Willow bark

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Willow bark

Willow bark

Willow bark, also known as Bay willow, Black willow, White willow or ‘bark of Salix tree species’, is the common name for the dried bark of Salix plant with more than 330–500 species and 200 hybrids, that include Salix alba, Salicis cortex, Salix purpurea L., Salix daphnoides Vill. and Salix fragilis L 1, 2, 3. Willow bark are fast growing deciduous trees, shrubs or prostrate plants; they can withstand a wide range of different weathers more than Populus species, as they grow in temperate, subtropic and tropic regions 2. Willow bark are widely distributed in Africa, North America, Europe, and Asia 4. Willow bark preparations are often obtained by reducing into tiny pieces (comminuting) or powdering the bark and as dry or liquid extracts. Extracts are obtained by putting the Salix plant material in a solvent such as ethanol or water to dissolve the compounds and form a liquid extract. The solvent is then evaporated to obtain a dry extract.

Salix egyptiaca L (Musk Willow) was important in the Middle East, especially in Iran, as it has been traditionally used to treat anemia and vertigo, as a cardiotonic agent, and also in the preparation of local candies as a fragrance additive 5. Salix alba L (white willow) was used in folk medicine to treat fever, chronic and acute inflammation, pain and infection 6, 7. Salix tetrasperma Roxb. had been used to treat diseases such as epilepsy, diabetes, fever, rheumatism, piles, swellings, stones in bladder, dysentery, wound, ear pain, cough and cold 8. Salix alba L. bark is traditionally used for treatment of flu, rheumatism (inflammatory disease that causes pain in the joints, muscles, or fibrous tissue), fever and headache 9.

Willow bark contains salicin, a prodrug for salicylic acid that metabolizes into salicylic acid in your body and is the basis of aspirin 10, 11. Although aspirin is developed from salicin, a direct comparison between aspirin benefits and willow bark benefits cannot be made. Although Willow bark anti-inflammatory activity is mostly attributed to salicin 12, the main bioactive compound in willow bark, catechol and flavonoid compounds have also been found to be responsible for its anti-inflammatory activity 13. Several studies have been conducted to analyze which component in the willow bark is responsible for its therapeutic effect. There were at least 13 different main compounds in willow bark, including saligenin, salicylic acid, salicin, isosalicin, picein, salidroside, triandrin, salicoylsalicin, salicortin, isosalipurposide, salipurposide, naringenin-7-O-glucoside, and tremulacin 14. As the precursor of aspirin, however, salicin cannot fully explain the clinical effect of willow bark 15. Both flavonoids and polyphenols in the willow bark were proven to be attributed to anti-inflammatory effects 16. For instance, willow bark inhibits pro-inflammatory cytokines such as tumor necrosis factor alpha (TNFα), cyclooxygenase-2 (COX-2), and the nuclear translocation of the transcription factor NF-κB in proinflammatory activated monocytes, resulting in its anti-inflammatory effect 17 in LPS-activated human monocytes and differentiated macrophages. Phytomedicine. 2010 Dec 1;17(14):1106-13. doi: 10.1016/j.phymed.2010.03.022)). Moreover, willow bark extract has the therapeutic effect of preventing oxidative stress 18 and induces apoptosis in human colon and lung cancer cells 19. Antiproliferative effects in human colon and lung cancer cells are due to growth inhibition and apoptotic induction 20. In vitro and animal models suggest that salicin can inhibit ROS and ERK signaling pathways to produce antiangiogenic effects 21. Willow bark extract was also found to significantly raise low glutathione levels, thereby limiting lipid peroxidation 22.

Willow bark is traditionally used to treat fever, pain and inflammatory conditions 23, 24, but it is also found in some weight loss supplements as well as sports performance products 25, 26. 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. Willow bark contains a compound called salicin that has been shown to have anti-inflammatory effects. Several studies suggest willow bark extracts, can help reduce back pain and osteoarthritis. The Sumerians were noted to have used remedies derived from the Willow tree for pain management as far back as 4000 years ago 1, 27. Hippocrates used it for managing pain and fever 28. He even utilized tea brewed from it for pain management during childbirth 28. Willow bark may help relieve muscle and joint pain, but may have side effects similar to aspirin also known as acetylsalicylic acid (a nonsteroidal anti-inflammatory drug [NSAID] used to reduce pain, fever, and inflammation) 29, 30, 31.

Salicylic acid derived from willow bark is also used topically to chemically exfoliate the skin in the treatment of scaly skin diseases where the skin has become thickened, scaly and flaky, making it popular for treating acne, blackheads and whiteheads, seborrheic dermatitis of the skin and scalp and oily skin, depending on the dosage form and strength of the preparation. Salicylic acid works by dissolving dead skin cells and clearing clogged pores, which can also help improve skin texture, redness, and the appearance of fine lines. It is available in many topical products like cleansers, toners, serums, and spot treatments. When salicylic acid is used in combination with other medicines it takes off the upper layer of skin allowing the additional medicines to penetrate more effectively.

Side effects with willow bark medicines include allergic reactions, such as rash, exanthema (widespread rash), itching, and asthma, and stomach and gut symptoms such as nausea, vomiting, abdominal (belly) pain, diarrhea and heartburn 32, 33, 34, 35, 36. The frequency is not known.

Salicin in willow bark may affect blood clotting. The clinical significance in patients with impaired platelet functioning is yet to be determined.

  • Serious allergic reaction: In a 25-year-old woman with a history of aspirin allergy who used a supplement promoted for weight loss that contained willow bark 37.
  • Acute breathing distress: In a 61-year-old woman who suddenly became short of breath and coughed repeatedly after taking willow bark 38.
  • Fatal liver failure: In a 28-month-old boy after being treated for upper respiratory infection with acetaminophen and a tea containing willow bark 39.

Only a limited number of case reports indicated serious adverse events including anaphylactic reaction 40 and acute respiratory distress syndrome 41. Willow bark medicines must not be taken if your are hypersensitive (allergic) to salicylates such as aspirin or other anti-inflammatory medicines known as non-steroidal anti-inflammatory drugs (NSAIDs) 32, 42. Willow bark medicines must also not be taken by people with asthma due to salicylate sensitivity, active stomach ulcers, severe liver or kidney dysfunction, clotting disorders and glucose-6-phostphate dehydrogenase deficiency (G6PD deficiency), a genetic condition that can cause the destruction of red blood cells. Women in the third trimester of pregnancy, children and adolescents must not take willow bark medicines.

Patient Warnings

  • Due to possible bleeding complications, willow bark should be discontinued before surgery or chemotherapy.
  • Children should not be given willow bark because of the potential for developing Reye syndrome, a serious condition associated with the use of aspirin 43, 44.
  • Components in willow bark may interact with anticoagulants (increase bleeding tendency), beta-blockers and diuretics (decrease the effect of the drugs), and NSAIDs (increase the risk of stomach bleeding) 44.

Do Not Take Willow bark 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.

Willow bark health benefits

In test tube studies, Willow bark extracts and salicin have exhibited anti-inflammatory and anticancer effects, but data in humans are limited 17 in LPS-activated human monocytes and differentiated macrophages. Phytomedicine. 2010 Dec 1;17(14):1106-13. doi: 10.1016/j.phymed.2010.03.022)), 45, 21, 46, 47, 48. A few studies suggest that willow bark may help manage back pain, but studies of osteoarthritis are mixed with negative findings for rheumatoid arthritis 34, 49, 50, 35, 51, 52, 49.

In the ancient world, people in Egypt, South America, Classical Greece, and China used Willow bark (Salix plants) as medicine. Furthermore, Willow bark (Salix plants) have been linked to the discovery of acetylsalicylic acid and aspirin. Sumerians and Ancient Egyptians utilized Willow bark as a painkiller and to reduce fever. The therapeutic benefits of willow bark were recognized by ancient Roman and Greek physicians, including Hippocrates. In the fourth century BCE, Hippocrates used willow bark to treat inflammatory pain 53:8s–17s. doi: 10.1016/S0248-8663(00)88720-2)). Over time, the use of willow bark became more widespread. In a 1763 clinical trial, Reverend Edward Stone conducted the first clinical research study on willow bark powder, confirming its ability to treat fever 27. About 100 years later, the effects of the willow bark powder were studied for acute rheumatism. In 1827, salicylic acid, which was the active component of willow bark, was extracted and isolated by Professor Johann Andreas Buchner 54. Henri Leroux used it to treat rheumatism after isolating it in a crystalline form in 1829. In 1853, Charles Gerhardt manufactured acetylsalicylic acid 55. In 1869, the chemical structure of acetylsalicylic acid was accurately reported 56. In 1897, salicin was successfully refined into aspirin 27, 10. In the 1800s, the Heyden Chemical Company was the first to mass-produce salicylic acid commercially. In 1887, Bayer chemists synthesized a steady acetylated salicylate from salicylic acid. It was not until 1899 when a modified version named acetylsalicylic acid was registered and marketed by Bayer under the trade name Aspirin 57.

Aspirin could inhibit cyclooxygenase (COX), which inhibited prostaglandin synthesis and resulted in antipyretic (reduce fever), analgesic (pain reliever), and anti-inflammatory effects 58. Aspirin works by inhibiting the cyclooxygenase-1 (COX-1) enzyme, an enzyme that plays a crucial role in maintaining normal physiological functions by converting arachidonic acid into prostaglandins that regulate processes like stomach lining protection and blood clotting. Aspirin also blocks the enzymatic activity of cyclooxygenase-2 (COX-2) 59. However, unlike other nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen or naproxen, which bind reversibly to cyclooxygenase-1 (COX-1), aspirin binding is irreversible 60. The inhibition of cyclooxygenase-1 (COX-1) by aspirin can lead to side effects because it blocks the production of protective prostaglandins in the stomach lining. Nonsteroidal anti-inflammatory drugs (NSAIDs) like aspirin can cause upper and lower gastrointestinal adverse effects ranging from mild irritation to more severe adverse events such as gastrointestinal bleeding and perforation 61, 60. Upper gastrointestinal adverse effects are reported more frequently 62. Indigestion (dyspepsia), heartburn, and nausea are among the upper gastrointestinal adverse effects. Stomach or duodenal mucosal injury and ulceration may result as well. When ulceration develops into bleeding, endoscopic therapy and high-dose proton pump inhibitors (PPIs) are recommended and decrease mortality 63. However, proton pump inhibitors (PPIs) have not been shown to decrease the risk of lower gastrointestinal adverse effects, and their preventative effect does not extend beyond the stomach. Furthermore, there is increasing evidence regarding the concept that proton pump inhibitors (PPIs) increase the risk of small bowel damage 64.

Lower gastrointestinal adverse effects are present within 75% of patients taking nonsteroidal anti-inflammatory drugs (NSAIDs) 62. People taking nonsteroidal anti-inflammatory drugs (NSAIDs) can have ulceration, bleeding, strictures, or obstruction. Management always involves stopping the medication but can include endoscopic interventions as well 64. In severe circumstances, laparotomy (a surgical procedure that involves making a large incision in the abdomen to access and operate on internal organs) and bowel segment resection are necessary 60. Risk factors include patients older than 65, those with a history of peptic ulcer disease, or who are also on steroids or blood thinners. Nonsteroidal anti-inflammatory drugs (NSAIDs) are best avoided in these patients 65.

Aspirin also blocks thromboxane A2 on platelets in an irreversible fashion preventing platelet aggregation 28. Low-dose aspirin is a blood-thinning medicine. It helps prevent heart attacks and strokes if your risk of getting heart attacks and strokes is high.

Even though salicin in Willow bark served as a precursor to aspirin, its medical effect could not be solely attributed to it. Willow bark biologically active compounds include salicin (a prodrug for salicylic acid), flavonoids (flavonols, flavones, flavanones, isoflavones, flavan-3-ols [catechins and procyanidins], chalcones, dihydrochalcone, anthocyanins, dihydroflavonols), phenolic glycosides, organic acids, and non-phenolic glycosides, sterols and terpenes, simple phenolics and lignans in addition to volatiles and fatty acids 1, 66, 5, 67, 68, 69, 70, 71.

Willow bark uses

One of the active compounds of Willow bark, salicin, is known to have effects on inflammation, fever and pain. Salicin is converted into salicylic acid in your body. It may work similarly to aspirin (acetylsalicylic acid), which is structurally related to salicylic acid by blocking the cyclooxygenase (COX-1 and COX-2) enzymes which are involved in inflammation and pain. However, the amount of salicylic acid produced from salicin is small and the effects of the medicine may be due to its other components.

Willow bark extract is commonly employed as a complementary therapy for pain and inflammation management, such as those related to low back pain, osteoarthritis, tendinitis, bursitis, and headaches.

  • 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 suggest willow bark extract is effective in treating low back pain. Other study results are mixed for osteoarthritis pain.

Willow bark extract is now widely used for conditions associated with inflammation or fever, and it can be applied to various types of pain, such as joint or knee pain, acute back pain, osteoarthritis, headache, menstrual cramps, tendonitis, and generalized pain 26. For arthritis per se, the efficacy of willow bark from various studies is diverse. Three randomized controlled trials showed that both willow bark extract alone and compound drugs had an analgesic effect versus placebo 72, 73, 74. In contrast, another three randomized controlled trials showed that willow bark extract yielded no significant benefit 52, 75. According to Biegert et al 52, although salicin derivatives in the willow bark were metabolized in the body to salicylic acid, serum salicylate concentration was too low to reach clinical effects. In addition, the inhibition mechanism of the COX-2-mediated release of prostaglandin E2 was confirmed in test tube study, but still short of proof of in human trials 76.

Prior research reported that willow bark may improve physical function and relieve pain in patients with joint disorders 72. However, there is no systematic review to assess the efficacy and safety of willow bark in patients with arthritis.

The European Medicines Agency Committee on Herbal Medicinal Products (HMPC) concluded that willow bark prepared as a dry extract can be used for short-term treatment of lower back pain 32. The European Medicines Agency Committee on Herbal Medicinal Products (HMPC)  also concluded that, on the basis of its long-standing use, Willow bark preparations can be used for relief of minor joint pain, relief of fever linked with the common cold and for headaches. And Willow bark medicines should only be used in adults. Willow bark medicines should not be taken for longer than 4 weeks for back or joint pain. If symptoms worsen or last longer than 3 days whilst taking the medicine for fever or 1 day for headache, a doctor should be consulted. Detailed instructions on how to take willow bark medicines and who can use them can be found in the package leaflet that comes with the medicine.

The European Medicines Agency Committee on Herbal Medicinal Products (HMPC) conclusions on the use of these willow bark medicines for lower back pain are based on their ‘well-established use’. This means that there are bibliographic data providing scientific evidence of their effectiveness and safety when used in this way, covering a period of at least 10 years in the European Union.

In its assessment, the HMPC considered a number of clinical studies that showed that willow bark was more effective than placebo (a dummy treatment) at reducing lower back pain.

The HMPC conclusions on the use of these willow bark medicines for relief of minor joint pain, relief of fever linked with the common cold and for headaches are based on their “traditional use”. This means that, although there is insufficient evidence from clinical trials, the effectiveness of willow bark medicines is plausible and there is evidence that they have been used safely in this way for at least 30 years, including at least 15 years within the European Union 32. Moreover, the intended use does not require medical supervision 32.

In its assessment, the HMPC also considered clinical studies with willow bark medicines for joint pain and headache. Although a possible effect in reducing joint pain was observed, there were shortcomings in the studies such as small numbers of patients and short duration. Therefore, the HMPC conclusions on the use of willow bark medicines for relief of minor joint pain and headache are based on their long-standing use 32.

Willow bark side effects

Side effects with willow bark medicines include allergic reactions, such as rash, exanthema (widespread rash), itching, and asthma, and stomach and gut symptoms such as nausea, vomiting, abdominal (belly) pain, diarrhea and heartburn 32, 33, 34, 35, 36. The frequency is not known.

Salicin in willow bark may affect blood clotting. The clinical significance in patients with impaired platelet functioning is yet to be determined.

  • Serious allergic reaction: In a 25-year-old woman with a history of aspirin allergy who used a supplement promoted for weight loss that contained willow bark 37.
  • Acute breathing distress: In a 61-year-old woman who suddenly became short of breath and coughed repeatedly after taking willow bark 38.
  • Fatal liver failure: In a 28-month-old boy after being treated for upper respiratory infection with acetaminophen and a tea containing willow bark 39.

Only a limited number of case reports indicated serious adverse events including anaphylactic reaction 40 and acute respiratory distress syndrome 41. Willow bark medicines must not be taken if your are hypersensitive (allergic) to salicylates such as aspirin or other anti-inflammatory medicines known as non-steroidal anti-inflammatory drugs (NSAIDs) 32, 42. Willow bark medicines must also not be taken by people with asthma due to salicylate sensitivity, active stomach ulcers, severe liver or kidney dysfunction, clotting disorders and glucose-6-phostphate dehydrogenase deficiency (G6PD deficiency), a genetic condition that can cause the destruction of red blood cells. Women in the third trimester of pregnancy, children and adolescents must not take willow bark medicines.

Patient Warnings

  • Due to possible bleeding complications, willow bark should be discontinued before surgery or chemotherapy.
  • Children should not be given willow bark because of the potential for developing Reye syndrome, a serious condition associated with the use of aspirin 43, 44.
  • Components in willow bark may interact with anticoagulants (increase bleeding tendency), beta-blockers and diuretics (decrease the effect of the drugs), and NSAIDs (increase the risk of stomach bleeding) 44.

Do Not Take Willow bark 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.
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