and with dietary supplements or medications containing willow bark extracts
Historical Background
Remedies made from the leaves and bark of the willow (Salicis cortex) have held a firm place in medicine for centuries. Willow bark was already used as a medicine in the ancient civilizations of India, the Near East, and Egypt. Hippocrates of Kos (460–370 BC) prescribed willow bark infusions for joint inflammation and fever, while the Roman military physician Padanios Dioscorides recommended willow bark tincture for ear and eye ailments. Hildegard of Bingen (1098–1179 CE) used willow bark to treat bleeding, fever, gout, rheumatism, and urinary disorders. Even back then, willow bark was believed to have anti-inflammatory (antiphlogistic), pain-relieving (analgesic), fever-reducing (antipyretic), and astringent effects.
The active ingredient in willow bark, salicylic acid, was first isolated in 1827 by Johann Andreas Buchner; two years later, Henri Leroux succeeded in extracting approximately 30 g of purified salicin from 1.5 kg of bark (1). At that time, several pharmacists were experimenting with a variety of chemicals related to salicin, the active component of willow extract. They succeeded in producing sodium salicylate—the world’s first industrially manufactured drug—from carbon dioxide and sodium phenolate. However, this preparation was associated with severe side effects (nausea, vomiting) and damage to the stomach lining.
In 1897, the chemist Felix Hofmann synthesized acetylsalicylic acid from salicylic acid. With this derivative of salicylic acid, he had found a compound that had none or only minor side effects compared to sodium salicylate. The Bayer dye factories brought the drug to worldwide fame starting in 1899 under the trademarked name “Aspirin” (2,3).
Chemical and pharmacological composition:
Willows are trees and shrubs with mostly elongated to lance-shaped leaves that belong to the willow family, which comprises approximately 500 species. Their active ingredients are usually extracted from the white willow (Salix alba), the purple willow (Salix purpurea), or the daphne willow (Salix daphnoides). They belong to the willow family (Salicaceae), bloom from March to May, are native to Europe and Asia, and prefer to grow in moist locations.
In addition to salicin, which is converted into salicylic acid in the liver, willow bark also contains other derivatives of salicin (such as salicortin, tremulacin, populin, and fagilin), flavonoids (such as isoquercitrin, kaempferol, and quercetin), catechin tannins, and caffeic acid derivatives. Numerous studies have shown that the content of salicin, flavonoids, tannins, and other components in the plant depends on numerous factors (4,5). One of these factors is the species of willow used. Thus, the average salicin content ranges between 1.5% and 15% depending on the willow species (6,25). The tannins not only give the bark its bitter taste but are also believed to have antimicrobial effects (7).
Uses of willow bark preparations
In traditional medicine, willow bark extracts are used as tea (e.g., Sidroga Cold Tea®, which also contains elderflower and linden blossom, or teas made from chopped willow bark), tinctures, dry extracts, or infusions. In addition to willow bark tea, various willow bark extracts are available in capsules as OTC (over-the-counter) preparations , e.g., as dietary supplements from brands such as Natura vidalis, Herbafit, and Gall Pharma. Combination preparations with devil’s claw and/or stinging nettle are also available. The herbal, non-prescription medicine Assalix (Bionorica®) is no longer available in Germany.
According to the monograph on willow bark by the European Scientific Cooperative on Phytotherapy (ESCOP ), a daily dose of salicin between 120 and 240 mg is typically used (https://escop.com/downloads/salix). In the studies listed below, a willow bark extract standardized to salicin was frequently used. When willow bark extract is consumed as tea, only a portion of the active substances is dissolved. In this case, 8–15 grams of willow bark per day, divided into 3–4 cups of tea, should be administered.
In naturopathy, willow bark extracts are now mostly used for the following indications: rheumatic complaints, gout, back pain, headaches, and menstrual cramps.
Effects in vitro and in animal models
The following effects of willow bark extracts have been demonstrated in various in vitro assays as well as in animal models: inhibition of COX-1, COX-2, LOX (8,9), cytokines (interleukin-1β, TNF-alpha) (10), elastase, hyaluronidase (11), and an antioxidant effect (12). In addition to various salicylates, other components of willow bark, such as polyphenols, flavonoids, and tannins, appear to be responsible for the observed effects (7,8,13).
Results of a PubMed search:
A PubMed search for scientific articles using the keyword “willow bark” yielded (as of July 12, 2024) 185 references, and 60 references for the keyword “willow bark extract.”
Of these, 6 are clinical studies. These exclusively concern musculoskeletal conditions such as chronic back pain, osteoarthritis, and rheumatoid arthritis.
No studies were found for other indications mentioned above, such as fever, menstrual cramps, or headaches.
The PubMed analysis yielded 3 systematic reviews on willow bark extracts, including one Cochrane review on the effects of willow bark extract for “chronic low back pain.”
Use of willow bark extract for chronic back pain
The 2014 Cochrane analysis (14) concludes that daily doses of Salix alba (white willow bark), standardized to 120 mg or 240 mg of salicin, are likely more effective than placebo for short-term pain relief (two studies, 261 participants, moderate quality) (15,16). Another study demonstrated relative equivalence with 12.5 mg of rofecoxib per day (one study, 228 participants), but this was classified as very weak evidence (17). Salix alba had only a minimal effect on platelet aggregation compared to a cardioprotective dose of acetylsalicylate (one study, 51 participants) (16).
Osteoarthritis
A 2-week randomized, double-blind German study investigated the pain-relieving effect of 240 mg of salicin per day in patients with osteoarthritis compared to placebo. The primary endpoint was pain intensity (WOMAC Osteoarthritis Index). Secondary endpoints included the stiffness and physical function dimensions of the WOMAC, daily visual analog scales (VAS) for pain and physical function, and the final overall assessment by patients and investigators. A total of 78 patients (39 receiving willow bark extract, 39 receiving placebo) participated in the study. A statistically significant difference was observed between the active treatment group and the placebo group; the WOMAC pain score had decreased by 14% from baseline after 2 weeks of active treatment, while it had increased by 2% in the placebo group. The patients’ VAS diary confirmed this result, and the final overall assessment also showed the superiority of willow bark extract over the placebo (patient assessment, p = 0.0002; investigator assessment, p = 0.0073).
The authors conclude that willow bark extract exhibits a moderate analgesic effect with good tolerability (18).
In a further 3-arm randomized double-blind study over 6 weeks, the same research group found no statistically significant difference in the WOMAC pain score between willow bark extract (Assplant® from Robugen) and placebo in 127 osteoarthritis patients. The reduction in the pain score was 8 mm (willow extract 240 mg/day), 23 mm (diclofenac 100 mg/day), and 5 mm (placebo) (19). It was concluded that willow bark extract had no relevant efficacy.
In an open-label, multicenter observational study (AWB, funded by Hermes Arzneimittel Munich), 90 patients with knee osteoarthritis or hip osteoarthritis were treated with a standardized willow bark extract preparation (Optovit Actiflex®), 41 patients with conventional analgesic therapy, and 8 patients with a combination of both. After 6 weeks, physicians and patients assessed the efficacy in both groups as comparable; however, the onset of action for the willow bark extracts was delayed compared to standard therapy (20).
Rheumatoid arthritis (RA)
A small German study investigated the efficacy of 240 mg of willow extract (Assplant® from Robugen) compared to placebo in 26 RA patients (19). After 6 weeks of treatment, no significant difference was found between the active substance and placebo regarding the parameters examined (pain VAS, DAS28, HAQ, SF-36). Pain intensity decreased by 8 mm (15%) in the willow extract group and by 2 mm s (4%) in the placebo group, although this study was likely “underpowered” (21). No further studies on RA or other inflammatory rheumatic diseases are available (22).
This is supplemented by an open-label, descriptive observational study by Saller et al. (23), which included 877 patients with various types of musculoskeletal pain (specifically OA, RA, “chronic back pain,” and “soft tissue disorders”). The study duration was 6–8 weeks. The authors assessed the frequency of adverse drug reactions and the efficacy of a willow bark extract. Pain intensity was measured, and the data were compared with the corresponding baseline values. The results showed a tendency toward higher pain scores in patients treated with willow bark; however, the changes over time were not significant compared to the baseline. 38 patients (4.3%) reported 46 adverse drug reactions, which involved the gastrointestinal tract (3.1%) and the skin (1.6%) but were not classified as severe. The absence of a control group was one of several weaknesses of the study.
In an open-label study (AWB), the long-term tolerability of willow bark extract (Proaktiv® from Steigerwald) was investigated in 436 patients with chronic back pain and osteoarthritis. Good tolerability was observed over a 34-week observation period. No relevant interactions with other analgesics (NSAIDs or opioids) were observed (24).
A risk assessment of white willow (Salix alba) in food conducted by the German Federal Institute for Risk Assessment concludes that, despite its long history of use, very little data on the toxicity of white willow bark is available. However, anaphylactic reactions may occur in people with an allergy to salicylates. Some other adverse effects of salicylates are considered to be of little relevance for the long-term use of white willow bark preparations, primarily due to the relatively low concentrations of salicin and the presence of compounds with gastroprotective effects. It is recommended that future studies address the content of heavy metals, primarily cadmium, in the risk assessment of white willow bark in food (25). A value of 0.5 ppm should not be exceeded.
The U.S. Pharmacopeia Safety Review (USP) notes that no data are available on the use of willow bark preparations in pregnant women and children and therefore recommends a warning on the packaging: Not suitable for children, pregnant or breastfeeding women, or individuals with known aspirin hypersensitivity (26).
The scientific evidence is insufficient to recommend the prescription and use of willow bark extracts for patients with symptoms resulting from a defined inflammatory rheumatic condition. The effects of components from willow bark extracts on inflammatory mediators in vitro do not allow for the conclusion that the plant’s anti-inflammatory components are effective in vivo. Larger systematic controlled clinical trials in patient cohorts with clearly defined rheumatological conditions are not available.
A mild, short-term analgesic effect has been reported for osteoarthritis pain. Therefore, if there is no rheumatological indication for new or intensified antirheumatic or analgesic therapy, but the patient has an urgent desire for treatment, treatment initiated by the patient with commercially available willow bark preparations need not be discouraged.
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Last updated: October 1, 2024