Willow bark has analgesic effects but lacks antithrombotic effects. It should not be used in salicylate-sensitive individuals.
[LFODPKM ] Letter Key
Latin Name
Salix alba L. (white willow) and other species
Family
Salicaceae
Other Common Names
None identified
Description
- Willows encompass woody trees, stemmed shrubs, and creeping shrublets; there are about 400 species worldwide, including about 150 in the Western hemisphere. It is often difficult to identify individual species because of variability and hybridization.
Part Used
Bark (trunk or branch) or young twigs. The outer bark is removed in older trees.
Known Active Constituents
- Willow contains phenolic glycosides including salicin (usually less than 1%). This is the basis for aspirin and salicin esters (salicortin 0.03% to 4% or 2’-O-acetlysalicortin 0.5% to 10%); 2’-O-acetlysalicin, also called fragilin (0.03% to 4%); and tremulacin (0.12% to 2%). Total salicin content varies; species rich in salicin include S. daphnoides, S. purpurea, and S. fragilis, which may contain up to 10%. Other phenolic glycosides vary by species.
- Willow also contains flavonoid glycosides including (+)- and (—)-naringenin-5-glucoside, naringenin-7-glucoside, eriodictyol-7-glucoside, polyphenols, and chalcone glycosides, biflavones, flavanones, and condensed flavanones (1).
Mechanism/Pharmacokinetics
- Salicortin is hydrolyzed in the small intestines into salicin and esters (which are subsequently hydrolyzed to saligenin and glucose). Saligenin is oxidized to salicylic acid.
- In a pharmacokinetic study in 10 participants, 1,360 mg extract (containing 240 mg total salicin) was administered in two doses 2 hours apart. The half-life was 2.45 hours; peak levels were reached at 4 to 6 hours, and the C max was 10 mmol/L (this is less than 10% of salicylate levels after administration of 500 mg aspirin). A 24-hour urine collection showed that 16% of administered salicylate was excreted in urine (71% as salicyluric acid).
- Administration of salicin (4 g, equivalent to 1,730 mg saligenin) to a single individual resulted in a C max of 100 µg/mL (2). The bioavailability of salicylic acid from salicin is estimated to be less than 20% (1).
[Outline]
[CAO ] Letter Key
Clinical Trials
- Pain
- A randomized, double-blind trial of willow bark in 210 participants (191 completed) with chronic low back pain tested two doses (60 mg b.i.d. or 120 mg b.i.d.) for 4 weeks (3). Use of tramadol was allowed. The primary endpoint was being pain-free without tramadol for 5 days in the last week of the trial. Willow bark was significantly more effective than placebo; the primary endpoint was achieved by 7% of the placebo group, 25% of the group treated with 120 mg/day willow bark, and 41% of the group treated with 240 mg/day. One treated patient experienced an allergic reaction (rash, swollen eyes, pruritus) that resolved within 2 days of discontinuing treatment.
- A proprietary willow bark extract (Assalix, containing 240 mg salicin/day) was compared with rofecoxib (12.5 mg/day) for 4 weeks in an open, randomized trial in 228 participants (183 completed) with low back pain (4). Participants were allowed to use other analgesics or treatments (most did not, and there were no significant differences between groups in this respect). After 4 weeks, treatments were equivalent, as assessed by a modified Arhus index and the Total Pain index.
- A randomized, placebo-controlled double-blind study of 78 patients with osteoarthritis of the knee and hip compared placebo with coated tablets containing 1,360 mg willow bark extract (in divided doses) for 2 weeks. There was a significant difference between the groups receiving willow and placebo on a visual analog scale, a pain index, and patient assessment (5).
- Platelet aggregation (see questions and answers)
- Willow bark has a mild effect on platelet aggregation but is not equivalent to aspirin. In 35 patients randomized to white willow extract (containing 240 mg salicin/day) or placebo, the mean maximal arachidonic acid-induced platelet aggregation was 61% in the willow-treated group and 78% in the placebo-treated group (6). In a separate group of patients with heart disease, given 100 mg/day acetylsalicylate, the mean maximal arachidonic acid-induced platelet aggregation was 13%. Compared with placebo, willow bark significantly reduced arachidonic acid-induced and adenosine diphosphate (ADP)-induced (but not collagen-induced) platelet aggregation.
Animal/In Vitro
- Tremulacin administered subcutaneously exerts an antiinflammatory effect in two animal models: the carrageenan-induced rat paw edema test and the croton oil-induced mouse ear edema test.
- In vitro tests did not show prostaglandin inhibition with salicin, salicortin, or crude extracts; salicin and salicortin marginally inhibited 5-lipoxygenase. Tremulacin inhibited leukotriene production by 30% in a test of stimulated rat pleural leukocytes.
- Antifungal effects in vitro have been demonstrated against Penicillium digitatum, Botrytis cinerea, and three species of Aspergillus (1).
Other Claimed Benefits/Actions
- Antiseptic
- Antiinflammatory
- Antipyretic
- Antifungal
- Plantar warts (topical)
- Burns and wounds (topical)
[Outline]
Q: Can willow preparations be used as antithrombotic agents?
A: No. Although aspirin (acetylsalicylic acid) causes irreversible inhibition of platelet aggregation, salicin lacks this effect. White willow extract has a mild inhibiting effect on platelet aggregation, but aspirin is much more potent and has been shown to be effective in clinical trials with cardiovascular disease endpoints.
Q: Can willow be used in salicylate-sensitive individuals?
A: I would avoid this use, although the amount of salicylate is low.
Q: How long has willow been used?
A: The first recorded description of therapeutic use of willow is from Hippocrates, who recommended chewing willow bark for analgesia in childbirth. Dioscorides recommended it as an analgesic, and Galen was the first to describe its antipyretic and anti-inflammatory properties (8). White willow was a folk remedy in England and was studied in about 50 patients with fevers or inflammatory conditions by Reverend Edward Stone of Oxfordshire, England, who was looking for an antipyretic substitute for the expensive cinchona imported from South America (8).