Willow Bark, Meadowsweet and the Natural Salicylates Behind Aspirin

When Felix Hoffmann wrote up his pure, stable acetylsalicylic acid in the laboratory at Elberfeld in August 1897, he was finishing a story that had begun in the plant world thousands of years earlier. The molecule he started from, salicylic acid, takes its name from Salix, the Latin name of the willow. The name of the finished medicine, aspirin, is generally explained as “a” for acetyl plus “spir” from Spiraea, the old botanical name of meadowsweet. Both of the plants that gave aspirin its chemistry and its name had been used as folk remedies long before any chemist could say what was in them.

This page follows that natural-medicine thread: willow bark in the ancient world as the historians of medicine describe it, the country clergyman who reported willow powder for fevers to the Royal Society in 1763, the chemists who pulled the bitter principle salicin out of the bark, meadowsweet and its “Spirsäure”, the move from plant extract to laboratory synthesis, and the first bedside reports of 1876. It then turns to what modern science has found about salicylates themselves: why plants make salicylic acid, how much of it turns up in ordinary fruit, vegetables, herbs, spices and tea, why people who never take aspirin still carry some in their blood, and what the modern trials of willow bark extract reported. The story of Hoffmann’s own synthesis and of the credit dispute around it is told on a separate page of this wing.

Table of Contents

  1. Willow Bark in the Ancient World
  2. Edward Stone’s Letter to the Royal Society, 1763
  3. Salicin: Buchner and Leroux Extract the Bitter Principle
  4. Meadowsweet and the ‘Spir’ in Aspirin
  5. From Plant to Laboratory: Piria and Kolbe
  6. Salicin and Salicylic Acid at the Bedside, 1876
  7. Why Plants Make Salicylic Acid
  8. Salicylates in Fruit, Vegetables, Herbs, Spices and Tea
  9. Salicylic Acid in the Blood of People Not Taking Aspirin
  10. Willow Bark Extract in Modern Trials
  11. Key Research Papers
  12. Connections
  13. Featured Videos

1. Willow Bark in the Ancient World

Willows grow along riverbanks and in wet ground across Europe, Asia, North Africa and North America, and their bark and leaves have a long history as folk remedies for pain and fever. Modern reviews of aspirin’s history begin the story with the earliest civilisations. Montinari, Minelli and De Caterina, writing in 2019 under the title “The first 3500 years of aspirin history from its roots”, trace the use of willow from the Sumerians and the ancient Egyptians through the physicians of Greece and Rome. John Wood’s 2015 commentary for the Royal Society covers the same ground in outline before reaching the eighteenth century.

The figure most often named in these accounts is Hippocrates, the Greek physician of the fifth and fourth centuries BC. The reviews state that Hippocrates knew willow bark or leaves as a remedy for inflammatory pain. It is worth being clear about what kind of claim this is. The Hippocrates–willow story is repeated from review to review; the reviews cited here do not quote a specific Hippocratic passage, so on this page it is reported as what the historians of aspirin say rather than as a demonstrated fact from the ancient text.

What the bark actually contains

What the ancients could not know is why willow might ease pain. The answer, worked out in the nineteenth century, is that willow bark contains salicin, a bitter compound in which a salicyl alcohol unit is joined to a sugar (glucose). Chemists call this kind of molecule a glycoside. In the body, salicin is broken down and converted into salicylic acid, the same active core that every later salicylate medicine, aspirin included, delivers. Willow bark is therefore not “natural aspirin” in a strict sense: it delivers salicylate by a slower, indirect route, and it lacks the acetyl group that gives aspirin its particular, long-lasting effect on blood platelets (explained on the How Aspirin Works page of this wing).

The bark also carries other plant compounds besides salicin. How willow bark extract performs when it is tested as a whole returns in section 10.

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2. Edward Stone’s Letter to the Royal Society, 1763

The first account of willow bark written in the form of a clinical report came not from a physician but from a clergyman. The Reverend Edward Stone of Chipping Norton in Oxfordshire sent a letter to the Earl of Macclesfield, then President of the Royal Society, describing his success in treating “agues” with powdered willow bark. It was printed in the Society’s Philosophical Transactions in 1763 under the title “An account of the success of the bark of the willow in the cure of agues”.

What an “ague” was

“Ague” was the everyday English word for an illness of recurring fevers and shivering fits. In the marshy parts of eighteenth-century England much of it was probably malaria. The established remedy was Peruvian bark — cinchona, the source of quinine — which was imported and expensive. Stone was looking for a cheaper home-grown substitute, and he was drawn to willow by its taste: like cinchona, willow bark is intensely bitter.

His reasoning and his method

Stone explained his choice with a piece of reasoning common in his day: the idea that the remedies for a disease are often found growing close to its causes. Agues were common in damp, low-lying ground, and willows flourish in exactly that ground. Modern readers will recognise this as a pre-scientific “doctrine” rather than evidence, but it led him to the right plant.

Wood’s 2015 commentary summarises Stone’s method from the letter. Stone gathered about a pound of willow bark, dried it for some three months in a warm place by a baker’s oven, and powdered it. He first tried it on himself, then over roughly five years gave it to about fifty people with agues, reporting success in his letter’s title and text. Hedner and Everts, in their 1998 history of salicylates in rheumatology, likewise place Stone’s report at the start of the modern clinical story.

Two cautions keep this account honest. Stone’s report is a series of observations without a comparison group, and agues often wax and wane by themselves; and willow does not cure malaria the way quinine does — it can lower fever and ease aches, not kill the parasite. What Stone did was describe a remedy, a preparation and a set of results publicly, in a learned journal, so that others could repeat the trial. That is why his letter is treated as the starting point of the scientific history of salicylates.

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3. Salicin: Buchner and Leroux Extract the Bitter Principle

By the early nineteenth century chemists had learned to extract the “active principles” of medicinal plants as pure substances: morphine from opium, quinine from cinchona bark. Willow bark was an obvious next target. Hedner and Everts summarise the period by saying that the active principles of the salicylate plants were isolated by Italian, German and French scientists between 1826 and 1829.

Johann Andreas Buchner

The German pharmacologist Johann Andreas Buchner obtained a bitter substance from willow bark in the late 1820s and named it salicin, after Salix. (Sources differ by a year on the date, giving 1827 or 1828. Wood’s commentary calls Buchner’s product “salicylic acid”, but what he isolated was salicin, the glycoside; salicylic acid came later.)

Henri Leroux

Shortly afterwards the French pharmacist Henri Leroux improved the extraction and obtained salicin in purer, crystalline form. Wood reports that Leroux obtained about 30 grams of purified salicin from 1.5 kilograms of bark — a yield of roughly two per cent, which gives an idea of how much bark lay behind a small amount of active substance. Again the year varies between sources, at about 1829 or 1830.

The isolation of salicin mattered for two reasons. It showed that willow’s bitterness and its medicinal effect could be traced to a definite chemical, and it gave chemists a pure starting material whose structure and reactions they could study. Every later step, from salicylic acid to aspirin, depended on it.

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4. Meadowsweet and the ‘Spir’ in Aspirin

Willow was not the only salicylate plant in the old European herbals. Meadowsweet, a tall perennial of damp meadows and riverbanks with creamy, sweet-smelling flower heads, was used in folk medicine for fevers, aches and stomach complaints. In Hoffmann’s time it was classified in the genus Spiraea, as Spiraea ulmaria; botanists now place it in its own genus as Filipendula ulmaria.

Spirsäure

Chemists working on meadowsweet obtained an acid from it that they called Spirsäure (“spiraea acid”). It turned out to be the same compound that could be made from willow’s salicin: salicylic acid. The two plants, one a tree and one a meadow flower, had led chemists to the same molecule.

The name “Aspirin”

When acetylsalicylic acid was put on the market in 1899 it was given a coined name rather than its chemical one. The usual explanation, given by the Science History Institute and by Wood, is that “A” stands for the acetyl group and “spir” recalls Spiraea, the old name of meadowsweet (Wood words it as acetyl plus Spirsäure). The two versions agree on the essential point: aspirin is named after meadowsweet, not after willow. Wood goes further and states that the 1897 product used salicylic acid derived from meadowsweet; historians of chemistry generally note that by the 1890s salicylic acid was being made synthetically on an industrial scale (see the next section), so the meadowsweet connection is best understood as one of name and lineage rather than of raw material.

What modern analysis finds in the plant

Meadowsweet’s chemistry has since been measured in detail. A 2023 study by Savina and colleagues compared extracts from the flowers, upper and lower leaves, roots and fruits of Filipendula ulmaria and reported salicylic acid among the phenolic acids found in the flowers, fruits and roots, together with flavonoids such as spiraeoside in the flowers and fruits. The site’s Meadowsweet pages cover the herb itself in more depth.

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5. From Plant to Laboratory: Piria and Kolbe

Salicin was a glycoside, not yet an acid. The step from salicin to salicylic acid is credited to the Italian chemist Raffaele Piria, who broke salicin down into its sugar and its aromatic part and oxidised the latter to salicylic acid. With that step the medicinal core of willow was available as a pure acid, and physicians could give it in measured amounts. (Piria’s work is usually dated to the late 1830s; this page leaves the exact year aside, as no source fetched for it confirms it.)

Making salicylic acid without the plant

The next move was to make salicylic acid without any plant at all. Hedner and Everts state that salicylic acid was first synthesised by the German chemist Gerland in 1852. In 1860 the German chemist Hermann Kolbe published a short paper, “Ueber Synthese der Salicylsäure” (“On the synthesis of salicylic acid”), in the Annalen der Chemie, describing a route to the acid from simple starting materials rather than from a plant. Kolbe’s chemistry, later refined by others into an industrial process, made salicylic acid cheap and plentiful.

Why it mattered

This was a turning point in the natural-medicine story. Until then, a salicylate medicine had to start in a willow plantation or a meadow, with all the variation that plant material brings: different species, seasons and soils give different amounts of salicin. Once salicylic acid could be made in a factory, it became uniform and inexpensive. That availability, more than anything else, is what put salicylates into general medical use in the 1870s and set the stage for chemists, Hoffmann among them, to try to improve the molecule two decades later. The chemistry of the 1853 acetylated compound and of Hoffmann’s 1897 synthesis is described on the 1897 Synthesis page.

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6. Salicin and Salicylic Acid at the Bedside, 1876

The year 1876 is remembered in the history of rheumatology as the year salicylates arrived at the bedside in a systematic way. Two lines of work appeared almost together.

Thomas Maclagan in Dundee

Thomas Maclagan, a physician in Dundee, Scotland, published “The treatment of acute rheumatism by salicin” in The Lancet in March 1876, with further instalments in later issues that year. Acute rheumatism — rheumatic fever, with hot, swollen, painful joints and fever — was a common and frightening illness. Maclagan gave salicin, the willow principle, and reported that it relieved the fever and joint inflammation of his patients.

Stricker and Reiss in Germany

In the same year, according to Hedner and Everts, the German physicians Stricker and Reiss gave the first reports of salicylic acid in rheumatic disorders. (Hedner and Everts spell the first name “Stricher”.) Salicylic acid and its sodium salt, sodium salicylate, quickly became the standard treatment for acute rheumatism and were widely used for pain and fever.

The problem that followed

The new medicines were effective but hard to take. Salicylic acid irritates the mouth and stomach, and the large doses given for rheumatic fever often brought nausea, ringing in the ears and stomach upset. Hedner and Everts note that gastrointestinal intolerance and bleeding with salicylates were reported early but were largely neglected until the 1950s. It was this burden of side effects that chemists in the 1890s hoped to reduce by modifying the molecule — the problem that led to Hoffmann’s acetylsalicylic acid. More on aspirin’s own effects on the stomach appears on the site’s Aspirin page.

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7. Why Plants Make Salicylic Acid

For most of the history above, salicylates were seen only from the human side: something in bark or flowers that eased fever and pain. Twentieth-century plant science asked a different question — why do plants make salicylic acid at all? The answer is that salicylic acid is one of the plant’s own hormones.

A defence signal

Plants cannot run from infection, so they rely on chemical signalling. When a leaf is attacked by a bacterium, fungus or virus, salicylic acid levels rise at the site of infection and help switch on defence genes. The signal also travels, so that parts of the plant far from the original infection become more resistant to later attack, an effect plant biologists call systemic acquired resistance. Duthie and Wood, in their 2011 review of natural salicylates, describe salicylic acid in exactly these terms, as a compound plants produce in response to pathogens and other stresses.

The same molecule, many targets

Dempsey and Klessig, in a 2017 review in BMC Biology, describe salicylic acid as a multifaceted plant hormone that acts through many different protein targets in plants, and they discuss evidence that it also binds a range of proteins in animal and human cells. Their review frames an interesting question for the aspirin story: the medicine that humans developed from willow is built on a molecule that plants evolved for their own protection, and some of the ways it acts may be shared across the two kingdoms.

One practical consequence follows from the plant’s biology. Because salicylic acid rises when a plant is under attack or stress, the amount in any given fruit, vegetable or herb is not fixed; it varies with variety, growing conditions, ripeness and processing. That is one reason the food measurements in the next section differ so much from study to study.

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8. Salicylates in Fruit, Vegetables, Herbs, Spices and Tea

If plants make salicylic acid, then plant foods would be expected to contain it, and they do. Measuring how much has proved difficult, and published figures vary widely depending on the method.

The 1985 survey of 333 foods

The most widely cited early survey is that of Anne Swain, S. P. Dutton and A. Stewart Truswell, published in the Journal of the American Dietetic Association in 1985 under the title “Salicylates in foods”. They analysed 333 foods. Their main findings were:

Spices are eaten in small amounts, so a high concentration per 100 g does not necessarily mean a large intake; fruit and tea, eaten and drunk daily, contribute in a steadier way.

The 2011 review

Duthie and Wood’s 2011 review in Food & Function brought the picture up to date. In the United Kingdom, they reported, the main dietary sources of salicylates are tomato-based sauces, fruit and fruit juice, tea, wine, and herbs and spices. Published estimates of daily dietary salicylate intake ranged from 0.4 to 200 mg per day — a five-hundred-fold range that reflects both real differences in diet and large differences in analytical method. The authors also cautioned against over-emphasising salicylates as the explanation for the health associations of plant-rich diets, since fruit, vegetables and spices carry many other active compounds.

Where the site’s food pages fit

Several of the foods and herbs in these surveys have their own pages on the site, among them Thyme, Rosemary and Green Tea. Those pages describe each plant’s wider chemistry; salicylate is only one part of it.

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9. Salicylic Acid in the Blood of People Not Taking Aspirin

A natural follow-up question is whether the salicylates in food actually reach the bloodstream. A Scottish research group that included John Paterson set out to measure this.

Vegetarians, non-vegetarians and aspirin users (2001)

Blacklock and colleagues, publishing in the Journal of Clinical Pathology in 2001, measured salicylic acid in the serum of three groups: 37 vegetarians living in a Buddhist monastery, 39 non-vegetarians, and patients taking low-dose (75 mg daily) aspirin. The findings were:

The authors connected the vegetarians’ higher levels to their larger intake of plant foods. The study was small and observational, and it measured blood levels, not any health outcome.

The body makes some salicylic acid itself (2008)

A later paper by Paterson and colleagues in the Journal of Agricultural and Food Chemistry (2008), titled “Salicylic acid sans aspirin in animals and man”, added a surprise. Salicylic acid persisted in human plasma even during fasting, when no food was being eaten. Using benzoic acid labelled with a heavy, non-radioactive form of carbon (13C), the researchers showed that the body converts some benzoic acid into salicylic acid: after a labelled benzoic acid load, a median of 33.9 per cent of the salicyluric acid in the urine (the main breakdown product of salicylate) carried the label. Benzoic acid itself occurs naturally in many fruits and spices and is also used as a food preservative.

Taken together, these papers show that salicylic acid is a normal, low-level constituent of human blood, coming both from plant foods and from the body’s own chemistry. Whether these small amounts have any measurable effect on health remains a research question; the levels involved are far below those produced by medicinal doses of aspirin.

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10. Willow Bark Extract in Modern Trials

The plant at the start of the story has also been tested in its own right. Willow bark extract, standardised to its salicin content, has been studied in randomised trials, mainly for back pain and joint pain. The findings below are reported as research results.

Low back pain (2000)

Chrubasik and colleagues, in a randomised double-blind study published in the American Journal of Medicine in 2000, gave 210 patients with flare-ups of low back pain either a willow bark extract providing 240 mg of salicin a day, an extract providing 120 mg, or a placebo. In the final week of treatment, 39 per cent of patients in the higher-dose group were pain-free, compared with 21 per cent in the lower-dose group and 6 per cent in the placebo group (P<0.001). The authors reported one severe allergic reaction in the study. The dose-related pattern — more salicin, more patients pain-free — was one of the trial’s key points.

The 2009 systematic review

Vlachojannis, Cameron and Chrubasik reviewed the trials of willow bark for musculoskeletal pain in 2009 in Phytotherapy Research. They concluded that there was moderate evidence for an ethanolic willow bark extract in low back pain; that the results in osteoarthritis were conflicting; and that a trial in rheumatoid arthritis found no significant effect but was underpowered, meaning it was too small to detect a modest benefit with confidence. (Chrubasik was an author on both the 2000 trial and the review.)

Hazards reported in the research

Because willow bark is a source of salicylate, the research raises the same kinds of concern for people who react to salicylates or aspirin, and the 2000 trial recorded an allergic reaction. The site’s Willow Bark pages set out the herb’s reported benefits, interactions and safety findings in detail, and the Aspirin page covers the drug that grew out of it.

Full circle

The modern trials bring the story back to its beginning. Edward Stone dried a pound of willow bark by a baker’s oven and gave the powder to about fifty people; two and a half centuries later, standardised extracts of the same bark were tested against placebo in randomised trials. In between, chemists traced the bark’s effect to salicin, the meadow flower Spiraea gave the finished medicine its name, and Felix Hoffmann’s acetylated version of the plant molecule became one of the most widely used medicines in the world. How that medicine works in the body is the subject of the next page in this wing, which follows John Vane’s 1971 discovery of its effect on prostaglandins.

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Key Research Papers

  1. Stone E. An account of the success of the bark of the willow in the cure of agues. Philosophical Transactions of the Royal Society of London. 1763;53:195-200. DOI: 10.1098/rstl.1763.0033
  2. Wood JN. From plant extract to molecular panacea: a commentary on Stone (1763) ‘An account of the success of the bark of the willow in the cure of the agues’. Philos Trans R Soc Lond B Biol Sci. 2015;370(1666):20140317. PubMed PMID: 25750237
  3. Montinari MR, Minelli S, De Caterina R. The first 3500 years of aspirin history from its roots - A concise summary. Vascul Pharmacol. 2019;113:1-8. PubMed PMID: 30391545
  4. Hedner T, Everts B. The early clinical history of salicylates in rheumatology and pain. Clin Rheumatol. 1998;17(1):17-25. PubMed PMID: 9586674
  5. Kolbe H. Ueber Synthese der Salicylsäure. Justus Liebigs Annalen der Chemie. 1860;113(1):125-127. DOI: 10.1002/jlac.18601130120
  6. Maclagan T. The treatment of acute rheumatism by salicin. The Lancet. 1876;107(2740):342-343. DOI: 10.1016/s0140-6736(02)46434-3
  7. Savina T, Lisun V, Feduraev P, Skrypnik L. Variation in Phenolic Compounds, Antioxidant and Antibacterial Activities of Extracts from Different Plant Organs of Meadowsweet (Filipendula ulmaria (L.) Maxim.). Molecules. 2023;28(8):3512. PubMed PMID: 37110746
  8. Dempsey DA, Klessig DF. How does the multifaceted plant hormone salicylic acid combat disease in plants and are similar mechanisms utilized in humans? BMC Biol. 2017;15(1):23. PubMed PMID: 28335774
  9. Duthie GG, Wood AD. Natural salicylates: foods, functions and disease prevention. Food Funct. 2011;2(9):515-20. PubMed PMID: 21879102
  10. Swain AR, Dutton SP, Truswell AS. Salicylates in foods. J Am Diet Assoc. 1985;85(8):950-60. PubMed PMID: 4019987
  11. Blacklock CJ, Lawrence JR, Wiles D, Malcolm EA, Gibson IH, Kelly CJ, Paterson JR. Salicylic acid in the serum of subjects not taking aspirin. Comparison of salicylic acid concentrations in the serum of vegetarians, non-vegetarians, and patients taking low dose aspirin. J Clin Pathol. 2001;54(7):553-5. PubMed PMID: 11429429
  12. Paterson JR, Baxter G, Dreyer JS, Halket JM, Flynn R, Lawrence JR. Salicylic acid sans aspirin in animals and man: persistence in fasting and biosynthesis from benzoic acid. J Agric Food Chem. 2008;56(24):11648-52. PubMed PMID: 19053387
  13. Chrubasik S, Eisenberg E, Balan E, Weinberger T, Luzzati R, Conradt C. Treatment of low back pain exacerbations with willow bark extract: a randomized double-blind study. Am J Med. 2000;109(1):9-14. PubMed PMID: 10936472
  14. Vlachojannis JE, Cameron M, Chrubasik S. A systematic review on the effectiveness of willow bark for musculoskeletal pain. Phytother Res. 2009;23(7):897-900. PubMed PMID: 19140170

PubMed Topic Searches

  1. PubMed: salicylates willow bark
  2. PubMed: dietary salicylates
  3. PubMed: Filipendula ulmaria
  4. PubMed: salicylic acid plant defense
  5. PubMed: aspirin history

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Connections