Willow Bark

• How It Works

  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. A case of allergic reaction was reported following use of a weight-loss product that contained willow bark.
• Patient Warnings
  • Due to possible bleeding complications, willow bark should be discontinued before surgery or chemotherapy.
• 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
  • Salicin affects platelet aggregation, although to a lesser extent compared to acetylsalicylate. The clinical significance of this effect in patients with impaired thrombocyte function is yet to be determined.

  Case reports:

  • 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.
  • Fatal Fulminant liver failure in a 28-month-old boy after being treated for upper respiratory infection with acetaminophen and a tea containing 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.
• Scientific Name

  Salix alba, Salicis cortex

• Clinical Summary

  Willow is a deciduous tree native to Europe, Asia and some parts of North America. Its bark has been used for thousands of years in China and Europe as a remedy for fevers and pain. Aspirin is derived from salicin, an active compound in willow bark.

  Willow bark extracts demonstrated anti-inflammatory ⁽¹⁾, antiproliferative ⁽³⁾ and skin-protective ⁽²³⁾ effects in vitro. Clinical studies indicate that willow bark may help manage back pain ^{(5) (6) (24)}, although studies of osteoarthritis are mixed ^{(7) (8) (9)}, with negative findings for rheumatoid arthritis ^(6) (9). Topical application of salicin may help reduce skin aging ⁽¹⁰⁾.

  Preclinical studies have shown that salicin has antiangiogenic ⁽⁴⁾ , anticancer ⁽²⁵⁾ and chemopreventive effects ⁽²⁶⁾. It was also found to modulate neurite growth in human neuroblastoma cells ⁽²⁷⁾. Aspirin has been studied for the prevention of cardiovascular diseases as well as cancer ⁽²¹⁾. However, willow bark should not be used as a substitute for aspirin because of the variation in its potency. Children should not be given willow bark because of the potential for developing Reye syndrome, a serious condition associated with the use of aspirin ⁽²²⁾.

• Purported Uses
  • Arthritis
  • Fever
  • Headaches
  • Inflammation
  • Influenza
  • Pain
  • Weight loss
• Mechanism of Action

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

  Antiproliferative effects in human colon and lung cancer cells are due to growth-inhibition and apoptotic induction ⁽¹⁵⁾. In vitro and animal models suggest that 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 increased risk of bleeding ⁽²⁰⁾, willow bark should be discontinued before surgery or chemotherapy.
• Contraindications

  Allergy or sensitivity to salicylates such as aspirin.

• Adverse Reactions

  Gastrointestinal discomfort; allergic reaction, erythema, pruritus (sudden rash, itching) ^{(5) (7) (17)}
  Salicin affects platelet aggregation, although to a lesser extent compared to acetylsalicylate ⁽²⁾. The clinical significance of this effect in patients with impaired thrombocyte function is yet to be determined.
  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⁾.
  Fatal Fulminant liver failure: In a 28-month-old boy after being treated for upper respiratory infection with acetaminophen and a tea containing willow bark ⁽²⁸⁾.

• Herb-Drug Interactions

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

• 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.

  21. Brotons C, Benamouzig R, Filipiak KJ, Limmroth V, Borghi C. A Systematic Review of Aspirin in Primary Prevention: Is It Time for a New Approach? Am J Cardiovasc Drugs. 2014 Dec 12. [Epub ahead of print]

  22. Beutler AI, Chesnut GT, Mattingly JC, Jamieson B. FPIN’s Clinical Inquiries. Aspirin use in children for fever or viral syndromes. Am Fam Physician. 2009 Dec 15;80(12):1472.

  23. Bassino E, Gasparri F, Munaron L. Pleiotropic Effects of White Willow Bark and 1,2-Decanediol on Human Adult Keratinocytes. Skin Pharmacol Physiol. 2018;31(1):10-18.

  24. Gagnier JJ, Oltean H, van Tulder MW, Berman BM, Bombardier C, Robbins CB. Herbal Medicine for Low Back Pain: A Cochrane Review. Spine (Phila Pa 1976). 2016 Jan;41(2):116-33.

  25. Sabaa M, ELFayoumi HM, Elshazly S, Youns M, Barakat W. Anticancer activity of salicin and fenofibrate. Naunyn Schmiedebergs Arch Pharmacol. 2017 Oct;390(10):1061-1071.

  26. Bounaama A, Enayat S, Ceyhan MS, Moulahoum H, Djerdjouri B, Banerjee S. Ethanolic Extract of Bark from Salix aegyptiaca Ameliorates 1,2-dimethylhydrazine-induced Colon Carcinogenesis in Mice by Reducing Oxidative Stress. Nutr Cancer. 2016;68(3):495-506.

  27. Wölfle U, Haarhaus B, Kersten A, Fiebich B, Hug MJ, Schempp CM. Salicin from Willow Bark can Modulate Neurite Outgrowth in Human Neuroblastoma SH-SY5Y Cells. Phytother Res. 2015 Oct;29(10):1494-500.

  28. Dinakaran D, Bristow E, Armanious H, et al. Co-ingestion of willow bark tea and acetaminophen associated with fatal infantile fulminant liver failure. Pediatr Int. 2017 Jun;59(6):743-745.