Home Ingredients Flexigo™ (Devil's Claw Joint Health)
Joint Health

Flexigo™ (Devil's Claw Joint Health)

Harpagophytum procumbens
Evidence Level
Limited
2 Clinical Trials
5 Documented Benefits
2/5 Evidence Score

Flexigo™ is a standardized Devil's Claw extract (Harpagophytum procumbens, also Harpagophytum zeyheri) from Southern Africa, made by Nexira (France). Nexira states harpagoside content up to 20% (HPLC method), 100% Devil's Claw with no carrier, and sustainable wild-harvest sourcing. Two EU joint-health claims for Harpagophytum procumbens are pending and have not been assessed by EFSA. Used for joint comfort and mobility. Human studies of Devil's Claw extracts (not this brand) include open studies and several placebo-controlled trials, which reviewers rate as low quality or generally poor.

Studied Dose Devil's Claw extracts in trials: 600 or 1,200 mg a day of extract WS 1531 (50 or 100 mg harpagoside) for low back pain, and 2,400 mg a day of an aqueous extract (50 mg harpagoside) in hip and knee osteoarthritis. No Flexigo dose has been tested.
Active Compound Harpagosides (iridoid glycosides) are the marker actives; Flexigo is a high-standardization Devil's Claw extract, with harpagoside content up to about 20 percent by HPLC (Nexira).

Benefits

Joint Comfort and Mobility

Human studies of Devil's Claw extracts report less pain and better mobility in hip and knee osteoarthritis and in low back pain. A 2006 review counted 4 double-blind placebo-controlled trials among 14 osteoarthritis studies but rated their quality as generally poor. In low back pain, two placebo-controlled trials (50 or 100 mg harpagoside a day) gave low quality evidence. None tested Flexigo.

Supported by Trial 2, Trial 1

Anti-Inflammatory Activity (Laboratory Evidence)

In laboratory cell and animal models, harpagoside and other iridoid compounds inhibit COX-2, lipoxygenase and the NF-kB pathway. This is a plausible anti-inflammatory mechanism, but reduction of blood inflammation markers has not been demonstrated in human trials, which measured pain and function rather than markers.

Supported by Trial 2, Trial 1

EFSA Pending Claims

Two pending EFSA claims for Harpagophytum procumbens: (1) 'Helps to maintain joint health'; (2) 'Helps to maintain flexible joints and good mobility'. These claims sit unassessed in the EFSA botanical backlog and have not been authorised; pending status is not an endorsement of efficacy.

Supported by Trial 1

Athletic Use (Not Studied)

Devil's Claw has not been tested in athletes or for exercise recovery. The human studies were done in adults with osteoarthritis, rheumatic joint complaints, low back pain, or mild muscle tension and pain in the back, shoulders and neck, so any use for sport-related joint stress is an extrapolation, not a studied outcome.

Supported by Trial 1, Trial 2

Carrier-Free Extract (Supplier Claim)

Nexira states Flexigo is 100% Devil's Claw with no carrier, made by water extraction and concentration, with harpagoside up to 20% by HPLC. Carrier-free means no filler such as maltodextrin, not that the whole extract is active compound, and no published trial has tested Flexigo itself.

Supported by Trial 1, Trial 2

Mechanism of action

1

Harpagoside Anti-Inflammatory Activity

Harpagoside, harpagide and procumbide are iridoid glycosides considered the primary actives. In cell studies harpagoside suppressed COX-2 and iNOS expression by blocking NF-κB activation, and extract lowered leukotriene (lipoxygenase pathway) formation in human blood in the lab and after oral doses. In 25 healthy volunteers, 21 days of Devil's Claw powder caused no NSAID-like change in blood eicosanoids.

2

Cytokine Modulation

In a cell study, an ethanol Devil's Claw extract reduced release of the pro-inflammatory cytokines TNF-α, IL-6 and IL-1β from stimulated human monocytes, possibly by blocking the AP-1 pathway. Whether this lowers joint inflammation in people has not been shown.

3

Cartilage Protection (Theoretical)

In human cartilage cells in the lab, Devil's Claw extract lowered cartilage-degrading enzymes (MMP-1, MMP-3, MMP-9), and harpagoside lowered IL-6 and MMP-13 in osteoarthritic cells. Harpagoside reduced cartilage and bone damage in mice with induced arthritis, but an extract did not significantly limit cartilage loss in rabbits with experimental osteoarthritis. Not shown in people.

4

Wild-Harvest Sourcing (Supplier Statement)

Devil's Claw is a wild plant of southern Africa, where it is a traditional remedy for rheumatic complaints. Nexira states that Flexigo is wild-harvested with sustainable sourcing; this is a supplier statement, not a finding of any cited study.

Clinical trials

1
Devil's Claw for Hip and Knee Osteoarthritis (Uncontrolled Open Study)
PubMed

Uncontrolled, open multicentre drug-surveillance study of an aqueous Devil's Claw extract for about 12 weeks, with no placebo group. (Wegener et al. 2003, Phytother Res)

75 patients with osteoarthritis (arthrosis) of the hip or knee.

Patients took 2400 mg/day of an aqueous extract (Doloteffin) providing 50 mg harpagoside. WOMAC total score fell 22.9 percent and visual analogue pain scores fell 22.6 to 25.8 percent; two possible adverse reactions (dyspepsia, fullness) were reported. With no control group, these changes cannot be separated from natural fluctuation or expectation. The product was not Flexigo.

2
Devil's Claw Compared With an NSAID (One Small Pilot Trial)
PubMed

One randomized double-blind pilot comparing an aqueous Devil's Claw extract with rofecoxib for low back pain. (Chrubasik et al. 2003, Rheumatology (Oxford))

Adults with acutely exacerbated low back pain.

In one 88-patient pilot, an aqueous Devil's Claw extract (Doloteffin, 60 mg harpagoside per day) showed no significant difference from rofecoxib 12.5 mg over 6 weeks, but the authors stated the study was too small to prove equivalence. A 2014 Cochrane update rated this comparison very low quality evidence, and one small study does not make Devil's Claw a substitute for prescribed medication.

Side effects and drug interactions

Common Potential side effects

Generally well-tolerated.
GI distress (nausea, diarrhea), the most common.
Headache.
Theoretical bleeding risk; an antiplatelet effect is unproven (21 days of oral powder did not change serum thromboxane B2 in 25 healthy volunteers).
Allergic reactions rare.
Bitter taste of extract.
Gallstones: the EU herbal monograph advises people with gallstones to consult a physician before use.
Children and adolescents under 18: use has not been established (EU herbal monograph).

Important Drug interactions

Anticoagulants: theoretical bleeding risk; consult a clinician.
Diabetes medications: injected extract lowered blood glucose in rats; human effect unknown, so monitor glucose.
Gastric or duodenal ulcer: the EU herbal monograph (EMA/HMPC) lists active gastric or duodenal ulcer as a contraindication; avoid with active ulcer disease.
Anti-arrhythmic and blood pressure drugs: in rats, high oral doses of the extract lowered blood pressure and heart rate, and it protected against induced arrhythmias; use caution.
Pregnancy: extract caused strong contractions of isolated rat uterus, and the root has folk use to induce labour; avoid in pregnancy.
Lactation: limited safety data; avoid.

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Frequently asked questions about Flexigo™ (Devil's Claw Joint Health)

What is Flexigo?

Flexigo™ is a standardized Devil's Claw extract (Harpagophytum procumbens, also Harpagophytum zeyheri) from Southern Africa, made by Nexira (France). Nexira states harpagoside content up to 20% (HPLC method), 100% Devil's Claw with no carrier, and sustainable wild-harvest sourcing.

What is Flexigo used for?

Flexigo is researched primarily for Joint Health. Human studies of Devil's Claw extracts report less pain and better mobility in hip and knee osteoarthritis and in low back pain.

What is the recommended dosage of Flexigo?

The clinically studied dose is Devil's Claw extracts in trials: 600 or 1,200 mg a day of extract WS 1531 (50 or 100 mg harpagoside) for low back pain, and 2,400 mg a day of an aqueous extract (50 mg harpagoside) in hip and knee osteoarthritis. No Flexigo dose has been tested. Always follow the product label and check with a healthcare provider for personal advice.

Is Flexigo safe, and does it have side effects?

Side effects and cautions reported for Flexigo include: Generally well-tolerated. GI distress (nausea, diarrhea), the most common. It may also interact with some medications. Flexigo is not right for everyone, so check with a healthcare provider first if you are pregnant or breastfeeding, have a medical condition, or take prescription medication.

Does Flexigo interact with any medications?

Possible interactions include: Anticoagulants: theoretical bleeding risk; consult a clinician. Diabetes medications: injected extract lowered blood glucose in rats; human effect unknown, so monitor glucose. If you take prescription medication, check with a pharmacist or doctor before using it.

How strong is the scientific evidence for Flexigo?

NutraSmarts rates the evidence for Flexigo as Limited (2 out of 5). It is backed by 2 study summaries and 21 cited references summarized on this page. A higher rating reflects more, larger, and better-designed human studies.

References(21 citations)

Evidence ratings on NutraSmarts are based on the totality of human clinical research, with emphasis on randomized controlled trials, meta-analyses, and systematic reviews. The references below directly support claims made throughout this page.

  1. Wegener T, Lüpke NP. Treatment of patients with arthrosis of hip or knee with an aqueous extract of devil's claw (Harpagophytum procumbens DC.). Phytother Res. 2003;17(10):1165-72. doi: 10.1002/ptr.1322.PubMedUsed to support: Uncontrolled, open-label drug-surveillance study in 75 patients with hip or knee osteoarthritis taking an aqueous Devil's Claw extract (Doloteffin, 2400 mg providing 50 mg harpagoside daily) for 12 weeks. WOMAC and pain scores fell by roughly 22 to 26 percent, but with no placebo group these changes cannot be separated from natural symptom fluctuation and expectation. The product tested was not Flexigo.
  2. Warnock M, McBean D, Suter A, Tan J, Whittaker P. Effectiveness and safety of Devil's Claw tablets in patients with general rheumatic disorders. Phytother Res. 2007;21(12):1228-33. doi: 10.1002/ptr.2288.PubMedUsed to support: Single-group open study with no placebo control in 259 UK patients with degenerative rheumatic disorders taking a Devil's Claw product (Bioforce, A.Vogel) for 8 weeks. Pain, stiffness and function improved from baseline and 60 percent of patients reduced or stopped other pain medication. Without a control group the true effect size is uncertain, and the product was not Flexigo.
  3. Gagnier JJ, van Tulder M, Berman B, Bombardier C. Herbal medicine for low back pain. Cochrane Database Syst Rev. 2006;2006(2):CD004504. doi: 10.1002/14651858.CD004504.pub3.PubMedUsed to support: Cochrane review of herbal medicines for low back pain (2006 version). Based on two high quality trials, it judged the evidence strong that Devil's Claw standardized to 50 or 100 mg harpagoside per day beat placebo for short-term improvements in pain and rescue medication use in low back pain, and another high quality trial showed relative equivalence to rofecoxib 12.5 mg per day. The 2014 update (PMID 25536022) downgraded these to low and very low quality evidence respectively. Low back pain only, not osteoarthritis or athletic use.
  4. Huang TH, Tran VH, Duke RK, Tan S, Chrubasik S, Roufogalis BD, Duke CC. Harpagoside suppresses lipopolysaccharide-induced iNOS and COX-2 expression through inhibition of NF-kappa B activation. J Ethnopharmacol. 2006;104(1-2):149-55. doi: 10.1016/j.jep.2005.08.055.PubMedUsed to support: Laboratory cell-based study showing harpagoside suppresses LPS-induced iNOS and COX-2 expression by inhibiting NF-kB activation. This describes a plausible anti-inflammatory mechanism in vitro and is not evidence of reduced inflammation in people.
  5. Grant L, McBean DE, Fyfe L, Warnock AM. A review of the biological and potential therapeutic actions of Harpagophytum procumbens. Phytother Res. 2007;21(3):199-209. doi: 10.1002/ptr.2029.PubMedUsed to support: Narrative review of the pharmacology and reported clinical effects of Devil's Claw in joint and musculoskeletal complaints. As a review it summarises other studies rather than providing direct trial evidence, and it concerns Devil's Claw generally, not the Flexigo brand.
  6. Chrubasik S, Model A, Black A, Pollak S. A randomized double-blind pilot study comparing Doloteffin and Vioxx in the treatment of low back pain. Rheumatology (Oxford). 2003;42(1):141-8. doi: 10.1093/rheumatology/keg053.PubMedUsed to support: Randomized double-blind pilot in 88 adults with acutely exacerbated low back pain comparing an aqueous Devil's Claw extract (Doloteffin, 60 mg harpagoside per day) with rofecoxib 12.5 mg per day over 6 weeks. Pain fell similarly in both groups (about 23 percent versus 26 percent) with no significant difference, but the authors concluded the trial was too small to demonstrate equivalence. It tested a low back pain population, not osteoarthritis, and not the Flexigo brand.
  7. Oltean H, Robbins C, van Tulder MW, Berman BM, Bombardier C, Gagnier JJ. Herbal medicine for low-back pain. Cochrane Database Syst Rev. 2014;2014(12):CD004504. doi: 10.1002/14651858.CD004504.pub4.PubMedUsed to support: 2014 update of the Cochrane review of herbal medicines for low back pain, replacing the 2006 version. Two trials (315 participants) gave low quality evidence that Devil's Claw standardized to 50 or 100 mg harpagoside per day may be better than placebo for short-term pain and may reduce rescue medication use; a third trial (88 participants) showing relative equivalence to rofecoxib 12.5 mg per day was rated very low quality. Low back pain only, not osteoarthritis, and not the Flexigo brand.
  8. Fiebich BL, Muñoz E, Rose T, Weiss G, McGregor GP. Molecular targets of the antiinflammatory Harpagophytum procumbens (devil's claw): inhibition of TNFα and COX-2 gene expression by preventing activation of AP-1. Phytother Res. 2012;26(6):806-11. doi: 10.1002/ptr.3636.PubMedUsed to support: Cell study: an ethanol Devil's Claw extract dose-dependently reduced TNF-alpha, IL-6, IL-1beta and PGE2 release from LPS-stimulated human monocytes and prevented COX-2 expression in RAW 264.7 cells, possibly by blocking the AP-1 pathway (NF-kB binding was unaffected). In vitro only, not evidence of reduced joint inflammation in people, and not the Flexigo product.
  9. Loew D, Möllerfeld J, Schrödter A, Puttkammer S, Kaszkin M. Investigations on the pharmacokinetic properties of Harpagophytum extracts and their effects on eicosanoid biosynthesis in vitro and ex vivo. Clin Pharmacol Ther. 2001;69(5):356-64. doi: 10.1067/mcp.2001.115445.PubMedUsed to support: Harpagophytum extract (WS1531) inhibited stimulated cysteinyl-leukotriene formation in human whole blood in vitro, and after oral dosing in male volunteers basal leukotriene formation showed a biphasic decrease of 28 and 58 percent; peak plasma harpagoside came 1.3 to 2.5 hours after intake. This is a biomarker study, not a clinical outcome trial.
  10. Moussard C, Alber D, Toubin MM, Thevenon N, Henry JC. A drug used in traditional medicine, harpagophytum procumbens: no evidence for NSAID-like effect on whole blood eicosanoid production in human. Prostaglandins Leukot Essent Fatty Acids. 1992;46(4):283-6. doi: 10.1016/0952-3278(92)90036-i.PubMedUsed to support: In 25 healthy volunteers taking Devil's Claw powder (4 x 500 mg daily, 3% glucoiridoids) for 21 days, serum PGE2, thromboxane B2, 6-keto-PGF1alpha and LTB4 did not change significantly; the authors concluded it lacks NSAID-like effects on arachidonic acid metabolism in healthy humans.
  11. Mahomed IM, Ojewole JA. Analgesic, antiinflammatory and antidiabetic properties of Harpagophytum procumbens DC (Pedaliaceae) secondary root aqueous extract. Phytother Res. 2004;18(12):982-9. doi: 10.1002/ptr.1593.PubMedUsed to support: Animal study: aqueous Devil's Claw root extract given by intraperitoneal injection (50-800 mg/kg) lowered blood glucose in fasted normal and streptozotocin-diabetic rats and was analgesic and anti-inflammatory in rodent models. Basis for the diabetes-medication caution; not tested in humans.
  12. Circosta C, Occhiuto F, Ragusa S, Trovato A, Tumino G, Briguglio F, de Pasquale A. A drug used in traditional medicine: Harpagophytum procumbens DC. II. Cardiovascular activity. J Ethnopharmacol. 1984;11(3):259-74. doi: 10.1016/0378-8741(84)90072-2.PubMedUsed to support: Animal study: methanolic Devil's Claw root extract lowered blood pressure and heart rate in conscious rats at high oral doses, altered contractility of isolated rabbit heart, and protected against chemically induced arrhythmias. Basis for the cardiac-medication caution; human relevance is unknown.
  13. Mahomed IM, Ojewole JA. Uterotonic effect of Harpagophytum procumbens DC (Pedaliaceae) secondary root aqueous extract on rat isolated uterine horns. J Smooth Muscle Res. 2009;45(5):231-9. doi: 10.1540/jsmr.45.231.PubMedUsed to support: In vitro study: aqueous Devil's Claw root extract raised baseline tone and caused powerful contractions of isolated uterine muscle strips from non-pregnant and pregnant rats, consistent with its traditional South African use to induce labour. Basis for avoiding use in pregnancy.
  14. Schulze-Tanzil G, Hansen C, Shakibaei M. [Effect of a Harpagophytum procumbens DC extract on matrix metalloproteinases in human chondrocytes in vitro]. Arzneimittelforschung. 2004;54(4):213-20. doi: 10.1055/s-0031-1296962.PubMedUsed to support: In vitro study (article in German): Devil's Claw secondary root extracts (Jucurba and Jucurba forte) significantly reduced production of the cartilage-degrading enzymes MMP-1, MMP-3 and MMP-9 in untreated and IL-1beta-stimulated human chondrocytes. Lab data only, not a Flexigo product, and not evidence of cartilage protection in people.
  15. Haseeb A, Ansari MY, Haqqi TM. Harpagoside suppresses IL-6 expression in primary human osteoarthritis chondrocytes. J Orthop Res. 2017;35(2):311-320. doi: 10.1002/jor.23262.PubMedUsed to support: In vitro study in primary human osteoarthritis chondrocytes: pre-treatment with harpagoside inhibited IL-1beta-induced IL-6 and MMP-13 expression by suppressing c-FOS/AP-1 activity (NF-kB and C/EBPbeta activation were not inhibited). Cell data only, not evidence of cartilage protection in people.
  16. Kim JY, Cheon YH, Ahn SJ, Kwak SC, Chung CH, Lee CH, Lee MS. Harpagoside attenuates local bone Erosion and systemic osteoporosis in collagen-induced arthritis in mice. BMC Complement Med Ther. 2022;22(1):214. doi: 10.1186/s12906-022-03694-y.PubMedUsed to support: Mouse study of collagen-induced arthritis (a rheumatoid arthritis model): harpagoside lowered clinical scores and serum TNF-alpha, IL-6 and IL-1beta, and histology showed less local destruction of bone and cartilage. Pure compound in animals, not a Devil's Claw extract or Flexigo, and not tested in people.
  17. Wachsmuth L, Lindhorst E, Wrubel S, Hadzhiyski H, Hudelmaier M, Eckstein F, Chrubasik S. Micro-morphometrical assessment of the effect of Harpagophytum procumbens extract on articular cartilage in rabbits with experimental osteoarthritis using magnetic resonance imaging. Phytother Res. 2011;25(8):1133-40. doi: 10.1002/ptr.3410.PubMedUsed to support: Rabbit study (16 animals, 8 given a proprietary Devil's Claw extract) after surgically induced knee osteoarthritis: MRI showed the loss of medial tibial cartilage thickness and volume was slightly but not significantly smaller in the extract group, so in vivo cartilage protection was not demonstrated.
  18. 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. doi: 10.1089/acm.2006.12.981.PubMedUsed to support: Review of 14 clinical studies of Devil's Claw in osteoarthritis: 8 observational studies, 2 comparator trials and 4 double-blind, placebo-controlled randomized trials. Many trials lacked important quality criteria; the higher quality studies suggested Devil's Claw reduced pain, but the authors rated the methodological quality as generally poor and concluded the evidence cannot give a definitive answer on efficacy or safety. Devil's Claw generally, not Flexigo.
  19. 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):118-29. doi: 10.1046/j.1365-2346.1999.00435.x.PubMedUsed to support: Randomized, double-blind, placebo-controlled 4-week trial in 197 adults with flare-ups of chronic low back pain: Harpagophytum extract WS 1531 at 600 or 1,200 mg a day (50 or 100 mg harpagoside). More patients were pain free without rescue medication on the extract (3 placebo, 6 and 10 on the two doses; p = 0.027). Low back pain only, not Flexigo.
  20. Göbel 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]. Schmerz. 2001;15(1):10-8. doi: 10.1007/s004820170043.PubMedUsed to support: Randomized, double-blind, placebo-controlled 4-week trial (article in German) in 63 adults with slight to moderate muscle tension or mild muscle pain of the back, shoulder and neck: 480 mg twice a day of Harpagophytum extract LI 174 improved pain ratings, pressure pain, muscle stiffness and global scores compared with placebo. Not an athletic population and not Flexigo.
  21. European Medicines Agency, Committee on Herbal Medicinal Products (HMPC). European Union herbal monograph on Harpagophytum procumbens DC. and/or Harpagophytum zeyheri Decne., radix (EMA/HMPC/627057/2015) European Medicines Agency. 2016;Final monograph, 12 July 2016..SourceUsed to support: Not PubMed-indexed (EU regulatory monograph). Lists hypersensitivity and active gastric or duodenal ulcer as contraindications, without stating a reason; advises people with gallstones to consult a physician before use; states use under 18 has not been established and safety in pregnancy and lactation has not been established; reports no known interactions.