Cat's Claw

Metadata

Approved Indications

Commission E (Germany)

• No monograph. Commission E has not issued a monograph (positive or negative) for Uncaria tomentosa. The plant is not part of the traditional European phytotherapy canon and was never evaluated by the Commission.

ESCOP

• Monograph available. ESCOP has published a monograph for Uncariae tomentosae cortex (Cat’s Claw Bark). The therapeutic indication listed is as an adjuvant for the treatment of mild inflammatory conditions. The monograph summarizes scientific data on efficacy, dosage, and safety, including studies on oxindole alkaloids, quinovic acid glycosides, polyphenols, and procyanidins.

EMA/HMPC

• No monograph adopted. The EMA Committee on Herbal Medicinal Products (HMPC) conducted an assessment of Uncaria tomentosa cortex but ultimately did not adopt a European Union herbal monograph. The HMPC concluded that although preparations containing powdered stem bark have been in medicinal use for at least 15 years in the EU, evidence for at least 30 years of medicinal use outside the EU (as required by Directive 2004/24/EC for traditional use registration) was not adequately documented. A public statement was issued instead of a monograph.

WHO

• Monograph published. The World Health Organization published a monograph on Uncaria tomentosa in the WHO Monographs on Selected Medicinal Plants, Volume 3 (2007). This monograph describes the traditional uses, phytochemistry, pharmacology, and safety profile of the inner bark.

Agreement/Disagreement Analysis

The regulatory picture for Cat’s Claw is fragmented:

• Commission E: Not evaluated (plant falls outside the European herbal tradition)
• ESCOP: Positive monograph for adjuvant treatment of mild inflammatory conditions
• EMA/HMPC: Assessed but no monograph adopted due to insufficient documentation of long-term traditional use
• WHO: Published monograph acknowledging traditional use and pharmacological rationale
• NCCIH (United States): States that “there have been very few high-quality clinical trials” and that there is “no conclusive scientific evidence” for any health purpose

The overall picture reflects acknowledged pharmacological interest but insufficient clinical trial evidence for broad regulatory endorsement. ESCOP’s monograph is the most favorable assessment, limited to adjuvant use in mild inflammation.

Historical and Ethnobotanical Context

Botanical Description

Uncaria tomentosa is a large woody vine (liana) growing up to 30 meters in length in the canopies of Central and South American tropical rainforests. The plant is named for its curved, claw-like thorns at the leaf juncture. It is native to the Amazon basin, found at elevations of 250-900 meters in Peru, Colombia, Ecuador, Brazil, and Bolivia.

A closely related species, Uncaria guianensis, is also sold under the same common name. The two species have overlapping but distinct phytochemical profiles. Some clinical studies used U. guianensis rather than U. tomentosa, which complicates the evidence base.

Traditional Use in Amazonian Medicine

Cat’s Claw has been used medicinally by indigenous peoples of the Amazon for at least 2,000 years. The Ashaninka (Campa) tribe of central Peru has the longest recorded history of use, but the Aguaruna, Cashibo, Conibo, and Shipibo peoples also used the plant.

Ashaninka traditional uses: Arthritis and bone pain, urinary tract inflammation, gastric ulcers, recovery from childbirth, wound healing, cancer (traditional concept), kidney cleansing, asthma, and general immune strengthening.

Preparation methods: Indigenous tribes prepared decoctions of the bark and root, boiling them to produce medicinal teas. Shamans used bark decoctions for internal bleeding, rheumatic pain, ulcers, and infections.

Modern Discovery

Western scientific interest began in the 1970s when Austrian researcher Klaus Keplinger investigated the plant’s immunomodulatory properties. Keplinger was granted several patents for oxindole alkaloid extracts during the 1980s-1990s. Cat’s Claw became a top-selling herbal supplement in the United States and Europe during the late 1990s.

Conditions Treated

Primary (Limited RCT Evidence)

• Osteoarthritis — One randomized controlled trial (Piscoya et al. 2001) demonstrated that freeze-dried Uncaria guianensis (100 mg daily for 4 weeks) significantly reduced pain associated with activity, and improved medical and patient assessment scores compared to placebo in 45 patients with knee osteoarthritis. Pain at rest or at night and knee circumference were not significantly reduced during this brief trial. Cat’s Claw was well tolerated with no serious adverse events. A second trial (Rosenbaum et al. 2010) using an extract called Vincaria found reduction in knee pain at rest in a 4-week study.

Secondary (Preliminary Clinical Evidence)

• Rheumatoid arthritis — Mur et al. (2002) conducted a 52-week, two-phase RCT with 40 patients receiving sulfasalazine or hydroxychloroquine. In the double-blind phase (24 weeks), the POA-chemotype extract reduced painful joints by 53.2% vs. 24.1% for placebo (p = 0.044). In the open-label second phase, additional reductions in painful joints, swollen joints, and Ritchie Index were observed.
• Immune stimulation — Lamm et al. (2001) studied C-Med-100 (350 mg twice daily for 2 months) in male volunteers receiving a 23-valent pneumococcal vaccine. The supplement group showed elevated lymphocyte-to-neutrophil ratios and reduced decay in antibody titers at 5 months post-vaccination, suggesting enhanced and more persistent vaccine response.
• DNA repair enhancement — Sheng et al. (2001) demonstrated that C-Med-100 (250 and 350 mg/day for 8 weeks) significantly decreased DNA damage and increased DNA repair in human volunteers compared to non-supplemented controls, with elevated white blood cell counts. An earlier animal study (Sheng et al. 2000) confirmed enhanced repair of DNA single- and double-strand breaks after whole-body irradiation.

Traditional (Ethnobotanical, No Clinical Trials)

• Gastric ulcers and gastrointestinal inflammation
• Urinary tract infections and inflammation
• Cancer support (traditional concept; no clinical evidence of anti-cancer efficacy in humans)
• Wound healing
• General immune tonic and anti-infectious agent
• Asthma and respiratory support
• Gonorrhea and sexually transmitted infections (traditional use)
• Contraception (some historical reports of indigenous contraceptive use)

Mechanism of Action

Oxindole Alkaloid Pharmacology: POA vs. TOA

The pharmacology of Cat’s Claw is dominated by the interplay between two classes of oxindole alkaloids. These exist as two distinct chemotypes in wild populations of U. tomentosa, a critical factor for both quality control and therapeutic efficacy.

Pentacyclic Oxindole Alkaloids (POA) — Therapeutic chemotype:

• Include isopteropodine, pteropodine (uncarine C), isomitraphylline, mitraphylline, speciophylline, and uncarine F
• POAs induce human endothelial cells (EA.hy926) to release a factor that enhances proliferation of resting or weakly activated B and T lymphocytes (Wurm et al. 1998)
• Stimulate phagocytosis by granulocytes
• Considered the primary immunomodulatory alkaloids
• Most commercial preparations are standardized for high POA dominance (minimum 0.3% total pentacyclic oxindole alkaloids)

Tetracyclic Oxindole Alkaloids (TOA) — Antagonistic chemotype:

• Include rhynchophylline and isorhynchophylline
• Dose-dependently reduce the immunostimulatory activity of POAs on human endothelial cells
• Considered pharmacologically antagonistic to the therapeutic POA effects
• Quality preparations aim to minimize TOA content
• Isorhynchophylline has shown independent phagocytosis-inducing activity, suggesting the POA-TOA antagonism may be more nuanced than initially proposed

NF-kB Inhibition and TNF-alpha Suppression

One of the best-characterized mechanisms of Cat’s Claw is its inhibition of the pro-inflammatory transcription factor NF-kB and downstream suppression of TNF-alpha.

• In LPS-stimulated THP-1 monocytic cells, U. tomentosa extracts suppressed TNF-alpha production by 65-85% compared to LPS-only controls (Aguilar et al. 2002)
• Treatment simultaneously augmented LPS-dependent IL-1-beta expression by 2.4-fold while inhibiting TNF-alpha expression by 5.5-fold, demonstrating differential cytokine regulation
• The mechanism is NF-kB-dependent: when NF-kB activation was pharmacologically blocked, the ability of U. tomentosa to inhibit TNF-alpha was diminished (Aguilar et al. 2002)
• Cat’s Claw extracts blocked ERK1/2 and MEK1/2 phosphorylation in a dose-dependent manner
• Slight inhibition of COX-1 and COX-2 contributes additional anti-inflammatory activity
• Sandoval et al. (2002) demonstrated that the anti-inflammatory and antioxidant activities are independent of alkaloid content, indicating that non-alkaloid constituents (quinovic acid glycosides, procyanidins) also contribute significantly

Additional Mechanisms

Anti-inflammatory (in vivo):

• Oral U. tomentosa produced dose-dependent anti-inflammatory effects in animal models, with 1000 mg/kg achieving 74% anti-inflammatory effect versus 97% for naproxen sodium 40 mg/kg
• A 2024 systematic review and meta-analysis (Frontiers in Pharmacology) confirmed in vivo anti-inflammatory and immunomodulatory activities across multiple aqueous and hydroethanolic extracts with low toxicity

Immunomodulatory:

• Stimulation of phagocytosis by granulocytes and macrophages
• Enhancement of B- and T-lymphocyte proliferation
• Stimulation of myeloid progenitor cell proliferation (Nunez et al. 2012)
• Increased white blood cell counts in both animal and human studies

DNA repair:

• C-Med-100 (aqueous extract standardized to 8-10% carboxy alkyl esters, low alkaloid content) enhanced DNA single- and double-strand break repair after irradiation in rats (Sheng et al. 2000)
• Human volunteer study confirmed decreased DNA damage and increased DNA repair at doses of 250-350 mg/day (Sheng et al. 2001)

Antioxidant:

• Procyanidins and catechins contribute to radical scavenging activity
• U. tomentosa and U. guianensis were equivalent at quenching DPPH radicals (EC50: 13.6-21.7 mcg/mL)
• TNF-alpha inhibition occurs at much lower concentrations (EC50: 10.2-10.9 ng/mL) than antioxidant activity, suggesting the anti-inflammatory mechanism is primary

Gastroprotective:

• Animal studies demonstrated accelerated gastric healing, supporting traditional use for gastric ulcers, via suppression of TNF-alpha mRNA expression and inhibition of apoptosis in gastric tissue

Antiviral:

• Quinovic acid glycosides demonstrated in vitro antiviral activity; molecular modeling suggested potential SARS-CoV-2 activity (Yepes-Perez et al. 2021), though this remains unconfirmed clinically

Clinical Evidence Summary

Clinical evidence for Cat’s Claw is sparse. Only a handful of randomized controlled trials have been published, and most are small, short-duration studies. The majority of pharmacological evidence comes from in vitro and animal studies.

Osteoarthritis

Note: The Piscoya 2001 trial used U. guianensis, not U. tomentosa. While both species are sold as “Cat’s Claw” and share overlapping phytochemistry, they are distinct species, limiting direct applicability to U. tomentosa products.

Rheumatoid Arthritis

Immune Enhancement and DNA Repair

Evidence Limitations

• Very few RCTs: Only two properly designed RCTs for osteoarthritis and one for rheumatoid arthritis have been published
• Small sample sizes: The largest trial included only 95 patients (Rosenbaum 2010)
• Short duration: Most trials lasted only 4 weeks, insufficient to assess long-term efficacy and safety
• Species confusion: Some pivotal trials used U. guianensis rather than U. tomentosa, complicating the evidence base for the latter species
• Preparation heterogeneity: Studies used different extracts (freeze-dried whole bark, POA-enriched extracts, aqueous C-Med-100/AC-11), making cross-study comparison difficult
• Funding: Several key studies (Sheng, Lamm) used proprietary C-Med-100/AC-11 extracts with potential industry ties
• 2024 systematic review: A meta-analysis of in vivo studies (Front Pharmacol. 2024) confirmed anti-inflammatory and immunomodulatory activities but noted high heterogeneity and the absence of adequate clinical trials
• NCCIH conclusion: “No conclusive scientific evidence based on studies in people that supports using cat’s claw for any health purpose”

Safety Profile

General Assessment

Cat’s Claw preparations appear to be generally well tolerated in published clinical trials at standard doses for periods up to 52 weeks. No serious adverse events have been attributed to Cat’s Claw in controlled studies. The LiverTox database states that Cat’s Claw has not been implicated in causing clinically apparent liver injury. However, systematic long-term safety data from large controlled trials is lacking.

Contraindications

• Pregnancy: Contraindicated (Category X). Traditional contraceptive use by some indigenous groups; insufficient safety data, and potential uterotonic effects present unacceptable risk.
• Lactation: Insufficient data. Avoid use during breastfeeding.
• Autoimmune disorders: Immunostimulatory properties could theoretically exacerbate autoimmune conditions (SLE, RA, MS). The Mur 2002 RA trial used Cat’s Claw as adjunctive therapy with conventional immunomodulators, not as monotherapy.
• Organ transplant recipients: Immunostimulatory effects may antagonize immunosuppressive therapy. Avoid concurrent use.
• Pre-surgical: Discontinue at least 2 weeks before surgery due to potential antiplatelet effects.

Drug Interactions

Adverse Effects (at Recommended Doses)

• Common: Generally well tolerated. Mild gastrointestinal discomfort (nausea, diarrhea, stomach upset) reported infrequently.
• Uncommon: Headache, dizziness.
• Rare: Gastritis has been the only adverse event possibly attributable to Cat’s Claw bark in clinical studies. Acute renal failure has been reported in isolated case reports but causality was not established.
• Very rare: Allergic reactions in sensitized individuals.

Clinical Dosage

Dried Bark (Capsules/Tablets)

• Standard dose: 300-500 mg daily, divided into 2-3 doses
• WHO recommendation: 20-350 mg of dried stem bark for extracts, or 300-500 mg for capsule form, in 2-3 divided doses
• Traditional decoction: 20 g bark boiled in 1 liter of water for traditional preparation

Standardized Extracts (POA-enriched)

• Standard dose: 60-300 mg daily of standardized extract
• Mur 2002 (RA trial): 60 mg/day of pentacyclic alkaloid-chemotype extract
• Piscoya 2001 (OA trial): 100 mg/day of freeze-dried bark
• Standardization: Powdered Cat’s Claw should contain no less than 0.3% total pentacyclic oxindole alkaloids (sum of speciophylline, uncarine F, mitraphylline, isomitraphylline, pteropodine, and isopteropodine)

Aqueous Extract (C-Med-100/AC-11)

• Standard dose: 250-350 mg/day
• Standardization: 8-10% carboxy alkyl esters (CAEs); less than 0.05% oxindole alkaloids
• Used in DNA repair and immune studies (Sheng et al. 2000, 2001; Lamm et al. 2001)

Duration of Use

• Clinical trials have studied periods ranging from 4 weeks to 52 weeks
• ESCOP and WHO do not specify a maximum duration but recommend medical supervision for prolonged use
• No long-term safety data (beyond 1 year) from controlled studies is available

Sources

• Piscoya J, Rodriguez Z, Bustamante SA, Okuhama NN, Miller MJ, Sandoval M. Efficacy and safety of freeze-dried cat’s claw in osteoarthritis of the knee: mechanisms of action of the species Uncaria guianensis. Inflamm Res. 2001;50(9):442-448. PMID: 11603848
• 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 Rheumatol. 2002;29(4):678-681. PMID: 11950006
• Lamm S, Sheng Y, Pero RW. Persistent response to pneumococcal vaccine in individuals supplemented with a novel water soluble extract of Uncaria tomentosa, C-Med-100. Phytomedicine. 2001;8(4):267-274. PMID: 11515716
• 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 Ethnopharmacol. 2000;69(2):115-126. PMID: 10687868
• Sheng Y, Li L, Holmgren K, Pero RW. DNA repair enhancement of aqueous extracts of Uncaria tomentosa in a human volunteer study. Phytomedicine. 2001;8(4):275-282. PMID: 11515717
• Aguilar JL, Rojas P, Marcelo A, et al. Anti-inflammatory activity of two different extracts of Uncaria tomentosa (Rubiaceae). J Ethnopharmacol. 2002;81(2):271-276. PMID: 12065162
• Sandoval M, Okuhama NN, Zhang XJ, et al. Anti-inflammatory and antioxidant activities of cat’s claw (Uncaria tomentosa and Uncaria guianensis) are independent of their alkaloid content. Phytomedicine. 2002;9(4):325-337. PMID: 12120814
• 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 Med. 1998;64(8):701-704. PMID: 9933988
• Aguilar JL, Rojas P, Marcelo A, et al. Treatment of THP-1 cells with Uncaria tomentosa extracts differentially regulates the expression of IL-1beta and TNF-alpha. J Ethnopharmacol. 2006;104(3):297-304. PMID: 16959454
• Nunez C, Lozada-Requena I, Ysmodes T, Bah M, Aguilar JL. Uncaria tomentosa stimulates the proliferation of myeloid progenitor cells. J Ethnopharmacol. 2012;142(3):723-729
• Heitzman ME, Neto CC, Winiarz E, Vaisberg AJ, Hammond GB. Ethnobotany, phytochemistry and pharmacology of Uncaria (Rubiaceae). Phytochemistry. 2005;66(1):5-29. PMID: 15649507
• Aquino R, De Feo V, De Simone F, Pizza C, Cirino G. Plant metabolites: new compounds and anti-inflammatory activity of Uncaria tomentosa. J Nat Prod. 1991;54(2):453-459. PMID: 1919590
• 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. J Nat Prod. 1989;52(4):679-685
• 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;7(4):273-282. PMID: 10969720
• Rosenbaum CC, O’Mathuna DP, Chavez M, Shields K. Antioxidants and antiinflammatory dietary supplements for osteoarthritis and rheumatoid arthritis. Altern Ther Health Med. 2010;16(2):32-40
• de Oliveira LZ, de Oliveira Caleffi PM, Acco A, et al. Anti-inflammatory and/or immunomodulatory activities of Uncaria tomentosa (cat’s claw) extracts: a systematic review and meta-analysis of in vivo studies. Front Pharmacol. 2024;15:1378408. PMID: 38881881
• WHO. WHO Monographs on Selected Medicinal Plants. Volume 3. Geneva: World Health Organization; 2007
• ESCOP. Uncariae tomentosae cortex (Cat’s Claw Bark). ESCOP Monographs. European Scientific Cooperative on Phytotherapy
• EMA/HMPC. Final assessment report on Uncaria tomentosa (Willd. ex Schult.) DC., cortex. European Medicines Agency; 2015
• EMA/HMPC. Final public statement on Uncaria tomentosa (Willd. ex Schult.) DC., cortex. European Medicines Agency; 2015
• NCCIH. Cat’s Claw: Usefulness and Safety. National Center for Complementary and Integrative Health (nccih.nih.gov)
• LiverTox. Cat’s Claw. In: Clinical and Research Information on Drug-Induced Liver Injury. NCBI Bookshelf (NBK548323)
• Memorial Sloan Kettering Cancer Center. Cat’s Claw. Integrative Medicine: About Herbs, Botanicals and Other Products (mskcc.org)

Connections

• Echinacea — Compare immune-stimulation mechanisms; echinacea has far more clinical trial support for upper respiratory tract infections, while Cat’s Claw immune evidence is more preliminary
• Astragalus — Another immune-modulating herb from a different tradition (TCM); both stimulate phagocytosis and lymphocyte proliferation but through different pathways
• Andrographis — Anti-inflammatory herb with stronger clinical evidence for acute respiratory infections; compare NF-kB inhibition mechanisms
• Turmeric/Curcumin — Both inhibit NF-kB and TNF-alpha; curcumin has substantially more clinical trial evidence for anti-inflammatory applications, including osteoarthritis
• Boswellia — Anti-inflammatory resin with stronger clinical evidence for osteoarthritis; works through 5-LOX inhibition rather than NF-kB, complementary mechanism
• Devil’s Claw (Harpagophytum procumbens) — Another traditionally used anti-inflammatory with better clinical evidence for osteoarthritis and musculoskeletal pain; more directly comparable as both are used for joint conditions with limited European regulatory endorsement
• The CYP3A4 inhibition potency of Cat’s Claw is notable and parallels concerns with St. John’s Wort (CYP inducer) and grapefruit (CYP3A4 inhibitor) regarding herb-drug interactions
• Cat’s Claw represents a broader pattern of Amazonian ethnobotanicals entering Western markets with strong traditional use claims but limited clinical validation