Supporting Research & Clinical Studies

Below are the research references and clinical studies which validate the information documented on this website.

1) P.M. Brooks, S.R. Potter and W.W. Buchanan, "NSAID and Osteoarthritis-- Help or Hindrance," J Rheutatol 9 (19820: 3-5.

2) N.M.Newman, R.S.M. Ling, "acetabular Bone Destruction Related to Non-Steroidal Anti-inflammatory Drugs," Lancet 2 (1985):11-13]

3) Shield MJ, Anti-inflammatory drugs and their effects on cartilage synthesis and renal function. Eur J Rheumatol Inflam 13:7-16, 1993

4) Ronningen H and Langeland N, Indomethacin treatment in osteoarthritis of the hip joint. Acta Orthop Scand 50:169-74, 1979

5) Solomon L, Drug induced arthropathy and necrosis of the femoral head. J Bone Joint Surg 55B:246-51, 1973

6) Clinical Gastroenterology and Hepatology, January 2005; vol 3. David Y. Graham, MD, head, gastroenterology, Michael DeBakey Medical Center and professor of medicine, Baylor College of Medicine, Houston

7) Knill-Jones RP, Pearce H, Batten J, et al. Comparative trial of Nutrizym in chronic pancreatic insufficiency. Brit Med J 1970;4:21.

8) Balakrishnan V, Hareendran A, Sukumaran Nair C. Double-blind cross-over trial of an enzyme preparation in pancreatic steatorrhea. J Asso Phys Ind 1981;29:207-209.

9) Seligman B. Bromelain-an anti-inflammatory agent thrombophlebitis. No toxicity. Angiology 1962;13:508-510.

10) Felton G. Does Kinin released by pineapple stem bromelain stimulate production of prostaglandin E1-like compound. Haw Med J 1976;2:39-47.

11) Mynott TL, Luke RK, Chandler DS. Oral administration of protease inhibits enterotoxigenic Escherichia coli receptor activity in piglet small intestine. Gut 1996;38:28-32.

12) Gupta I, Parihar A, Malhotra P, et al. Effects of Boswellia serrata gum resin in patients with ulcerative colitis. Eur J Med Res 1997;2(1):37-43.

13) Gupta I, Parihar A, Malhotra P, et al. Effects of gum resin of Boswellia serrata in patients with chronic colitis. Planta Med 2001;67(5):391-395.

14) Taussig SJ, Nieper HA. Bromelain: its use in prevention and treatment of cardiovascular disease, present status. J IAPM 1979;6:139-151.

15) Giacca S. Clinical experiments with bromelain in peripheral venous diseases and chronic bronchitic states. Minerva Med 1965;56:Suppl.104.

16) Nieper HA. Effect of bromelain on coronary heart disease and angina pectoris. Acta Med Empirica 1978;5:274-278.

17) Nieper HA. Decrease of the incidence of coronary heart infarct by Mg- and K-orotate and bromelain. Acta Med Empirica 1977;12:614-618.

18) Masson M. Bromelain in blunt injuries of the locomotor system. Fortschr Med 1995;113:303-306.

19) Tassman GC, Zafran JN, Zayon GM. Evaluation of a plant proteolytic enzyme for the control of inflammation and pain. J Dent Med 1964;19:73-77.

20) Blonstein JL. Control of swelling in boxing injuries. Practitioner 1960;185:78.

21) Mojcik C, Shevach E. Adhesion molecules: a rheumatologic perspective. Arthritis Rheum 1997;40:991–1004.

22) Bodi T. The effects of oral bromelains on tissue permeability to antibiotics and pain response to bradykinin: double blind studies on human subjects. Clin Med 1966;73:61–65.

23) Uhlig G, Seifert J. Die Wirkung proteolytischer Enzyme auf das posttraumatische Syndrom. Fortschritte der Medizin 1981;15:554–556.

24) Cohen A, Goldman J. Bromelain therapy in rheumatoid arthritis. Penn Med J 1964;67:27–30.

25) Leipner J, Iten F, Saller R. Therapy with proteolytic enzymes in rheumatic disorders. Biodrugs 2001;15:779–789.

26) Singer F, Oberleitner H. Drug therapy of activated arthrosis. On the effectiveness of an enzyme mixture versus diclofenac. Wien Med Wochenschr 1996;146:55–58.

27) Klein G, Kullich W. Short-term treatment of painful osteoarthritis of the knee with oral enzymes: a randomised, double-blind study versus Diclofenac. Clin Drug Invest 2000;19:15–23.

28) Singer F, Singer C, Oberleitner H. Phlyoenzym versus diclofenac in the treatment of activated osteoarthritis of the knee. Int J Immunother 2001;17:135–141.

29) Tilwe GH, Beria S, Turakhia NH, Daftary GV, Schiess W. Efficacy and tolerability of oral enzyme therapy as compared to diclofenac in active osteoarthritis of the knee joint: an open randomised controlled clinical trial. Journal of the Association of Physicians of India. JAPI 2001;49:621.

30) Walker AF, Bundy R, Hicks SM, Middleton RW. Bromelain reduces mild acute knee pain and improves well being in a dose dependant fashion in an open study of otherwise healthy adults. Phytomedicine 2002;9:681–686.

31) Bellamy N, Buchanan W, Goldsmith C, Campbell J, Stitt L. Validation study of WOMAC: a health status instrument for measuring clinically important patient relevant outcomes to anti-rheumatic drug therapy in patients with osteoarthritis of the hip or knee. Rheumatology 1988;15:1833–1840.

32) Ammon HP. Boswellic acids (components of frankincense) as the active principle in treatment of chronic inflammatory diseases [article in German]. Wien Med Wochenschr 2002;152(15-16):373-378.

33) Etzel R. Special extract of Boswellia serrata (H15) in the treatment of rheumatoid arthritis. Phytomed 1996;3(1):91-94.

34) Kimmatkar N, Thawani V, Hingorani L, Khiyani R. Efficacy and tolerability of Boswellia serrata extract in treatment of osteoarthritis of knee: a randomized double blind placebo controlled trial. Phytomedicine 2003;Jan, 10(1):3-7.

35) Singh GB, Bani S, Singh S. Toxicity and safety evaluation of boswellic acids. Phytomed 1996;3(1):87-90.

36) Singh GB, Singh S, Bani S. Anti-inflammatory actions of boswellic acids. Phytomed 1996;3(1):81-85.

37) Chrubasik S, Model A, Black A, et al. A randomized double-blind pilot study comparing Doloteffin® (Devils Claw Extract) and Vioxx® in the treatment of low back pain. Rheumatology 2003;42:141-148.

38) Mahomed IM, Ojewole JA. Analgesic, antiinflammatory and antidiabetic properties of Harpagophytum procumbens DC (Pedaliaceae) secondary root aqueous extract. Department of Pharmacology, Faculty of Health Sciences, University of KwaZulu-Natal, Private Bag X54001, Durban 4000, South Africa.

39) Wegener T, Lupke NP. Treatment of patients with arthrosis of hip or knee with an aqueous extract of devil's claw (Harpagophytum procumbens DC.). Phytother Res. Dec2003;17(10):1165-72.

40) Chantre P, Cappelaere A, Leblan D, Guedon D, Vandermander J, Fournie B. Efficacy and tolerance of Harpagophytum procumbens versus diacerhein in treatment of osteoarthritis. Phytomedicine. 2000 Jun;7(3):177-83.

41) Baghdikian B, Lanhers MC, Fleurentin J, Ollivier E, Maillard C, Balansard G, Mortier F. An analytical study, anti-inflammatory and analgesic effects of Harpagophytum procumbens and Harpagophytum zeyheri. Planta Med. 1997 Apr;63(2):171-6.

42) L. Long, K. Soeken1 and E. Ernst. Herbal medicines for the treatment of osteoarthritis: a systematic review. Department of Complementary Medicine, School of Postgraduate Medicine and Health Studies, University of Exeter, 25 Victoria Park Road, Exeter EX2 4NT, UK and University of Maryland School of Medicine, Complementary Medicine Program, Kernan Hospital Mansion, 2200 Kernan Drive, Baltimore, MD 21207-6697, USA

43) Chrubasik S, Junck H, Breitschwerdt H, et al. Effectiveness of Harpagophytum extract WS 1531 in the treatment of exacerbation of low back pain: a randomized, placebo-controlled, double- blind study. Eur J Anaesthesiol 1999;16(2):118-129.

44) Franci B, Campagna S, Battisti E, et al. The Efficacy and Safety of Glucosamine Sulfate in the Treatment of Gonarthritis. Clin Ter. Mar1996;147(3):99-105.

45) Pavelka K, Gatterova J, Olejarova M, Machacek S, Giacovelli G, Rovati LC. Glucosamine Sulfate Use and Delay of Progression of Knee Osteoarthritis: A 3-Year, Randomized, Placebo-Controlled, Double-blind Study. Arch Intern Med. Oct2002;162(18):2113-23.

46) Yves RJ,et al. Long-term effects of glucosamine sulphate on osteoarthritis progression: a randomised, placebo-controlled clinical trial. Lancet. 2001 Jan 27;357(9252):251-6.

47) Lippiello L, Woodward J, Karpman R, Hammad TA. In vivo chondroprotection and metabolic synergy of glucosamine and chondroitin sulfate. Clin Orthop. Dec2000;(381):229-40.

48) Shankland WE 2nd. The Effects of Glucosamine and Chondroitin Sulfate on Osteoarthritis of the TMJ: A Preliminary Report of 50 Patients. Cranio. Oct1998;16(4):230-35.

49) McCarty MF. Glucosamine for Wound Healing. Med Hypotheses. Oct1996;47(4):273-75.

50) Noack W, et al.: Glucosamine sulfate in osteoarthritis of the knee. Osteoarthritis Cartilage 2:51-9, 1994.

51) Crolle G and D'este E: Glucosamine sulfate for the management of arthrosis: a controlled clinical investigation. Curr Med Res Opin 7:104-9, 1980.

52) Pujalte JM, et al.: Double-blind clinical evaluation of oral glucosamine sulphate in the basic treatment of osteoarthrosis. Curr Med Res Opin 7:110-4, 1980.

53) Drovanti A, et al.: Therapeutic activity of oral glucosamine sulfate in osteoarthrosis: a placebo-controlled double-blind investigation. Clin Ther 3:260-72, 1980.

54)D'Ambrosia ED et al.: Glucosamine sulphate: a controlled clinical investigation in arthrosis. Pharmatherapeutica 2:504-8, 1982.

55) Vaz AL: Double-blind clinical evaluation of the relative efficacy of ibuprofen and glucosamine sulfate in the management of osteoarthrosis of the knee in out-patients. Curr Med Res Opin 8:145-9, 1982.

56) Muller-Fassbender H, et al.: Glucosamine sulfate compared to ibuprofen in osteoarthritis of the knee. Osteoarthritis Cartilage 2:61-9, 1994.

57) Rovati LC, et al.: A large, randomized, placebo controlled, double-blind study of glucosamine sulfate vs piroxicam and vs their association, on the kinetics of the symptomatic effect in knee osteoarthritis. Osteoarthritis Cartilage 2(Suppl.1):56, 1994.

58) Tapadinhas MJ, et al.: Oral glucosamine sulfate in the management of arthrosis: report on a multi-centre open investigation in Portugal. Pharmatherapeutica 3:157-68, 1982.

59) Sullivan MX and Hess WC: Cystine content of finger nails in arthritis. J Bone Joint Surg 16:185-8, 1935.

60) Senturia BD: Results of treatment of chronic arthritis and rheumatoid conditions with colloidal sulphur. J Bone Joint Surg 16:119-25, 1934.

61) Vignon E, Richard M and Annefeld M: An in vitro study of glucosamine sulfate on human osteoarthritic cartilage metabolism. Manuscript in preparation.

62) Setnikar I, et al.: Pharmacokinetics of glucosamine in man. Arzneim Forsch 43(10):1109-13, 1993.

63) Kelly GS. The Role of Glucosamine Sulfate and Chondroitin Sulfates in the Treatment of Degenerative Joint Disease. Altern Med Rev. Feb1998;3(1):27-39.

64) Bourgeois P, Chales G, Dehais J, et al. Efficacy and tolerability of chondroitin sulfate 1200 mg/day vs chondroitin sulfate 3 x 400 mg/day vs placebo. Osteoarthritis Cartilage 1998;6 Suppl A:25-30.

65) Bucsi L, Poor G. Efficacy and tolerability of oral chondroitin sulfate as a symptomatic slow-acting drug for osteoarthritis (SYSADOA) in the treatment of knee osteoarthritis. Osteoarthritis Cartilage 1998;6 Suppl A:31-36.

66) Cohen M, Wolfe R, Mai T, et al. A randomized, double blind, placebo controlled trial of a topical cream containing glucosamine sulfate, chondroitin sulfate, and camphor for osteoarthritis of the knee. J Rheumatol 2003;30(3):523-528.

67) Conrozier T. [Anti-arthrosis treatments: efficacy and tolerance of chondroitin sulfates (CS 4&6)]. Presse Med 1998;27(36):1862-1865.

68) Das A, Jr., Hammad TA. Efficacy of a combination of FCHG49 glucosamine hydrochloride, TRH122 low molecular weight sodium chondroitin sulfate and manganese ascorbate in the management of knee osteoarthritis. Osteoarthritis Cartilage 2000;8(5):343-350.

69) Leeb BF, Petera P, Neumann K. [Results of a multicenter study of chondroitin sulfate (Condrosulf) use in arthroses of the finger, knee and hip joints]. Wien Med Wochenschr 1996;146(24):609-614.

70) Leeb BF, Schweitzer H, Montag K, et al. A metaanalysis of chondroitin sulfate in the treatment of osteoarthritis. J Rheumatol 2000;27(1):205-211.

71) Mazieres B, Loyau G, Menkes CJ, et al. [Chondroitin sulfate in the treatment of gonarthrosis and coxarthrosis. 5-months result of a multicenter double-blind controlled prospective study using placebo]. Rev Rhum Mal Osteoartic 1992;59(7-8):466-472.

72) Morreale P, Manopulo R, Galati M, et al. Comparison of the antiinflammatory efficacy of chondroitin sulfate and diclofenac sodium in patients with knee osteoarthritis. J Rheumatol 1996;23(8):1385-1391.

73) Shankland WE. The effects of glucosamine and chondroitin sulfate on osteoarthritis of the TMJ: a preliminary report of 50 patients. Cranio 1998;16(4):230-235.

74) 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;12(4):269-276.

75) Van Blitterswijk WJ, Van De Nes JC, Wuisman PI. Glucosamine and chondroitin sulfate supplementation to treat symptomatic disc degeneration: Biochemical rationale and case report. BMC Complement Altern Med 2003;3(1):2.

76) Verbruggen G, Goemaere S, Veys EM. Chondroitin sulfate: S/DMOAD (structure/disease modifying anti- osteoarthritis drug) in the treatment of finger joint OA. Osteoarthritis Cartilage 1998;6 Suppl A:37-38.

77) Newnham RE. Essentiality of boron for healthy bones and joints. Environ Health Perspect. 1994 Nov;102 Suppl 7:83-5.

78) Rainey CJ, Nyquist LA, Christensen RE, Strong PL, Culver BD, Coughlin JR. Daily boron intake from the American diet. J Am Diet Assoc. 1999 Mar;99(3):335-40.

79) Jacob SW, Appleton J. MSM: The Definitive Guide. A Comprehensive Review of the Science and Therapeutics of Methylsulfonylmethane. Topanga, CA: Freedom Press; 2003:107-121.

80) Leblan D, Chantre P, Fournie B. Harpagophytum procumbens in the Teatment of Knee and Hip Osteoarthritis. Four-month Results of a Prospective, Multicenter, Double-blind Trial Versus Diacerhein. Joint Bone Spine. 2000;67(5):462-7.

81) Qui GX, et al. Efficacy and Safety of Glucosamine Sulfate Versus Ibuprofen in Patients with Knee Osteoarthritis. Arzneimittelforschung. May1998;48(5):469-74.

82) Inoue K, Motonaga A, Nishimura T, Yokota M, Miki N, Fujisawa H, Ueda F, Shibata Y, Kimura K. Mechanism of anti-inflammatory action of etodolac. Arzneimittelforschung. 1991 Mar;41(3):235-9.

83) Felton G. Does Kinin released by pineapple stem bromelain stimulate production of prostaglandin E1-like compound. Haw Med J 1976;2:39-47.

84) Lehto M, Jarvinen M. Collagen and gly-cosaminoglycan synthesis of injured gastroc-nemius muscle in rat. Eur Surg Res 1985;17:179-185. Cancer. Austin, TX: R.G. Landes Company; 1994:45-52.

85) Zupanets IA, Bezdetko NV, Dedukh NV, Otrishko IA. Experimental study of the effect of glucosamine hydrochloride on metabolic and repair processes in connective tissue structures. Eksp Klin Farmakol 2002;65:67-69.

86) Reddy GK, Chandrakasan G, Dhar SC. Studies on the metabolism of glycosaminoglycans under the influence of new herbal anti-inflammatory agents. Biochem Pharmacol 1989;38(20):3527-3534.

87) Usha PR, Naidu MUR, Randomized, double-blind, parallel, placebo-controlled study of oral glucosamine, methylsulfonylmethane and their combination in osteoarthritis. Clin Drug Invest. 2004;24:353-363

88) Dingle JT. The effects of NSAID on the matrix of human articular cartilages. Addenbrooke's Hospital, UK-Cambridge. Z Rheumatol. 1999 Jun;58(3):125-9.

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