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Willow Bark

Scientific Name(s): Salicis cortex, Salix alba L., Salix fragilis L., Salix purpurea L.
Common Name(s): Crack willow, Purple osier willow/basket willow, Weidenrinde, White willow, Willow

Medically reviewed by Drugs.com. Last updated on Nov 22, 2022.

Clinical Overview

Use

Willow bark can be an effective analgesic if the salicylate content is adequate. Clinical trials have demonstrated efficacy in treating dysmenorrhea, moderate efficacy in treating lower back pain and less efficacy in treating arthritic conditions.

Dosing

Willow is available in various dosage forms, including tablets, capsules, powders, and liquids. Clinical studies evaluating the analgesic effects of willow bark (eg, for lower back pain, dysmenorrhea) used extracts delivering daily salicin doses of 120 to 240 mg.

Contraindications

Willow-containing products should be avoided in patients with known hypersensitivity to aspirin, asthma, impaired thrombocyte function, need for vitamin K antagonistic treatment, diabetes, gout, kidney or liver conditions, peptic ulcer disease, and any other medical condition for which aspirin is contraindicated.

Pregnancy/Lactation

Avoid use. Information regarding safety and efficacy in pregnancy and lactation is lacking.

Interactions

In general, drug interactions associated with salicylates may apply to willow-containing products; however, actual salicylate content of willow species is likely low. Avoid use with alcohol, barbiturates, sedatives, and other salicylate-containing products because of potential additive irritant effects, including GI tract and platelet function adverse reactions. Willow bark may also interact with oral anticoagulants such as warfarin.

Adverse Reactions

Reports from clinical trials primarily document GI discomfort (eg, nausea, stomachache) as well as dizziness and skin rash. An anaphylactic reaction to willow bark has been reported.

Toxicology

There is little or no toxicity information on the use of willow bark. However, toxicities associated with salicylates apply to willow bark. Patients should be monitored for blood in stools, tinnitus, nausea or vomiting, and stomach or kidney toxicity.

Scientific Family

Botany

The genus Salix consists of nearly 450 species. Most willows are found in temperate and arctic zones, but some species can be located in subtropical and tropical zones; willows are geographically distributed on all continents except Antarctica and Australia. Willows include small trees, shrubs, and groundcovers, and many species are dioecious with male and female catkins (flowers) on separate plants. The catkins are cylindrical in shape, measuring 6 to 7 cm in length. The male flowers are yellow, and the female flowers are green. Because they are insect pollinated, different species of willow hybridize freely. Willow trees may grow 6 to 18 m in height. Medicinal willow bark is collected in the early spring from young branches (2 to 3 years of age). Other species of Salix have similar chemistry and pharmacology. The plant species has been used in various ecosystem restoration projects, particularly for erosion control, because of its fibrous root system.Chevallier 1996, Kuzovkina 2005

History

The medicinal use of willow dates back 6,000 years. Ancient civilizations used willow tree extracts to treat pain, inflammation, and musculoskeletal conditions. Assyrian clay tablets excavated by archaeologists document these uses of willow as well as use in treating fever. Egyptians used willow to treat joint pain and inflammatory conditions associated with wounds. Chinese civilizations used willow to treat fever, pain, colds, hemorrhages, goiter, and rheumatic fever, and applied willow as an antiseptic for wounds and abscesses. Physicians of ancient Greece, including Dioscorides who wrote the precursor to all modern pharmacopeias, prescribed willow for its analgesic and anti-inflammatory properties.Hedner 1998, Jones 2001, Mahdi 2006

North American willows have also been used in folk medicine. Most of the European medicinal willows were introduced to the Americas and escaped cultivation. In the late 19th century, salicylic acid was widely used in place of willow bark, and its derivative, aspirin, was discovered to be less irritating to the mouth and stomach.Jourdier 1999, Weissmann 1991

Chemistry

Salicylate derivatives are the primary medicinal constituents of willow bark. While small amounts of salicylic acid can be detected in most species, the principle salicylates of S. alba are the phenolic ester glycoside salicortinPearl 1971, Thieme 1965 and glycoside salicin, its acid hydrolysis product. Although salicin is considered the major active constituent, there is research interest in the anticancer activity of polyphenols and flavonoids of willow bark.Nahrstedt 2007

Salicin is hydrolyzed in the intestine to saligenin (o-hydroxybenzyl alcohol), which is absorbed and then oxidized to salicylic acid.Meier 1988 Salicortin and other related salicylates are chemically unstable to the boiling water used in teasSteele 1973; to avoid the loss of these compounds, careful drying of the bark is required.Julkunen-Tiitto 1989, Julkunen-Tiitto 1992, Steele 1973 Extraction protocols to avoid decomposition of the native glycosides have been developed. Most standards for medicinal willow bark require salicylates to be present in more than 1% of the dry weight. The leaves generally contain lower concentrations of salicylates than the bark; several species contain medicinally useful quantities of salicylates in their leaves.Julkunen-Tiitto 1986

A number of analytical approaches have been used to quantify salicylates in willows, including spectrophotometry,Afsharypour 1995 thin-layer chromatography,Vanhaelen 1983 high-performance liquid chromatography (HPLC) after enzymatic deglycosylation,Luo 1998 capillary electrophoresis,Zaugg 1997 and an electrochemical method known as square wave voltammetry.Petrek 2007 An HPLC study led to the identification of 13 compounds in 2 pharmaceutical preparations used in clinical trials containing willow bark extract.Kammerer 2005 Naringenin glycosidesPearl 1970 and oligomeric procyanidinsKolodziej 1990 as well as condensed tannins, presumably derived from the simpler flavonols, have been obtained from commercial willow barks.

Although traditionally salicin was considered the active principle, it may not explain the whole range of effects of willow bark extract; phytochemicals such as polyphenols and flavonoids, which show cyclooxygenase-2 (COX-2) inhibitory activity and decreased synthesis of proinflammatory mediators in vitro, might be involved.Dragos 2017

Uses and Pharmacology

Willow bark was traditionally thought to possess anti-inflammatory, antirheumatic, antipyretic, analgesic, antiseptic, and astringent properties.(Barnes 2007) The ester glycosides salicortin, tremulacin, and fragilin are considered prodrugs of salicylic acid and deliver salicylic acid into the systemic circulation without irritating the GI tract.(Kaul 1999) Salicylic acid inhibits COX-2 enzymes, which are involved in prostaglandin synthesis. The inflammation-suppressing effect of willow bark extract relies, at least partially, on its ability to antagonize the activated monocytes by blocking the activity of proinflammatory cytokines (tumor necrosis factor [TNF]), COX-2 enzymes, and mediators (nuclear factor kappa B).(Dragos 2017)

Cancer

In vitro data

In vitro, the young leaves of willow (Salix safsaf) inhibited growth of acute myeloid leukemia cells.(El-Shemy 2003) Another report found that willow extract killed 75% to 80% of abnormal cells harvested from 7 patients with acute lymphoblastic leukemia and 13 patients with acute myeloid leukemia.(El-Shemy 2003) Willow bark extract inhibited tumor cell growth and induced apoptosis in human colon and lung cancer cell lines. The inhibitory effects were dose dependent.(El-Shemy 2007)

Anti-inflammatory and antioxidant activity

In vitro data and animal data

Phenolic compounds are responsible for the antioxidant and free radical scavenging properties of the willow plant species.(Kahkonen 1999, Khayyal 2005) An animal model in rats demonstrated that a standardized willow bark extract, on a milligram per kilogram basis, was as effective as acetylsalicylic acid (ASA) in reducing various inflammatory mediators.(Kahkonen 1999)

In an animal model, Salix extract (willow bark extract) demonstrated potent antioxidant activity in vitro and slowed the development of osteoarthritis by reducing inflammatory cytokines (eg, TNF-alpha, interleukin [IL]-1beta, IL-6) and nitric oxide production.(Henrotin 2018)

Arthritis

Clinical data

In a double-blind study, patients with chronic arthritic pain (N=82) were randomly assigned to receive a combination herbal preparation containing willow bark or placebo for 2 months. Mild improvement in pain symptoms with few adverse reactions was reported for the herbal preparation.(Mills 1996) Analysis of blood samples from a small study of 3 patients receiving a single dose of willow bark extract equivalent to salicin 240 mg found only moderate inhibition of COX-1.(Wagner 2003)

Two 6-week, randomized, double-blind trials examined the efficacy of willow bark in treating outpatients with hip or knee osteoarthritis (N=127) and outpatients with active rheumatoid arthritis (N=26). Patients with osteoarthritis received willow bark extract (corresponding to 240 mg/day of salicin), diclofenac 100 mg/day, or placebo. Patients with rheumatoid arthritis received willow bark extract (salicin 240 mg/day) or placebo. Willow bark extract did not demonstrate efficacy in either disease state.(Biegert 2004) An open-label, 6-week study evaluated a standardized willow bark extract product containing salicin 120 to 240 mg/day compared with conventional treatment in patients (N=128) with coxarthrosis and gonarthrosis. No difference in therapeutic effect was observed, and fewer adverse events occurred in the group receiving the willow bark product.(Beer 2008)

Dysmenorrhea

Clinical data

In a double-blind, controlled, crossover study of female students with level 2 or 3 primary dysmenorrhea (N=96), the efficacy of Salix extract was investigated. Patients received a Salix capsule (400 mg daily) or control (mefenamic acid 750 mg capsule) daily. Both the treatment group and control group consisted of the same number of participants (n=48). Pain intensity (measured using a visual analog scale [VAS]), amount of bleeding, and severity of dysmenorrhea symptoms were observed outcomes. Results showed that students in the mefenamic acid group had a significantly higher VAS score than students in the Salix group over time (1.61±0.06; P<0.001). Estimated odds of the bleeding level for the 2 groups were not significantly different (P=0.31). On average, 77.39%±16.18% of students in the Salix group showed no symptoms; 22.18%±14.08% experienced mild symptoms. On average, 44.58%±20.16% of students in the mefenamic acid group had mild symptoms; 28.12%±15.29% experienced moderate symptoms. Salix extract significantly decreased dysmenorrhea compared to mefenamic acid.(Raisi Dehkordi 2019)

Gout

Clinical data

The American College of Rheumatology guidelines on the management of gout (2012) voted that use of various oral complementary agents, including willow bark, is inappropriate for the treatment of an acute gout attack. The new guideline (2020) based on additional evidence regarding the management of gout no longer included a statement regarding the use of willow bark.(Fitzgerald 2020, Khanna 2012)

Lower back pain

Clinical data

A systematic review evaluated randomized trials of various herbal therapies in patients with acute, subacute, and chronic low back pain. Compared with placebo, topical cayenne had the best evidence for effectiveness followed by oral white willow bark. However, there were methodologic limitations to the trials, outcomes assessed were short-term, and it was not clear how these treatments compared with over-the-counter analgesics.(Oltean 2014)

In a 4-week, double-blind, clinical trial of patients with exacerbation of chronic low back pain (N=191), 2 oral doses of willow bark extract (containing salicin 120 mg or 240 mg) were compared with placebo. The primary outcome measure was the proportion of patients requiring relief medication (tramadol) 5 out of 7 days during the final week of the study. Pain index measures showed a reduction in use of relief medication with both doses of salicin. Patients receiving the 240 mg dose demonstrated greater improvement in pain index measures. Moderate efficacy was demonstrated with both doses of salicin for short-term treatment of acute episodes of chronic nonspecific lower back pain.(Chrubasik 2000) Postmarketing surveillance of a proprietary willow bark extract product for use in outpatient treatment of low back pain reported no serious adverse reactions.(Chrubasik 2001)

Another 4-week, randomized, controlled study in outpatients with acute exacerbations of low back pain (N=183) tested a daily dose of oral willow bark extract (Assalix; containing salicin 240 mg) against rofecoxib 12.5 mg/day. While rofecoxib is no longer available, it should be noted that VAS score pain index improved by approximately 44% in both the salicin and rofecoxib groups. There was no difference in efficacy between the 2 treatment groups, and incidence of adverse events was similar.(Chrubasik 2001)

Platelet aggregation

Clinical data

A 4-week trial in 51 patients evaluated whether platelet aggregation was affected during pain treatment with Salicis cortex extract (salicin 240 mg/day). S. cortex had little effect on platelet aggregation when compared with a daily cardioprotective dose of acetylsalicylate 100 mg. The total serum salicylate concentration of salicin was bioequivalent to acetylsalicylate 50 mg.(Krivoy 2001)

Rheumatic pain

Clinical data

A multicenter, observational study evaluated the long-term safety, efficacy, and tolerability, as well as comedication patterns with concomitant analgesics, during administration of a willow bark extract product (23% to 26% total salicin) in adults with rheumatic pain mostly due to osteoarthritis and back pain (N=436). The study employed no strict drug regimen by protocol. More than 60% of patients used the willow bark extract as monotherapy, almost 30% used concomitant nonsteroidal anti-inflammatory drugs (NSAIDS) such as diclofenac and ibuprofen, 5.7% used other analgesics such as gabapentin, and only 3.9% comedicated with an NSAID plus an opioid. Reductions in mean pain intensity were observed after 3 weeks via both patient and physician ratings, which were clinically relevant at 6 months, with a 45.6% reduction from baseline. The herbal product was well tolerated and no adverse effects were related to use of willow bark extract.(Uehleke 2013)

Weight loss/Sports performance

Clinical data

No direct evidence exists for the use of willow bark extract in weight loss and sports performance products, although several studies involving combination products containing willow bark have reported positive results; beneficial effects may be due to anti-inflammatory, antioxidant, and analgesic activities because obesity and intense exercise involve inflammatory processes and pain relief increases mobility, exercise performance, and energy consumption.(Shara 2015)

Dosing

Willow is available in various dosage forms, including tablets, capsules, powders, and liquids. A proprietary extract of willow bark, Assalix, has been standardized to contain 15% salicin.Chrubasik 2001 Clinical studies evaluating the analgesic effects of willow bark (eg, for lower back pain, dysmenorrhea) used extracts delivering daily salicin doses of 120 to 240 mg.Chrubasik 2000, Raisi Dehkordi 2019

The pharmacokinetics of salicylic acid delivered from willow bark extract have been investigated, with studies describing a plasma half-life of approximately 2.5 hours.Pentz 1989, Raisi Dehkordi 2019, Schmid 2001 A pharmacokinetic study evaluating salicylic acid from salicin found peak levels within 2 hours after oral administration.Schmid 2001

Pregnancy / Lactation

Avoid use. Information regarding safety and efficacy during pregnancy and lactation is lacking.

Interactions

In general, drug interactions associated with salicylates may apply to willow-containing products; however, actual salicylate content of willow species is likely low.(Vlachojannis 2011) Alcohol, barbiturates, sedatives, and other salicylate-containing products should be avoided because of potential additive irritant effects, including GI tract and platelet function adverse reactions.

Willow bark may also interact with oral anticoagulants, methotrexate, metoclopramide, phenytoin, probenecid, spironolactone, and valproate.(Barnes 2007, Shalansky 2007)

Warfarin: White willow may enhance the anticoagulant effect of warfarin. No action needed.(Shalansky 2007)

Adverse Reactions

Individuals with known hypersensitivity to aspirin, as well as patients with asthma, peptic ulcers, diabetes, gout, hemophilia, hypoprothrombinemia, or kidney or liver disease should be aware of the possible risks associated with the ingestion of willow bark.Barnes 2007 Children younger than 16 years should not use white willow bark extract because of the potential for development of Reye syndrome.Shara 2015

Reports from clinical trials primarily document GI discomfort (eg, nausea, stomachache), dizziness, and rash.

A dog developed life-threatening intestinal bleeding after eating food containing willow bark.Rohner Machler 2004

One review article reported an anaphylactic reaction to willow bark in a 25-year-old patient.Boullata 2003 Acute respiratory syndrome was reported in a 61-year-old female with a medical history of hypertension and osteoarthritis who was taking a dietary supplement containing white willow bark. She presented with sudden onset of shortness of breath and nonproductive cough.Oketch-Rabah 2019

One case of fatal fulminant hepatic failure (FHF) was reported in a 28-month-old boy following treatment with acetaminophen and a traditional aboriginal medicine ("Lake Twig tea"). The herbal medicine contained willow bark and the authors concluded that FHF was the result of toxic synergism between acetaminophen and ASA, which may have been due to salicylates in the willow component.Oketch-Rabah 2019

Toxicology

Information regarding toxicity with use of willow bark is limited. However, toxicities associated with salicylates also apply to willow bark; individuals using willow bark should be monitored for blood in stools, tinnitus, nausea or vomiting, and stomach or kidney irritation.Barnes 2007

References

Disclaimer

This information relates to an herbal, vitamin, mineral or other dietary supplement. This product has not been reviewed by the FDA to determine whether it is safe or effective and is not subject to the quality standards and safety information collection standards that are applicable to most prescription drugs. This information should not be used to decide whether or not to take this product. This information does not endorse this product as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this product. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this product. This information is not specific medical advice and does not replace information you receive from your health care provider. You should talk with your health care provider for complete information about the risks and benefits of using this product.

This product may adversely interact with certain health and medical conditions, other prescription and over-the-counter drugs, foods, or other dietary supplements. This product may be unsafe when used before surgery or other medical procedures. It is important to fully inform your doctor about the herbal, vitamins, mineral or any other supplements you are taking before any kind of surgery or medical procedure. With the exception of certain products that are generally recognized as safe in normal quantities, including use of folic acid and prenatal vitamins during pregnancy, this product has not been sufficiently studied to determine whether it is safe to use during pregnancy or nursing or by persons younger than 2 years of age.

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