Cat's Claw Detailed Scientific Review

Overview

Background

Cat’s claw is a member of the plant family Rubiaceae, genus Uncaria that consists of at least 34 different species found in tropical forests of Southeast Asia, Africa, Central and South America^1-3. At least 12 different and unrelated herbs have been marketed as Uña de gato or cat’s claw because of their curved thorns resembling the claws of a cat^3-5. The two Latin American species are Uncaria guanensis, a shrub that grows at lower altitudes, and Uncaria tomentosa, a woody vine that grows at higher altitudes, especially in Peru^2,3.

The root and inner bark of the stalk of the Uncaria tomentos vine have equivalent antioxidative properties according to laboratory research published in 1997⁶. Citing such research, the Peruvian government has now banned the harvesting of the roots in order to protect this cat’s claw species from destruction due to the rapid increase in worldwide demand for it. Responsible harvesting of wild plants is now accomplished by chopping the vine about three feet above the ground and leaving the root undisturbed so that the vine can re-grow to maturity and be re-harvested in about four years⁵. Laboratory studies of root extracts have been able to continue by using cultivated plants from experimental university plots in Peru^7,8. Active components have also been identified within the leaves⁹.

Traditional/Historical Uses

Despite confusion in the marketplace between the two Latin American species of cat’s claw, traditional uses have differed related to the area in which they were harvested or sold or who was prescribing them. For example, the root and inner bark of the stalk of Uncaria tomentosa have been used medicinally for centuries by the indigenous peoples of Peru. Priests of the Ashaninka tribe, the largest group of indigenous peoples of Peru, traditionally used the root to treat anxiety, which they considered the major disrupter of communication between body and spirit³.

Other purposes for which both species of cat’s claw have been sold have included contraception, arthritis, gastritis, asthma, gastric ulcers, diabetes, tumors, viral infections, menstrual disorders, convalescence, general debility and gonorrhea^3,10-13.

Current Uses Under Investigation

Uncaria guianensis is currently being investigated for anti-inflammatory effects and relief of arthritis. An in vitro study of human cartilage surgical specimens demonstrated protection of cartilege growth factors from inhibition by inflammatory immune components¹⁴. Osteoarthritic pain associated with activity was significantly reduced in one double blind placebo-controlled human study¹⁵.

Uncaria tomentosa is currently being investigated for effects upon pain, inflammation, mutagenesis, cancer and the immune system^10,16,17. Some of these investigations have indicated that effects may differ according to the type of type of extract (aqueous or alcoholic) and/or proportions of major constituents.

Major Constituents and Mechanisms of Action

Fifty different compounds have been identified in cat’s claw, with three classes of compounds thought to play a major role: alkaloids, quinic acid glycosides and polyhydroxylated triterpenes”^7,18. 

Alkaloids

Oxindole Alkaloids. Research concerning Uncaria tomentosa alkaloids was initially undertaken by Keplinger³ and later reviewed by Reinhard². Keplinger directly observed the choices of Ashinaka healer-priests and saw that they were choosing specific plants known as saventaro (saveshi =plant, antearo = potent) within the Uncaria tomentosa species. Although all plants within this species looked alike to him, he subsequently realized that there were two distinctly different chemical subtypes.

Both subtypes contained alkaloids, but one subtype, saventaro, contained predominantly pentacyclic (five-ring) alkaloids (pteropodine, isopteropodine, speciophylline, uncarine F, mitraphylline and isomitraphylline), while the other subtype contained mostly tetracyclic (four-ring) alkaloids (rhynchopphylline and isorhynchophylline)^2,3. Keplinger’s subsequent laboratory research determined that distinctly different and sometimes counteracting effects occurred with these two subtypes³.

Pentacyclic alkaloids appear to indirectly stimulate the immune system through increased phagocytosis by granulocytes^1,3,19 and increased proliferation of normal resting or weakly activated human lymphocytes^9,20. They have also been associated with reduction of nerve fiber reception and transmission of pain (nociception) in mice subjected to a variety of painful stimuli. Pre-treatment with a variety of systemic blocking agents indicated that these anti-nociceptive effects appeared to be due to involvement of serotonin pathways²¹. 

Tetracyclic alkaloids have opposite effects within the immune system and can counteract the stimulating effects of the pentacyclic alkaloids^2,3. Other tetracyclic effects include sedative effects within the central nervous system and inhibition of platelet aggregation and thrombosis within the vascular system². 

Proportions of pentacyclic and tetracyclic alkaloids are affected by the parent plant, rainfall and seasonal variations². Keplinger analyzed 50 cat’s claw products from the United States, Central America and Peru and found varying mixtures of pentacyclic and tetracyclic alkaloids³. A purified extract limited to pentacyclic alkaloids is marketed in Austria under the brand name of Krallendorn or "claw thorn"². A recent search of U. S. brands advertised on the Internet identified brands with pentacyclic alkaloid content ranging from 5% to 50%. According to Valerio, alkaloids tend to be unstable, so mixtures are likely to have been present in experiments¹⁸.

Quinic, Quinovic Acid. Quinic acid is present in cat’s claw and many other plants such as coffee, tobacco and carrots²². It was identified by two investigators as the active compound within alkaloid free water extracts of cat’s claw (C-MED-100, Activar AC-11)²³.  

In vitro and animal studies have reported anti-viral activity¹⁰, antiproliferative activity²⁴, prolonged lymphocyte survival²⁵, improved DNA repair^26,27, inhibition of cell growth without cell death²³ and reduced skin cell death from UV exposure²⁸. 

Terpenes, Triterpenes, Terpenoids. Terpenes are biologically active compounds found in cat’s claw and in the essential oils of many other plants and flowers^29,30, but publications describing specific activities have not been identified.

Other Constituents

Additional constituents include polyphenols (flavonoids, proanthocyanidins, tannins) and saponins^18,31.

Whole Plant Extracts

Whole plant extracts have been associated with several properties demonstrated through in vitro studies: anti-inflammation and scavenging of free radicals^6-8, inhibition of the activation of the inflammation promoting factor, NF-kappaB^8,32, reduction of chemically induced apoptosis¹⁸, activation of insulin-like growth factor(IGF-1) protection of chondrocytes challenged by pro-inflammatory cytokines in surgical specimens¹⁴, reduction of ozone induced lung inflammation in mice³³ and antiproliferative effects in a breast cancer cell line⁹. Anti-mutagenic effects have been identified in samples of urine from smokers^16,18.

Method of preparation may affect potency. Comparison of alcoholic and water extracts fed to mice reported greater evidence of anti-inflammatory activity with the alcoholic extract; however, that extract also contained a higher percentage of oxindole alkaloids (5.71% vs 0.26%)³¹. In another laboratory study, freeze dried extracts had greater potency than micropulverized extracts¹⁵.

Toxicity – Side Effects

In vitro and Animal Studies

The Ames test (Salmonella/mammalian microsome test) on various extracts and fractions showed no mutagenic effect with or without metabolic activation¹⁶, but rather a protective antimutagenic effect³, and no toxicity in mammalian (Chinese hamster) or bacterial cells³⁴. The acute median lethal dose (LD₅₀) for an aqueous extract in mice was found to be greater than 16 g/kg bodyweight, and no effect was found in rats³. A review by Valerio et al. of animal toxicological studies reported concluded that there is a lack of evidence to support the potential for genotoxic or mutagenic activity¹⁸. However, predicting the magnitude of effects with in vitro studies is always challenging, and potentially dangerous effects such as anti-platelet activity³⁵, modulation of immune function³ and estrogen receptor binding have also been reported from other in vitro studies³⁶.

Human Reports and Studies

Renal failure has been reported in a patient with lupus erythematosus³⁷. A clinical trial for patients with rheumatoid arthritis excluded any with pre-existing renal or other disease and reported that one patient developed gastritis attributed to the Uncaria tomentosa species of cat’s claw³⁸.

Extracts of Uncaria tomentosa with a high proportion of tetracyclic oxindole alkaloids would be expected to be associated with hypotension (low blood pressure)². Extracts of the other Latin American species of cat’s claw, Uncaria guianensis, were used in one study in which side effects of headache, dizziness and vomiting were reported, but these did not differ significantly from those in the placebo group¹⁵. No toxicity was observed in two studies of human volunteers^26,27.

Plant Identification

The chief risk of toxicity is from contamination or substitution with look-alike plants. One such plant is a small shrub (botanical name: Acacia gregii) that grows along the border between Mexico and Texas. Some of these shrubs are potentially poisonous as they are believed to contain a cyanide-based compound. Harvested samples of the shrub would look different from cat’s claw bark because they would consist of small twigs and leaves in contrast to the pieces of bark from the vine or root of any species of cat’s claw^11,39.

Potential Drug Interactions

An in vitro evaluation of the effects upon the human cytochrome P450 (CYP450) enzyme system that metabolizes many drugs and other compounds, found that cat’s claw inhibitory effects were among the lowest of commercial herbal extracts tested⁴⁰. However, it is difficult to predict the magnitude of inhibition from in vitro studies, and caution with CYP450 substrates should be used.

Because of anti-platelet effects, this herb should not be used by anyone taking aspirin or other medicines that increase the risk of bleeding². Because of unknown effects upon immature immune systems², it should not be used by anyone who is pregnant or nursing a baby. Potential interactions may occur with hormones, insulin, vaccines or other drugs.

Treatment of Diseases (Non-Cancer)

Although beneficial treatment of herpes and AIDS in humans has been reported⁴¹, such reports have not been identified in peer-reviewed scientific journals.

Results of studies in other diseases have been reported in peer-reviewed journals. A small randomized placebo-controlled clinical trial identified modest reductions in painful or swollen joints; however, patients in both groups were also receiving conventional arthritis medications³⁸. Accordingly, conclusions concerning this trial are limited to safety issues. A randomized, placebo-controlled study for patients with osteoarthritis of the knee reported significantly reduced pain with the Uncaria guianensis species. Related in vitro testing reported that both Uncaria guianensis and Uncaria tomentosa were equally active. One randomized controlled study and one non-randomized controlled study reported decreased DNA damage in the urine of smokers¹⁸. 

Cat’s claw combined with other supplements was evaluated in a small series of patients from the general population. Although one patient with a high level of DNA damage had significant reduction after taking the supplement for four weeks, this finding could not be confirmed in the other patients⁴². Investigators proposed that this could be because those subjects had initial damage levels within the normal range at baseline⁴².

Treatment of Cancer

Identification and reviews of studies among patients with cancer are described in the Summary of Research.

Summary of Research

Amount and Type of Research

A search of the Medline and SCOPUS database (includes European database) between 1/1/2004 and 5/30/2006 identified 18 articles concerning cat’s claw, Uncaria tomentosa or Uña de gato.  No new studies in humans were identified.

A previous search as of 12/31/2003 identified 32 references of which 29 were relevant to the Uncaria tomentosa species of cat’s claw root or stalk. Of these, 15 were relevant to effects upon cancer or the immune system and six specifically examined potential cancer effects. (The remainder of the articles examined components, toxicity, inflammation or effects in other diseases.)

A separate search as of 12/31/2003 was conducted of the European database, Embase. That review identified 13 additional relevant articles, of which five specifically mentioned cancer or immune effects with three specifically addressing the treatment of cancer. (The remainder of the articles examined reported surveys of herbal usage that included cat’s claw, or components or toxicity or effects upon inflammation.) Two additional reviews mentioning cancer related potential were identified in the lay press.

Initial searches in 1997 identified 43 references, of which 32 (74%) were applicable to cancer and/or immune effects, and we retrieved the 14 (44%) that were directly relevant to cancer.

Combining the results of all of these literature searches yielded a total of 105 articles applicable to cat’s claw (Uncaria tomentosa), of which 57 were applicable to cancer, anti-inflammatory or immune effects and 27 were specifically applicable to cancer. We retrieved these 27 articles and classified them into the following types of information:

*One animal study and one in vitro study were reported in the same article²³.
**The review by Keplinger³ included reports of in vitro studies.

*Non-peer-reviewed

Summary of Human Research in Cancer

Three case reports and two clinic series⁴³ can not be evaluated because they were only preliminary results published within a provider’s literature rather than the peer-reviewed literature⁴⁴.

No studies of cat’s claw among patients with cancer have been identified within the peer-reviewed scientific literature.

Conclusions concerning effects of cat’s claw among patients with cancer are not possible based upon these preliminary human studies that lack peer review and well controlled or randomized clinical studies.

Brief notes concerning these preliminary reports of use in humans are provided in a Table of Human Studies (pdf) and the Annotated Bibliography.

Annotated Bibliography

Human Studies

(No new human studies identified as of 5/31/2006)

³⁴Oswald, H. Case reports (Unpublished; provided by Meditest International, V. Nijenrodeweg 626, 1082 HX Amsterdam).

³⁵Immodal Pharmaka. Therapy records over a 10 year period. Krallendorn - Medicaments: Special Information for Physicians and Dispensing Chemists. 2nd Revised ed. Austria: 1993:15-6.

³⁶Immodal Pharmaka. Application in the treatment of brain tumours. Krallendorn - Medicaments: Special Information for Physicians and Dispensing Chemists. 2nd Revised ed. Austria: 1993:16-7.

For a full list of citations, see the Reference List.

Reference List

1. Anonymous. Cat's claw. The Lawrence Review of Natural Products 1996 Apr;1-3.
2. Reinhard KH. Uncaria tomentosa (Willd.) D.C.: cat's claw, una de gato, or saventaro. J of Alternative & Complementary Medicine 1999 Apr;5(2):143-51.
3. Keplinger K, Laus G, Wurm M, Dierich MP, Teppner H. Uncaria tomentosa (Willd.) DC. - Ethnomedicinal use and new pharmacological, toxicological and botanical results. J of Ethnopharmacology 1999;64:23-34.
4. Duke J. Una de gato. The Business of Herbs 1994 May-1994 Jun;15:12-3.
5. Steinberg PN. Cat's Claw: Medicinal properties of this amazon vine. Nutrition Science News 1995 Oct;8-10.
6. Desmarchelier C, Mongelli E, Coussio J, Ciccia G. Evaluation of the in vitro antioxidant activity in extracts of Uncaria tomentosa. Phytotherapy Research 1997;11(3):254-6.
7. Sandoval M, Okuhama NN, Zhang X-J et al. Anti-inflammatory and antioxidant activities of cat's claw (Uncaria tomentosa and Uncaria guianensis) are independent of their alkaloid content. Phytomedicine 2002 May;9(4):325-37.
8. Sandoval M, Charbonnet RM, Okuhama NN, Roberts J, Krenova Z, Trentacosti AM et al. Cat's Claw inhibits TNFalpha production and scavenges free radicals: role in cytoprotection. Free Radical Biology & Medicine 2000 Jul;29(1):71-8.
9. Riva L, Coradini D, Di Fronzo G, De Feo V, De Tommaso N, De Simone F et al. The antiproliferative effects of Uncaria tomentosa extracts and fractions on the growth of breast cancer cell line. Alternative Medicine Review 2001 Jul-2001 Aug;21(4A):2457-61.
10. Aquino R, De Simone F, Pizza C, Conti C, Stein ML. Plant metabolites. Structure and in vitro antiviral activity of quinovic acid glycosides from Uncaria tomentosa and Guettarda platypoda. Journal of Natural Products 1989 Jul-1989 Aug;52(4):679-85.
11. Blumenthal M. Una de Gato (Cat's Claw): Rainforest herb gets scientific and industry attention. Whole Foods (Herb Clip) 1995 Oct;62-5.
12. Biasco G, Amadori D. Chemoprevention in oncology: Foreword. European Journal of Cancer Prevention 1994;3(4):361-85.
13. Rotblatt M, Ziment I, editors. Evidence-Based Herbal Medicine. Philadelphia: Hanley and Belfus, Inc., 2002.
14. Miller MJS, Ahmed S, Bobrowski P, Haqqi TM. The chrondoprotective actions of a natural product are associated with the activation of IGF-1 production by human chondrocytes despite the preseence of IL-1B. BMC Complementary and Alternative Medicine 2006 Apr;6(13).
15. Piscoya J, Rodriguez Z, Bustamante SA, Okuhama NN, Miller MJS, Sandoval M. Efficacy and safety of freeze-dried cat's claw in osteoarthritis of the knee: mechanisms of action of the species Uncaria guianensis. Inflammation Research 2001;50:442-8.
16. Rizzi R, Re F, Bianchi A, De Feo V, de Simone F, Bianchi L et al. Mutagenic and antimutagenic activities of Uncaria tomentosa and its  extracts. Journal of Ethnopharmacology 1993 Jan;38(1):63-77.
17. Williams JE. Review of Antiviral and Immunomodulating Properties of Plants of the Peruvian Rainforest With a Particular Emphasis on Una De Gato and Sangre De Grado 2001 Dec;6(6):567-79.
18. Valerio LG Jr, Gonzales GF. Toxicological aspects of the South American herbs Cat's Claw (Uncaria tomentosa) and Maca (Lepidium meyenii): a critical synopsis. Toxicological Reviews 2005;24(1):11-35.
19. Lemaire I, Assinewe V, Cano P, Awang DV, Arnason JT. Stimulation of interleukin-1 and -6 production in alveolar macrophages by the neotropical liana, Uncaria tomentosa (una de gato). J of Ethnopharmacology 1999 Feb;64(2):109-15.
20. Wurm M, Kacani l, Laus G, Keplinger K, Dierich MP. Pentacyclic oxindole alkaloids from Uncaria tomentosa induce human endothelial cells to release a lymphocyte-proliferation-regulating factor. Planta Medica 1998;64(8):701-4.
21. Jurgensen S, DalBo S, Angers P, Santos ARS, Ribeiro-do-Valle RM. Involvement of 5-HT2 receptors in the antinociceptive effect of Uncaria tomentosa. Pharmacology, Biochemistry and Behavior 2005;81:466-77.
22. Anonymous. Quinic acid. in. Webster's New World Dictionary. United Kingdom, New York: Simon & Schuster, Inc., 1988.
23. Sheng Y, Akesson C, Holmgren K, Bryngelsson C, Giamapa V, Pero RW. An active ingredient of Cat's Claw water extracts: Identification and efficacy of quinic acid. J of Ethnopharmacology 2005;96:577-84.
24. Sheng Y, Pero RW, Amiri A, Bryngelsson C. Induction of apoptosis and inhibition of proliferation in human tumor cells treated with extracts of Uncaria tomentosa. Anticancer Research 1998;18(5):3363-8.
25. Akesson CH, Pero RQ, Ivars F. C-Med 100, a hot water extract of Uncaria tomentosa, prolongs lymphocyte survival in vivo. Phytomedicine 2003 Jan;10(1):23-33.
26. Sheng Y, Bryngelsson C, Pero RW. Enhanced DNA repair, immune function and reduced toxicity of C-MED-100, a novel aqueous extract from Uncaria tomentosa. J of Ethnopharmacology 2000 Feb;69(2):115-26.
27. Soto-Sobenis A, Castillo B, Delgado A, Gonzalez A, Montenegro RA. Alkaloid screening of herbarium samples of rubiaceae from Panama. Pharmaceutical Biology 2001;39(3):161-9.
28. Mammone T, Akesson Christina, Gan D, Giampapa V, Pero RW. A water soluble extract from Uncaria tomentosa (Cat's Claw) is a potent enhancer of DNA repair in primary organ cultures of human skin. Phytotherapy Research 2006;20:178-83.
29. Aquino R, De Simone F, Vincieri FF, Pizza C, Gacs-Baitz E. New polyhydroxylated triterpenes from Uncaria tomentosa. Journal of Natural Products 1990 May-1990 Jun;53(3):559-64.
30. montoro P, Carbone V, Dioz Zuniga Quiroz J, De Simone F, Pizza C. Identification and quantification of components in extracts of Uncaria tomentosa by HPLC-ES/MS. Phytochemical Analysis 2004;15:55-64.
31. Aguilar JL, Rojas P, Marcelo A, Plaza A, Bauer R, Reininger E et al. Anti-inflammatory activity of two different extracts of Uncaria tomentosa (Rubiaceae). J of Ethnopharmacology 2002 Jul;81(2):271-6.
32. Sandoval-Chacon M, Thompson JH, Zhang XJ, Liu X, Mannick EE et al. Antiinflammatory actions of cat's claw: the role of NF-kappaB. Alimentary Pharmacology & Therapeutics 1998 Dec;12(12):1279-89.
33. Cisneros FJ, Jayo M, Niedziela L. An Uncaria tomentosa (cat's claw) extract protects mice against ozone-induced lung inflammation. J of Ethnopharmacology 2005;96:355-64.
    Santa Maria A, Lopez A, Diaz MM, Alb an J, Galan de Mera A, Vicente Orellana JA et al. Evaluation of the toxicity of Uncaria tomentosa by bioassays in vitro. J of Ethno-Pharmacology 1997;57:183-87.
34. Jones SC, Miederhoff P, Karnes HT. The development of a human tissue model to determine the effect of plant-derived ketary supplements on prothrombin time. J. of Herbal Pharmacotherapy 2001;1(1):21-34.
35. Salazar EL JV. Depletion of specific binding sites for estrogen receptor by uncaria tomentosa. 41. 1998;41:123-4.
36. Hilepo JN, Bellucci AG, Mossey RT. Acute renal failure caused by 'cat's claw' herbal remedy in a patient with systemic lupus erythematosus. Nephron 1997;77(3):361.
37. Mur E, Hartig F, Eibl G, Schirmer M. Randomized double blind trial of an extract from the pentacyclic alkaloid-chemotype of uncaria tomentosa for the treatment of rheumatoid arthritis. J of Rheumatology 2002 Apr;29(4):678-81.
38. Anonymous. Cat's Claw Confusion. Herb Clip 1995 Sep.
39. Budzinski JW, Foster BC, Vandenhoek S, Arnason JT. An in vitro evaluation of human cytochrome P450 3A4 inhibition by selected commercial herbal extracts and tinctures. Phytomedicine 2000 Jul;7(4):273-82.
40. Steinberg P. Cat's Claw (una De Gato). The Herb Quarterly 1994 Winter.
41. Pero RW, Amiri A, Sheng Y, Welther M, Rich M. Formulation and in vitro/in vivo evaluation of combining DNA repair and immune enhancing nutritional supplements. Phytomedicine 2005;12:255-63.
42. Immodal Pharmaka. Application in the treatment of brain tumours. Krallendorn -Medicaments: Special Information for Physicians and Dispensing Chemists. 2nd Revised ed. Austria: 1993:16-7.
43. Oswald H. Case reports (unpublished).
    Immodal Pharmaka. Therapy records over a 10 year period. Krallendorn - Medicaments: Special Information for Physicians and Dispensing Chemists. 2nd Revised ed. Austria: 1993:15-6.