Chondroitin

Chondroitin/Drug Interactions:

  • AntiarthriticsAntiarthritics: Chondroitin sulfates have been shown to influence the formation of new cartilage matrix by stimulating chondrocyte metabolism and synthesis of collagen and proteoglycan (4). In arthritic horses, a combination of glucosamine and chondroitin reduced pain, although the reduction was less than the undenatured type II collagen comparison group (151). According to a review, protective effects of chondroitin sulfate for the treatment of hip and knee osteoarthritis include stimulation of extracellular matrix production by chondrocytes, suppression of inflammatory mediators, and inhibition of cartilage degeneration (49).
  • AntiasthmaticsAntiasthmatics: In a case report, asthma exacerbation occurred following use of a glucosamine-chondroitin combination product (81).
  • Anticoagulants and antiplateletsAnticoagulants and antiplatelets: As chondroitin is related to heparin, concurrent use of chondroitin with agents that predispose one to bleeding may theoretically enhance the effect and increase the risk of bleeding. In animal research, hematocrit, hemoglobin, platelet count, and white blood cells significantly decreased; neutrophils segmented; and aggregation was reduced in response to adenosine diphosphate and collagen (80). In a venous thrombosis experimental model, oversulfated chondroitin sulfate was less antithrombotic than fucosylated chondroitin sulfate (152). Secondary sources caution against taking antiplatelets with high-dose glucosamine (3g daily) plus high-dose chondroitin (2.4g daily) because the combination of these agents may increase the risk of bleeding, and according to a meta-analysis and case report, glucosamine and chondroitin may interact with warfarin, causing an elevated international normalized ratio (INR) (110; 153). Knudsen et al. reported that according to the U.S. Food and Drug Administration (FDA) MedWatch database, that there were 20 reports of glucosamine or glucosamine-chondroitin sulfate and warfarin interactions causing increased INR, bleeding, or bruising (153).
  • AntidiabeticsAntidiabetics: 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 (38).
  • Antigout agentsAntigout agents: According to secondary sources, chondroitin may interact with antigout agents.
  • Antihypertensive agentsAntihypertensive agents: In human research, hypertension was reported following chondroitin administration (83). In a published letter, Danao-Camara noted three case reports of reversible elevations in systolic blood pressure (by 20-30mmHg) associated with glucosamine-chondroitin combination products (82). Specific brands were not mentioned; however, it was noted that the effects may have been due to other concurrent medications or impurities in glucosamine-chondroitin products.
  • Anti-inflammatoriesAnti-inflammatories: In animal research, chondroitin sulfate had anti-inflammatory effects in an atherosclerosis model (154).
  • AntilipemicsAntilipemics: In human research, cholesterol levels decreased after treatment with chondroitin 4-sulfate, chondroitin 6-sulfate, and chondroitin polysulfate for 64 months (20).
  • Antimalarial agentsAntimalarial agents: In vitro, chondroitin sulfate may have intervention strategies against placental malaria (24).
  • AntineoplasticsAntineoplastics: According to reviews, specific saccharide structures in chondroitin sulfate and dermatan sulfate chains may be involved in tumor cell proliferation and metastasis, and there is evidence of biochemical changes of chondroitin sulfate and dermatan sulfate in squamous cell laryngeal carcinoma (155; 156). Additionally, chondroitin sulfate proteoglycans (CSPGs) may play a role in tumor growth and invasion; a self-organizing nanogel with acetylated chondroitin sulfate was found useful in an in vitro study as an anticancer drug carrier (157; 158).
  • AntiviralsAntivirals: In vitro, chondroitin sulfate E had antiviral activity, resulting in entry inhibition (14).
  • Calcium saltsCalcium salts: One case series using a combination of chondroitin, glucosamine, and calcium ascorbate indicated that chondroitin decreased symptoms of temporomandibular joint (TMJ) disorder (159).
  • Cardiovascular agentsCardiovascular agents: In human research following combined chondroitin and glucosamine therapy, congestive heart failure (84), myocardial infarction (85), pulmonary and upper respiratory effects, and hemorrhage or bleeding (93), and hypertension (83) were reported. In other human researched, extrasystoles were reported following chondroitin administration (4). One patient taking chondroitin sulfate via the bladder experienced a lethal myocardial infarction (86).
  • ContraceptivesContraceptives: In young women, oral hormonal contraceptives affected the concentration and composition of urinary glycosaminoglycans (160). In addition, chondroitin sulfate increased by 100% (p<0.004).
  • Dermatologic agentsDermatologic agents: Chondroitin sulfate is found in artificial dermal substitutes (161; 162; 163; 164; 165; 166; 167; 168; 169; 170; 171; 172; 173; 174; 175; 176). Photosensitization that was reproducible with rechallenge was reported in one case report of treatment with glucosamine-chondroitin products (82). In human research, skin symptoms, eyelid edema, lower limb edema, alopecia, dermatological disorders, and skin rash were also reported following chondroitin administration (4; 87; 88).
  • Drugs used for osteoporosisDrugs used for osteoporosis: Chondroitin sulfate has been used as part of scaffolding with collagen and other tissues to aid in bone defect treatment in animal models (177; 178). Other authors discussed the use of materials containing chondroitin sulfate in bone reconstruction (179). In vitro, undersulfation of proteoglycans, such as chondroitin sulfate proteoglycans, contributed to reduced long bone growth (180).
  • Gastrointestinal agentsGastrointestinal agents: In human research, gastrointestinal effects such as nausea, dyspepsia, vomiting, abdominal pain, diarrhea, constipation, epigastric burning, gastric ulcer, pyrosis, and erosive gastritis have been reported following chondroitin supplementation (69; 89; 90; 4; 91; 83; 92; 93; 94; 95; 96; 97; 98; 88; 147).
  • HepatotoxinsHepatotoxins: According to secondary sources, elevated liver enzymes have been reported, and two patients developed hepatotoxicity associated with Chinese skullcap contained in Move Free? Advanced dietary supplement, a supplement that also contained chondroitin (102).
  • HyaluronanHyaluronan: In a clinical trial involving intra-articular injection of hyaluronan for the treatment of osteoarthritis of the knee, effects on joint levels of chondroitin sulfate were lacking (181).
  • HyaluronidaseHyaluronidase: According to a case report, hyaluronidase degraded both hyaluronan (hyaluronic acid) and chondroitin sulfate (182).
  • Hydrophilic agentsHydrophilic agents: Reports have discussed chondroitin as having hydrophilic properties, but further evidence on this is lacking, and interactions with other hydrophilic agents are lacking (183).
  • ImmunostimulantsImmunostimulants: The modulation of inflammation by chondroitin sulfate was discussed in a review (184). Chondroitin sulfate may decrease NF-kappaB activation and nuclear translocation in chondrocytes and synovial membrane. Also, systemic CS reduced NF-kappaB nuclear translocation in macrophages and hepatocytes.
  • ImmunosuppressantsImmunosuppressants: The modulation of inflammation by chondroitin sulfate was discussed in a review (184). Chondroitin sulfate may decrease NF-kappaB activation and nuclear translocation in chondrocytes and synovial membrane. Also, systemic CS reduced NF-kappaB nuclear translocation in macrophages and hepatocytes. Intravitreous infliximab in experimental choroidal neovascularization increased expression of chondroitin sulfate in the retina (185).
  • Iron saltsIron salts: In human research, ferric chondroitin sulfate increased iron levels (10).
  • Neurologic agentsNeurologic agents: In human research, headache, motor uneasiness, and euphoria were reported following intramuscular chondroitin sulfate administration (101). In other human research, headache and vertigo were reported following sterile sodium chondroitin sulfate via catheter (92), and neurologic adverse effects were reported in individuals receiving combined chondroitin and glucosamine therapy (93). In a meta-analysis, one of the most frequent adverse effects reported following combination therapy with glucosamine was headache (97).
  • Nonsteroidal anti-inflammatory agents (NSAIDs)Nonsteroidal anti-inflammatory agents (NSAIDs): As chondroitin is related to heparin, concurrent use of chondroitin with agents that predispose one to bleeding may theoretically enhance the effect and increase the risk of bleeding. Studies in animals found significantly decreased hematocrit, hemoglobin, and white blood cells; segmented neutrophils; reduced aggregation in response to adenosine diphosphate and collagen; and a significantly reduced platelet count (80). However, some studies have used concomitant NSAIDs with chondroitin for up to six months with reports of adverse effects (113; 186; 9). Secondary sources caution against taking the following agents when also taking high-dose glucosamine (3g daily) plus high-dose chondroitin (2.4g daily) because the combination of these agents may increase the risk of bleeding or gastrointestinal bleeding: aspirin; heparins; aspirin, caffeine and CNS depressants; muscle relaxant combinations; aspirin and dipyridamole; aspirin and opiates; bivalirudin; drotrecogin alfa; fondaparinux; iloprost inhaled; NSAIDs; pentosan polysulfate sodium; platelet GP IIb/IIIa inhibitors; thrombin inhibitors; treprostinil; or warfarin.
  • Ophthalmic agentsOphthalmic agents: Chondroitin is similar to sodium hyaluronate and has viscoelastic properties, which make it desirable for ophthalmologic applications (187). In in vitro and in ex vivo organ cultures of the cornea, chondroitin sulfate inhibited adhesion of Candida albicans (188). Intravitreous infliximab in experimental choroidal neovascularization increased expression of chondroitin sulfate in the retina (185).
  • PhotosensitizersPhotosensitizers: Photosensitization that was reproducible with rechallenge was reported in one case report of treatment with glucosamine-chondroitin products (82).
  • Polyethylene glycolPolyethylene glycol: Strehin described the synthesis and characterization of a chondroitin sulfate-polyethylene glycol corneal adhesive (189). In animal research, the adhesive restored intraocular pressure and withstood pressures greater than 200mmHg after being applied to a full-thickness corneal incision.

    • Chondroitin/Herb/Supplement Interactions:

  • AntiarthriticsAntiarthritics: Chondroitin sulfates have been shown to influence the formation of new cartilage matrix by stimulating chondrocyte metabolism and synthesis of collagen and proteoglycan (4). In arthritic horses, a combination of glucosamine and chondroitin reduced pain, although the reduction was less than the undenatured type II collagen comparison group (151). According to a review, the protective effects of chondroitin sulfate for the treatment of hip and knee osteoarthritis include stimulation of extracellular matrix production by chondrocytes, suppression of inflammatory mediators, and inhibition of cartilage degeneration (49).
  • AntiasthmaticsAntiasthmatics: In a case report, asthma exacerbation occurred following use of a glucosamine-chondroitin combination product (81).
  • Anticoagulants and antiplateletsAnticoagulants and antiplatelets: As chondroitin is related to heparin, concurrent use of chondroitin with agents that predispose one to bleeding may theoretically enhance the effect and increase the risk of bleeding. In animal research, hematocrit, hemoglobin, platelet count, and white blood cells significantly decreased; neutrophils segmented; and aggregation was reduced in response to adenosine diphosphate and collagen (80). In a venous thrombosis experimental model, oversulfated chondroitin sulfate was less antithrombotic than fucosylated chondroitin sulfate (152). Secondary sources caution against taking antiplatelets with high-dose glucosamine (3g daily) plus high-dose chondroitin (2.4g daily) because the combination of these agents may increase the risk of bleeding, and according to a meta-analysis and case report, glucosamine and chondroitin may interact with warfarin, causing an elevated international normalized ratio (INR) (110; 153). Knudsen et al. reported that according to the U.S. Food and Drug Administration (FDA) MedWatch database, there were 20 reports of glucosamine or glucosamine-chondroitin sulfate and warfarin interactions causing increased INR, bleeding, or bruising (153).
  • Antigout agentsAntigout agents: According to secondary sources, chondroitin may interact with antigout herbs and supplements.
  • Antihypertensive agentsAntihypertensive agents: In human research, hypertension was reported following chondroitin administration (83). In a published letter, Danao-Camara noted three case reports of reversible elevations in systolic blood pressure (by 20-30mmHg) associated with glucosamine-chondroitin combination products (82). Specific brands were not mentioned; however, it was noted that the effects may have been due to other concurrent medications or impurities in glucosamine-chondroitin products.
  • Anti-inflammatoriesAnti-inflammatories: In animal research, chondroitin sulfate had anti-inflammatory effects in an atherosclerosis model (154).
  • AntilipemicsAntilipemics: In human research, cholesterol levels decreased after treatment with chondroitin 4-sulfate, chondroitin 6-sulfate and chondroitin polysulfate for 64 months (20).
  • Antimalarial agentsAntimalarial agents: In vitro, chondroitin sulfate may have intervention strategies against placental malaria (24).
  • AntineoplasticsAntineoplastics: According to reviews, specific saccharide structures in chondroitin sulfate and dermatan sulfate chains may be involved in tumor cell proliferation and metastasis, and there is evidence of biochemical changes of chondroitin sulfate and dermatan sulfate in squamous cell laryngeal carcinoma (155; 156). Additionally, chondroitin sulfate proteoglycans (CSPGs) may play a role in tumor growth and invasion, and a self-organizing nanogel with acetylated chondroitin sulfate was found useful in an in vitro study as an anticancer drug carrier (157; 158).
  • AntioxidantsAntioxidants: In vitro, antioxidants, such as alpha-tocopherol, ascorbic acid, and selenium may combat oxidative stress and cytokine-induced matrix degradation in chondrocytes (190).
  • AntiviralsAntivirals: In vitro, chondroitin sulfate E had antiviral activity, resulting in entry inhibition (14).
  • Avocado unsaponifiablesAvocado unsaponifiables: Avocado and soybean unsaponifiables, with or without glucosamine and chondroitin, appear to be beneficial in patients with osteoarthritis, according to a meta-analysis (191). In vitro, a combination of avocado and soybean unsaponifiables and chondroitin sulfate decreased expression of inflammatory cytokines and prostaglandin E2 synthesis vs. either treatment alone (192).
  • CalciumCalcium: One case series using a combination of chondroitin, glucosamine, and calcium ascorbate indicated that chondroitin may decrease symptoms of temporomandibular joint (TMJ) disorder (159).
  • CamphorCamphor: One randomized controlled trial indicated that topical application of a cream containing chondroitin, shark cartilage, glucosamine, camphor, and peppermint oil may alleviate osteoarthritic pain (193).
  • Cardiovascular agentsCardiovascular agents: In human research following combined chondroitin and glucosamine therapy, congestive heart failure (84), myocardial infarction (85), pulmonary and upper respiratoryeffects, and hemorrhage or bleeding (93), and hypertension (83) were reported. In other human researched, extrasystoles were reported following chondroitin administration (4). One patient taking chondroitin sulfate via the bladder experienced a lethal myocardial infarction (86).
  • ContraceptivesContraceptives: In young women, oral hormonal contraceptives affected the concentration and composition of urinary glycosaminoglycans (160). Chondroitin sulfate increased by 100% (p<0.004).
  • Fish oilFish oil: In cats with joint disease, a diet high in EPA, DHA, green-lipped mussel extract, and glucosamine and chondroitin improved mobility (194).
  • Gastrointestinal agentsGastrointestinal agents: In human research, gastrointestinal effects such as nausea, dyspepsia, vomiting, abdominal pain, diarrhea, constipation, epigastric burning, gastric ulcer, pyrosis, and erosive gastritis have been reported following chondroitin supplementation (69; 89; 90; 4; 91; 83; 92; 93; 94; 95; 96; 97; 98; 88; 147).
  • GlucosamineGlucosamine: There are numerous studies evaluating the concomitant use of glucosamine and chondroitin sulfate, suggesting that they may work synergistically (195; 196; 197; 159; 193; 198; 199). However, information that indicates the optimal dose of each substance if they are taken together is lacking (71). One human study suggested a slightly higher incidence of adverse effects with glucosamine and chondroitin use (93).
  • HepatotoxinsHepatotoxins: According to secondary sources, elevated liver enzymes have been reported, and two patients developed hepatotoxicity associated with Chinese skullcap contained in Move Free? Advanced dietary supplement, a supplement that also contained chondroitin (102).
  • Hydrophilic agentsHydrophilic agents: Reports have discussed chondroitin as having hydrophilic properties, but further evidence on this is lacking, and interactions with other hydrophilic agents are lacking (183).
  • HypoglycemicsHypoglycemics: 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 (38).
  • ImmunomodulatorsImmunomodulators: The modulation of inflammation by chondroitin sulfate was discussed in a review (184). Chondroitin sulfate may decrease NF-kappaB activation and nuclear translocation in chondrocytes and synovial membrane. Also, systemic CS reduced NF-kappaB nuclear translocation in macrophages and hepatocytes.
  • IronIron: In human research, ferric chondroitin sulfate increased iron levels (10).
  • Neurologic agentsNeurologic agents: In human research, headache, motor uneasiness, and euphoria were reported following intramuscular chondroitin sulfate administration (101). In other human research, headache and vertigo were reported following sterile sodium chondroitin sulfate via catheter (92), and neurologic adverse effects were reported in individuals receiving combined chondroitin and glucosamine therapy (93). In a meta-analysis, one of the most frequent adverse effects reported following combination therapy with glucosamine was headache (97).
  • Osteoporosis agentsOsteoporosis agents: Chondroitin sulfate has been used as part of scaffolding with collagen and other tissues to aid in bone defect treatment in animal models (177; 178). Other authors discussed the use of materials containing chondroitin sulfate in bone reconstruction (179). Undersulfation of proteoglycans, such as chondroitin sulfate proteoglycans, may contribute to reduced long bone growth (180).
  • Peppermint oilPeppermint oil: One randomized controlled trial indicated that topical application of a cream containing chondroitin, shark cartilage, glucosamine, camphor, and peppermint oil alleviates osteoarthritic pain (193).
  • PhotosensitizersPhotosensitizers: Photosensitization that was reproducible with rechallenge was reported in one case report of treatment with glucosamine-chondroitin products (82).
  • Shark cartilageShark cartilage: One randomized controlled trial indicated that topical application of a cream containing chondroitin, shark cartilage, glucosamine, camphor, and peppermint oil alleviates osteoarthritic pain (193).
  • Soybean unsaponifiablesSoybean unsaponifiables: Avocado and soybean unsaponifiables, with or without glucosamine and chondroitin, appear to be beneficial in patients with osteoarthritis, according to a meta-analysis (191). In vitro, a combination of avocado and soybean unsaponifiables and chondroitin sulfate decreased expression of inflammatory cytokines and prostaglandin E2 synthesis vs. either treatment alone (192).
  • Vulnerary agentsVulnerary agents: Chondroitin sulfates from sturgeon increased cell adhesion and induced proliferation and migration of fibroblasts in vitro; MAPK signaling pathways were implicated (200).

    • Chondroitin/Food Interactions:

  • Avocado unsaponifiablesAvocado unsaponifiables: Avocado and soybean unsaponifiables, with or without glucosamine and chondroitin, appear to be beneficial in patients with osteoarthritis, according to a meta-analysis (191). In vitro, a combination of avocado and soybean unsaponifiables and chondroitin sulfate decreased expression of inflammatory cytokines and prostaglandin E2 synthesis vs. either treatment alone (192).
  • HaddockHaddock: In vitro, purified glycosaminoglycans from cooked haddock, including chondroitin, may enhance iron uptake via endocytosis in a Caco-2 cell culture model (201).
  • IronIron: In human research, ferric chondroitin sulfate increased iron levels (10).
  • Soybean unsaponifiablesSoybean unsaponifiables: Avocado and soybean unsaponifiables, with or without glucosamine and chondroitin, appear to be beneficial in patients with osteoarthritis, according to a meta-analysis (191). In vitro, a combination of avocado and soybean unsaponifiables and chondroitin sulfate decreased expression of inflammatory cytokines and prostaglandin E2 synthesis vs. either treatment alone (192).

    • Chondroitin/Lab Interactions:

  • Blood pressureBlood pressure: In human research, hypertension was reported following chondroitin administration (83). In a published letter, Danao-Camara noted three case reports of reversible elevations in systolic blood pressure (by 20-30mmHg) associated with glucosamine-chondroitin products (82).
  • Cartilage oligomeric matrix proteinCartilage oligomeric matrix protein: In human research, levels of cartilage oligomeric matrix protein (COMP) decreased (90).
  • CholesterolCholesterol: In humans, cholesterol levels decreased after treatment with chondroitin 4-sulfate, chondroitin 6-sulfate, and chondroitin polysulfate for 64 months (20).
  • Coagulation panelCoagulation panel: In animal research, aggregation reduced in response to adenosine diphosphate and collagen (80). In human research, thrombus forming time (TFT) was 14 minutes in the chondroitin polysulfate (CPS) group compared to nine minutes in the control group; thrombus weights were lower in the CPS group (10.6mg) than the control group (12.6mg) (p <0.10) (20).
  • Complete blood countComplete blood count: In animal research, hematocrit, hemoglobin, white blood cells, and platelet count significantly decreased, and neutrophils segmented (80).
  • EKGEKG: In human research, a single intravenous injection of chondroitin sulfate C resulted in moderate ST and T improvement (12).
  • INRINR: According to a meta-analysis and case report, glucosamine and chondroitin may interact with warfarin, causing an elevated international normalized ratio (INR) (110; 153). Knudsen et al. reported that according to the U.S. Food and Drug Administration (FDA) MedWatch database, there were 20 reports of glucosamine or glucosamine-chondroitin sulfate and warfarin interactions causing increased INR (153).
  • IronIron: In human research, ferric chondroitin sulfate increased iron levels (10), and serum concentrations of iron increased following chondroitin sulfonic acid iron complex administration (202).
  • Potassium Sensitivity TestPotassium Sensitivity Test: In human research, sodium chondroitin sulfate caused 90.6% participants to have a positive PST (Potassium Sensitivity Test) (92).