization within chondrocytes and potentially lead to increased glucosamine effects.
  • PhotosensitizersPhotosensitizers: In human research, photosensitization has been reported with glucosamine use (121).
  • PotassiumPotassium: Some glucosamine sulfate products are sources of potassium. Theoretically, use of glucosamine products may increase potassium intake (117).
  • Renally eliminated agentsRenally eliminated agents: In human research, hindered renal excretion of glucosamine hydrochloride occurred (120).
  • Soybean unsaponifiablesSoybean unsaponifiables: In clinical research and meta-analysis, avocado and soybean unsaponifiables, with or without glucosamine and chondroitin, appeared to be beneficial in patients with osteoarthritis (208).
  • Topical agentsTopical agents: Several studies have reported skin reactions, including itch, with the use of glucosamine (112; 113; 130; 131; 116).
  • Vitamin CVitamin C: There are anecdotal reports that concomitant use of glucosamine with vitamin C may lead to increased glucosamine effects (secondary source.) Vitamin C strengthens collagen and is an essential cofactor for collagen fibers; collagen is an essential component in the extracellular matrix of cartilage.

    • Glucosamine/Food Interactions:

  • Avocado unsaponifiablesAvocado unsaponifiables: According to clinical research and meta-analysis, avocado and soybean unsaponifiables, with or without glucosamine and chondroitin, appear to be beneficial in patients with osteoarthritis (208).
  • BromelainBromelain: According to anecdotal reports, the concomitant use of glucosamine and bromelain, an enzyme extracted from pineapple, may result in synergistic effects. It is unclear if a specific form of glucosamine has been implicated in this interaction.
  • Fish oilFish oil: In clinical research, concomitant use of glucosamine and fish oil may have additive effects as a treatment for psoriasis (7). When used in combination, glucosamine and omega-3 fatty acids were superior to glucosamine only in osteoarthritis patients (213). In cats with joint disease, a diet high in EPA, DHA, green-lipped mussel extract, and glucosamine-chondroitin improved mobility (214).
  • GingerGinger: In human research, the daily use of ginger combined with 1,000mg of glucosamine effectively treated osteoarthritis and lacked the adverse effects on stomach mucosa seen with diclofenac treatment (215).
  • SaltSalt: In animal research, conjugation of Maillard reacted peptides with glucosamine altered human salt taste (218).
  • Soybean unsaponifiablesSoybean unsaponifiables: According to clinical research and meta-analysis, avocado and soybean unsaponifiables, with or without glucosamine and chondroitin, appear to be beneficial in patients with osteoarthritis (208).

    • Glucosamine/Lab Interactions:

  • Blood glucoseBlood glucose: Animal models suggest that glucosamine may decrease the effectiveness of insulin and other oral hypoglycemics by increasing insulin resistance (104). However, limited human studies suggest that glucosamine lacks a clinically significant effect on glucose metabolism (189). In a systematic review, four studies found decreased insulin sensitivity or increased fasting glucose in subjects taking glucosamine (219). This has been discussed by other authors, but details are limited (220). Theoretically, glucosamine may increase blood glucose levels and alter test results.
  • Cartilage and bone biomarkersCartilage and bone biomarkers: In soccer players, glucosamine decreased CTX-II (type II collagen degradation biomarker) (221). In animals, glucosamine decreased CTX-II and increased CPII (a marker of type II collagen synthesis) (222). In human research, the addition of glucosamine to physical training in patients with osteoarthritis reduced levels of serum cartilage oligomeric matrix protein (COMP) by 13% (223).
  • Hemostatiac markersHemostatiac markers: In the WHO-ADR database, a total of 19 cases of coagulating disorders were reported, with the interaction of glucosamine and warfarin as a suspected cause (119). The effect was usualy observed within three weeks to nine months of beginning glucosamine supplementation with stable INR levels and long-term warfarin use. INR levels were normalized after discontinuation of glucosamine in 16 of the 19 cases.
  • Inflammatory markersInflammatory markers: In osteoarthritis patients, glucosamine reduced levels of metalloproteinase inhibitor-1 from cartilage samples (224).
  • PotassiumPotassium: Some glucosamine sulfate products are sources of potassium, potentially increasing potassium intake (117; 131).