Small-leaved Lime

The small-leaved lime, Tilia cordata Mill., is a long-lived tree of the mallow family, Malvaceae, native across most of Europe and east into western Asia. What herbal medicine uses is not the tree but the flower. The drug is the whole dried inflorescence, gathered at full bloom with its pale, tongue-shaped bract still attached, and in European pharmacy it is called Tiliae flos, lime flower. The European Pharmacopoeia monograph 01/2008:0957 defines Tiliae flos as the dried inflorescence of Tilia cordata Miller, Tilia platyphyllos Scop., Tilia x vulgaris Heyne or a mixture of these, so the small-leaved lime is one of three species that may lawfully supply the same official tea.

In the European Union lime flower is regulated as a traditional herbal medicine. The European Medicines Agency's monograph of 22 May 2012 (EMA/HMPC/337066/2011) recognises two uses on the strength of long-standing use, the relief of symptoms of common cold and the relief of mild symptoms of mental stress. The German Commission E approved lime flower for colds and cold-related coughs, and ESCOP lists feverish colds, cold-related cough, upper respiratory catarrh and restlessness. Controlled clinical trials are essentially absent. Lime flower therefore stands on a long, unusually well-documented tradition and on the regulators' recognition of it.

The lime was part of European village life long before it was a remedy. The tree supplied bast for rope and matting, a soft pale wood prized by carvers, a heavy summer perfume and one of the great European honeys. In Greek myth the nymph Philyra begged the gods not to leave her among mortals and was turned into a lime tree. The flower as a medicine appears later. The assessment report behind the European monograph records that since the middle ages lime flowers have been used as a diaphoretic to promote perspiration, and also as a tranquilliser and for headaches, indigestion and diarrhoea, added to baths and steeped as a tea for anxiety-related complaints. Several sources also carry the old lore that lime flowers were once thought so effective against epilepsy that sitting under the tree would cure it, which is folklore, not pharmacology.

The English record is older than the pharmacopoeias. In his Herball of 1597 John Gerard describes the lime growing wild in the woods of Northamptonshire and along the highway from London into Essex, where people called it broad-leaved elm. He valued the tough inner bark for ropes and halters, noted that gunpowder made from lime charcoal was better than gunpowder made from willow charcoal, and wrote that the flowers were commended against headache from a cold cause, against dizziness, apoplexy and the falling sickness, as epilepsy was then called, and that their distilled water served as well. Gerard's list of headache, giddiness and fits is the same nervous reputation that the lore about sitting under the tree kept in simpler form.

From the middle of the twentieth century the flower moved from household custom into the pharmacopoeias. Tiliae flos appears in the first Czechoslovak Pharmacopoeia of 1947 and in the current Czech Pharmacopoeia, in the Hungarian handbook of Augustin and colleagues of 1948 and in the sixth Hungarian Pharmacopoeia of 1967, in the Polish Pharmacopoeia of 1970 and in Ożarowski and colleagues of 1978, and in the British Herbal Pharmacopoeia of 1976 and Bradley of 1992. In Germany lime flower teas have been on the market since 1976 with the indication of a diaphoretic in feverish colds, the tea form is covered by the German Standard Licence, and lime flower is a core component of the classic German sweating tea, the Schweißtreibender Tee. In Austria a lime flower herbal tea has been registered as a traditional herbal medicinal product since 1994 for the relief of early symptoms of common cold. The European monograph of 2012 gathered that record together, and a periodic review completed in 2022 left it unchanged.

Lime flower tea has its place in literature too. In the first volume of Marcel Proust's In Search of Lost Time, published in 1913, the narrator's memory of Combray returns with the taste of a madeleine his aunt Léonie had dipped in her lime-blossom tea, tilleul in French. When she felt restless she asked for her tisane, and it was the boy's job to tip the right amount of dried flowers from the chemist's bag onto a plate before they went into the boiling water. Proust lingers on what he calls the leaves, which looked to him like a fly's transparent wing, and those are the bracts the pharmacopoeia still uses to define the drug. The tree carries symbolism of its own as well. In German folklore the lime stood for fairness and justice. In France and Switzerland it stands for liberty, and limes were planted there to celebrate battles.

Lime flower is a gentle drug chemically as well as in taste. The constituents listed in the European assessment report are flavonoids, chiefly kaempferol, quercetin and myricetin and their glycosides, with tiliroside, kaempferol-3-O-beta-D-(6''-E-p-coumaroyl)-glucopyranoside, as the signature compound; mucilage polysaccharides at around three percent, yielding arabinose, galactose and rhamnose with smaller amounts of glucose, mannose and xylose plus galacturonic and glucuronic acids; a small volatile oil of 0.02 to 0.1 percent containing citral, citronellal, citronellol, eugenol, limonene, nerol, alpha-pinene and terpineol among the monoterpenes and farnesol among the sesquiterpenes; the phenolic acids caffeic, chlorogenic and p-coumaric; and condensed tannins. The balance of tannin to mucilage decides how a lime flower tea tastes. Teas with two percent tannin or more and little mucilage are the most flavourful, and the flowers of Tilia cordata and Tilia platyphyllos carry relatively more tannin than mucilage, which is why these two species are preferred for tea. In 2021 Symma and colleagues at the University of Münster described six previously unknown alkaloids with piperidine and 3,4-dihydro-2H-pyrrole skeletons in the flowers of Tilia cordata and Tilia platyphyllos, named tiliines, tiliamines and tilacetines. They also turn up in a hot-water infusion, which means in the cup.

Laboratory work explains some of the tradition but shows nothing yet about effects in people. The assessment report attributes the sweating effect of the tea to quercetin, kaempferol and p-coumaric acid, a plausible explanation rather than a demonstrated mechanism. In vitro, an ethanol extract of Tilia cordata flowers made isolated guinea pig intestinal muscle cells contract, an effect that atropine blocked, and aqueous extracts acted on lymphocytes in cell culture. In 2022 the Münster group of Hake, Symma and colleagues showed that alkaloid-enriched fractions strengthened acetylcholine-driven contractions of mouse windpipe muscle by about 30 percent. The alkaloids inhibit the enzyme acetylcholinesterase, but roughly a hundred times more weakly than the drug galantamine, and a whole flower extract showed no effect at all. The often-quoted calming study used silver lime, Tilia tomentosa, with a purified fraction injected into mice, a different species, so it says nothing direct about Tilia cordata. The regulator found no pharmacokinetic data on lime flower extracts. The regulator's own summary is that the traditional use is plausible on the strength of in vitro and animal data, while controlled clinical studies are lacking.

Lime flower has almost no modern clinical literature. When the European monograph was prepared, the assessors found only two clinical references worth reporting. One was a survey of 310 people with diabetes in Jordan, of whom 96 used herbal products and about one percent of those named Tilia cordata. That says something about usage and nothing about effect. The other was an open controlled study in which fifteen people with an uncomplicated catarrhal illness inhaled steam from a lime flower preparation for ten minutes and fifteen inhaled steam from coloured water. The lime flower group reported further improvement, but the report carried no statistical analysis, so the assessors judged that an objective assessment was not possible. Their overall verdict on clinical pharmacology and efficacy was that due to the lack of data no conclusion can be drawn.

Nothing has changed that since. A periodic review completed in November 2022 screened 244 references published between 2014 and early 2022, narrowed them to twenty-four and judged four relevant, and concluded that no revision of the monograph was needed. What the newer work adds is chemistry and preclinical pharmacology. Symma and colleagues characterised six previously unreported piperidine and dihydropyrrole alkaloids in the flowers of Tilia cordata and Tilia platyphyllos in 2021, and the same Münster group reported in 2022 that these alkaloids strengthen contractions of mouse airway muscle. The same review noted an antioxidant study of a Tilia platyphyllos infusion in rats and an Iranian screen of plant extracts against influenza A, in which Tilia platyphyllos flower was tested but was not among the most active extracts. All of that is in vitro or animal work.

One gap concerns safety rather than efficacy. Lime flower preparations have never been put through adequate genotoxicity, carcinogenicity or reproductive and developmental toxicity studies, and for that reason the assessors declined to place lime flower on the Community list of traditional herbal substances. A fruit fly assay found the infusions protective rather than harmful against a chemical mutagen, but it does not replace the standard tests. The regulator relied instead on the fact that lime flower has been used as a traditional remedy without safety problems for much more than thirty years.

1. Review · 2012

   For the 2012 monograph the European Medicines Agency's assessors reviewed the whole literature on lime flower. They found centuries of consistent use, pharmacopoeia entries from 1947 and registered teas in several member states, but only two clinical references, a survey and a small open inhalation study without statistics, and concluded that no conclusion on efficacy can be drawn. On that basis lime flower is accepted as a traditional medicine for cold symptoms and mild mental stress, and a 2022 review of 244 newer papers changed nothing.

   Chinou I (rapporteur), EMA HMPC. European Medicines Agency, Committee on Herbal Medicinal Products. Assessment report on Tilia cordata Miller, Tilia platyphyllos Scop., Tilia x vulgaris Heyne or their mixtures, flos. EMA/HMPC/337067/2011, rapporteur I. Chinou, 22 May 2012. Source
2. Observational study · 2009 · 200 participants

   Researchers in Argentina tested 100 samples of loose linden flowers and 100 samples from tea bags for spores of Clostridium botulinum, the cause of infant botulism. Three percent of the loose samples carried spores of types A and B, about 30 per 100 grams, and none of the tea-bag samples did. It is a small laboratory survey from one country, but it is the reason lime flower tea does not belong in a baby's bottle.

   Bianco MI, Lúquez C, de Jong LI, Fernández RA. Bianco MI, Lúquez C, de Jong LI, Fernández RA. Linden flower (Tilia spp.) as potential vehicle of Clostridium botulinum spores in the transmission of infant botulism. Rev Argent Microbiol. 2009;41(4):232-236. PMID:20085187
3. Observational study · 2005 · 371 participants

   In Cova da Beira, a high-pollen region of central Portugal, 371 children with suspected allergy were skin-prick tested between 1995 and 2000. Of them, 11.4 percent were sensitised to Tilia cordata pollen, about as often as to plane tree pollen and far less often than to grasses at 44.9 percent. This is an allergy clinic population rather than the general public, and pollen sensitisation is not the same as reacting to the tea, but it shows that lime pollen allergy is real and, among allergic children, not rare.

   Loureiro G, Rabaça MA, Blanco B, Andrade S, Chieira C, Pereira C. Loureiro G, Rabaça MA, Blanco B, Andrade S, Chieira C, Pereira C. Aeroallergens sensitization in an allergic paediatric population of Cova da Beira, Portugal. Allergol Immunopathol (Madr). 2005;33(4):192-198. PMID:16045856
4. Animal study · 2022

   A University of Münster team tested the newly discovered lime flower alkaloids on isolated mouse windpipe muscle. A whole flower extract had no effect, while alkaloid-enriched fractions strengthened acetylcholine-induced contractions by about 30 percent, because three of the alkaloids inhibit acetylcholinesterase, roughly a hundred times more weakly than the drug galantamine. This is animal tissue work on a new compound class and says nothing yet about the tea in people. The authors have filed a patent application on the compounds.

   Hake A, Symma N, Esch S, Hensel A, Düfer M. Hake A, Symma N, Esch S, Hensel A, Düfer M. Alkaloids from lime flower (Tiliae flos) exert spasmodic activity on murine airway smooth muscle involving acetylcholinesterase. Planta Med. 2022;88(8):639-649. doi:10.1055/a-1534-3766

Forms and preparation

Lime flower is prepared as a plain infusion, and the traditional point of it is heat. Pour 150 ml of boiling water over about 1.5 g of the cut dried flowers, cover the cup so the volatile oil stays in, leave it for five to ten minutes and drink it hot. In the German and Austrian household tradition the tea is taken hot in bed as a sweating tea, often blended with elder flower, meadowsweet or peppermint. It tastes faintly sweet and honeyed rather than bitter, which is why children usually take it without argument. Lime flower rarely works alone in Central European tea blends. The classic German sweating tea, Schweißtreibender Tee, combines it with peppermint leaf, meadowsweet flower and bitter orange, and the German marketing authorisations have long provided for one to two cups of lime flower tea, very hot, as a sweat infusion before bed. In the Czech Republic a cold tea on the market since 1997 pairs equal parts of lime flower and elder flower, a quarter each, with fennel, ribwort plantain leaf and liquorice root, for colds with raised temperature. Elder and lime are natural partners, both mild, fragrant flowers of early summer. Beyond the cup, the European monograph recognises two liquid preparations: a liquid extract at a drug to extract ratio of 1 to 1 with 25 percent ethanol, and a tincture at 1 to 5 with 45 percent ethanol. Both are covered by the same two traditional-use indications as the tea. When buying the dried flower, look for whole inflorescences with the pale bract still attached, because that is what the pharmacopoeia defines as the drug, and store it dry and dark, since the fragrance degrades quickly in damp conditions. The lime is a food plant as well as a medicine. The Council of Europe lists lime flower as a natural source of food flavouring, in Spain the dried flowers may be sold freely as a food, and in wartime Britain the flowers stood in for ordinary tea when leaf tea was hard to come by. The tender young leaves that sprout from the base of the trunk are mild and slightly mucilaginous and make a good salad or sandwich leaf from spring into early autumn. The tree's sweet sap was once made into wine, and the blossom gives a fragrant honey.

Dosage

The European monograph sets the posology precisely. For adolescents, adults and the elderly, and for both indications, the herbal tea single dose is 1.5 g of the cut dried flowers in 150 ml of boiling water, taken two to four times daily, giving a daily dose of 3 to 6 g. The liquid extract single dose is 2 ml, one to two times daily, for a daily dose of 2 to 4 ml. The tincture single dose is 1 ml, one to two times daily, for a daily dose of 1 to 2 ml. For children between 4 and 12 years, and only for the common cold indication, the single dose is 1 g of the cut dried flowers in 150 ml of boiling water, two to four times daily, giving 2 to 4 g daily. Use below 4 years is not recommended for that indication, and use below 12 years is not recommended for mild mental stress. For a cold, therapy starts at the first signs; if symptoms persist longer than one week, a doctor or qualified health care practitioner should be consulted.

Special populations

The monograph is explicit about who it covers. Adolescents, adults and the elderly are covered for both indications. Children between 4 and 12 years are covered for the relief of common cold symptoms only; below 4 years that use has not been established for lack of data, and below 12 years the mental stress indication has not been established either. On pregnancy and lactation the monograph states that safety has not been established and that, in the absence of sufficient data, use is not recommended. No fertility data are available. Infants deserve a separate line. Lime flower tea is given to babies as a calming drink in many countries, and an Argentinian study of one hundred samples of loose linden flowers and one hundred samples in tea bags found Clostridium botulinum spores, about 30 per 100 grams, in three percent of the loose samples and in none of the industrially packed ones. Linden flower should therefore be treated like honey with respect to infant botulism and kept out of the bottle in the first year of life.

Drug interactions

The European monograph records interactions as none reported, and the assessment report reached the same conclusion, so there is no regulator interaction list for lime flower. The periodic review completed in 2022 looked at pharmacovigilance data and found several reports in which Tilia had been taken alongside other herbal or chemical medicines; the committee stated that no causal relation to Tilia was proven and that the reported potential adverse reactions were not confirmed, and that these data did not trigger a revision of the monograph. The sensible practical line is that no interaction is established, and that anyone taking a medicine with a narrow safety margin can mention regular herbal tea use to their doctor or pharmacist.

Contraindications

Hypersensitivity to the active substance, which is the only contraindication named in the European monograph. Known allergy to lime pollen or to lime flowers: sensitisation is documented and the tea is best avoided. Pregnancy and lactation: safety has not been established and the monograph recommends against use in the absence of sufficient data. Children under 4 years for the common cold indication, and children under 12 years for the mild mental stress indication, because the use has not been established. Infants in the first year of life: loose linden flowers can carry Clostridium botulinum spores, so lime flower tea does not belong in a bottle.

Side effects

The European monograph records undesirable effects as none known, and adds that if adverse reactions occur a doctor or a qualified health care practitioner should be consulted. The assessment report notes that some cases of allergic reactions have been reported, with unknown frequency, and ESCOP likewise names allergic reactions among undesirable effects. No other adverse effects have been reported, and no case of overdose has been recovered from the literature.

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