INGREDIENTS & RESEARCH

Chondroitin

BACKGROUND

Ingredient Type: Constituent, Substance to supplement the diet

Also Known As: CDS, Chondroitin, Chondroitin polysulphate, Calcium chondroitin sulfate, CS, Condrosulf

Chondroitin sulfate is a naturally occurring compound that can be found in joint cartilage of the body. Chondroitin sulfate is the structural element in cartilage that provides the strength and resistance to compression. It is considered a sulfated glycosaminoglycan, or GAG, mostly made up of sugars and typically found linked to proteins in a proteoglycan chain (1). The history of chondroitin sulfate is not well known but is believed to have been discovered in the early 1860’s. Majority of chondroitin sulfate supplements are made from cow and pig cartilage, although other animals such as fish, sharks, and birds can be used to obtain the extract. Chondroitin sulfate is typically used in conjunction with glucosamine, an amino sugar that acts as an antecedent to glycosylated fats and proteins (2).

 

TRADITIONAL USES

Chondroitin sulfate has primarily been used to treat disorders of the joint, specifically osteoarthritis. It can be taken orally and is sometimes combined with other compounds. Although osteoarthritis is the main condition treated with chondroitin sulfate, it can be used for the management of osteoporosis, interstitial cystitis, urinary tract infections, cataracts, dry eye, Kashin-Beck disease, heart attacks, gastroesophageal reflux disease (GERD), and muscle soreness from exercise (3).

 

WHAT DOES SCIENCE TELL US?

  Chondroitin Sulfate Probably Supports Healthy Joints:

Chondroitin sulfate is typically used in conjunction with other supplements to treat osteoarthritis, but there is sufficient evidence suggesting that it is very useful when used both alone and with other supplements. Extensive research has shown chondroitin sulfate is beneficial for reducing osteoarthritis symptoms and slowing the progression of the condition.

A randomized, double-blind, placebo-controlled study compared the effect of different doses of chondroitin sulfate in 353 patients with knee osteoarthritis. Participants were either given 1,200 mg chondroitin sulfate once a day, 400 mg chondroitin sulfate three times a day, or a placebo for three months. While results showed no significant difference between the different dose groups, a significant improvement in functional ability was seen in both supplementation groups when compared to the placebo group (p<0.001) (4).

Other long-term, randomized, double-blind, placebo-controlled research gave 622 patients with knee osteoarthritis either 800 mg chondroitin sulfate or a placebo once a day for two years. It was concluded that supplementation with chondroitin sulfate significantly decreased loss of joint space width (p<0.0001), slowed disease progression (p<0.0005), and improved pain faster (p<0.01) than placebo (5).

In a randomized, double-blind study among 129 patients with symptomatic osteoarthritis of the knee and psoriasis, participants were given 800 mg chondroitin sulfate or a placebo one time daily for three months. At the end of the trial period, chondroitin sulfate in comparison to a placebo was significantly more useful in reducing knee pain (p<0.01), improving knee function (p<0.05), and lessening the number of participants who took acetaminophen for pain (p<0.05) (6).

A prospective longitudinal study evaluated the effects of chondroitin sulfate on knee osteoarthritis, in comparison to nonsteroidal anti-inflammatory medication. Participants were elderly adults with osteoarthritis of the knee and after the study period, it was determined that there was a significant lowering of stiffness and pain with chondroitin supplementation (7).

A double-blind, placebo-controlled, randomized trial consisting of 605 adult patients with chronic knee pain investigated the effects of either chondroitin sulfate (800 mg), glucosamine sulfate (1,500 mg), or both on osteoarthritis of the knee. Participants orally took the supplements or a placebo, once daily for two years, after which knee pain and knee radiographs to measure joint space narrowing were evaluated. While all supplementation resulted in a decrease of knee pain, the most significant improvement in joint space narrowing was seen in the combination of chondroitin sulfate and glucosamine sulfate supplementation (p=0.046) (8).

Another randomized trial among patients with osteoarthritis of the knee was administered either 400mg chondroitin sulfate and 500 mg glucosamine sulfate three times a day, 400 mg chondroitin sulfate and 500 mg glucosamine hydrochloride three times a day, or sachet preparations once a day for 16 weeks. Out of 1,120 participants, it was discovered that knee pain significantly decreased for all groups (p<0.001). Disease activity and use of acetaminophen were also improved for all treatment group (p<0.005) (9).

A large analysis was conducted on 43 placebo-controlled, randomized studies among approximately 9,000 patients with osteoarthritis. The results indicated that chondroitin sulfate supplementation for three months was significantly more effective at reducing pain than a placebo, and pain was reduced even further when taken for six months. It was also discovered that chondroitin sulfate significantly decreased disability scores as well (10).

However, one study looked at supplementation with either 400 mg chondroitin sulfate three times a day, 500 mg glucosamine three times a day, a combination of chondroitin sulfate and glucosamine, 200 mg of celecoxib once a day, or a placebo for two years. The results indicated that none of the treatment groups experienced an improvement in pain reduction when compared to the placebo (11). It was also reported that joint space width loss was not reduced in any of the treatment groups (12).

  Chondroitin Sulfate Possibly Reduces Pain:

Research on the effects of chondroitin sulfate to treat interstitial cystitis and bladder pain is not extensive, and most studies have been conducted on small sample sizes or in combination with other supplements. However, available research indicates that chondroitin sulfate may be useful for treating the symptoms and reducing pain associated with interstitial cystitis.

A double-blind, randomized study of 98 women with interstitial cystitis and bladder pain syndrome were assigned to get bladder instillations of either 20 mL of 2% chondroitin sulfate, or 20 mL of an inactive solution once a week for eight weeks. Four weeks after the last bladder instillation, results showed that women who received the chondroitin sulfate instillations reported less pain and symptoms than those who received the control. However, none of these differences between the groups were statistically significant (13).

Comparable results were seen in another double-blind randomized study among 65 patients with interstitial cystitis. Participants either received 2.0% sodium chondroitin sulfate or a control intravesical treatment once a week for six weeks. After the treatment period, a six-week follow-up period revealed that more patients stated clinical benefits with chondroitin sulfate than the control, although again, these results were not statistically significant (14). A small, similar study of 53 patients with interstitial cystitis received intravesical treatment of 2.0% sodium chondroitin sulfate once a week for six weeks, followed by monthly treatments for 16 weeks. Follow-up results indicated that symptom and pain scores decreased (p<0.001) and no significant adverse effects occurred (15).

Another small study of 23 women with interstitial cystitis were treated with intravesical instillations of 2.0% chondroitin sulfate and 1.6% hyaluronic acid once a week for 20 weeks, then once a month for three months, and then followed for up to five months. A significant improvement was seen for pain (p=0.001), voiding urgency (p=0.005) and frequency (p=0.045), and overall symptom scores (p=0.004) (16). Another similar study administered endovesical treatments of 40 mL chondroitin sulfate and hyaluronic acid to 23 women once weekly for 12 weeks, followed by twice weekly for six months. After the trial period, symptoms, pain, voiding urgency and frequency, and voiding volumes all significantly improved (17). Although the sample size was small and no control group was used, these results indicate that chondroitin sulfate may be beneficial for treating interstitial cystitis.

An open-label uncontrolled study gave 252 patients with interstitial cystitis CystoProtek, a supplement containing 150 mg chondroitin sulfate, 120 mg glucosamine sulfate, 10 mg hyaluronate sodium, 150 mg quercetin, and 20 mg rutin four times a day for up to 12 months. Both males and females experienced a significant improvement in pain after 12 months in comparison to baseline (males p<0.0001); females p<0.0001) (18). Although these results were seen when chondroitin sulfate was taken in combination with other supplements, it may be beneficial for decreasing pain in those with interstitial cystitis.

  Chondroitin Sulfate Probably Helps Support a Healthy Urinary Tract:

The limited body of research of chondroitin sulfate for treating UTIs provides promising evidence that it is effective. However, most of the studies utilized chondroitin sulfate in combination with hyaluronic acid, which makes it difficult to determine if chondroitin sulfate alone is effective at reducing UTI occurrences and symptoms.

A double-blind, placebo-controlled, randomized study investigated the efficacy of intravesical treatment with chondroitin sulfate and hyaluronic acid in women with a history of recurring UTIs. 57 women were treated with 2.0% chondroitin sulfate and 1.6% hyaluronic acid once a week for 4 weeks, followed by once a month for five months, or a placebo. At the end of the follow-up period, it was found that women in the treatment group had significantly lower UTI rates (p=0.0002) and urinary pain, frequency, and urgency all improved as well (p<0.001), when compared to the placebo group (19).

Among a study of 28 women with recurrent UTIs, participants either received intravesical treatments of chondroitin sulfate and hyaluronic acid or long-term antibiotic prophylaxis. The rate of UTI reoccurrence was followed for up to 12 months and it was reported that those receiving the intravesical treatment had significant improvements in UTI reoccurrence (p=0.02), pain scores (p<0.001), voiding urgency and frequency (p<0.001), quality of life scores (p<0.001), and 3-day voiding mean scores (p=0.04) when compared to antibiotic prophylaxis (20).

In addition, it was discovered that chondroitin sulfate and hyaluronic acid supplementation reduced the number of bacteria in the urine. Three different groups of patients with recurring UTIs were given one of three intravesical treatment methods and followed for up to 12 months. Treatment groups consisted of either chondroitin sulfate and hyaluronic acid, chondroitin sulfate associated with fosfomycin (a broad-spectrum antibiotic), or fosfomycin only. It was concluded that those who received chondroitin sulfate and hyaluronic acid had improvements in the urothelium thickness and fewer bacteria in the urine (21).

A meta-analysis using four studies, consisting of 143 patients, evaluated the effects of chondroitin sulfate and glycosaminoglycan hyaluronic acid on UTI rates. The analysis concluded that supplementation significantly lowered the rate of UTIs (p<0.00001), as well as increased the amount of time between UTI reoccurrences (p<0.0001). Furthermore, it was also concluded that combination supplementation improved pain, urgency, and frequency scores (p<0.00001) (22).

  Chondroitin Sulfate Possibly Helps Support Healthy Eyes:

Results concerning the use of chondroitin sulfate for eye conditions such as cataract surgery and dry eye are inconclusive. Some results suggest significant improvements, while others found no change. More research is needed to determine the efficacy of chondroitin sulfate for eye conditions.

A prospective, randomized trial used 60 eyes to test the effects of chondroitin sulfate and sodium hyaluronate on intraocular pressure after cataract surgery. Some eyes received 4% chondroitin sulfate and 3% sodium hyaluronate, and others received the same treatment in addition to 1% sodium hyaluronate. Six hours after surgery, it was found that the group who received the extra sodium hyaluronate had lower intraocular pressure (p<0.05) (23). While the treatment was deemed successful, it is important to note that these results are most likely attributed to the extra sodium hyaluronate and cannot be directly linked to chondroitin sulfate.

A different randomized study among 100 patients gave instillations of either chondroitin sulfate and sodium hyaluronate or sodium hyaluronate alone after cataract surgery. Intraocular pressure was monitored and it was concluded that pressure was lower in those that received the combination treatment (24). This suggests that chondroitin sulfate is useful for cataract surgery when used with sodium hyaluronate.

A study conducted among 62 patients having a penetrating keratoplasty eye surgery tested the effects of 4% chondroitin sulfate and 3% sodium hyaluronate, or 1% sodium hyaluronate alone, on postoperative intraocular eye pressure. It was concluded that both treatments raised intraocular eye pressure, but sodium hyaluronate alone raised eye pressure for a significantly longer period of time (p=0.02) (25).

However, one randomized, clinical trial found no significant improvements with chondroitin sulfate treatment. In this study, researchers tested the use of injected chondroitin sulfate for protecting endothelial cells of the eye, as well as corneal thickness during cataract surgery. 100 eyes were either injected with a solution containing 4.0% chondroitin sulfate and 1.6% hyaluronic acid, 4.0% chondroitin sulfate and 3.0% sodium hyaluronate, or 1.0% sodium hyaluronate. Postoperative outcomes were monitored for up to three months, and results showed no significant differences between any of the treatment groups, although each one was effective (26).

A similar study of 114 patients undergoing cataract extraction surgery received either 2% hydroxypropylmethyl-cellulose, chondroitin sulfate and sodium hyaluronate, or sodium hyaluronate alone. Intraocular eye pressures were measured at various times after surgery. It was discovered that each treatment group besides the chondroitin sulfate and sodium hyaluronate group had a significant increase in intraocular pressure 24 hours after surgery (p<0.05). After a week, there were no significant differences between any treatment group (27).

Some research has been done on the effect of chondroitin sulfate for dry eyes. One such study enrolled 28 patients with dry eye to receive either chondroitin sulfate and xanthan gum eye drops, or Systane, a non-prescription eye drop product, four times a day for two months. Scores for dry eye disease were significantly lower in those receiving chondroitin sulfate and xanthan gum after two months (p=0.049), and supplementation was concluded to be as effective as Systane (28).

Another study enrolled 20 patients with keratoconjunctivitis sicca to take eye drops once every two hours while awake for two weeks. While the patients mostly favored the chondroitin sulfate solution, there were no statistically significant differences seen between the treatment groups in terms of effectiveness (29). More research is needed to determine the effectiveness of chondroitin sulfate as a treatment for dry eyes.

 

SAFETY

Chondroitin sulfate has been deemed safe for most people, including the elderly. Research has shown supplementation for up to two years is safe (5).

Interactions:

Major

  • No major interactions reported

Moderate

  • There is some evidence that chondroitin sulfate can act as an anticoagulant (30,31). Taking chondroitin sulfate with other anticoagulants such as heparin, warfarin, dalteparin, and edoxaban can increase the effects of the blood thinner medication and cause bruising or serious bleeding.

Side-Effects:

  • Stomach pain, bloating, diarrhea, constipation, alopecia, swelling of the lower limbs or eyelids, and skin irritations (32).

 

REFERENCES

  1. Baeurle SA, Kiselev MG, Makarova ES, Nogovitsin EA. Effect of the counterion behavior on the frictional–compressive properties of chondroitin sulfate solutions. Polymer (Guildf). 2009;50(7):1805-1813. doi:10.1016/J.POLYMER.2009.01.066
  2. Bray HG, Gregory JE, Stacey M. Chemistry of tissues: I. Chondroitin from cartilage. Biochem J1944;38(2):142-146.
  3. Volpi N. Chondroitin Sulfate : Structure, Role and Pharmacological Activityhttps://books.google.com/books?id=900alAEACAAJ&dq=chondroitin+sulfate&hl=en&sa=X&ved=0ahUKEwjwxKydgcLaAhXD41MKHQ8XDcoQ6AEIJjAA.  Accessed April 17, 2018.
  4. Zegels B, Crozes P, Uebelhart D, Bruyère O, Reginster JY. Equivalence of a single dose (1200 mg) compared to a three-time a day dose (400 mg) of chondroitin 4&amp;6 sulfate in patients with knee osteoarthritis. Results of a randomized double blind placebo controlled study. Osteoarthr Cartil. 2013;21(1):22-27. doi:10.1016/j.joca.2012.09.017
  5. Kahan A, Uebelhart D, De Vathaire F, Delmas PD, Reginster J-Y. Long-term effects of chondroitins 4 and 6 sulfate on knee osteoarthritis: The study on osteoarthritis progression prevention, a two-year, randomized, double-blind, placebo-controlled trial. Arthritis Rheum. 2009;60(2):524-533. doi:10.1002/art.24255
  6. Möller I, Pérez M, Monfort J, et al. Effectiveness of chondroitin sulphate in patients with concomitant knee osteoarthritis and psoriasis: a randomized, double-blind, placebo-controlled study. Osteoarthr Cartil. 2010;18:S32-S40. doi:10.1016/j.joca.2010.01.018
  7. Zotkin EG, Kharitonova T V, Shkireeva SI. [Clinical use of chondroitin sulfate in patients with osteoarthritis in geriatric practice]. Adv Gerontol = Uspekhi Gerontol2014;27(2):366-375.
  8. Fransen M, Agaliotis M, Nairn L, et al. Glucosamine and chondroitin for knee osteoarthritis: a double-blind randomised placebo-controlled clinical trial evaluating single and combination regimens. Ann Rheum Dis. 2015;74(5):851-858. doi:10.1136/annrheumdis-2013-203954
  9. Provenza JR, Shinjo SK, Silva JM, Peron CRGS, Rocha FAC. Combined glucosamine and chondroitin sulfate, once or three times daily, provides clinically relevant analgesia in knee osteoarthritis. Clin Rheumatol. 2015;34(8):1455-1462. doi:10.1007/s10067-014-2757-1
  10. Singh JA, Noorbaloochi S, MacDonald R, Maxwell LJ. Chondroitin for osteoarthritis. Singh JA, ed. Cochrane database Syst Rev. 2015;1:CD005614. doi:10.1002/14651858.CD005614.pub2
  11. Sawitzke AD, Shi H, Finco MF, et al. Clinical efficacy and safety of glucosamine, chondroitin sulphate, their combination, celecoxib or placebo taken to treat osteoarthritis of the knee: 2-year results from GAIT. Ann Rheum Dis. 2010;69(8):1459-1464. doi:10.1136/ard.2009.120469
  12. Sawitzke AD, Shi H, Finco MF, et al. The effect of glucosamine and/or chondroitin sulfate on the progression of knee osteoarthritis: A report from the glucosamine/chondroitin arthritis intervention trial. Arthritis Rheum. 2008;58(10):3183-3191. doi:10.1002/art.23973
  13. Nickel JC, Hanno P, Kumar K, Thomas H. Second multicenter, randomized, double-blind, parallel-group evaluation of effectiveness and safety of intravesical sodium chondroitin sulfate compared with inactive vehicle control in subjects with interstitial cystitis/bladder pain syndrome. Urology. 2012;79(6):1220-1224. doi:10.1016/j.urology.2012.01.059
  14. Nickel JC, Egerdie RB, Steinhoff G, Palmer B, Hanno P. A multicenter, randomized, double-blind, parallel group pilot evaluation of the efficacy and safety of intravesical sodium chondroitin sulfate versus vehicle control in patients with interstitial cystitis/painful bladder syndrome. Urology. 2010;76(4):804-809. doi:10.1016/j.urology.2010.03.016
  15. Nickel JC, Egerdie B, Downey J, et al. A real-life multicentre clinical practice study to evaluate the efficacy and safety of intravesical chondroitin sulfate for the treatment of interstitial cystitis. BJU Int. 2009;103(1):56-60. doi:10.1111/j.1464-410X.2008.08028.x
  16. Cervigni M, Natale F, Nasta L, Padoa A, Voi R Lo, Porru D. A combined intravesical therapy with hyaluronic acid and chondroitin for refractory painful bladder syndrome/interstitial cystitis. Int Urogynecol J. 2008;19(7):943-947. doi:10.1007/s00192-008-0572-4
  17. Porru D, Cervigni M, Nasta L, et al. Results of endovesical hyaluronic acid/chondroitin sulfate in the treatment of Interstitial Cystitis/Painful Bladder Syndrome. Rev Recent Clin Trials2008;3(2):126-129.
  18. Theoharides TC, Kempuraj D, Vakali S, Sant GR. Treatment of refractory interstitial cystitis/painful bladder syndrome with CystoProtek--an oral multi-agent natural supplement. Can J Urol2008;15(6):4410-4414.
  19. Damiano R, Quarto G, Bava I, et al. Prevention of recurrent urinary tract infections by intravesical administration of hyaluronic acid and chondroitin sulphate: a placebo-controlled randomised trial. Eur Urol. 2011;59(4):645-651. doi:10.1016/j.eururo.2010.12.039
  20. De Vita D, Giordano S. Effectiveness of intravesical hyaluronic acid/chondroitin sulfate in recurrent bacterial cystitis: a randomized study. Int Urogynecol J. 2012;23(12):1707-1713. doi:10.1007/s00192-012-1794-z
  21. Torella M, Schettino MT, Salvatore S, Serati M, De Franciscis P, Colacurci N. Intravesical therapy in recurrent cystitis: a multi-center experience. J Infect Chemother. 2013;19(5):920-925. doi:10.1007/s10156-013-0609-6
  22. De Vita D, Antell H, Giordano S. Effectiveness of intravesical hyaluronic acid with or without chondroitin sulfate for recurrent bacterial cystitis in adult women: a meta-analysis. Int Urogynecol J. 2013;24(4):545-552. doi:10.1007/s00192-012-1957-y
  23. Rainer G, Stifter E, Luksch A, Menapace R. Comparison of the effect of Viscoat and DuoVisc on postoperative intraocular pressure after small-incision cataract surgery. J Cataract Refract Surg. 2008;34(2):253-257. doi:10.1016/j.jcrs.2007.09.041
  24. Embriano PJ. Postoperative pressures after phacoemulsification: sodium hyaluronate vs. sodium chondroitin sulfate-sodium hyaluronate. Ann Ophthalmol1989;21(3):85-88, 90.
  25. Burke S, Sugar J, Farber MD. Comparison of the effects of two viscoelastic agents, Healon and Viscoat, on postoperative intraocular pressure after penetrating keratoplasty. Ophthalmic Surg1990;21(12):821-826.
  26. Praveen MR, Koul A, Vasavada AR, Pandita D, Dixit N V., Dahodwala FF. DisCoVisc versus the soft-shell technique using Viscoat and Provisc in phacoemulsification: Randomized clinical trial. J Cataract Refract Surg. 2008;34(7):1145-1151. doi:10.1016/j.jcrs.2008.03.019
  27. Lane SS, Naylor DW, Kullerstrand LJ, Knauth K, Lindstrom RL. Prospective comparison of the effects of Occucoat, Viscoat, and Healon on intraocular pressure and endothelial cell loss. J Cataract Refract Surg1991;17(1):21-26.
  28. Baiza-Durán LM, Saucedo-Rodríguez LM, Alaníz-De la O LR, Llamas-Moreno JF. Efficacy and safety of chondroitin sulfate/xanthan gum versus polyethylene glycol/propylene glycol/hydroxypropyl guar in patients with dry eye. Clin Ophthalmol. 2013;7:995. doi:10.2147/OPTH.S46337
  29. Limberg MB, McCaa C, Kissling GE, Kaufman HE. Topical application of hyaluronic acid and chondroitin sulfate in the treatment of dry eyes. Am J Ophthalmol1987;103(2):194-197.
  30. Wu M, Wen D, Gao N, et al. Anticoagulant and antithrombotic evaluation of native fucosylated chondroitin sulfates and their derivatives as selective inhibitors of intrinsic factor Xase. Eur J Med Chem. 2015;92:257-269. doi:10.1016/j.ejmech.2014.12.054
  31. Gray A, Litinas E, Jeske W, Fareed J, Hoppensteadt D. Interactions of Oversulfated Chondroitin Sulfate (OSCS) From Different Sources With Unfractionated Heparin. Clin Appl Thromb. 2012;18(2):166-173. doi:10.1177/1076029611421167
  32. Leeb BF, Schweitzer H, Montag K, Smolen JS. A meta-analysis of chondroitin sulfate in the treatment of osteoarthritis. J Rheumatol2000;27(1):205-211

See the MedlinePlus entry for chondroitin sulfate, the Drugs.com entry for chondroitin, the MedicineNet entry for chondroitin sulfate, the Examine.com entry for chondroitin, the Michigan Medicine Health Library entry for chondroitin sulfate, or the WebMD entry for chondroitin sulfate for more information.