Clinical Research

Proleeva was developed from intense research and produced with your health in mind.

Clinical Supporting Studies

1. Baghdikian B, Lanhers M, Fleurentin J, et al.

An analytical study, anti-inflammatory and analgesic effects of Harpagophytum procumbens and Harpagophytum zeyheri. Planta Med. 1997;63:171-176.

2. Brien S, Lewith GT, McGregor G

Devil’s Claw (Harpagophytum procumbens) as a Treatment for Osteoarthritis: A Review of Efficacy and Safety. J Altern Complement Med. 2006;12(10):981-93.

3. Cameron M, Gagnier JJ, Little CV, Parsons TJ, Blümle A, Chrubasik S

Evidence of effectiveness of herbal medicinal products in the treatment of arthritis. Part I: Osteoarthritis. Phytother Res. 2009 Nov;23(11):1497-515.

4. 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;7(3):177-83.

5. Chrubasik S, Junck H, Breitschwerdt H, Conradt C, Zappe H

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.

6. Chrubasik S, Pollak S, Black A

Effectiveness of devil’s claw for osteoarthritis. Rheumatology (Oxford). 2002;41(11):1332-3.

7. Ernst E, Chrubasik S

Phyto anti-inflammatories. A systematic review of randomized, placebo-controlled, double-blind trials. Rheum Dis Clin North Am. 2000;26(1):13-27.

8. Gagnier JJ, van Tulder MW, Berman B, Bombardier C

Herbal medicine for low back pain: a Cochrane review. Spine. 2007;32(1):82-92.

9. Gobel H, Heinze A, Ingwersen M, Niederberger U, Gerber D

Effects of Harpagophytum procumbens LI 174 (devil’s claw) on sensory, motor und vascular muscle reagibility in the treatment of unspecific back pain. [German] Schmerz. 2001;15(1):10-18.

10. Laudahn D, Walper A

Efficacy and tolerance of Harpagophytum extract LI 174 in patients with chronic non-radicular back pain. Phytother Res. 2001;15(7):621-4.

11. Leblan D, Chantre P, Fournie B

Harpagophytum procumbens in the treatment of knee and hip osteoarthritis. Four-month results of a prospective, multicenter, double-blind trial versus diacerhein. Joint Bone Spine. 2000;67(5):462-467.

12. Chrubasik S, Fiebich B, Black A, and et al.

Treating low back pain with an extract of Harpagophytum procumbens that inhibits cytokine release. Eur J Anaesthesiol 2002;19:209.

13. Ameye, L. G. and Chee, W. S.

Osteoarthritis and nutrition. From nutraceuticals to functional foods: a systematic review of the scientific evidence. Arthritis Res Ther 2006;8:R127. View abstract.

14. Lanhers MC, Fleurentin J, Mortier F, et al.

Anti-inflammatory and analgesic effects of an aqueous extract of Harpagophytum procumbens. Planta Med 1992;58:117-23 . View abstract.

15. Grahame R, Robinson BV

Devils’s claw (Harpagophytum procumbens): pharmacological and clinical studies. Ann Rheum Dis 1981;40:632. View abstract.

16. Chrubasik S, Sporer F, Dillmann-Marschner R, et al.

Physicochemical properties of harpagoside and its in vitro release from Harpagophytum procumbens extract tablets. Phytomedicine 2000;6:469-73. View abstract.

17. Bloomer RJ

The role of nutritional supplements in the prevention and treatment of resistance exercise-induced skeletal muscle injury. Sports Med. 2007;37(6):519-532. Review.

18. Brien S, Lewith G, Walker AF, et al.

Bromelain as an adjunctive treatment for moderate-to-severe osteoarthritis of the knee: a randomized placebo-controlled pilot study. QJM. 2006 Dec;99(12):841-850.

19. Chobotova K, Vernallis AB, Majid FA

Bromelain’s activity and potential as an anti-cancer agent: Current evidence and perspectives. Cancer Lett. 2010 Apr 28;290(2):148-156. Review.

20. Guo R, Canter PH, Ernst E

Herbal medicines for the treatment of rhinosinusitis: a systematic review. Otolaryngol Head Neck Surg. 2006 Oct;135(4):496-506. Review.

21. Klein G, Kullich W

Short-term treatment of painful osteoarthritis of the knee with oral enzymes. A randomized, double-blind study versus diclofenac. Clin Drug Invest. 2000;19(1):15-23.

22. 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.

23. Pillai K, Akhter J, Chua TC, Morris DL

Anticancer property of bromelain with therapeutic potential in malignant peritoneal mesothelioma. Cancer Invest. 2013; 31(4):241-250.

24. Szczurko O, Cooley K, Mills EJ, Zhou Q, Perri D, Seely D

Naturopathic treatment of rotator cuff tendinitis among Canadian postal workers: a randomized controlled trial. Arthritis Rheum. 2009 Aug 15;61(8):1037-1045.

25. Taussig SJ, Batkin S

Bromelain, the enzyme complex of pineapple (Ananas comosus) and its clinical application. An update. J Ethnopharmacol. 1998;22:191-203.

26. Wu SY, Hu W, Zhang B, Liu S, Wang JM, Wang AM

Bromelain ameliorates the wound microenvironment and improves healing of firearm wounds. J Surg Res. 2012; 176(2):503-509.

27. Walker AF, Bundy R, Hicks SM, Middleton RW (2002)

“Bromelain reduces mild acute knee pain and improves well-being in a dose-dependent fashion in an open study of otherwise healthy adults”. Phytomedicine 9 (8): 681–6. doi:10.1078/094471102321621269. PMID 12587686.

28. Brien S, Lewith G, Walker A, Hicks SM, Middleton D (2004)

“Bromelain as a Treatment for Osteoarthritis: a Review of Clinical Studies”. Evid Based Complement Alternat Med 1 (3): 251–7. doi:10.1093/ecam/neh035. PMC 538506. PMID 15841258.

29. Beuth J (2008)

“Proteolytic enzyme therapy in evidence-based complementary oncology: fact of fiction?”. Integr Cancer Ther 7 (4): 311–316. doi:10.1177/1534735408327251. PMID 19116226

30. Aggarwal BB

Curcumin-free tumeric exhibits anti-inflammatory and anticancer activities: Identification of novel components of tumeric. Mol Nutr Food Res. 2013; 57:1529-42.

31. Aggarwal BB, Sundaram C, Malani N, Ichikawa H

Curcumin: the Indian solid gold. Adv Exp Med Biol. 2007;595:1-75.

32. Asher GN, Spelman K

Clinical utility of curcumin extract. Altern Ther Health Med. 2013;19:20-2.

33. Darvesh AS, Aggarwal BB, Bishayee A

Curcumin and Liver Cancer: A Review. Curr Pharm Biotechnol. 2011 Apr 5. [Epub ahead of print]

34. Davis JM, Murphy EA, Carmichael MD, Zielinski MR, Groschwitz CM, Brown AS, Ghaffar A, Mayer EP

Curcumin effects on inflammation and performance recovery following eccentric exercise-induced muscle damage. Am J Physiol Regul Integr Comp Physiol. 2007 Mar 1

35. Dorai T, Cao YC, Dorai B, Buttyan R, Katz AE

Therapeutic potential of curcumin in human prostate cancer. III. Curcumin inhibits proliferation, induces apoptosis, and inhibits angiogenesis of LNCaP prostate cancer cells in vivo. Prostate. 2001;47:293-303.

36. Dorai T, Gehani N, Katz A

Therapeutic potential of curcumin in human prostate cancer. II. Curcumin inhibits tyrosine kinase activity of epidermal growth factor receptor and depletes the protein. Mol Urol. 2000;4:1-6.

37. Funk JL, Frye JB, Oyarzo JN, Kuscuoglu N, Wilson J, McCaffrey G, et al.

Efficacy and mechanism of action of turmeric supplements in the treatment of experimental arthritis. Arthritis Rheum. 2006;54:3452-64.

38. Hanai H, Iida T, Takeuchi K, Watanabe F, Maruyama Y, et al.

Curcumin maintenance therapy for ulcerative colitis: randomized, multicenter, double-blind, placebo-controlled trial. Clin Gastroenterol Hepatol. 2006;4:1502-6.

39. Handler N, Jaeger W, Puschacher H, Leisser K, Erker T

Synthesis of novel curcumin analogues and their evaluation as selective cyclooxygenase-1 (COX-1) inhibitors. Chem Pharm Bull (Tokyo). 2007;55:64-71.

40. Nagaraju GP, Aliya S, Zafar SF, Basha R, Diaz R, El-Rayes BF

The impact of curcumin on breast cancer. Integr Biol (Camb). 2012; 4:996-1007.

41. Rao CV

Regulation of COX and LOX by curcumin. Adv Exp Med Biol. 2007;595:213-26.

42. Sharma RA, Steward WP, Gescher AJ

Pharmacokinetics and pharmacodynamics of curcumin. Adv Exp Med Biol. 2007;595:453-70.

43. Shehzad A, Khan S, Shehzad O, Lee YS

Curcumin therapeutic promises and bioavailability in colorectal cancer. Drugs Today (Barc). 2010;46:523-32. Review.

44. Shehzad A, Rehman G, Lee YS

Curcumin in inflammatory diseases. Biofactors. 2013; 39:69-77.

45. White B, Judkins DZ

Clinical Inquiry. Does turmeric relieve inflammatory conditions? J Fam Pract. 2011;60:155-6. Review.

46. Priyadarsini KI (2014)

“The chemistry of curcumin: from extraction to therapeutic agent”. Molecules 19 (12): 20091–112. doi:10.3390/molecules191220091. PMID 25470276.

47. Bandyopadhyay; Ranajit K. Banerjee (10 July 2004)

“Turmeric and curcumin: Biological actions and medicinal applications” (PDF). Current Science (Indian Academy of Sciences) 87 (1): 44–53. ISSN 0011-3891. Retrieved 16 March 2013.

48. Nagpal M, Sood S (2013)

“Role of curcumin in systemic and oral health: An overview”. J Nat Sci Biol Med 4 (1): 3–7. doi:10.4103/0976-9668.107253. PMC 3633300. PMID 23633828.

49. National Institutes of Health

“Clinical trials on turmeric.” Clinical Trials Registry. December 2013. Retrieved December 29, 2013.

50. Mishra S, Palanivelu K (January–March 2008)

“The effect of curcumin (turmeric) on Alzheimer’s disease: An overview”. Ann Indian Acad Neurol 11 (1): 13–9. doi:10.4103/0972-2327.40220. PMC 2781139. PMID 19966973.

51. Maithili Karpaga, Selvi, N, Sridhar, MG, Swaminathan, RP, Sripradha, R (May 2014)

“Efficacy of turmeric as adjuvant therapy in type 2 diabetic patients.” Indian Journal of Clinical Biochemistry 30 (2): 180–186. doi:10.1007/s12291-014-0436-2.

52. Xin-Xin Zheng, Yan-Lu Xu, et al.

Green tea intake lowers fasting serum total and LDL cholesterol in adults: a meta-analysis of 14 randomized controlled trials Am J Clin Nutr August 2011.

53. Abdul G Dulloo, Claudette Duret, et al.

Efficacy of a green tea extract rich in catechin polyphenols and caffeine in increasing 24-h energy expenditure and fat oxidation in humans. American Journal of Clinical Nutrition, Vol. 70, No. 6, 1040-1045, December 1999.

54. Auvichayapat P1, Prapochanung M, Tunkamnerdthai O, Sripanidkulchai BO, Auvichayapat N, Thinkhamrop B, Kunhasura S, Wongpratoom S, Sinawat S, Hongprapas P

Effectiveness of green tea on weight reduction in obese Thais: A randomized, controlled trial. Physiol Behav. 2008 Feb 27;93(3):486-91. Epub 2007 Oct 18.

55. Kushiyama et al.

Relationship Between Intake of Green Tea and Periodontal Disease. Journal of Periodontology, 2009; 80 (3): 372 DOI: 10.1902/jop.2009.080510

56. McLarty, Jerry, Bigelow, Rebecca LH, Smith, Mylinh, Elmajian, Don, Ankem, Murali, Cardelli, James A

“Tea Polyphenols Decrease Serum Levels of Prostate-Specific Antigen, Hepatocyte Growth Factor, and Vascular Endothelial Growth Factor in Prostate Cancer Patients and Inhibit Production of Hepatocyte Growth Factor and Vascular Endothelial Growth Factor In vitro.” Cancer Prevention Research, Published Online First on June 19, 2009. DOI: 10.1158/1940-6207.CAPR-08-0167

57. Birdsall TC

5-Hydroxytryptophan: a clinically-effective serotonin precursor. Altern Med Rev. 1998;3:271–280.

58. Caruso I, Sarzi Puttini P, Cazzola M, et al.

Double-blind study of 5-hydroxytryptophan versus placebo in the treatment of primary fibromyalgia syndrome. J Int Med Res. 1990;18:201-209.

59. Ceci F, Cangiano C, Cairella M, Cascino A, et al.

The effects of oral 5-hydroxytryptophan administration on feeding behavior in obese adult female subjects. J Neural Transm. 1989;76:109-117.

60. DeBenedittis G, Massei R

Serotonin precursors in chronic primary headache. A double-blind cross-over study with L-5-hydroxytryptophan vs. placebo. J Neurosurg Sci. 1985;29:239-248.

61. Ribeiro CA

L-5-Hydroxytryptophan in the prophylaxis of chronic tension-type headache: a double-blind, randomized, placebo-controlled study. Headache. 2000;40:451-6.

62. Brett SE, Cockcroft JR, Mant TG, Ritter JM, and Chowienczyk PJ

Haemodynamic effects of inhibition of nitric oxide synthase and of L-arginine at rest and during exercise. J Hypertens. 1998;16:429-435. View abstract.

63. McCarter MD, Gentilini OD, Gomez ME, and Daly JM

Preoperative oral supplement with immunonutrients in cancer patients. JPEN J Parenter.Enteral Nutr 1998;22:206-211. View abstract.

64. Gianotti L, Braga M, Vignali A, Balzano G, Zerbi A, Bisagni P, and Di Carlo V

Effect of route of delivery and formulation of postoperative nutritional support in patients undergoing major operations for malignant neoplasms. Arch.Surg. 1997;132:1222-1229. View abstract.

65. Schilling J, Vranjes N, Fierz W, Joller H, Gyurech D, Ludwig E, Marathias K, and Geroulanos S

Clinical outcome and immunology of postoperative arginine, omega-3 fatty acids, and nucleotide-enriched enteral feeding: a randomized prospective comparison with standard enteral and low calorie/low fat i.v. solutions. Nutrition 1996;12:423-429. View abstract.

66. Kirk SJ, Hurson M, Regan MC, Holt DR, Wasserkrug HL, and Barbul A

Arginine stimulates wound healing and immune function in elderly human beings. Surgery 1993;114:155-159. View abstract.

67. Brittenden J, Heys SD, Miller I, Sarkar TK, Hutcheon AW, Needham G, Gilbert F, McKean M, Ah-See AK, and Eremin O

Dietary supplementation with L-arginine in patients with breast cancer (> 4 cm) receiving multimodality treatment: report of a feasibility study. Br J Cancer

68. Daly JM, Weintraub FN, Shou J, Rosato EF, and Lucia M

Enteral nutrition during multimodality therapy in upper gastrointestinal cancer patients. Ann.Surg. 1995;221:327-338. View abstract.

69. Jude EB, Dang C, and Boulton AJ

Effect of L-arginine on the microcirculation in the neuropathic diabetic foot in Type 2 diabetes mellitus: a double-blind, placebo-controlled study. Diabet.Med. 2010;27:113-116. View abstract.

70. Cahill NE, Dhaliwal R, Day AG, Jiang X, and Heyland DK

Nutrition therapy in the critical care setting: what is “best achievable” practice? An international multicenter observational study. Crit Care Med. 2010;38:395-401. View abstract.

71. Okamoto Y, Okano K, Izuishi K, Usuki H, Wakabayashi H, and Suzuki Y

Attenuation of the systemic inflammatory response and infectious complications after gastrectomy with preoperative oral arginine and omega-3 fatty acids supplemented immunonutrition. World J Surg. 2009;33:1815-1821. View abstract.

72. Kemen M, Senkal M, Homann HH, et al.

Early postoperative enteral nutrition with arginine-omega-3 fatty acids and ribonucleic acid-supplemented diet vs placebo in cancer patients: an immunologic evaluation of impact. Crit Care Med 1995;23:652-9. View abstract.

73. Senkal M, Kemen M, Homann HH, et al.

Modulation of postoperative immune response by enteral nutrition with a diet enriched with arginine, RNA, and omega-3 fatty acids in patients with upper gastrointestinal cancer. Eur J Surg 1995;161:115-22. View abstract.

74. Daly JM, Lieberman MD, Goldfine J, et al.

Enteral nutrition with supplemental arginine, RNA, and omega-3 fatty acids in patients after operation: immunologic, metabolic and clinical outcome. Surgery 1992;112:56-67. View abstract.

75. Sandrini G, Franchini S, Lanfranchi S, et al.

Effectiveness of ibuprofen-arginine in the treatment of acute migraine attacks. Int J Clin Pharmacol Res 1998;18:145-50. View abstract

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