Clinical Studies Used In The Research and Development of Heal-n-Soothe™

  1. G. Klein and W. Kullich, "Reducing Pain by Oral Enzyme Therapy in Rheumatic Diseases," Wien Med Wochenschr 149 (1999): 577-80.

  2. Stone MB, Merrick MA, Ingersoll CD, Edwards JE. Preliminary comparison of bromelain and Ibuprofen for delayed onset muscle soreness management. Clin J Sport Med. 2002 Nov;12(6):373-8.

  3. J. C. Dekkers, L. J. van Doornen, and H. C. Kemper. "The Role of Antioxidant Vitamins and Enzymes in Prevention of Exercise-Induced Muscle Damage, " Sports Med 21, no. 3 (March 1996): 213-38.

  4. Inderst, R.: Systemic enzyme therapy. Journal of Pharmacy 52 (1992).

  5. Ekerot, L. K; Ohlsson, K.; Necking, L.: Elimination of protease-inhibitor complexes from the arthritic joint. In. J. Tissue Reac. VII: 391 (1985).

  6. Miyamoto S, Kawano H, Takazoe K, Soejima H, Sakamoto T, Hokamaki J, Yoshimura M, Nakamura H, Yodoi J, Ogawa H. Vitamin E improves fibrinolytic activity in patients with coronary spastic angina. Thromb Res. 2004;113(6):345-51.

  7. Bounous G, Molson J. Competition for glutathione precursors between the immune system and the skeletal muscle: pathogenesis of chronic fatigue syndrome. Med Hypothesis 53;(4): 347-349

  8. Sen CK. Nutritional biochemistry of cellular glutathione. Nutr Biochem 1997;8:660-72.

  9. Johnston CS, Meyer CG, Srilakshmi JC. Vitamin C elevates red blood cell glutathione in healthy adults. Am J Clin Nutr 1993;58:103-5.

  10. Lenzi A, Culasso F, Gandini L, et al. Placebo-controlled, double-blind, cross-over trial of glutathione therapy in male infertility. Hum Reprod 1993;8:1657-62.

  11. Lands LC, Grey VL and Smountas AA. Effect of a cysteine donor on muscular performance.J Appl Physiol. 87 (4):1381-1385 1999.

  12. Powers SK, JI LL, Leeuwenburgh C. Exercise training-induced alterations in skeletal muscle antioxidant capacity:a brief review. Med. Sci. Sports Exerc. Vol31#7:987-997 1999.

  13. Sen CK. Glutathione homeostasis in response to exercise training and nutritional supplements. Molecular & Cellular Biochemistry. 196:31-42 1999

  14. Julius M, Lang C, Gleiberman L, et al. Glutathione and morbidity in a community-based sample of elderly. J Clin Epidemiol 1994;47:1021-6.

  15. Hagen TM, Wierzbicka GT, Sillau AH, et al. Fate of dietary glutathione: disposition in the gastrointestinal tract. Am J Physiol 1990;259(4Pt1):G530-5.

  16. Favilli F, Marraccini P, Iantomasis T, Vincenzini MT. Effect of orally administered glutathione on glutathione levels in some organs of rats: role of specific transporters. Br J Nutr 1997;78:293-300.

  17. Witschi A, Reddy S, Stofer B, Lauterburg BH. The systemic availability of oral glutathione. Eur J Clin Pharmacol 1992;43:667-9.

  18. Hunjan MK, Evered DF. Absorption of glutathione from the gastro-intestinal tract. Biochim Biophys Acta 1985;815:184-8.

  19. Emele, J. F.; Shanaman, J.; Winbury, M. M.: The analgesic-anti-inflammatory activity of papain. Arch. Int. Pharmacyn. Ther. 159: 126 (1996).

  20. Kameke, E. v.: Inflammation and its treatment with hydrolytic enzymes and rutin. Forum of the General Practitioner (Forum des Praktischen- und Allgemeinarztes) 9 (1981).

  21. Amborse, A. M.; De Eds, F.: Effects of rutin on permeability of cutaneous capillaries. Pharmacol. Esp. Ther. 90: 359 (1989).

  22. Ambrus, J. L. et al.: Absorption of exogenous and endogenous proteolytic enzymes. Clin. Pharmacol. Ther. 8: 362 (1967).

  23. Bartsch, W.: Treatment of zoster with proteolytic enzymes. The Informed Physician 2: 424 - 429 (l974).

  24. Baumhackl, U.; Fordermair, S.: Enzyme therapy in multiple sclerosis. A preliminary report on a multicenter study. General Medicine (Allgemeinmedizin) 19 (4): 169 - 172 (1990).

  25. Baumuller, M.: XXIV FMS World Congress of Sport Medicine. Symposium on Enzyme Therapy in Sports Injuries. May 29, 1990, p 9. Elsevier Science Publisher, Amsterdam (1990).

  26. Blonstein, J. L.: Oral enzyme tablets in the treatment of boxing injuries. Practitioner 198: 547 (1967).

  27. Dittmar; F. W.: Enzyme therapy in inflammatory pelvic disease. The Medical World (Die Medizinische Welt) 37: 562 - 565 (1986).

  28. Dunkel, R: Therapy investigations with proteolytic enzymes in camel pox. Veterinary Review (Tieraztliche Umschau) 11:580 (1973).
    Goebel, K. M.: Enzyme therapy in ankylosing spondylitis. In: Medical Enzyme Research Society. Systemic Enzyme Therapy, 17th meeting. Vienna (1991).

  29. Goldberg, D. M.: Enzymes as agents for the treatment of disease. Clin. Chimi. Acta 206: 45 - 76 (1992).

  30. Hiss, W. F.: Enzymes in sport medicine and traumatology. Journal for Natural Therapy Methods (Zeitschrift fur Naturheilmethoden) Volume 2: 1 (1979).

  31. Isaaksson, J. I.; Ihse, I.: Pain reduction by oral pancreatic enzyme preparation in chronic pancreatitis. Dig. Dis. Sci. 28: 97 - 102 (1983).

  32. Klein, G.; Pollmann, G.; Kullich, W.: Clinical experience with enzyme therapy in patients with rheumatoid arthritis in comparison with gold. General Medicine (Allgemeinmedizin 19 (4): 144 - 147 (1990).

  33. Klein, G.; Schwann, H.; Kullich, W.: Enzyme therapy in chronic polyarthritis. Natural and hollistic Medicine (Natur- und Ganzheitsmedizin) 1: 112 - 116 (1988).

  34. Kleine, M.-W.; Volger, W.: Systemic enzyme therapy. Introduction and overview. General Medicine (Allgemeinmedizin) 19 (4): 119 - 124 (1990).

  35. Kleine, M.-W.; Pabst, H.: Action of an oral enzyme therapy in experimentally induced hematomas. Forum of the General Practitioner (Forum des Praktischen- und Allgemeinarztes) 27: 42 (1988).

  36. Kleine, M.-W.: Treatment of herpes zoster with proteolytic enzymes. Therapy Week (Therapiewoche) 37: 1108 - 1112 (1987).

  37. Laffaioli, R. V. et al: Prognostic significance of circulating immune complexes in a long-term follow up of breast cancer patients. Oncology 45: 337 - 343 (1988).

  38. Mahr, H.: Enzyme treatment of inflammatory venous diseases, of deep vein thrombosis and of post-thrombotic syndrome. Experience Therapy (Erfahrungsheilkunde) 32: 117 - 121 (1983).

  39. Matthews, D. M. Protein absorption - then and now. Gastroenterology 73: 1267 - 1279 (1977).

  40. Matthews, D. M.: Protein absorption. Wiley-Liss, New York (1992).

  41. Netti, C; Bandi, G. L.; Pecile, A.: Anti-inflammatory action of proteolytic enzymes of animal, vegetable or bacterial origin administered orally compared with that of known antiphlogistic compounds. II Farmaco Ed. Pr. 27: 453 (1972).

  42. Neuhofer, C. H. et al: Pathogenic immune complexes in multiple sclerosis. Their elimination by hydrolytic enzymes - a therapeutic approach. International Multiple Sclerosis Conference, Rome, Sept 14 - 17, Monduzzi Editore S. p. A., Bologna (1988)

  43. Neuhofer, Ch.: Enzyme therapy in multiple sclerosis. Hufeland Journal 2: 47 - 50 (1986).

  44. Rosner, L. J.; Ross, S.: Multiple Sclerosis: New hope and practical advice for people with MS and their families. Prentice Hall Press, New York (1987).

  45. Scheel, W.; Pischnamazadeh, M.: Proteolytic enzymes as a simple and safe method for the prevention of lymphedema after mastectomy. Med. World (Med. Welt) 35: 1032 - 1033 (1984).

  46. Seifert, J. et al.: Quantitative analysis about the absorption of trypsin, chymotrypsin, amylase, papain and pancreatin in the G.I. tract after oral administration. General Physician (Allgemeinarzt) 19 (4): 132 - 137 (1990).

  47. Seifert, J.; Ganser, R.; Brendel, W.: Absorption of proteolytic enzymes of plant origin from the GI tract into the blood and lymph of adult rats. German Journal of Gastroenterology (Z. Gastroenterol.) 71: 1 (1979).

  48. Stauder, G.; Streichhan, P.; Steffen, C.: Enzyme therapy - a complete description. Natural and Hollistic medicine (Natur- und Ganzheitsmedizin) 1: 68 - 89 (1988).

  49. Stauder, G. et al.: Adjuvant therapy of HIV infections with hydrolytic enzymes: Course of  neopterin, CD4 T-cells, immune complexes (IC), and clinical efficacy. 8th International Workshop of Biochemical and Clinical Aspects of Peridines. St. Christoph (Tyrol), Febr. 11 - 18 (1989).

  50. TW Magazin: Systemic enzyme therapy - Present status and advances. Therapy Week (Therapiewoche) 37 (1987)

  51. Wolf, M.; Ransberger, K: Enzyme therapy. Maudrich-Verlag, Vienna 1970.

  52. Wrba, H.: Treatment of cancer with proteolytic enzymes. In: Wrba H. (editor): Combined Tumor Therapy pp 131 - 145, Hippokrates-Verlag, Stuttgart 1990.

  53. Aftab J. Ahmed and Edmund A. Byrke, "Difference between Systemic Enzymes and Digestive Enzymes"; "Role of Ribose in Stimulating Natural Energy Production"; "Importance of methyl-sulfonyl-methane."

  54. D. V. Graham, "Enzyme Replacement Therapy of Exocrine Pancreatic Insufficiency in Man," N Engle J Med 296 (1977): 1314-17

  55. Robert Michael Kaplan, "Losing Weight Wisely, "Alive: Canadian Journal of Health & Nutrition, March 1992, no. 117: 16.

  56. R. Fiasse et al., "Circulating Immune Complexes and Disease Activity in Crohn's Disease, Gut 19 (1978): 611-17.

  57. M. Wolf, "Der Einfluss von Proteasen auf Venenentzundungen," in M. Wolf and K. Ransberger, Enzymthempie (Vienna: 1971). 

  58. K. Nouza, "Outlooks of Systemic Enzyme Therapy in Rheumatoid Arthritis and Other Immunopatholgical Diseases," Acta Univ Carol (Med) (Praha) 40 (1994): 101-4.

  59. W. F. Hiss, "Enzymes in Sports Medicine and Traumatology," Journal for Natural Therapy Methods (Zeitschrift fur Naturheilmethoden) 2 (1979): 1.

  60. S. Worschhauser, "Conservative Therapy in Sports Injuries. Enzyme Preparations for Treatment and Prophylaxis," General Medicine (Allgemeinmedizin) 19, no. 4 (1990): 173.

  61. The Associated Press, "Report: Celebrex Linked to 10 Deaths," April 20, 1999. See also D. R. Lichtenstein and M. M. Wolfe, "COX-2-Selective NSAIDS," JAMA 284, no. 10 (2000): 1297-99.

  62. H. Wrba. "Systemic Enzyme Therapy: Newest Status and Progress," Therapie Woche 37, no. 7 (1987).

  63. J. Anderson and J. Stine, "Detoxing from Toxins," in T. Nichols and N. Faas, eds. Optimal Digestion (New York: Harper Collins, 1999).

  64. Shoskes D, Lapierre C, Cruz-Correa M, Muruve N, Rosario R, Fromkin B, Braun M, Beneficial effects of the bioflavonoids curcumin and quercetin on early function in cadaveric renal transplantation: a randomized placebo controlled trial. 2005 Dec 15;80(11):1556-9.

  65. Niederau C, Gopfert E.  The effect of chelidonium- and turmeric root extract on upper abdominal pain due to functional disorders of the biliary system. Results from a placebo-controlled double-blind study Med Klin (Munich). 1999 Aug 15;94(8):425-30. German.

  66. Petruzzellis V, Troccoli T, Candiani C, Guarisco R, Lospalluti M, Belcaro G, Dugall M.

  67. Oxerutins (Venoruton): efficacy in chronic venous insufficiency--a double-blind, randomized, controlled study. Angiology. 2002 May-Jun;53(3):257-63

  68. Cesarone MR, Incandela L, DeSanctis MT, Belcaro G, Griffin M, Ippolito E, Acerbi G. Treatment of edema and increased capillary filtration in venous hypertension with HR (Paroven, Venoruton; 0-(beta-hydroxyethyl)-rutosides): a clinical, prospective, placebo-controlled, randomized, dose-ranging trial. J Cardiovasc Pharmacol Ther. 2002 Jan;7 Suppl 1:S21-4.

  69. Cataldi A, Gasbarro V, Viaggi R, Soverini R, Gresta E, Mascoli F. Effectiveness of the combination of alpha tocopherol, rutin, melilotus, and centella asiatica in the treatment of patients with chronic venous insufficiency. Minerva Cardioangiol. 2001 Apr;49(2):159-63. Italian.

  70. Ortolani O, Conti A, De Gaudio AR, Masoni M, Novelli G. Protective effects of N-acetylcysteine and rutin on the lipid peroxidation of the lung epithelium during the adult respiratory distress syndrome. Shock. 2000 Jan;13(1):14-8.

  71. Noroozi M, Angerson WJ, Lean ME.  Effects of flavonoids and vitamin C on oxidative DNA damage to human lymphocytes. Am J Clin Nutr. 1998 Jun;67(6):1210-8.

  72. Klein G, Kullich W, Schnitker J, Schwann H. Efficacy and tolerance of an oral enzyme combination in painful osteoarthritis of the hip. A double-blind, randomised study comparing oral enzymes with non-steroidal anti-inflammatory drugs. Clin Exp Rheumatol. 2006 Jan-Feb;24(1):25-30.

  73. Tilwe GH, Beria S, Turakhia NH, Daftary GV, Schiess W.  Efficacy and tolerability of oral enzyme therapy as compared to diclofenac in active osteoarthrosis of knee joint: an open randomized controlled clinical trial. J Assoc Physicians India. 2001 Jun;49:617-21.

  74. Itoh H,Ohkuwa T,Yamazaki Y,Shimoda T,Wakayama A, Tamura S, Yamamoto Vitamin E supplementation attenuates leakage of enzymes following 6 successive days of running training.Int J Sports Med 2000 Jul;21(5):369-74

  75. Wu D, Han SN, Meydani M, Meydani SN.  Effect of concomitant consumption of fish oil and vitamin E on production of inflammatory cytokines in healthy elderly humans. Ann N Y Acad Sci. 2004 Dec;1031:422-4.

  76. Block G, Jensen C, Dietrich M, Norkus EP, Hudes M, Packer L. Plasma C-reactive protein concentrations in active and passive smokers: influence of antioxidant supplementation. J Am Coll Nutr. 2004 Apr;23(2):141-7.


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