Willow Bark

Generic name: Salicis Cortex, Salix Alba L., Salix Fragilis L., Salix Purpurea L.
Brand names: Crack Willow, Purple Osier Willow/basket Willow, Weidenrinde, White Willow, Willow

Usage of Willow Bark

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)

Willow Bark side effects

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

Before taking Willow Bark

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

How to use Willow Bark

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

Warnings

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

What other drugs will affect Willow Bark

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)

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