Joint Supplements

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Knee Pain is one of the most common running problems.

The joint supplements glucosamine and chondroitin provide marginal benefit, but are considered safe. They may be worth considering if you can justify the expense. Other supplements such as Omega 3 oils and Vitamin C/E may be worth considering.

1 Glucosamine and chondroitin

Chondroitin is an important component of joint cartilage and glucosamine is building block for other joint structures. Both chondroitin and glucosamine taken orally reach the joint space[1][2][3]. There have been over 500 studies of glucosamine and chondroitin[4], and analysis of the best of the studies show only a marginal benefit[5][6][7] or provide benefit only to a subgroup of suffers[8]. These benefits do not meet the requirements to be generally considered clinically important[5]. One review noted that the benefit of these suppliments is confused by a high rate of response to placebos[9], suggesting that the belief in their efficacy is important. However, given the safety of these supplements, they may be worth considering if your income is sufficient.

1.1 Dosage

Doses of less than 800 mg/day of chondroitin or less than 1500 mg/day of glucosamine are considered sub-therapeutic[5], but there is no indication of appropriate dose. The Mayo Clinic suggest 500mg Glucosamine sulfate three times a day or 20mg per Kg body weight[10] and 200-400mg chondroitin 2-3 times daily[11]. These doses are based on those commonly used in studies.

2 Cost

I found glucosamine and chondroitin available online for about $10/month. Look carefully at the ingredients to check how many capsules make up the stated dose when calculating the daily cost.

3 Cancer Risk

One study found a small reduction in the rates of colorectal cancer from glucosamine and chondroitin based on the review of two large groups of healthcare professionals[12]. Another study of found reduced rates colorectal cancer from glucosamine[13]. One theory is that glucosamine and chondroitin act as an anti-inflammatory.

4 Food for joints

There have been over 2,000 studies of related to nutrition and Osteoarthritis, but only 53 are of sufficient quality to be useful[14]. Some options that may be worth considering include:

  • Methylsulfonylmethane (MSM) is a less well known joint supplement than glucosamine and chondroitin, with far less studies available. There is some support for MSM helping with joint pain[15][16], but not enough to give confidence as to its effectiveness or safety[17]. MSM does cross the blood/brain barrier[18][19] and may cause headaches[15]. (I believe MSM was a trigger for my migraines.)
  • The supplement "avocado/soybean unsaponifiables" has shown positive results in studies[20][21][22][23]. However, this supplement has not been widely studies for effectiveness or long term safety.
  • There is some suggestion that Omega 3 oils may help with Osteoarthritis[24][25]. Given the other health benefits of Omega 3 oils, supplementation should be considered.
  • Higher Vitamin C intake may reduce Osteoarthritis[26] and 1000mg/day of Vitamin C reduced joint pain, though by less than half what would be expected from NSAIDs[27]. Like Omega 3 there may be other benefits to Vitamin C supplementation that make this worthwhile.
  • Some[28][29][30], but not all[31][32] studies have shown benefit from Vitamin E supplementation. Like the above two supplements, Vitamin E should be considered as there may be other health benefits.
  • Devil's Claw, a South African plan extract, may help with joint pain (60mg harpagoside)[33]. However, there is little known about its safety.

5 References

  1. A. Conte, N. Volpi, L. Palmieri, I. Bahous, G. Ronca, Biochemical and pharmacokinetic aspects of oral treatment with chondroitin sulfate., Arzneimittelforschung, volume 45, issue 8, pages 918-25, Aug 1995, PMID 7575762
  2. F. Ronca, L. Palmieri, P. Panicucci, G. Ronca, Anti-inflammatory activity of chondroitin sulfate., Osteoarthritis Cartilage, volume 6 Suppl A, pages 14-21, May 1998, PMID 9743814
  3. S. Persiani, R. Rotini, G. Trisolino, LC. Rovati, M. Locatelli, D. Paganini, D. Antonioli, A. Roda, Synovial and plasma glucosamine concentrations in osteoarthritic patients following oral crystalline glucosamine sulphate at therapeutic dose., Osteoarthritis Cartilage, volume 15, issue 7, pages 764-72, Jul 2007, doi 10.1016/j.joca.2007.01.019, PMID 17353133
  4. Florent Richy, Olivier Bruyere, Olivier Ethgen, Michel Cucherat, Yves Henrotin, Jean-Yves Reginster, Structural and Symptomatic Efficacy of Glucosamine and Chondroitin in Knee Osteoarthritis, Archives of Internal Medicine, volume 163, issue 13, 2003, pages 1514, ISSN 0003-9926, doi 10.1001/archinte.163.13.1514
  5. 5.0 5.1 5.2 S. Wandel, P. Juni, B. Tendal, E. Nuesch, P. M. Villiger, N. J. Welton, S. Reichenbach, S. Trelle, Effects of glucosamine, chondroitin, or placebo in patients with osteoarthritis of hip or knee: network meta-analysis, BMJ, volume 341, issue sep16 2, 2010, pages c4675–c4675, ISSN 0959-8138, doi 10.1136/bmj.c4675
  6. S. Reichenbach, R. Sterchi, M. Scherer, S. Trelle, E. Bürgi, U. Bürgi, PA. Dieppe, P. Jüni, Meta-analysis: chondroitin for osteoarthritis of the knee or hip., Ann Intern Med, volume 146, issue 8, pages 580-90, Apr 2007, PMID 17438317
  7. SC. Vlad, MP. LaValley, TE. McAlindon, DT. Felson, Glucosamine for pain in osteoarthritis: why do trial results differ?, Arthritis Rheum, volume 56, issue 7, pages 2267-77, Jul 2007, doi 10.1002/art.22728, PMID 17599746
  8. DO. Clegg, DJ. Reda, CL. Harris, MA. Klein, JR. O'Dell, MM. Hooper, JD. Bradley, CO. Bingham, MH. Weisman, Glucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis., N Engl J Med, volume 354, issue 8, pages 795-808, Feb 2006, doi 10.1056/NEJMoa052771, PMID 16495392
  9. Nicholas DiNubile, Glucosamine and Chondroitin Sulfate: What Has Been Learned Since the Glucosamine/chondroitin Arthritis Intervention Trial, Orthopedics, volume 41, issue 4, 2018, pages 200–207, ISSN 0147-7447, doi 10.3928/01477447-20180511-06
  10. Glucosamine: Dosing -
  11. Chondroitin sulfate: Dosing -
  12. Elizabeth D. Kantor, Xuehong Zhang, Kana Wu, Lisa B. Signorello, Andrew T. Chan, Charles S. Fuchs, Edward L. Giovannucci, Use of glucosamine and chondroitin supplements in relation to risk of colorectal cancer: Results from the Nurses' Health Study and Health Professionals follow-up study, International Journal of Cancer, volume 139, issue 9, 2016, pages 1949–1957, ISSN 00207136, doi 10.1002/ijc.30250
  13. Elizabeth D. Kantor, Christina C. Newton, Edward L. Giovannucci, Marjorie L. McCullough, Peter T. Campbell, Eric J. Jacobs, Glucosamine use and risk of colorectal cancer: results from the Cancer Prevention Study II Nutrition Cohort, Cancer Causes & Control, volume 29, issue 3, 2018, pages 389–397, ISSN 0957-5243, doi 10.1007/s10552-018-1003-6
  14. Laurent G Ameye, Winnie SS Chee, Arthritis Research & Therapy, volume 8, issue 4, 2006, pages R127, ISSN 14786354, doi 10.1186/ar2016
  15. 15.0 15.1 LS. Kim, LJ. Axelrod, P. Howard, N. Buratovich, RF. Waters, Efficacy of methylsulfonylmethane (MSM) in osteoarthritis pain of the knee: a pilot clinical trial., Osteoarthritis Cartilage, volume 14, issue 3, pages 286-94, Mar 2006, doi 10.1016/j.joca.2005.10.003, PMID 16309928
  16. PR. Usha, MU. Naidu, Randomised, Double-Blind, Parallel, Placebo-Controlled Study of Oral Glucosamine, Methylsulfonylmethane and their Combination in Osteoarthritis., Clin Drug Investig, volume 24, issue 6, pages 353-63, 2004, PMID 17516722
  17. S. Brien, P. Prescott, N. Bashir, H. Lewith, G. Lewith, Systematic review of the nutritional supplements dimethyl sulfoxide (DMSO) and methylsulfonylmethane (MSM) in the treatment of osteoarthritis., Osteoarthritis Cartilage, volume 16, issue 11, pages 1277-88, Nov 2008, doi 10.1016/j.joca.2008.03.002, PMID 18417375
  18. SE. Rose, JB. Chalk, GJ. Galloway, DM. Doddrell, Detection of dimethyl sulfone in the human brain by in vivo proton magnetic resonance spectroscopy., Magn Reson Imaging, volume 18, issue 1, pages 95-8, Jan 2000, PMID 10642107
  19. A. Lin, CH. Nguy, F. Shic, BD. Ross, Accumulation of methylsulfonylmethane in the human brain: identification by multinuclear magnetic resonance spectroscopy., Toxicol Lett, volume 123, issue 2-3, pages 169-77, Sep 2001, PMID 11641045
  20. M. Lequesne, E. Maheu, C. Cadet, RL. Dreiser, Structural effect of avocado/soybean unsaponifiables on joint space loss in osteoarthritis of the hip., Arthritis Rheum, volume 47, issue 1, pages 50-8, Feb 2002, PMID 11932878
  21. F. Blotman, E. Maheu, A. Wulwik, H. Caspard, A. Lopez, Efficacy and safety of avocado/soybean unsaponifiables in the treatment of symptomatic osteoarthritis of the knee and hip. A prospective, multicenter, three-month, randomized, double-blind, placebo-controlled trial., Rev Rhum Engl Ed, volume 64, issue 12, pages 825-34, Dec 1997, PMID 9476272
  22. T. Appelboom, J. Schuermans, G. Verbruggen, Y. Henrotin, JY. Reginster, Symptoms modifying effect of avocado/soybean unsaponifiables (ASU) in knee osteoarthritis. A double blind, prospective, placebo-controlled study., Scand J Rheumatol, volume 30, issue 4, pages 242-7, 2001, PMID 11578021
  23. E. Maheu, B. Mazières, JP. Valat, G. Loyau, X. Le Loët, P. Bourgeois, JM. Grouin, S. Rozenberg, Symptomatic efficacy of avocado/soybean unsaponifiables in the treatment of osteoarthritis of the knee and hip: a prospective, randomized, double-blind, placebo-controlled, multicenter clinical trial with a six-month treatment period and a two-month followup demonstrating a persistent effect., Arthritis Rheum, volume 41, issue 1, pages 81-91, Jan 1998, doi <81::AID-ART11>3.0.CO;2-9 10.1002/1529-0131(199801)41:1<81::AID-ART11>3.0.CO;2-9, PMID 9433873
  24. L. Knott, N.C. Avery, A.P. Hollander, J.F. Tarlton, Regulation of osteoarthritis by omega-3 (n-3) polyunsaturated fatty acids in a naturally occurring model of disease, Osteoarthritis and Cartilage, volume 19, issue 9, 2011, pages 1150–1157, ISSN 10634584, doi 10.1016/j.joca.2011.06.005
  25. K.R. Baker, N.R. Matthan, A.H. Lichtenstein, J. Niu, A. Guermazi, F. Roemer, A. Grainger, M.C. Nevitt, M. Clancy, C.E. Lewis, J.C. Torner, D.T. Felson, Association of plasma n-6 and n-3 polyunsaturated fatty acids with synovitis in the knee: the MOST study, Osteoarthritis and Cartilage, volume 20, issue 5, 2012, pages 382–387, ISSN 10634584, doi 10.1016/j.joca.2012.01.021
  26. TE. McAlindon, P. Jacques, Y. Zhang, MT. Hannan, P. Aliabadi, B. Weissman, D. Rush, D. Levy, DT. Felson, Do antioxidant micronutrients protect against the development and progression of knee osteoarthritis?, Arthritis Rheum, volume 39, issue 4, pages 648-56, Apr 1996, PMID 8630116
  27. NH. Jensen, [Reduced pain from osteoarthritis in hip joint or knee joint during treatment with calcium ascorbate. A randomized, placebo-controlled cross-over trial in general practice]., Ugeskr Laeger, volume 165, issue 25, pages 2563-6, Jun 2003, PMID 12854267
  28. I. Machtey, L. Ouaknine, Tocopherol in Osteoarthritis: a controlled pilot study., J Am Geriatr Soc, volume 26, issue 7, pages 328-30, Jul 1978, PMID 350940
  29. G. Blankenhorn, Clinical effectiveness of Spondyvit (vitamin E) in activated arthroses. A multicenter placebo-controlled double-blind study., Z Orthop Ihre Grenzgeb, volume 124, issue 3, pages 340-3, doi 10.1055/s-2008-1044572, PMID 3529677
  30. O. Scherak, G. Kolarz, C. Schödl, G. Blankenhorn, High dosage vitamin E therapy in patients with activated arthrosis., Z Rheumatol, volume 49, issue 6, pages 369-73, PMID 2085059
  31. C. Brand, J. Snaddon, M. Bailey, F. Cicuttini, Vitamin E is ineffective for symptomatic relief of knee osteoarthritis: a six month double blind, randomised, placebo controlled study., Ann Rheum Dis, volume 60, issue 10, pages 946-9, Oct 2001, PMID 11557651
  32. AE. Wluka, S. Stuckey, C. Brand, FM. Cicuttini, Supplementary vitamin E does not affect the loss of cartilage volume in knee osteoarthritis: a 2 year double blind randomized placebo controlled study., J Rheumatol, volume 29, issue 12, pages 2585-91, Dec 2002, PMID 12465157
  33. JJ. Gagnier, S. Chrubasik, E. Manheimer, Harpgophytum procumbens for osteoarthritis and low back pain: a systematic review., BMC Complement Altern Med, volume 4, pages 13, Sep 2004, doi 10.1186/1472-6882-4-13, PMID 15369596