WILLOW BARK


By Biomedical Engineer Mark Lubin

13 Patents issued or pending with USPTO



Willow bark has been documented nearly continuously use for some 4,000 years to treat fever and rheumatism.  Herbalists Foster and Hobbs (2002) documented that willow has anti-inflammatory, analgesic, antipyretic, and antiseptic properties.  The bark was often traditionally used, but Culpeper suggested the sap from inside the bark (which also contains salicylic acid) could be used to produce beneficial effects against these same complaints.  The leaves have also been defused (steeped into a tea) or even eaten raw to alleviate headaches, arthritis, colds, flu and urinary tract infections.  American Indians also chewed the bark to lower fevers, sore throats, relieve toothaches, sore throats and tonsil inflammation and also prepared poultices from willow for rashes, sores, itching, and cuts.  Willow contains several salicin glycoside compounds.  The salicin molecule will split off in the body, providing a good portion of willow’s anti-inflammatory and analgesic effects.  Natural salicin from willow is slower acting than aspirin, but it does not come with aspirin’s adverse gastrointestinal effects because of its constituent complex of buffers and digestive aid components (Kammerer et al, 2005).  The bark is especially high in certain tannins, which help reduce gastrointestinal discomfort.   


Blumenthal M, et al.  Expanded Commission E Monographs.  Integrative Medicine Communicatons, 2000.

  

Culpeper, N.  The English Physitian. 1653.


Duke, JA.  CRC Handbook of Medicinal Herbs. CRC Press: Boca Raton, FL, 1985


Duke, JA.  CRC Handbook (and Database) of Biological Activities of Phytochemicals, CRC Press: Boca Raton, FL, 1992.

 Database http://www.ars-grin.gov/duke   


Ellingwood F.  American Materia Medica, Therapeutics, and Pharmacognosy. Portland: Eclectic Med. Publ., 1983


Foster S, Hobbs C.  Medicinal Plants & Herbs. Boston, Houghton Mifflin, 2002.


Griffith HW. Healing Herbs:  The Essential Guide.  Tuscon: Fisher Books,2000.


Hobbs C. Stress & Natural Healing. Loveland, CO: Interweave Press, 1997


Kammerer B, et al.  HPLC-MS/MS analysis of willow bark extracts contained in pharmaceutical preparations.

 Phytochem Anal. 2005 Nov-Dec;16(6):470-8.


Mabey R,  Mcintyre, M.  The New Age Herbalist.  Prentice Hall, 1988.


Schauenberg P, Paris F.  Guide to Medicinal Plants.  Keats Publ., 1977


Weiss RF.  Herbal Medicine. Gothenburg, Sweden: Beaconsfield, 1988.


Wood M.  The Book of Herbal Wisdom. Berkely, CA: North Atlantic, 1997.


Willow Bark - Research

 

Probably the first clinical study on willow bark was performed by Rev. Edward Stone of Oxfordshire.  In the 1760s, he gave 1 dram (1.8 gram) to 50 patients with rheumatic fever, and cured them all to one degree or another (Vane 2000).  


While salicylic acid has been shown to inhibit both COX enzymes, other flavonoids in willow have also been shown to inhibit or moderate both COX-1 and COX-2 enzymes as well (Li et al. 2008).  In another study of willow and its constituents at Cairo Univ. (Khayyal et al 2005) it was found that the extract produced the same or greater ability to inhibit COX-enzymes, reduce inflammatory cytokines, reduce leukocyte infiltration, and suppress prostaglandins compared to both aspirin and celecoxib.  This study also showed that willow extract has a significant ability to reduce malondialdehyde (a reactive species causing toxicity) levels, and exhibited profound superiority in the area of reducing free radicals.  The researchers found that a number of the polyphenols in willow have free radical scavenger properties.  


Some of the studies of the analgesic (and other) properties of willow bark extract are referenced here.  In one review of randomized human clinical studies on willow bark, three studies confirmed results with analgesic effects similar (and not inferior) to rofecoxib for backache and one confirmed analgesic effects for osteoarthritis (Vlachojannis et al 2009).  


In a randomized, placebo-controlled double-blind clinical trial at the Univ. of Sydney (Chrubasik et al 2001), 228 outpatients with acute low-back pain took either willow bark extract or COX-2 inhibitor drug rofecoxib.  After four weeks of treatment, about 60% of the 114 patients that took a 240 mg extract from willow bark experienced at least a 30% improvement in the Total Pain Index to the treatment, and 60% of the 114 patients that took rofecoxib (now withdrawn from the market) also responded well.  In other words, the two groups responded practically identically.  The authors noted that the primary difference between the two treatments was the cost, the willow bark being a lot less expensive.

 

In an open German university study, Chrubasik (2001), with some of the same researchers as the previous Chrubasik study, tested three groups of patients who used either 240 mg of willow extract supplemented with conventional pain drugs, 120 mg of willow bark supplemented with conventional pain drugs, or only conventional drugs.  Only 18% of the 224 control patients (only conventional drugs) were pain-free after 18 months.  On the other hand, 40% of the 115 patients who used 240 mg of willow extract plus conventional drugs were pain-free, and 19% of the 112 patients who used the 120 mg of willow extract were pain-free after 18 months.  This study also shows that willow bark extracts can be taken in therapeutic dosages for extended periods with no observed adverse effects.


Taxis and Heide (2004), in a study of willow bark at the Eberhard Karls Univ. in Germany, tested 127 outpatients with osteoarthritis and 26 patients with rheumatoid arthritis in two trials of six weeks duration.  Randomized patients took either 240 mg of salicin extracted from willow per day, diclofenac, or a placebo. In the OA trial, those taking the salicin extract averaged a 17% reduction in pain compared with 10% reduction in the placebo group.  Among the RA patients, the mean pain reduction was 15% compared to 4% among the placebo group.  It should be noted that this was specifically a salicin extract of willow, less efficacious than the more active willow constituent salicylic acid and the other co-resident chemicals in a complete extract.  A whole herb extract containing the various other efficacious constituents would likely have faired better.


This was illustrated by a clinical trial at Germany’s Univ. of Tübingen (Schmid et al 2001).  Ten healthy volunteers took a whole willow bark extract with the equivalent of 240 mg of salicin in two doses three hours apart.  Over the next 24 hours, the blood of the volunteers was tested for salicylates in the blood stream.  Salicylic acid was 86% of the total salicylate content in the blood.  Salicyuric acid was 10%.  Gentisic acid was 4%.  The amount of salicylic acid in the blood corresponded to the metabolism of only 87 mg of synthetic acetylsalicylic acid.  The researchers concluded that the formation of salicylic acid alone was unlikely to explain analgesic or anti-rheumatic effects of willow bark, and that the total effect could only be explained by the combined synergistic action of all the extract's constituent phytochemicals.  This is reinforced by the conclusions reached by Phillipson (2001) that there is much beneficial synergism in herbal medicine both within and between individual plants that allows them to generally be gentler while being as, if not more, effective in many ways than products made of a single chemical specie (drugs) with one specific physiologic action.   


In another randomized, double-blind study at the University of Tübingen (Schmid et al. 2001), 78 patients took either 240 mg of willow bark extract or placebo for two weeks.  After the two week period, the average pain score (WOMAC standardized index) of the willow bark group was reduced by 14%, while the placebo group was reduced by 2%.  The authors concluded that the study confirmed willow’s analgesic effects.  


Willow bark does cause a mild reduction in platelet aggregation like aspirin does, but nowhere near the sometimes dangerous levels that aspirin produces.  This is because willow bark contains a variety of other constituents that moderate these effects.  In a study at the Rambam Medical Center in Israel (Krivoy et al. 2001) 51 patients were studied for platelet aggregating reduction comparing willow bark extract with aspirin and a placebo.  The mean platelet aggregating factor from arachidonic acid was 78% (baseline) in the placebo group.  The aspirin group’s platelet aggregating factor was 13% in comparison.  The platelet aggregating factor was 61% for the willow bark extract group.  This illustrated some reduction (78% to 61%), but nowhere near the extreme reduction (that can sometimes cause internal bleeding) of aspirin.


In another randomized, double-blinded study at the Rambam Medical Center (Chrubasik et al 2000) published in the American Journal of Medicine, 210 low back pain patients were given willow bark in either 120 mg doses (67 patients) or 240 mg doses (65 patients), while 59 patients were given a placebo. After four weeks, 39% of the high dose (240 mg) willow treatment group was pain-free. Meanwhile, 21% of the 120 mg willow group was pain-free and 6% (four) of the placebo group was pain-free after the four weeks.  


In order to compare willow extract's results with the pharmaceutical COX-inhibitors for pain reduction, Chrubasik and some of the same researchers as in the previous study (2001,2002) did another randomized, double-blind low back pain study in which 183 patients took either 240 mg willow bark extract or rofecoxib for four weeks.  Both the willow extract group and the rofecoxib resulted in an identical 44% decrease in pain.  This is a second clinical trial illustrating willow bark extract’s nearly identical effect as COX-2 inhibitor rofecoxib.  


Botanical medicines have been shown to multiple positive side effects, as illustrated by a study at Zürich's Univ. Hospital (Hostanska et al. 2007) with willow bark on the proliferation of colon cancer cells.  It was found that the whole extract and many of willow’s constituents inhibited the growth of these cells.  This was further confirmed by the study of Khayyal et al (2005).


Phillipson (2001) also found that multi-ingredient extracts and/or plant parts impart much gentler, more inclusive, and longer lasting symptomatic remediation that single chemical entity solutions (drugs).



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.


Chrubasik S, et al.  Potential economic impact of using a proprietary willow bark extract in outpatient treatment of low back pain: an open non-randomized study. Phytomedicine. 2001 Jul;8(4):241-51.


Chrubasik S, et al.  Treatment of low back pain with a herbal or synthetic anti-rheumatic: a randomized controlled study. Willow bark extract for low back pain. Rheumatology. 2001 Dec;40(12):1388-93.


Hostanska K, et al.  Willow bark extract and its fractions suppress growth and induce apoptosis in human colon and lung cancer cells. Cancer Detect Prev. 2007;31(2):129-39.


Kammerer B, et al.  HPLC-MS/MS analysis of willow bark extracts contained in pharmaceutical preparations.

 Phytochem Anal. 2005 Nov-Dec;16(6):470-8.


Khayyal M, et al.  Mechanisms involved in the anti-inflammatory effect of a standardized willow bark extract.

 Arzneimittelforschung. 2005; 55 (11): 677-687.


Krivoy N, et al.  Effect of salicis cortex extract on human platelet aggregation.  Planta Medica. 2001; 67 (3): 209-212.


Li X, Liu Z, et al.  Isolation and characterization of phenolic compounds from the leaves of Salix matsudana.

 Molecules. 2008 Aug 3;13(8):1530-7.


Phillipson JD.  Phytochemistry and medicinal plants.  Phytochemistry. 2001 56:237-243.


Schmid B, et al.  Efficacy and tolerability of a standardized willow bark extract in patients with osteoarthritis: randomized placebo controlled, double blind clinical trial. Phytother Res. 2001 Jun; 15(4):344-50.


Taxis K, et al.  Efficacy and safety of willow bark extract in the treatment of osteoarthritis and rheumatoid arthritis: results of 2 randomized double-blind controlled trials. J Rheumatol. 2004 Nov;31(11):2121-30.


Vane JR. The fight against rheumatism: from willow bark to COX-1 sparing drugs. J Physiol Pharmacol. 2000


Vlachojannis JE, et al.  A systematic review on the effectiveness of willow bark for musculoskeletal pain.

 Phytother Res. 2009 Jul;23(7):897-900.



Willow – Safety & Toxicity


Chrubasik et al (2001) showed that willow is safe in patients without contraindications and at the recommended dosages (Blumenthal et al, 2000) for extended periods of time.  The pharmacologic actions and metabolism of salicylates in humans are well-documented and are applicable to willow and the compounds found in it.  Salicin is a prodrug metabolized to saligenin in the GI tract and to salicylic acid after absorption (Meier et al, 1988).  However, as with all herbal medicines that contain various salicylate compounds, some caution is recommended when first prescribing willow bark preparations for patients with a hypersensitivity to salicylates, those already taking aspirin or NSAID's, or those taking pharmaceutical drugs that contain salicylates, oral anticoagulants, methotrexate, metoclopromide, phenytoin, spironolactone, and others.  (This is not meant to be considered as a complete list.)


Some literature sources contain cautionary statements implicating herbal preparations from plants known to contain salicylates (mainly Willow and Meadowsweet) in cases of Reyes syndrome in children.  Nothing could be further from the truth since the salicylates and their derivatives from the plant are metabolized differently than acetyl salicylic acid, the real culprit in Reyes syndrome.     


Other willow bark-drug interactions in individual case reports are include anti-platelet medications or drugs that prolong prothrombin time (PT) (Wichtl and Bisset, 1992).


There are no known health hazards when using willow bark preparations in approved dosages (Blumenthal et al, 2000, Barnes et al, 2002), but the herb should not be taken by patients with asthma, patients with gastrointestinal ulcers, or pregnant or nursing women.


Herbal liquid extracts are expressed as [1:1 (g/ml)], meaning that each ml is 50% pure extract, or 500mg.  Typical recommended therapeutic dosage of willow bark liquid extract is 2ml (Blumenthal et al, 2000, Barnes et al, 2002), 3 t.i.d. or 6,000mg, equivalent to 3,000mg pure willow bark extract.   


Each 2-capsule dose of Arthri Comfort contains less than 0.3mg pure willow bark extract (less than 0.05mg salicin), or approximately 0.07% of the standard dose.  


This amount of willow contains a few dozen active phytochemicals, of which salicins are only a small number and a low percentage.  The quantity of these phytochemicals in a daily dose of Arthri-Zen Relief is not enough to instigate, cause, or prolong any clinically measureable level of anti-coagulation (aka “blood thinning”).   


Abebe W. Herbal medication: potential for adverse interactions with analgesic drugs. J Clin Pharm Ther. 2002 Dec;27(6):391-401.


Barnes J, et al.  Herbal Medicines, 2nd ed.  Pharmaceutical Press:London, 2002


Duke, JA.  CRC Handbook of Medicinal Herbs. CRC Press: Boca Raton, FL, 1985


Duke, JA.  CRC Handbook (and Database) of Biological Activities of Phytochemicals, CRC Press: Boca Raton, FL, 1992.

 Database http://www.ars-grin.gov/duke   


Meier B, et al. Pharmaceutical aspects of the use of willows in herbal remedies.  Planta Med 1988; 54:559-560.


Wichtl M, Bisset NG, eds.  Herbal Drugs and Pharmaceuticals.  1994 Stuttgart: Medpharm Scientific Publishers.