Osteoarthritis and Joint Pain

Osteoarthritis is the flagship use for devil's claw, and it is the one where the trials are longest. The centrepiece is a four-month, multicentre, double-blind randomised trial in 122 people with knee or hip osteoarthritis, in which devil's claw was compared not with a sugar pill but with a prescription osteoarthritis drug. That is a serious study design, and it produced a result worth knowing about. It also has a structural limitation that most write-ups skip over, and this article does not.

Table of Contents

1. What Osteoarthritis Is, and What a Herb Can Do About It
2. The Four-Month Trial Against Diacerein
3. The NSAID Question — Diclofenac and Rofecoxib, Stated Precisely
4. The Doloteffin Studies — 250 Patients and 75 Patients
5. The 259-Patient Open Study, and What “Open” Costs You
6. What the Systematic Reviews Concluded
7. Why It Might Work — the Laboratory Story
8. The Doses Actually Used in the Osteoarthritis Trials
9. How to Run a Fair Eight-to-Twelve Week Trial on Yourself
10. Cautions That Matter Specifically in Osteoarthritis
11. The Bottom Line
12. Key Research Papers
13. Connections

What Osteoarthritis Is, and What a Herb Can Do About It

Osteoarthritis is not simply cartilage wearing out. It is a whole-joint disease: the cartilage thins and fissures, the bone underneath thickens and grows spurs, the joint lining (synovium) becomes intermittently inflamed, ligaments loosen, and the muscles around the joint weaken. The pain comes partly from that low-grade synovial inflammation and partly from bone, capsule and nerve changes — which is why the amount of damage on an X-ray correlates so poorly with how much a person hurts.

That matters for what to expect from devil's claw. A plant extract with anti-inflammatory activity has a plausible target: the inflammatory component of the pain. It has no plausible route to regrowing cartilage, and nobody has shown it does. Every honest claim about devil's claw in osteoarthritis is a claim about symptoms — pain, stiffness, how far you can walk, how much paracetamol or ibuprofen you end up taking — over weeks to months.

If you are being told devil's claw “rebuilds joints,” “reverses arthritis” or “regenerates cartilage,” the seller has left the evidence behind. There is no imaging trial, no joint-space-width endpoint, no biomarker study supporting any of that.

The Four-Month Trial Against Diacerein

The single most important osteoarthritis study on devil's claw was run by a French group and published twice in 2000 — once in a phytotherapy journal and once in a rheumatology journal, with slightly different emphasis. The design:

• Participants: 122 patients with osteoarthritis of the knee and/or hip.
• Design: multicentre, randomised, double-blind, parallel-group.
• Duration: four months — long by herbal-trial standards.
• Devil's claw arm: Harpadol, six capsules per day, each containing 435 mg of cryoground devil's claw root powder — 2,610 mg of powdered root daily. Note that this was crude cryoground powder, not a concentrated extract.
• Comparator arm: diacerein 100 mg/day — a slow-acting anti-inflammatory used for osteoarthritis in parts of Europe, which works through interleukin-1 inhibition.
• Endpoints: spontaneous pain on a 10 cm visual analogue scale, functional disability, and the Lequesne index of osteoarthritis severity.

What it found

Both groups improved significantly and progressively over the four months, on pain, on functional disability and on the Lequesne index — and there was no statistically significant difference between them on any efficacy measure. Devil's claw held its own against the drug.

Two secondary findings were arguably more interesting than the primary one. By the end of the study, patients in the devil's claw group were using significantly fewer rescue analgesics and non-steroidal anti-inflammatories than the diacerein group. And adverse events were significantly less frequent on devil's claw: diarrhoea, the commonest complaint in both arms, occurred in 8.1 percent of the devil's claw group versus 26.7 percent of the diacerein group. Patients' own global tolerance rating favoured devil's claw.

The limitation nobody mentions

Here is the structural problem: there was no placebo arm. Osteoarthritis pain is famously responsive to placebo — meta-analyses of osteoarthritis trials routinely find large placebo responses, and a four-month study with regular clinic visits and attentive investigators is exactly the setting that maximises them. Both groups improving substantially is therefore consistent with two very different stories:

1. Devil's claw and diacerein are both genuinely effective and roughly equal, or
2. Neither did much beyond what an inert capsule plus four months of attention would have done.

This trial cannot distinguish those. What it establishes solidly is non-inferiority to diacerein with better tolerability — which is a real and useful finding, especially because diacerein itself has been repeatedly questioned and restricted in Europe over efficacy and diarrhoea. Being as good as a modest drug is not the same as being proven effective. Say that out loud and the literature becomes much easier to read.

The NSAID Question — Diclofenac and Rofecoxib, Stated Precisely

Devil's claw is often described as “tested against diclofenac and rofecoxib.” Two different things are being blurred together there, and the distinction is worth getting right.

So: there is no adequately powered randomised trial of devil's claw against diclofenac, or against ibuprofen, or against naproxen, in osteoarthritis. Anyone who tells you devil's claw “matched diclofenac” is over-reading a rescue-medication count. The rofecoxib pilot is covered properly in the low back pain article, because that is the condition it studied.

The analgesic-sparing signal is still worth something. If you take an NSAID daily for knee osteoarthritis, needing less of it is a genuinely valuable outcome — NSAIDs carry gastrointestinal bleeding, kidney and cardiovascular risks that accumulate with dose and duration, and those risks fall as the dose falls.

The Doloteffin Studies — 250 Patients and 75 Patients

A German group ran a series of post-marketing surveillance studies on a proprietary aqueous extract called Doloteffin. These are not randomised trials, and the authors did not pretend otherwise, but they are large and they report their dose properly.

The 250-patient study

250 patients with either non-specific low back pain (n = 104), knee osteoarthritis (n = 85) or hip osteoarthritis (n = 61) took an eight-week course of Doloteffin providing 60 mg of harpagoside per day. 227 completed. Every outcome measure — validated ones like the WOMAC index and the Arhus index, plus generic quality-of-life measures — improved by week four and improved further by week eight.

Two details from this study are genuinely informative. The hip group improved more convincingly than the back group; the knee group sat in between. And among the back-pain patients who needed NSAIDs during the eight weeks, NSAID use declined with time. Roughly 10 percent of patients had minor adverse events possibly attributable to the extract. The authors' summary was that between 50 and 70 percent of patients benefited.

That last figure needs a translation. “50 to 70 percent benefited” in an open study is not the same as “50 to 70 percent benefited because of the herb.” With no control group, the natural history of an osteoarthritis flare, regression to the mean, and expectation are all folded into that number.

The 75-patient study

A separate 12-week multicentre surveillance study enrolled 75 patients with hip or knee arthrosis and gave 2,400 mg of aqueous extract daily, corresponding to 50 mg of harpagoside. The WOMAC subscales fell by 23.8 percent for pain, 22.2 percent for stiffness and 23.1 percent for physical function; the total WOMAC index fell 22.9 percent. Visual-analogue pain scores dropped by 22–26 percent depending on which pain question was asked. Physicians recorded improvement in pain on palpation (45.5 percent), limitation of mobility (35 percent) and joint crepitus (25.4 percent). Only two possible adverse drug reactions were reported, both digestive: dyspepsia and a sensation of fullness.

A 23 percent fall in WOMAC is a clinically meaningful size — it is roughly what you would hope for from an NSAID. But again: uncontrolled, open, and industry-adjacent. The authors said so themselves in their conclusion, writing that the results “suggest” a beneficial effect.

The 259-Patient Open Study, and What “Open” Costs You

The largest devil's claw study in a British population enrolled 259 patients with arthritis and other rheumatic conditions in a single-group open study lasting eight weeks. It measured global pain, stiffness and function on numeric rating scales, plus the WOMAC index and a hand-osteoarthritis index, with safety assessed by self-report, blood analysis and liver function tests.

Results were strongly positive: statistically significant improvements (p < 0.0001) in global pain, stiffness and function; significant reductions in pain scores for hand, wrist, elbow, shoulder, hip, knee and back; significant improvement in SF-12 quality of life; and — the headline that gets quoted everywhere — 60 percent of patients either reduced or stopped their concomitant pain medication.

Now the honest reading. A single-group open study has no comparison. Every patient knew what they were taking, every patient had signed up hoping it would help, and every patient was being seen and assessed regularly for eight weeks. The p-value of 0.0001 tells you the improvement was very unlikely to be chance variation; it tells you nothing about whether the herb caused it. A placebo arm in the same study would almost certainly also have improved significantly.

What the study does contribute solidly is safety data in a decent-sized real-world population, including bloods and liver function — and there the news was reassuring. Read it as a tolerability study with encouraging efficacy signals, not as proof of effect.

What the Systematic Reviews Concluded

Reviewers who pooled this literature converged on a similar verdict, and it has barely moved in twenty years.

• The 2004 systematic review covering both osteoarthritis and low back pain found moderate evidence of effectiveness, while flagging that the trials differed in extract, dose, duration and quality — and that several were methodologically weak.
• The 2006 osteoarthritis review judged devil's claw promising, with an acceptable safety profile, and called for larger, better-designed trials. Those trials have still not been done.
• The 2019 overview of preclinical and clinical data reached the same place: plausible mechanism, supportive but heterogeneous clinical data, need for standardised preparations and better trials.
• A critique of trial quality published in 2003 — written, notably, by the field's most prolific investigator — catalogued the methodological problems in the existing studies rather than defending them.

The most telling verdict is the regulatory one. As set out on the Benefits hub, the European Medicines Agency's herbal committee reviewed this entire body of work and kept devil's claw in the traditional use category rather than promoting it to well-established use — declining an explicit industry request to reclassify it during the 2016 revision. If the osteoarthritis evidence had been strong enough, that is where it would have shown.

Why It Might Work — the Laboratory Story

The mechanistic work is genuinely interesting, and it is genuinely preclinical. Label it as such.

• Cytokine suppression. Devil's claw extract inhibited synthesis of TNF-α in lipopolysaccharide-stimulated primary human monocytes — human cells, but in a dish.
• Transcription-factor level action. A 2012 study found the extract suppressed TNF-α and COX-2 gene expression by preventing activation of AP-1, a transcription factor. That is upstream of the enzyme itself — a different mechanism from the way ibuprofen blocks COX enzyme activity directly.
• NF-κB. Purified harpagoside suppressed inducible nitric oxide synthase and COX-2 expression through inhibition of NF-κB activation.
• Antioxidant effects. Devil's claw preparations inhibited free-radical generation in vitro.
• Whole-animal analgesia. An aqueous extract showed anti-inflammatory and analgesic effects in classical rodent models.

The gap between all that and a human knee is the concentration problem. Cell studies use concentrations achieved by pipetting extract into a well. Whether swallowing a capsule produces anything like those concentrations in synovial fluid has not been demonstrated, and harpagoside's behaviour in the acidic stomach complicates the question further — see the dosing article. Treat “devil's claw is anti-inflammatory” as a well-supported hypothesis, not an established fact about people.

The Doses Actually Used in the Osteoarthritis Trials

Notice the convergence: where harpagoside was reported, it was 50 to 60 mg per day. That band is the practical target. Turning any given label into that number is arithmetic, and the dosing article works it through step by step.

How to Run a Fair Eight-to-Twelve Week Trial on Yourself

Devil's claw is cheap, generally well tolerated and slow-acting. That combination makes a structured personal trial reasonable — provided nothing in the cautions below applies to you and your doctor knows.

1. Buy on harpagoside, not on price or milligrams of root. Find a product that states its harpagoside content and work out how many units per day reach 50–60 mg. If the label will not let you do that sum, buy a different product.
2. Write down a baseline before you start. Three numbers, each 0–10: worst pain in the last week, average pain in the last week, and how much the joint limits what you do. Add one function marker you can actually measure — how many stairs, how far you walk before stopping, whether you can open a jar.
3. Record what else you take. Count your paracetamol and NSAID tablets for a week before starting. Reduced painkiller use was one of the most consistent findings in the trials, and it is easier to notice than a two-point pain change.
4. Give it eight weeks minimum, twelve if you can. The surveillance studies showed improvement at four weeks and more at eight. Judging it at day five is judging the wrong thing.
5. Change one thing at a time. Starting devil's claw, a new exercise programme and turmeric in the same week guarantees you will learn nothing.
6. Take it with food if your stomach objects. Digestive upset is the main reason people quit, and food usually fixes it.
7. Score again at week eight, against the same numbers. If nothing has moved — pain, function, or tablet count — stop. Devil's claw does not work for everybody, and continuing to pay for a supplement that is doing nothing is its own kind of harm.
8. Keep doing the thing that actually works. For knee and hip osteoarthritis, the interventions with the strongest evidence are exercise therapy, strength training around the joint and weight management. No herb replaces those. Devil's claw is at best a useful addition at the margin.

Cautions That Matter Specifically in Osteoarthritis

The full safety discussion is in the safety, interactions and sustainability article. Three of those cautions are disproportionately relevant to people with osteoarthritis, because of who tends to have it.

• You are probably older, and more likely to be on warfarin or another anticoagulant. Atrial fibrillation, prior clots and valve disease all cluster in the same age range as osteoarthritis. Devil's claw has a plausible and case-reported interaction with warfarin. Do not add it silently.
• You may already be on an NSAID and a stomach-protective drug. Devil's claw stimulates gastric acid. If you are on a proton-pump inhibitor because an NSAID upset your stomach, adding an acid-stimulating bitter is working against yourself. Discuss it.
• Heart rhythm and rate-control drugs. Animal work found dose-dependent falls in heart rate and blood pressure and effects on cardiac conduction. If you take an antiarrhythmic, digoxin, or a beta-blocker for rate control, treat devil's claw as something to clear with your prescriber first.

Add the standard ones: avoid in active peptic ulcer disease, gastritis and gallstones; avoid in pregnancy; stop a week or two before planned surgery and tell the surgical team.

The Bottom Line

For knee and hip osteoarthritis, devil's claw has the best evidence base of almost any single herb sold for the condition — a four-month randomised double-blind trial showing it matched a prescription drug with fewer side effects, plus several hundred patients' worth of open surveillance data showing WOMAC improvements around 20 percent and substantial reductions in painkiller use.

And: the pivotal trial had no placebo arm, the supporting studies were open and uncontrolled, no adequately powered head-to-head against a common NSAID exists, the European regulator declined to promote it out of the traditional-use category, and the effect — where real — is modest and symptomatic.

A fair summary is that devil's claw is a reasonable, low-risk thing to try for eight to twelve weeks at 50–60 mg of harpagoside a day, particularly if your goal is to lean less heavily on anti-inflammatory tablets, and particularly if you have checked the cautions. It is not a substitute for exercise therapy, weight management or a proper assessment of your joint. And if it has not moved any of your numbers by week twelve, it is not going to.

Key Research Papers

Every identifier below was verified live against NCBI E-utilities — first author, title, journal and year all had to match before the number was written.

The randomised comparison trials

1. 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):177–183.
2. Leblan D, Chantre P, Fournié 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.
3. 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):141–148.

Open and surveillance studies

1. Chrubasik S, Thanner J, Künzel O, Conradt C, Black A, Pollak S. Comparison of outcome measures during treatment with the proprietary Harpagophytum extract Doloteffin in patients with pain in the lower back, knee or hip. Phytomedicine. 2002;9(3):181–194.
2. Wegener T, Lüpke NP. Treatment of patients with arthrosis of hip or knee with an aqueous extract of devil's claw (Harpagophytum procumbens DC.). Phytotherapy Research. 2003;17(10):1165–1172.
3. Warnock M, McBean D, Suter A, Tan J, Whittaker P. Effectiveness and safety of devil's claw tablets in patients with general rheumatic disorders. Phytotherapy Research. 2007;21(12):1228–1233.
4. Chrubasik S, Chrubasik C, Künzel O, Black A. Patient-perceived benefit during one year of treatment with Doloteffin. Phytomedicine. 2007;14(6):371–376.

Reviews and critical appraisal

1. Gagnier JJ, Chrubasik S, Manheimer E. Harpagophytum procumbens for osteoarthritis and low back pain: a systematic review. BMC Complementary and Alternative Medicine. 2004;4:13.
2. Brien S, Lewith GT, McGregor G. Devil's claw (Harpagophytum procumbens) as a treatment for osteoarthritis: a review of efficacy and safety. Journal of Alternative and Complementary Medicine. 2006;12(10):981–993.
3. Chrubasik S, Conradt C, Black A. The quality of clinical trials with Harpagophytum procumbens. Phytomedicine. 2003;10(6–7):613–623.
4. Chrubasik JE, Roufogalis BD, Chrubasik S. Evidence of effectiveness of herbal antiinflammatory drugs in the treatment of painful osteoarthritis and chronic low back pain. Phytotherapy Research. 2007;21(7):675–683.
5. Denner SS. A review of the efficacy and safety of devil's claw for pain associated with degenerative musculoskeletal diseases, rheumatoid, and osteoarthritis. Holistic Nursing Practice. 2007;21(4):203–207.
6. Menghini L, Recinella L, Leone S, et al. Devil's claw (Harpagophytum procumbens) and chronic inflammatory diseases: a concise overview on preclinical and clinical data. Phytotherapy Research. 2019;33(9):2152–2162.

Mechanism — laboratory and animal work

1. 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. Phytotherapy Research. 2012;26(6):806–811.
2. Fiebich BL, Heinrich M, Hiller KO, Kammerer N. Inhibition of TNF-alpha synthesis in LPS-stimulated primary human monocytes by Harpagophytum extract SteiHap 69. Phytomedicine. 2001;8(1):28–30.
3. Huang TH, Tran VH, Duke RK, et al. Harpagoside suppresses lipopolysaccharide-induced iNOS and COX-2 expression through inhibition of NF-kappaB activation. Journal of Ethnopharmacology. 2006;104(1–2):149–155.
4. Grant L, McBean DE, Fyfe L, Warnock AM. The inhibition of free radical generation by preparations of Harpagophytum procumbens in vitro. Phytotherapy Research. 2009;23(1):104–110.
5. Lanhers MC, Fleurentin J, Mortier F, Vinche A, Younos C. Anti-inflammatory and analgesic effects of an aqueous extract of Harpagophytum procumbens. Planta Medica. 1992;58(2):117–123.
6. Kaur H, Kumar D, Gauttam VK, et al. Decoding the mechanistic landscape of harpagoside: from molecular targets to translational pharmacology. Fitoterapia. 2026;188:107029.

Live PubMed Searches

1. Harpagophytum and osteoarthritis
2. Devil's claw and knee pain
3. Harpagophytum and WOMAC index
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5. Diacerein in osteoarthritis
6. Herbal medicine for osteoarthritis, randomised trials
7. Placebo response in osteoarthritis trials
8. Exercise therapy for knee osteoarthritis

Connections

• All Herbs
• Devil's Claw Benefits — hub
• Low Back Pain — the placebo-controlled trials
• Harpagoside, Dosing and Extract Types
• Safety, Interactions and Sustainability
• Devil's Claw — main topic page
• Osteoarthritis
• Orthopedics
• Rheumatology
• Boswellia
• Turmeric
• Willow Bark
• Ginger

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