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From The June 2001 Issue of Nutrition Science News
Herb Monograph
Willow Bark: The Aspirin Raw Material
Willow bark (Salix spp.) has been used therapeutically for 2,000 years. Dioscorides, the first century Greek physician, recommended it as a poultice for treating inflammation in his De Materia Medica Libri Quinque. After him, many medical authorities hailed willow bark for its anthelmintic (destruction of parasitic organisms), anti-inflammatory, antipyretic (fever reduction), and hemostatic (hemorrhage control) properties.1
The modern use of willow bark focuses on the discovery and isolation of salicin, the herb's primary active ingredient. In 1860, Hermann Kolbe synthesized salicyclic acid, which was cheaper to produce, and ultimately led to a diminished commercial interest in crude willow bark preparations.2
Willow was officially recognized in the United States Pharmacopoeia (USP) from its 1st edition (1820) until the 10th edition (1926), after which acetyl-salicylic acid—commonly known as aspirin—replaced crude willow bark and willow bark-derived preparations.
Aside from a few clinical studies, knowledge of the therapeutic properties of willow bark preparations is inferred from studies on individual salicylates. Salicylates have demonstrated analgesic, anti-inflammatory, and antipyretic activity. The most commonly used salicylate in use today is acetylsalicylic acid—aspirin.
Salicin-containing plants such as willow bark act in a manner that is therapeutically similar to the actions of aspirin. Significant differences also exist, however, and direct correlative activity cannot be assumed. Historical use and the scant clinical evaluations available suggest that willow preparations have analgesic, anti-inflammatory, and antipyretic activity. However, more studies are necessary since doubts remain regarding the therapeutic efficacy of crude willow preparations. These doubts are due predominantly to the relatively low concentration of salicin contained in crude herb preparations. In contrast, the efficacy of isolated salicylates is well established.
Quantities of salicylates present in willow bark preparations are far less than the quantities of salicylates commonly administered on their own. This has brought the effectiveness of willow bark preparations into question.3 Recent studies have reported a peak plasma level of 10 mM/L following administration of 1,360 mg extract containing 240 mg salicin. This plasma level is far below that of 130 mM/L that occurs following the administration of 500 mg aspirin, a dose common for analgesic and antipyretic activity.4
Much research has been done on the ability of salicylates to suppress the synthesis of prostaglandins—hormones thought to play a role in inflammation, pain, and fever. Two specific enzymes are presently considered to be predominantly involved in the process, cyclooxygenase-1 and -2 (cox-1 and cox-2). Cox-1 is mainly present in platelets, blood vessels, and other organs, whereas cox-2 occurs in inflamed tissues.5
Aspirin (acetylsalicylic acid) blocks the synthesis of prostaglandins through the acetylation of the enzyme cyclooxygenase (PGH-synthase), especially in platelets (cox-1) by an irreversible transfer of the acetyl group into the enzyme. Salicylic acid and salicylates, which lack an acetyl group, are effective only in inhibiting platelet aggregation and only at concentrations that are so high (greater than 300 microgram/ml) as to be clinically irrelevant. However, salicylates have been shown to reduce prostaglandins in body tissues through an inhibition of PGH-synthase in inflamed tissue (cox-2) and are predominantly used for their analgesic properties.5
There may be an advantage to using cox-2 over cox-1 inhibitors since most of the side effects associated with non-steroidal anti-inflammatories (NSAIDs) may be due to a blockage of cox-1.
The anti-inflammatory actions of salicylates may be due to mechanisms independent of prostaglandins. Sodium salicylate has been shown to inhibit the functioning of neutrophils, the most abundant cells associated with acute inflammation.2
Human Clinical Studies
A randomized, double-blind, placebo-controlled clinical trial investigated the analgesic effects of a standardized willow bark extract. Seventy-eight patients with osteoarthritis of the knee and/or hip were given either four tablets/day of 1,360 mg extract containing 240 mg total salicin/day or placebo for two weeks. The pain subscale of the WOMAC index, a questionnaire developed at McMaster's University in Western Ontario to measure symptoms of osteoarthritis, was used as the primary outcome measure. Secondary outcomes measures included total WOMAC scale (including pain, stiffness, and function subscales), daily visual analog scales for pain and function, and final assessment by the physicians and patients. As determined by a change in the WOMAC pain index, a significant analgesic effect was observed by day 14. According to the researchers, the analgesic effect was reported to be comparable to the effect of tenoxicam (20 mg/day) and approximately 40 percent lower than the effect of diclofenac (150 mg/day). In this study, adverse events were reported to be less frequent in the treatment group than in the placebo group.4
Structure/Function Claim:
Direct evidence regarding the anti-inflammatory activity of willow is lacking. Most data regarding the activity of willow are inferred from pharmacological research of aspirin. Based on the lack of understanding of the physiological mechanisms associated with the activity of willow, a conclusive determination cannot be made. |
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Early clinical observations of 120 patients with varying rheumatic diseases found that 70 percent of patients experienced improvement up to the point where respective joints were completely free of pain and fully mobile. In cases of chronic rheumatic illness, improvement did not occur immediately but did after one to four weeks of treatment. The preparation used was described as a total extract (1:l) of fresh willow bark. The usual dose was one teaspoon diluted in half a glass of water three times daily after meals. The dose was increased to two to three teaspoons three times daily in cases of acute illness or fever. The authors found the preparation to be a strong antirheumatic, antineuralgic, and antipyretic with no undesirable side effects. One patient with a stomachache was improved by a dose of sodium carbonate.1
A recent Israeli study found that willow bark was effective in treating lower back pain. In a four-week, randomized, double-blind, placebo-controlled study, 210 patients with chronic lower back pain were divided into three groups and given either a placebo or an extract containing either 120 mg or 240 mg salicin for a daily dose of 480 mg or 960 mg, respectively. Of the 191 patients who completed the study, four (6 percent) in the placebo group became pain-free, 15 (21 percent) in the 120 mg dosage group, and 27 (39 percent) in the 240 mg group. Researchers concluded that willow bark, especially at higher dosages, was an effective alternative to treatment with NSAIDs.6
During the 1970s in Europe, willow bark preparations were used intermittently with NSAIDs, with the NSAIDs used only when acute arthritis pain did not respond to salicin-containing preparations such as willow bark. Such a therapeutic strategy may lessen the side effects associated with NSAIDs. Improvement from willow bark treatment is usually observable within one to four weeks, sometimes preceded by a transient worsening of symptoms, then followed by a significant decrease in discomfort, swelling, and inflammation. In some cases, improvement is seen within the first few days of therapy.1,4
Other Considerations
Historically, willow bark has been used as an antipyretic, anti-inflammatory, and analgesic. Despite a lack of clinical trials, these uses have persisted for several hundred years. This, along with willow bark's similarities to aspirin, suggest these indications are substantiated. In modern herbal therapy, willow bark is predominantly used as an anti-inflammatory for relief of gouty arthritis and as an analgesic for mild neuralgic pain, toothaches, and headaches. It is not widely used for its fever-fighting activity, having been replaced by diaphoretics (agents that cause sweating) and other antipyretics effective at lowering fevers.7,9
Of primary importance when addressing the general level of efficacy of willow bark preparations is evaluating whether to use anti-inflammatories at all. Inflammation is a homeostatic response to pathogens and tissue injury. Inhibiting such processes may do more harm than good and may be associated with some degree of cellular and organ system toxicity. The use of anti-inflammatories should therefore be carefully considered, restricted to a limited time, and followed up with more appropriate therapies to address the underlying cause of inflammation.
Although aspirin is the best-known salicylate, it has a distinction in its ability to inhibit platelet aggregation. Salicin-containing preparations, because they lack an acetyl group, do not inhibit platelet aggregation and therefore should not be used as substitutes for aspirin in a preventive thrombolytic protocol against strokes and heart attacks.2,7,8 On the other hand, salicin preparations from crude willow bark do not present a hemorrhagic risk and may be clinically advantageous for some.
More clinical studies are needed to establish the therapeutic effectiveness of willow bark preparations. Upon determination of efficacy, additional questions need to be investigated. These include the possible pharmacokinetic advantage of the glycosidic form present in the bark in sustaining plasma salicylate levels and the possibility of activity of constituents other than salicylates. In the meantime, due to the wide variation of salicin content in willow bark, care should be taken to obtain products that deliver an effective concentration of salicin.
Excerpted with permission from American Herbal Pharmacopoeia and Therapeutic Compendium, a bimonthly series of peer-reviewed monographs. Complete monographs are available individually or by subscription and are published by the American Herbal Pharmacopoeia, Santa Cruz, Calif.
References
1. Mayer R, Mayer M. Mayer R, Mayer M. Biological salicyltherapy with cortex salicus [Weidenrinde]. Pharmazie 1949;4:77-81.
2. Weissmann G. Aspirin. Sci Am 1991;264(1):84-90.
3. Tyler VE. Herbs of choice: the therapeutic use of phytomedicinals, 3rd ed. New York: Pharmaceutical Prod Pr:1994 209 p.
4. Schmid BM. Schmid BM. Handling of Cox and Gonarthroses with a dry extract of salix purpurea x daphnoides [dissertation]. Tubingen 1998:233 p.
5. Hardman J. editors, et al. The pharmacological basis of therapeutics, 9th ed. New York: McGraw-Hill;1996:1,905 p.
6. Chrubasik S, et al. Treatment of low back pain exacerbations with willow bark extract: a randomized double-blind study. Am J Med 2000 Jul;109(1):9-14.
7. Bradley PR, editor. British herbal compendium, vol. 1. Bournemouth (UK): British Herbal Medicine Assoc. 238 p.
8. Meier B, Leibi M. Salicinhaltige pflanzliche arzneimittel. Z. Phytother; 1990 11:50-8.
9. Blumenthal M, et al. The complete German Commission E monographs—therapeutic guide to herbal medicines. Klein S, translator. Austin: American Botanical Council, 1992. 685 p.
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