Life Extension Magazine March 2007
Next-Generation Nutrients for Rapid Relief of Joint Pain
Hyaluronic Acid: Essential Lubrication to Cushion Joints
Comfortable joint movement depends on the presence of synovial fluid in the joint cavities. Hyaluronic acid is the primary natural polymer compound present in the synovial fluid of joints. Produced by specialized cells lining the fluid-filled sac surrounding joints, hyaluronic acid creates a viscous, cushioning environment for joint cartilage, preventing friction from damaging these hard-working tissues. In the presence of osteoarthritis, however, hyaluronic acid in the synovial fluid becomes less viscous and loses elasticity, while simultaneously decreasing in concentration. Ensuring optimal levels of hyaluronic acid is thus crucial to healthy joint function.
Recognizing the importance of hyaluronic acid in ensuring joint comfort, the American College of Rheumatology issued guidelines recommending the use of hyaluronic acid preparations for injection directly into the synovial spaces of joints affected by arthritis.20 While hyaluronic acid was once believed to offer only symptomatic relief from arthritis, in recent years physicians have noted that it may actually treat fundamental aspects of the disease. In addition to improving joint lubrication, supplemental hyaluronic acid appears to stimulate the body’s generation of new hyaluronic acid, while alleviating pain and inflammation.20-22
Recently published findings from a veterinary trial conducted in Lexington, Kentucky, show that orally administered hyaluronic acid improved the prognoses of yearling horses that underwent surgery on an equine joint that is roughly analogous to the human knee. The surgery’s purpose is to prevent degenerative joint disease and improve the performance of these equine athletes. In a blinded, placebo-controlled experiment involving 48 thoroughbreds, 30 days of post-operative use of oral hyaluronic acid significantly improved outcomes. According to the study investigators, “The oral hyaluronic acid showed benefit over the orally administered placebo for all lesions at all locations and of all sizes.” Noting that “anecdotal reports supporting the efficacy of these preparations already exist,” the researchers added that “the oral form is convenient and, therefore, may be preferable for routine use.”23,24
To see whether these encouraging results could be duplicated in humans, scientists performed a randomized, placebo-controlled, double-blind study of 20 patients with osteoarthritis of the knee. Each subject received 80 mg of a specially formulated, orally ingested hyaluronic acid supplement called Hyal-Joint™ or a placebo daily for two months. Although results are as yet unpublished, they indicate that the supplemented patients reported a statistically significant improvement in a standardized score of pain, as compared to those who received placebo. More specifically, patients who took the oral hyaluronic acid recorded a 33% improvement in their pain scores, compared to only a 6% improvement in the placebo group. Furthermore, this novel form of hyaluronic acid was found to be well tolerated and safe within the study parameters. Additional human trials using lower doses are reportedly under way. Research indicates that this unique form of hyaluronic acid is well absorbed from the small intestine. Importantly, Hyal-Joint™ (which is derived from natural tissues) demonstrates a superior ability to stimulate joint synovial fluid production, as compared to hyaluronic acid derived from bacterial synthesis.Scientists believe this hyaluronic acid formulation begins to increase the body’s natural production of hyaluronic acid within two to four weeks after beginning supplementation.25
Korean Angelica: A Fast-Acting Analgesic and Anti-Inflammmatory
As noted earlier, a major drawback of many traditional joint-health supplements is the absence of a compound that provides fast-acting pain relief. With this in mind, Korean researchers set out to develop a powerful natural pain reliever containing active ingredients derived from the herb known as Korean Angelica (Angelica gigas Nakai). Research has shown that this powerful analgesic and anti-inflammatory agent goes to work almost immediately in the body.
Unlike most prescription and over-the-counter pain relievers that inhibit the COX (cyclooxygenase) enzymes, this specialized form of Korean Angelica fights pain through its effects on the central nervous system. Studies suggest that this mechanism of action may involve the mediation of receptors for serotonin and noradrenaline, two nervous system messengers. Korean Angelica has demonstrated efficacy against numerous types of pain, especially inflammatory pain.26,27 Recently published findings indicate that one active ingredient derived from Korean Angelica inhibits activation of nuclear factor-kappa B (NF-kB), a DNA transcription factor that is activated in many inflammatory and disease states, including cancer.28
This ability to block NF-kB is highly significant, as evidenced by the fact that NF-kB and the signaling pathways that regulate its activity are under intensive study in the field of drug development. This is because NF-kB regulates the transcription of numerous genes, particularly those involved in immune and inflammatory responses, as well as those that confer resistance to programmed cell death.29
Like many of nature’s most potent medicinal herbs, Korean Angelica offers multiple potential benefits for human health. Cancer researchers are now focused on the potential ability of its active ingredients to prevent or treat prostate and other cancers.30-32 Furthermore, compounds extracted from Korean Angelica appear to protect the brain from a variety of insults, and may help mitigate susceptibility to Alzheimer’s disease.33,34 Thus, potent pain relief may be just one of many benefits offered by Korean Angelica. These benefits have been captured in a specialized extract of Korean Angelica called Decursinol-50 ™.
A multitude of studies support the value of glucosamine, MSM, and other slower-acting joint health compounds in promoting long-term improvement in and maintenance of joint function.
For those seeking faster relief from the pain and discomfort of arthritis and similar joint afflictions, newly developed compounds from keratin, hyaluronic acid, and Korean Angelica provide much-needed complementary support. When joint pain and stiffness make it difficult to wait for the healing to begin, these products have been shown to promote more rapid pain relief, improved joint lubrication, and quick healing and regeneration of joint tissue.
Because of the many distinct ways in which joints can degrade with aging, combining these next-generation nutrients with traditional joint-health supplements may provide the most comprehensive support for optimal joint structure and function.
1. Qiu GX, Gao SN, Giacovelli G, Rovati L, Setnikar I. Efficacy and safety of glucosamine sulfate versus ibuprofen in patients with knee osteoarthritis. Arzneimittelforschung. 1998 May;48(5):469-74.
2. Muller-Fassbender H, Bach GL, Haase W, Rovati LC, Setnikar I. Glucosamine sulfate compared to ibuprofen in osteoarthritis of the knee. Osteoarthriti Cartilage. 1994 Mar;2(1):61-9.
3. Noack W, Fischer M, Forster KK, Rovati LC, Setnikar I. Glucosamine sulfate in osteoarthritis of the knee. Osteoarthritis Cartilage. 1994 Mar;2(1):51-9.
4. Yan Y, Wanshun L, Baoqin H, et al. The antioxidative and immunostimulating properties of d-glucosamine. Int Immunopharmacol. 2007 Jan;7(1):29-35.
5. Uebelhart D, Malaise M, Marcolongo R, et al. Intermittent treatment of knee osteoarthritis with oral chondroitin sulfate: a one-year, randomized, double-blind, multicenter study versus placebo. Osteoarthritis Cartilage. 2004 Apr;12(4):269-76.
6. Poolsup N, Suthisisang C, Channark P, Kittikulsuth W. Glucosamine long-term treatment and the progression of knee osteoarthritis: systematic review of randomized controlled trials. Ann Pharmacother. 2005 Jun;39(6):1080-7.
7. Richy F, Bruyere O, Ethgen O, et al. Structural and symptomatic efficacy of glucosamine and chondroitin in knee osteoarthritis: a comprehensive meta-analysis. Arch Intern Med. 2003 Jul 14;163(13):1514-22.
8. McAlindon TE, LaValley MP, Gulin JP, Felson DT. Glucosamine and chondroitin for treatment of osteoarthritis: a systematic quality assessment and meta-analysis. JAMA. 2000 Mar 15;283(11):1469-75.
9. Capone ML, Tacconelli S, Di Francesco L, Sacchetti A, Sciulli MG, Patrignani P. Pharmacodynamic of cyclooxygenase inhibitors in humans. Prostaglandins Other Lipid Mediat. 2007 Jan;82(1-4):85-94.
10. Available at: http://www.niams.nih.gov/hi/topics/arthritis/oahandout.htm#3. Accessed January 4, 2007.
11. Bradley H, Gough A, Sokhi RS, et al. Sulfate metabolism is abnormal in patients with rheumatoid arthritis. Confirmation by in vivo biochemical findings. J Rheumatol. 1994 Jul;21(7):1192-6.
12. Kontny E, Wojtecka-LUkasik E, Rell-Bakalarska K, et al. Impaired generation of taurine chloramine by synovial fluid neutrophils of rheumatoid arthritis patients. Amino Acids. 2002;23(4):415-8.
13. Parcell S. Sulfur in human nutrition and applications in medicine. Altern Med Rev. 2002 Feb;7(1):22-44.
14. Tappaz ML. Taurine biosynthetic enzymes and taurine transporter: molecular identification and regulations. Neurochem Res. 2004 Jan;29(1):83-96.
15. Wilkinson LJ, Waring RH. Cysteine dioxygenase: modulation of expression in human cell lines by cytokines and control of sulphate production. Toxicol In Vitro. 2002 Aug;16(4):481-3.
16. Roughley PJ, Lee ER. Cartilage proteoglycans: structure and potential functions. Microsc Res Tech. 1994 Aug 1;28(5):385-97.
17. Baker MS, Feigan J, Lowther DA. Chondrocyte antioxidant defences: the roles of catalase and glutathione peroxidase in protection against H2O2 dependent inhibition of proteoglycan biosynthesis. J Rheumatol. 1988 Apr;15(4):670-7.
18. Kurz B, Jost B, Schunke M. Dietary vitamins and selenium diminish the development of mechanically induced osteoarthritis and increase the expression of antioxidative enzymes in the knee joint of STR/1N mice. Osteoarthritis Cartilage. 2002 Feb;10(2):119-26.
19. Available at: http://www.keratec.co.nz/keratec/cynatineflx/. Accessed January 8, 2007.
20. Moskowitz RW. Hyaluronic acid supplementation. Curr Rheumatol Rep. 2000 Dec;2(6):466-71.
21. Altman RD. Status of hyaluronan supplementation therapy in osteoarthritis. Curr Rheumatol Rep. 2003 Feb;5(1):7-14.
22. Bagga H, Burkhardt D, Sambrook P, March L. Longterm effects of intraarticular hyaluronan on synovial fluid in osteoarthritis of the knee. J Rheumatol. 2006 May;33(5):946-50.
23. McIlwraith CW, Foerner JJ, Davis DM. Osteochondritis dissecans of the tarsocrural joint: results of treatment with arthroscopic surgery. Equine Vet J. 1991 May;23(3):155-62.
24. Bergin BJ, Pierce SW, Bramlage LR, Stromberg A. Oral hyaluronan gel reduces post operative tarsocrural effusion in the yearling Thoroughbred. Equine Vet J. 2006 Jul;38(4):375-8.
25. Available at: http://www.bioiberica.com/jointcare/hyaljoint.htm. Accessed January 8, 2007.
26. Choi SS, Han KJ, Lee HK, Han EJ, Suh HW. Antinociceptive profiles of crude extract from roots of Angelica gigas NAKAI in various pain models. Biol Pharm Bull. 2003 Sep;26(9):1283-8.
27. Choi SS, Han KJ, Lee JK, et al. Antinociceptive mechanisms of orally administered decursinol in the mouse. Life Sci. 2003 Jun 13;73(4):471-85.
28. Kim JH, Jeong JH, Jeon ST, et al. Decursin inhibits induction of inflammatory mediators by blocking nuclear factor-kappaB activation in macrophages. Mol Pharmacol. 2006 Jun;69(6):1783-90.
29. Lee JH, Jung HS, Giang PM, et al. Blockade of nuclear factor-kappaB signaling pathway and anti-inflammatory activity of cardamomin, a chalcone analog from Alpinia conchigera. J Pharmacol Exp Ther. 2006 Jan;316(1):271-8.
30. Jiang C, Lee HJ, Li GX, et al. Potent antiandrogen and androgen receptor activities of an Angelica gigas-containing herbal formulation: identification of decursin as a novel and active compound with implications for prevention and treatment of prostate cancer. Cancer Res. 2006 Jan 1;66(1):453-63.
31. Lee S, Lee YS, Jung SH, et al. Anti-tumor activities of decursinol angelate and decursin from Angelica gigas. Arch Pharm Res. 2003 Sep;26(9):727-30.
32. Ahn KS, Sim WS, Kim IH. Decursin: a cytotoxic agent and protein kinase C activator from the root of Angelica gigas. Planta Med. 1996 Feb;62(1):7-9.
33. Kang SY, Lee KY, Sung SH, Kim YC. Four new neuroprotective dihydropyranocoumarins from Angelica gigas. J Nat Prod. 2005 Jan;68(1):56-9.
34. Yan JJ, Kim DH, Moon YS, et al. Protection against beta-amyloid peptide-induced memory impairment with long-term administration of extract of Angelica gigas or decursinol in mice. Prog Neuropsychopharmacol Biol Psychiatry. 2004 Jan;28(1):25-30.