Health Care Professional Information

Scientific Name
Salix alba, Salicis cortex
Common Name

Bay willow, black willow, white willow

Clinical Summary

Willow bark has been used for thousands of years in China and Europe as a remedy for fevers, pain, and inflammation. It contains salicin, the phytotherapeutic precursor of aspirin (acetylsalicylic acid).

Willow bark extracts exert anti-inflammatory (1), antiplatelet (2), and antiproliferative (3) effects. In vitro and animal models also suggest salicin extract from willow bark can produce antitumor and antiangiogenic effects (4). Clinical studies indicate that willow bark may help to manage back pain (5) (6), although studies in osteoarthritis are mixed (7) (8) (9), and possibly negative for rheumatoid arthritis (6) (9). Topical application of salicin may help reduce skin aging (10).

Willow bark supplements can have additive effects with nonsteroidal anti-inflammatory drugs, and therefore should not be given concurrently. Children should not be given willow bark because of the potential for developing Reye syndrome, a serious condition associated with the use of aspirin.

Purported Uses
  • Arthritis
  • Fever
  • Headaches
  • Inflammation
  • Influenza
  • Pain
  • Weight loss
Constituents
  • Salicin and salicin derivatives
  • Catechol
  • Flavonoids
  • Phenols
  • Tannins
  • Ampelopsin, taxifolin, 7-O-methyltaxifolin-3'-O-glucoside, 7-O-methyltaxifolin and ethyl 1-hydroxy-6-oxocyclohex-2-enecarboxylate
    (11) (12) (13)
Mechanism of Action

Although the anti-inflammatory activity of willow bark extract is mostly attributed to salicin (13), catechol and flavonoid compounds are also indicated (12). Willow bark inhibits pro-inflammatory cytokines (tumor necrosis factor [TNF]-alpha), cyclo-oxygenase (COX)-2, and nuclear translocation of transcription factor NF-κB (1). It was also found to significantly raise low glutathione (GSH) levels, thereby limiting lipid peroxidation (14).

Antiproliferative effects on human colon and lung cancer cells are due to growth-inhibition and apoptotic induction (15). In vitro and animal models suggest salicin can inhibit reactive oxygen species (ROS) and extracellular signal-regulated kinase (ERK) signaling pathways to produce antiangiogenic effects (4).

Warnings

Due to potential for bleeding complications (16), willow bark should be discontinued before surgery or chemotherapy.
Those with impaired thrombocyte function should avoid willow bark, as it may interfere with blood clotting (2).

Contraindications

Allergy or sensitivity to salicylates such as aspirin.

Adverse Reactions

Gastrointestinal discomfort; allergic reaction, erythema, pruritus (sudden rash, itching) (5) (7) (17).
May inhibit platelet aggregation or cause bleeding complications (2) (16).

Monitor for aspirin-like toxicities that could occur with frequent use, including tinnitus, nausea or vomiting, and gastrointestinal or kidney irritation.

Case reports
Anaphylaxis: In a 25-year-old woman with a history of allergy to acetylsalicylic acid, from the use of a supplement promoted for weight-loss that contained willow bark (18).

Acute respiratory distress syndrome: In a 61-year-old woman with history of hypertension and osteoarthritis after taking a willow bark supplement. Symptoms included sudden dyspnea and non-productive cough, and there was no history of drug or supplement allergy (19).

Herb-Drug Interactions

Warfarin or other anticoagulants: When used concurrently, willow bark may increase the risk of bleeding (20).

Literature Summary and Critique

Beer AM, Wegener T. Willow bark extract (Salicis cortex) for gonarthrosis and coxarthrosis - Results of a cohort study with a control group. Phytomedicine. 2008 Nov;15(11):907-13.
In this open multicenter study, 88 patients aged 50–75 years with hip and knee osteoarthritis (OA) were treated with a standardized willow bark extract, and 40 patients received standard therapy. Most patients (92%) in the willow bark extract group were prescribed 1.572 g (equivalent to salicin 240 mg). Effectiveness of treatments was determined by clinical findings, recording of adverse events, global tolerance and by patient assessment: Western Ontario and McMaster Universities Arthritis Index (WOMAC) questions concerning pain and stiffness, and questions on general state of health. At 6 weeks from study initiation, researchers reported that the willow bark extract was superior to conventional therapy and well tolerated with no adverse effects.

Biegert C, et al. Efficacy and safety of willow bark extract in the treatment of osteoarthritis and rheumatoid arthritis: results of 2 randomized double-blind controlled trials. J Rheumatol . 2004;31:2121-2130.
This double-blind dual-RCT included the evaluation of standardized willow bark extract in patients with hip or knee OA. A total of 127 patients with WOMAC pain scores ≥30 mm were randomized to receive either willow bark extract (dosage equivalent to salicin 240 mg daily), diclofenac 100 mg daily, or placebo (n=43, 43, 41, respectively). At 6-week follow-up, differences in pain scores for those taking willow bark extract compared with placebo was not statistically significant, while the difference between diclofenac and placebo was highly significant. The investigators also conducted a pilot double-blind RCT to evaluate willow bark for rheumatoid arthritis at the same dosage, which did not show any benefit.

Schmid B, et al. Efficacy and tolerability of a standardized willow bark extract in patients with osteoarthritis: randomized placebo-controlled, double blind clinical trial. Phytother Res. 2001;15:344-350.
Willow bark extract (dosage equivalent to salicin 240 mg daily) was evaluated in this 2-week study to treat osteoarthritis. A total of 78 patients (39 extract, 39 placebo) participated in the trial. Primary outcome measured was WOMAC pain scores. Secondary outcomes included WOMAC stiffness and physical function and visual analogue scale (VAS) pain and physical function scale scores, plus final assessments by both patients and investigators. WOMAC pain score was reduced by 14% from baseline after 2 weeks of active treatment, compared with an increase of 2% in the placebo group, with significant differences between active treatment and placebo for WOMAC pain scores (d=6.5 mm, 95% CI=0.2–12.7 mm, P=.047). VAS and final overall assessments confirmed this result (patients, P=.0002; investigators, P=.0073). Investigators concluded willow bark produced a moderate analgesic effect in osteoarthritis and was well tolerated.

Chrubasik S, et al. Treatment of low back pain exacerbations with willow bark extract: a randomized double-blind study. Am J Med. 2000;109:9-14.
In this 4-week study, a total of 210 patients with exacerbated chronic low back pain were randomly assigned to receive oral willow bark extract, either low- or high-dose (120 mg or 240 mg salicin, respectively), or placebo, with tramadol as a sole rescue medication, in a 4-week blinded trial. Primary outcome measure was the proportion of patients who were pain-free without tramadol for ≥5 days during Week 4. Of 191 patients who completed the study, 27 (39%) of 65 in the high-dose group, 15 (21%) of 67 in the low-dose group, and 4 (6%) of 59 in the placebo group were pain-free during Week 4 (P<.001). Response in the high-dose group was demonstrated after only 1 week of treatment. Significantly more patients in the placebo group required tramadol (P<.001) during each week of the study. One patient in the low-dose group suffered a severe allergic reaction, possibly due to the extract.

Dosage (Inside MSKCC Only)
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References
  1. Bonaterra GA, Heinrich EU, Kelber O, et al. Anti-inflammatory effects of the willow bark extract STW 33-I (Proaktiv((R))) in LPS-activated human monocytes and differentiated macrophages. Phytomedicine. Dec 1 2010;17(14):1106-1113.
  2. Krivoy N, Pavlotzky E, Chrubasik S, et al. Effect of salicis cortex extract on human platelet aggregation. Planta Med. Apr 2001;67(3):209-212.
  3. Bonaterra GA, Kelber O, Weiser D, et al. In vitro anti-proliferative effects of the willow bark extract STW 33-I. Arzneimittelforschung. 2010;60(6):330-335.
  4. Kong CS, Kim KH, Choi JS, et al. Salicin, an Extract from White Willow Bark, Inhibits Angiogenesis by Blocking the ROS-ERK Pathways. Phytother Res. Feb 17 2014.
  5. Chrubasik S, Eisenberg E, Balan E, et al. Treatment of low back pain exacerbations with willow bark extract: a randomized double-blind study. Am J Med. Jul 2000;109(1):9-14.
  6. Vlachojannis JE, Cameron M, Chrubasik S. A systematic review on the effectiveness of willow bark for musculoskeletal pain. Phytother Res. Jul 2009;23(7):897-900.
  7. Schmid B, Ludtke R, Selbmann HK, et al. Efficacy and tolerability of a standardized willow bark extract in patients with osteoarthritis: randomized placebo-controlled, double blind clinical trial. Phytother Res. Jun 2001;15(4):344-350.
  8. Beer AM, Wegener T. Willow bark extract (Salicis cortex) for gonarthrosis and coxarthrosis—results of a cohort study with a control group. Phytomedicine. Nov 2008;15(11):907-913.
  9. Biegert C, Wagner I, Ludtke R, et al. Efficacy and safety of willow bark extract in the treatment of osteoarthritis and rheumatoid arthritis: results of 2 randomized double-blind controlled trials. J Rheumatol. Nov 2004;31(11):2121-2130.
  10. Gopaul R, Knaggs HE, Lephart JF, et al. An evaluation of the effect of a topical product containing salicin on the visible signs of human skin aging. J Cosmet Dermatol. Sep 2010;9(3):196-201.
  11. Agnolet S, Wiese S, Verpoorte R, et al. Comprehensive analysis of commercial willow bark extracts by new technology platform: combined use of metabolomics, high-performance liquid chromatography-solid-phase extraction-nuclear magnetic resonance spectroscopy and high-resolution radical scavenging assay. J Chromatogr A. Nov 2 2012;1262:130-137.
  12. Freischmidt A, Jurgenliemk G, Kraus B, et al. Contribution of flavonoids and catechol to the reduction of ICAM-1 expression in endothelial cells by a standardised Willow bark extract. Phytomedicine. Feb 15 2012;19(3-4):245-252.
  13. Fuster V, Sweeny JM. Aspirin: a historical and contemporary therapeutic overview. Circulation. Feb 22 2011;123(7):768-778.
  14. Khayyal MT, El-Ghazaly MA, Abdallah DM, et al. Mechanisms involved in the anti-inflammatory effect of a standardized willow bark extract. Arzneimittelforschung. 2005;55(11):677-687.
  15. Hostanska K, Jurgenliemk G, Abel G, et al. Willow bark extract (BNO1455) and its fractions suppress growth and induce apoptosis in human colon and lung cancer cells. Cancer Detect Prev. 2007;31(2):129-139.
  16. Maroon JC, Bost JW, Maroon A. Natural anti-inflammatory agents for pain relief. Surg Neurol Int. 2010;1:80.
  17. Chrubasik S, Kunzel O, Black A, et al. Potential economic impact of using a proprietary willow bark extract in outpatient treatment of low back pain: an open non-randomized study. Phytomedicine. Jul 2001;8(4):241-251.
  18. Boullata JI, McDonnell PJ, Oliva CD. Anaphylactic reaction to a dietary supplement containing willow bark. Ann Pharmacother. Jun 2003;37(6):832-835.
  19. Srivali N, Cheungpasitporn W, Chongnarungsin D, et al. White willow bark induced acute respiratory distress syndrome. N Am J Med Sci. May 2013;5(5):330.
  20. Shalansky S, Lynd L, Richardson K, et al. Risk of warfarin-related bleeding events and supratherapeutic international normalized ratios associated with complementary and alternative medicine: a longitudinal analysis. Pharmacotherapy. Sep 2007;27(9):1237-1247.

Consumer Information

How It Works

Bottom Line: Willow bark is useful in relieving muscle and joint pain, but may have side effects similar to aspirin.

Willow bark is commonly used to treat pain and reduce fevers. It contains a compound called salicin that has been shown to have anti-inflammatory effects. Several studies have shown that willow bark extracts are effective in reducing back pain and osteoarthritis. Although aspirin is developed from salicin, a direct comparison between aspirin benefits and willow bark benefits cannot be made. At the same time, aspirin-like side effects may occur with willow bark.

Purported Uses
  • To reduce fever
    Willow bark is thought to act in a similar way as aspirin, but clinical trials have not been performed.
  • To treat pain, including muscle and joint pain
    Clinical trials have shown that willow bark extract is effective in treating low back pain. Other study results are mixed for its ability to relieve osteoarthritis pain.
  • To aid in weight loss
    There are no studies to indicate that willow bark can aid in weight loss, and a case report of allergic reaction in someone who used a weight-loss product with willow bark.
Research Evidence

Arthritis of the knee and hip joint
Several small short-term studies lasting 2 weeks (with 78 patients) and 6 weeks (with 88 patients) have found that willow bark may help reduce pain associated with osteoarthritis, but only the 2 week study was a randomized trial. Another randomized trial lasting 6 weeks with the largest number of patients (127 patients) did not show benefit.

Low back pain
In a 4-week study, 210 patients with intense chronic low back pain were split randomly into 3 groups: low- or high-dose willow bark extract, or placebo. Of 191 patients completing the study, 39% of 65 patients in the high-dose group were pain-free during Week 4, and 21% of 67 in the low-dose group were also pain-free. Only 6% of 59 patients in the placebo group were pain-free during the same treatment period. In addition, the high-dose group had benefit after only 1 week of treatment. However, 1 patient in the low-dose group had a severe allergic reaction.

Patient Warnings

Due to possible bleeding complications, willow bark should be discontinued before surgery or chemotherapy.
Individuals with impaired platelet function should also avoid willow bark, as it may interfere with blood clotting.

Do Not Take If
  • You are taking warfarin or other blood thinners: Willow bark may increase the risk of bleeding.
  • You are taking non-steroidal anti-inflammatory drugs (NSAIDs): Willow bark may increase the risk of stomach and intestinal damage and bleeding.
  • You have sensitivity to aspirin or aspirin-containing products.
  • You have asthma, breathing problems, chest tightness, or throat tightness.
  • You have stomach problems or an ulcer.
  • You are having skin rash, hives, or itchy / swollen skin.
Side Effects
  • Stomach or intestinal discomfort, allergic reaction, sudden rash, or itching
  • May prevent blood clotting or cause bleeding problems

Watch for aspirin-like side effects that could occur when used often, such as ringing in the ears, nausea or vomiting, and gastrointestinal or kidney irritation.

Case reports of:

  • Serious allergic reaction in a 25-year-old woman with a history of allergy to aspirin products. The product used was a supplement promoted for weight-loss that contained willow bark. 
  • Acute breathing distress in a 61-year-old woman who suddenly became short of breath and coughed repeatedly after taking willow bark.
Special Point
  • Children should not be given willow bark because of the potential for developing Reye syndrome, a serious condition associated with the use of aspirin.

E-mail your questions and comments to aboutherbs@mskcc.org.