Willow

The medicine is the bark of young branches, stripped and dried ^{1Reference 1European Medicines Agency · 2017ReviewAssessment report on Salix [various species including S. purpurea L., S. daphnoides Vill., S. fragilis L.], cortex — regulatory monographView study →}. Dioscorides wrote of the willow’s medicinal uses in the first century AD, and Paracelsus did again in the sixteenth century. From the eighteenth century willow bark was a standard remedy for fever ^{1Reference 1European Medicines Agency · 2017ReviewAssessment report on Salix [various species including S. purpurea L., S. daphnoides Vill., S. fragilis L.], cortex — regulatory monographView study →}.

It has traditionally been used for muscular and joint rheumatism with pain and inflammation, for gouty arthritis, and for influenza and respiratory catarrh ^{1Reference 1European Medicines Agency · 2017ReviewAssessment report on Salix [various species including S. purpurea L., S. daphnoides Vill., S. fragilis L.], cortex — regulatory monographView study →}. The German Commission E approved it in 1984 for feverish illness, rheumatic complaints and headache ^{1Reference 1European Medicines Agency · 2017ReviewAssessment report on Salix [various species including S. purpurea L., S. daphnoides Vill., S. fragilis L.], cortex — regulatory monographView study →}.

Interest in the bark fell away once salicin had been identified and salicylic acid and then aspirin were made from it. It returned in the late twentieth century, with demand for herbal pain remedies that are better tolerated than conventional anti-inflammatory drugs ^{1Reference 1European Medicines Agency · 2017ReviewAssessment report on Salix [various species including S. purpurea L., S. daphnoides Vill., S. fragilis L.], cortex — regulatory monographView study →}.

In a 4-week double-blind trial, 210 patients with an exacerbation of chronic low back pain received extract standardized to 120 mg or 240 mg salicin, or placebo. In the final week, 39% of the high-dose group were pain-free, against 21% on the low dose and 6% on placebo (P < 0.001). The high-dose response was evident after one week ^{2Reference 2Chrubasik et al. · 2000RCTTreatment of low back pain exacerbations with willow bark extract: a randomized double-blind study — RCTView study →}.

An open randomized comparison in 228 patients found no significant difference between the 240 mg salicin dose and the COX-2 inhibitor rofecoxib 12.5 mg/day ^{4Reference 4Chrubasik et al. · 2001RCTTreatment of low back pain with a herbal or synthetic anti-rheumatic: a randomized controlled study — RCTView study →}.

A 2014 Cochrane review concluded that Salix alba standardized to 120–240 mg salicin is “probably better than placebo for short-term improvements in pain and rescue medication” and graded this moderate quality. It graded the rofecoxib comparison very low quality ^{3Reference 3Oltean et al. · 2014Systematic reviewHerbal medicine for low-back pain — Cochrane systematic reviewView study →}.

A systematic review reached a “moderate evidence” verdict for the ethanolic extract in low back pain ^{5Reference 5Vlachojannis et al. · 2009Systematic reviewA systematic review on the effectiveness of willow bark for musculoskeletal pain — systematic reviewView study →}.

Gap: All trials are short (≤ 6 weeks) and use salicin-standardized extracts; there is no long-term data and no evidence that teas or non-standardized products reproduce the effect.

In two rat models (air-pouch and adjuvant arthritis) the standardized extract STW 33-I reduced leukocyte infiltration, cytokines and prostaglandins at least as effectively as aspirin on a mg/kg basis. It suppressed leukotrienes more strongly than aspirin, and was more effective against COX-2 ^{10Reference 10Khayyal et al. · 2005AnimalMechanisms involved in the anti-inflammatory effect of a standardized willow bark extract — animal model (rat)View study →}.

In LPS-activated human monocytes and macrophages the aqueous extract lowered TNF-α, COX-2 and nitric oxide, and blocked NF-κB from entering the nucleus ^{12Reference 12Bonaterra et al. · 2010In vitroAnti-inflammatory effects of the willow bark extract STW 33-I in LPS-activated human monocytes and differentiated macrophages — in vitroView study →}. A pharmacological screen of the extract’s fractions found the polyphenol and flavonoid fractions contribute to the effect alongside salicin ^{11Reference 11Nahrstedt et al. · 2007ReviewWillow bark extract: the contribution of polyphenols to the overall effect — reviewView study →}. Salicin metabolites lack aspirin’s acetylating action, and the salicylic acid reaching the blood is too low to account for the full effect ^{11,19Reference 11Nahrstedt et al. · 2007ReviewWillow bark extract: the contribution of polyphenols to the overall effect — reviewView study →Reference 19Untergehrer et al. · 2019Identification of phase-II metabolites from human serum samples after oral intake of a willow bark extract — human pharmacokineticView study →}.

In THP-1 macrophages an aqueous willow bark extract lowered IL-6 and TNF-α, more strongly than meadowsweet or chamomile extracts ^{13Reference 13Drummond et al. · 2013In vitroInhibition of proinflammatory biomarkers in THP-1 macrophages by polyphenols derived from chamomile, meadowsweet and willow bark — in vitroView study →}.

The one direct human test gave 20 healthy adults a drink combining willow with chamomile and meadowsweet for 4 weeks. IL-1β fell by 21.7%, against 3% on the berry-extract control, but the difference was not statistically significant, and the study found no clear anti-inflammatory effect ^{14Reference 14Drummond et al. · 2013RCTAn in vivo study examining the anti-inflammatory effects of chamomile, meadowsweet, and willow bark in a novel functional beverage — randomised human trialView study →}.

No trial has shown willow bark on its own lowering inflammatory markers in people. The anti-inflammatory findings come from animal and cell-culture models.

Human osteoarthritis data conflict. A 2-week placebo-controlled RCT (n = 78) at 240 mg salicin/day found a statistically significant but modest reduction in WOMAC pain (−14% vs +2% on placebo; difference 6.5 mm, P = 0.047), with good tolerability ^{6Reference 6Schmid et al. · 2001RCTEfficacy and tolerability of a standardized willow bark extract in patients with osteoarthritis: randomized placebo-controlled, double-blind clinical trial — RCTView study →}.

A larger 6-week trial (n = 127, hip or knee osteoarthritis) found willow bark no better than placebo (−2.8 mm, P = 0.55), while the diclofenac comparator was clearly effective. Its parallel rheumatoid-arthritis trial was also negative, but had only 26 patients ^{7Reference 7Biegert et al. · 2004RCTEfficacy and safety of willow bark extract in the treatment of osteoarthritis and rheumatoid arthritis: results of 2 randomized double-blind controlled trials — RCTView study →}.

A 2023 meta-analysis of six arthritis RCTs (329 patients) reported significant pooled pain relief versus placebo, but rated the certainty inadequate because of risk of bias ^{8Reference 8Lin et al. · 2023Meta-analysisWillow bark (Salix spp.) used for pain relief in arthritis: a meta-analysis of randomized controlled trials — meta-analysisView study →}.

In an open observational study with a reference group, 90 patients with knee or hip osteoarthritis took willow bark extract and 41 took standard treatment. Doctors and patients rated the two as comparably effective, with willow slower to act and better tolerated ^{9Reference 9Beer et al. · 2008ObservationalWillow bark extract (Salicis cortex) for gonarthrosis and coxarthrosis — results of a cohort study with a control group — cohort/observationalView study →}.

Gap: The best-powered RCT was negative; positive results come from a short small trial and a low-certainty meta-analysis. Whether a dose above 240 mg salicin/day is needed for arthritis remains untested ^{5Reference 5Vlachojannis et al. · 2009Systematic reviewA systematic review on the effectiveness of willow bark for musculoskeletal pain — systematic reviewView study →}.

Willow bark and wood extracts show radical-scavenging capacity in standard in-vitro assays. The characterised material came from Salix purpurea and S. viminalis rather than S. alba, and from combined bark-plus-wood fractions ^{15Reference 15Ostolski et al. · 2021In vitroAntioxidant activity and chemical characteristics of supercritical CO2 and water extracts from willow and poplar — in vitroView study →}.

In the rat arthritis model the standardized extract raised reduced glutathione and lowered lipid-peroxidation markers more than aspirin or celecoxib. The authors linked this to the extract’s polyphenols ^{10Reference 10Khayyal et al. · 2005AnimalMechanisms involved in the anti-inflammatory effect of a standardized willow bark extract — animal model (rat)View study →}.

No human antioxidant endpoint has been measured.

Willow bark extract and its fractions inhibited growth and induced apoptosis in human colon cancer cells (COX-2-positive HT-29 and COX-2-negative HCT-116) and lung cancer cells. The salicylalcohol-derivative, flavonoid and proanthocyanidin fractions were all active ^{18Reference 18Hostanska et al. · 2007In vitroWillow bark extract (BNO 1455) and its fractions suppress growth and induce apoptosis in human colon and lung cancer cells — in vitroView study →}.

A separate study of the STW 33-I extract and a polyphenol-rich fraction found anti-proliferative and pro-apoptotic effects in HT-29 colon cancer cells, similar to those reported for aspirin ^{17Reference 17Bonaterra et al. · 2010In vitroIn vitro anti-proliferative effects of the willow bark extract STW 33-I — in vitroView study →}.

Gap: Cell-culture only — no animal tumor data and no human evidence.

A highly purified 2,3-trans procyanidin fraction from willow bark relaxed pre-contracted porcine coronary arteries in a concentration-dependent way. The effect depended on the endothelium and worked through redox-sensitive PI3-kinase/Akt signaling and nitric oxide ^{16Reference 16Kaufeld et al. · 2014In vitroA chemically defined 2,3-trans procyanidin fraction from willow bark causes redox-sensitive endothelium-dependent relaxation in porcine coronary arteries — ex vivo / in vitroView study →}.

The fraction also restored the arteries’ relaxation response after it had been blocked by oxidised LDL ^{16Reference 16Kaufeld et al. · 2014In vitroA chemically defined 2,3-trans procyanidin fraction from willow bark causes redox-sensitive endothelium-dependent relaxation in porcine coronary arteries — ex vivo / in vitroView study →}.

This is a single study on isolated arteries, using a purified fraction. The bark as consumed has not been tested for any cardiovascular endpoint.

Allergy. Willow bark should not be taken by anyone allergic to salicylates, aspirin or other NSAIDs, or with asthma triggered by salicylates ^{21Reference 21European Medicines Agency · 2017ReviewEuropean Union herbal monograph on Salix [various species including S. purpurea L., S. daphnoides Vill., S. fragilis L.], cortex — regulatory monographView study →}. One patient in the main low-back-pain trial had a severe allergic reaction, possibly to the extract ^{2Reference 2Chrubasik et al. · 2000RCTTreatment of low back pain exacerbations with willow bark extract: a randomized double-blind study — RCTView study →}.

Children. The EU monograph rules out willow bark under the age of 18, because of the risk of Reye’s syndrome ^{21Reference 21European Medicines Agency · 2017ReviewEuropean Union herbal monograph on Salix [various species including S. purpurea L., S. daphnoides Vill., S. fragilis L.], cortex — regulatory monographView study →}.

Bleeding and blood thinners. Willow bark may increase the effect of coumarin anticoagulants such as warfarin, and it is ruled out with coagulation disorders ^{21Reference 21European Medicines Agency · 2017ReviewEuropean Union herbal monograph on Salix [various species including S. purpurea L., S. daphnoides Vill., S. fragilis L.], cortex — regulatory monographView study →}. Its effect on platelets is much weaker than aspirin’s. In one study, arachidonic-acid-induced platelet aggregation was 61% on willow bark extract (240 mg salicin), 78% on placebo and 13% on 100 mg aspirin ^{20Reference 20Krivoy et al. · 2001Clinical trialEffect of Salicis cortex extract on human platelet aggregation — controlled human studyView study →}.

Other conditions. It is ruled out with an active peptic ulcer, G6PD deficiency, and severe liver or kidney disease ^{21Reference 21European Medicines Agency · 2017ReviewEuropean Union herbal monograph on Salix [various species including S. purpurea L., S. daphnoides Vill., S. fragilis L.], cortex — regulatory monographView study →}.

Other painkillers. Taking it with other salicylates or NSAIDs is not recommended without medical advice ^{21Reference 21European Medicines Agency · 2017ReviewEuropean Union herbal monograph on Salix [various species including S. purpurea L., S. daphnoides Vill., S. fragilis L.], cortex — regulatory monographView study →}.

Drug metabolism. In human liver cells, willow bark extracts reduced the activity of the drug-metabolising enzymes CYP1A2, CYP3A4 and CYP2C19 at high concentrations; this has not been studied in people ^{24Reference 24Gomes et al. · 2021In vitroDrug-Drug Interaction Potential, Cytotoxicity, and Reactive Oxygen Species Production of Salix Cortex Extracts Using Human Hepatocyte-Like HepaRG Cells — in vitroView study →}. In another cell study, a white willow infusion raised the expression of the CYP3A4 gene ^{25Reference 25Mazzari et al. · 2022In vitroIn vitro effects of European and Latin-American medicinal plants in CYP3A4 gene expression, glutathione levels, and P-glycoprotein activity — in vitroView study →}.

Side effects. Reported side effects include rashes, itching and other allergic reactions, and digestive upsets such as nausea, heartburn and diarrhoea ^{21Reference 21European Medicines Agency · 2017ReviewEuropean Union herbal monograph on Salix [various species including S. purpurea L., S. daphnoides Vill., S. fragilis L.], cortex — regulatory monographView study →}. Across the controlled trials the extract was generally well tolerated ^{5,6Reference 5Vlachojannis et al. · 2009Systematic reviewA systematic review on the effectiveness of willow bark for musculoskeletal pain — systematic reviewView study →Reference 6Schmid et al. · 2001RCTEfficacy and tolerability of a standardized willow bark extract in patients with osteoarthritis: randomized placebo-controlled, double-blind clinical trial — RCTView study →}.