Modern Research of Birch

Birch
Betula lentaB. papyriferaB. pendula (syn. B. verrucosa), and B. pubescens (syn. B. alba)
Family: Betulaceae

by Josef Brinckmann, Thomas Brendler

INTRODUCTION

The Betulaceae family includes an estimated 150 to 200 species of trees and shrubs,1 and, depending on the author, the Betula genus includes about 30 to 60 of those species. Betula species are deciduous trees or shrubs and are monoecious (they have both male and female catkins, spike-like inflorescences of unisexual flowers). Authorities differ on the precise number of Betula species. This is likely because birches hybridize easily, which confounds species delineation.2

In Europe, the main species used in herbal medicinal products, foods, and beverages are downy birch (B. pubescens) and silver birch (B. pendula), and their hybrids and subspecies. Betula pendula is a fast-growing tree that can reach up to about 25 m (82 ft) and occur more or less continuously from Europe and northwestern Africa (e.g., Morocco) into parts of Asia,3 including Kazakhstan, Mongolia, western Siberia (Russia), and the Altai Mountain area of northwestern Xinjiang Uyghur Autonomous Region.1 Betula pubescens, reaching up to 20 m (65.6 ft), occurs on the islands of Newfoundland (Canada), Greenland (Danish territory), Iceland, Ireland and Great Britain (United Kingdom), and throughout most of continental Europe (except for the very south), into western Asia (Turkey and the Caucasus), and northeast to the Lake Baikal region of Siberia.4

In North America, two main birch species are used in cosmetics, dietary supplements, foods, and natural health products: paper birch (B. papyrifera) and sweet birch (B. lenta). Betula lenta grows in the eastern United States and Canada; it is a common tree of northern hardwood forest ecosystems in the Appalachian Mountains.5 Betula papyrifera is distributed widely in North America, including most of Canada and the northern United States extending south to high-altitude forests of the southern Appalachian Mountains.6 Natural ingredients obtained from Himalayan birch (B. utilis) also are imported and used in North America.7

Almost all birch plant parts are harvested, including the inner or outer bark (Betulae cortex), flowers (Betulae flos), leaf buds (Betulae gemmae), leaves (Betulae folium), and sap (Betulae succus).8,9 Medicated wines (Betulae vinum) are also made from the leaves10 or sap.11 Essential oil is distilled from the bark (Betulae cortex aetheroleum)12 or from the leaf buds (Betulae gemmae aetheroleum),13 and a rectified oil of birch tar (Oleum betulae empyreumaticum rectificatum) is obtained from the bark and wood.14 Triterpenoids (e.g., betulin, betulinic acid, lupeol, and betulin caffeates) are also isolated from the outer bark of B. papyrifera15 and have been the subject of clinical trials.16 The sugar replacement compound xylitol, which is used in chewing gums, dental hygiene products, and pharmaceuticals, can be produced from birch tree fiber but can also be produced from less costly sources such as corn (Zea mays, Poaceae).17

Betulae folium is defined by the European Pharmacopoeia as the dried leaves of B. pendula and/or B. pubescens as well as hybrids of both species.18 The State Pharmacopoeia of the Russian Federation more specifically prescribes use of the dried leaf buds of either species, collected from wild trees in the winter-spring period (January to April) prior to blooming, as well as leaves of either species collected from wild trees from June through July.19

The commercial supply of birch plant parts and products of B. pendulaB. pubescens, and their hybrids or subspecies comes mainly from wild collection in Europe, especially Belarus,7 Bosnia and Herzegovina,8,20 Bulgaria (both cultivated and wild),21 Croatia,20 Finland,22 Hungary,22 North Macedonia,7 Poland,22,23 Romania,11,22,24 Russia,25 Serbia,26 and Ukraine.25 The supplies of B. lenta and B. papyrifera come from the United States and Canada, and B. utilis from Nepal.7

HISTORY AND CULTURAL SIGNIFICANCE

The genus name Betula is not derived from Latin but more likely stems from the Celtic word betu, meaning “birch.”27,28 The English word birch likely stems from the Proto-Germanic “berkjon” (Birke in modern German), which refers to a slender forest tree with white bark. Swedish botanist Carl Linnaeus (1707-1778) named a North American species B. lenta in his 1753 work Species Plantarum, wherein he wrote that the species’ habitat was Virginia and Canada.29 In 1785, American botanist and plant dealer Humphry Marshall (1722-1801) named another North American species B. papyrifera, which he called white paper birch, in the publication Arbustrum Americanum.30 German botanist Albrecht Wilhelm Roth (1757-1834) named B. pendula in the 1788 publication of Tentamen Florae Germanicae.31 In Latin, pendula means “drooping” or “hanging down,” referring to the branches of this species. In 1789, German botanist Jakob Friedrich Ehrhart (1742-1795) named the species B. pubescens.32 Pubescens means “downy” or “hairy” in Latin, referring to the twigs of this species.

Archaeological evidence indicates that Neanderthals, which are believed to have gone extinct about 39,000 years ago,33 burned birch tree bark to produce birch tar used for hafting of tools.34 Birch bark tar sealings also have been identified among archaeobotanical grave materials in Nordic Iron Age (ca. 500 BCE to 800 CE) burial sites, as well as in earlier Nordic Bronze Age (ca. 1700 to 500 BCE) coffins and “tar decorations used for inlays and appendages on grave gifts.”35 Recently, a human genome (set of genes) and oral microbiome (collective genome of microorganisms that reside in the oral cavity) were analyzed from a piece of chewed birch (B. pendula) bark pitch, found in southern Denmark, which was determined to be about 5,700 years old (from about 3680 BCE at the onset of the Neolithic period in Denmark). The individual who chewed the pitch was a female hunter- gatherer, likely with dark skin, dark brown hair, and blue eyes.36

One of the oldest known Hungarian words (5,000 to 6,000 years old) is nyír, meaning “birch.” The Csángós and Székelys peoples, Hungarian ethnic groups, brought their traditional knowledge of birch on their migration to settle around birch forests in Transylvania, Romania.13 Hungarians invaded and conquered this part of present-day Romania between 895 and 907 CE, and the culturally isolated Csángós and Székelys still live there.37 To this day, they harvest birch tree sap, which they call nyírvíz (meaning “birch water”), then cook or ferment it to prepare wine, beer, syrup, or vinegar.13 The Csángós people reportedly apply freshly collected birch leaves as a diaphoretic foment spread on bedding. They also relieve painful legs by filling their trousers with birch leaves during the day or by lying in a bed of birch leaves to treat rheumatism.13

There is a long tradition of extracting birch sap in eastern Europe, especially Belarus, Hungary, Poland,38 Romania, Russia, Slovakia, and Ukraine, as well as in parts of northern Europe, including Denmark, Estonia, Finland, Latvia, Lithuania, and Sweden.39 As early as 921, people of the Turkic Bulgar tribes living along the Volga River in present-day European Russia were observed to prepare fermented birch sap.39 In 1772, a monograph for birch sap appeared in the Pharmacopoea Danica, the first Danish pharmacopeia. Up until the early 20th century in Poland, spring birch tree sap was commonly drunk, usually fresh, but sometimes concentrated or fermented. In the 21st century, the tradition of drinking fresh birch sap in Poland is experiencing a revival due to reported health benefits.38 In Russia, birch sap is drunk fresh, but also fermented by adding malt, wax, beans, or rye (Secale cereale, Poaceae) bread.25 An alcoholic beverage called birch beer is also made from the American species B. lenta by fermenting the stem sap in the spring.40

Birch leaf wine traditionally is used in Germany as a diuretic in urinary tract disorders.10 In Romanian traditional medicine, fresh birch sap is used for anemia, infusion of the leaves as a tonic and for hair growth, infusion of the leaf buds as a diuretic and anti-inflammatory for edema and urinary disorders, and decoction of the bark as an anti-inflammatory, diuretic, febrifuge, and cardiotonic.41 There is also a centuries-long use of birch bud preparations in traditional Russian medicine. Besides uses as a diuretic, expectorant, cholagogue, diaphoretic, blood purifier, and analgesic, birch bud tea infusions and decoctions are used in Russian stomatology (medicine of the oral cavity) and otolaryngology (ear, nose, and throat medicine) for their anti-inflammatory action.42

In the first edition of the Dispensatory of the United States of America (USD I, 1833), a monograph titled “OLEUM GAULTHERIA. U.S. Oil of Partridge-berry” noted that, while the Pharmacopoeia of the United States of America (USP I, 1830)43 prescribed preparation of the oil from the leaves of Gaultheria procumbens (Ericaceae), an oil prepared from the bark of B. lenta could be considered as comparable and interchangeable. Pharmacist William Procter Jr. (1817-1874) published a paper asserting that the oils of Betula and Gaultheria were identical in composition.44 In 1890, a monograph for Betulae oleum, the essential oil obtained by maceration and distillation of the bark of sweet birch (B. lenta), entered the seventh decennial revision of the Pharmacopoeia of the Unites States of America (USP VII).45 In the subsequent USP VIII of 1900, a monograph for Methyl Salicylate also referenced Betulae oleum as a source material for the drug.12 In the USP IX of 1910, the Methyl Salicylate monograph was revised to state: “It is produced synthetically or is obtained by distillation from Gaultheria procumbens or from Betula lenta. The label must indicate whether the methyl salicylate has been made synthetically or distilled from either of the above mentioned plants.”46

The use of European B. pubescens (then referred to as B. alba) entered the American medical literature in the mid-19th century. A monograph titled “BETULA ALBA. Common European Birch,” appearing in the 10th edition of the Dispensatory of the United States of America (USD X, 1854), stated that the inner bark was bitter and astringent and employed for treatment of intermittent fever. The USD also referred to the leaves, prepared as an aqueous infusion, for treating gout, rheumatism, dropsy, and cutaneous diseases, and furthermore reported:

The same complaints, particularly dropsy, are said to have been successfully treated by enveloping the body in the fresh leaves, which thus applied excite perspiration. When the stem of the tree is wounded, a saccharine juice flows out which is considered useful in complaints of the kidneys and bladder, and is susceptible, with yeast, of the vinous fermentation. A beer, wine, spirit, and vinegar are prepared from it and used in some parts of Europe.47

Regarding an American species, B. papyrifera, the USD monograph stated: “The bark of B. papyrifera is employed by the Northern Indians for making canoes; and thin layers of the epidermis are placed inside of boots to prevent the access of moisture.” In the early 20th century, a monograph for Rectified Oil of Birch Tar entered the fourth edition of the National Formulary (NF IV, 1916), defined as the oil obtained by the dry distillation of the bark and wood of B. alba, rectified by steam distillation.14

In 1986, the German Commission E published a positive monograph for birch leaf (Birkenblätter – “Betulae folium”), prepared as powdered leaf, dry extract for making tea, or fresh-pressed plant juice. The juice, powder, and tea were indicated for use as a diuretic drug in “irrigation therapy for bacterial and inflammatory diseases of the urinary tract and for kidney gravel; supportive therapy for rheumatic ailments.”48 In 2007, and in its 2014 revision, the European Medicines Agency (EMA) published a labeling standards monograph for birch leaf that superseded the German Commission E monograph for purposes of product marketing authorization in the European Union (EU).49 In Canada, a labeling standards monograph for both European species (B. pendula and B. pubescens) was published in 2008. In subsequent revisions, a separate B. pendula monograph was published in 201850 and a B. pubescens monograph followed in 2019.51 The only known official quality standards monographs for birch plant parts are published in the European Pharmacopoeia18 and the State Pharmacopoeia of the Russian Federation.19 Monographs for xylitol appear in currently valid editions of the Food Chemicals Codex (FCC 11)52 and National Formulary (NF 37).53

CURRENT AUTHORIZED USES IN COSMETICS, FOODS, AND MEDICINES

In the United States, birch plant parts may be used in dietary supplement products, which require FDA notification within 30 days of marketing if a structure-function claim is made and product manufacturing that adheres to current Good Manufacturing Practices (cGMPs).54

In Canada, the leaves of European species of birch (B. pendula and B. pubescens) are regulated as active ingredients of licensed natural health products (NHPs), which require pre-marketing authorization from the Natural and Non-prescription Health Products Directorate (NNHPD). Licensed NHPs prepared from pharmacopeial quality birch leaf may be labeled and marketed for use as diuretic drugs, in dosage forms including (a) powdered leaf, (b) dry extract, (c) fluidextract, (d) tincture, (e) aqueous decoction, or (f) aqueous infusion.50,51 The essential oil of sweet birch (B. lenta) bark is permitted as a non-medicinal fragrance ingredient of licensed NHPs for its odorous, odor-enhancing, or blending properties (to impart a unique aroma or mask a malodor).55

In the EU, birch (B. pendula or B. pubescens) leaf may be used as an active ingredient of registered traditional herbal medicinal products (THMPs) labeled with the therapeutic indication “to increase the amount of urine to achieve flushing of the urinary tract as an adjuvant in minor urinary complaints.” For this use, the birch may be prepared in the forms of (a) powdered leaf, (b) aqueous dry extract (drug-to-extract ratio [DER] range 3-8:1), (c) liquid extract prepared from fresh leaves (DER 1:2-2.4), or (d) liquid extract prepared from fresh leaves stabilized by 96% ethanol vapors (DER 1:1).49 The dried leaf used for production of registered THMPs must conform to the quality standards monographs of the European Pharmacopoeia (Betulae folium PhEur).18 There is also an authorized prescription-only topical drug preparation, Episalvan gel (Amryt AG; Niefern-Öschelbronn, Germany); 1 g gel contains 100 mg refined dry extract of birch bark (from B. pendulaB. pubescens, or hybrids), equivalent to 0.5-1 g birch bark, corresponding to 72-88 mg betulin. Episalvan gel is indicated for treatment of partial thickness wounds (i.e., wounds in which upper layers of the skin have been lost, such as burn or skin grafting wounds).56

MODERN RESEARCH

According to the European Pharmacopoeia monograph, birch leaves should contain not less than 1.5% flavonoids, expressed as hyperoside.18 Flavonoid content of the leaves can be as high as 3.5% with, next to hyperoside, other quercetin glycosides (avicularin, quercetin-3-O-glucuronide, quercitrin), kaempferol, and myricetin glycosides as the most prominent.57-64 Other compounds from birch leaf include caffeic and chlorogenic acids, malonyl esters of dammarane-type triterpenes, lignans, and diarylheptanoids.57,58,62,65-71 Birch leaves also contain proanthocyanidins,72,73 varying amounts of lipids and fatty acids,74 and 0.05-0.1% of essential oil.75 Birch bark contains betulin, betulinic acid, lupeol, and esters of these triterpenes, and birch tar contains creosol and guaiacol. Depending on the region and climatic conditions, the main components of essential oil distilled from Betula pendula flower buds may vary; for example, α-betulenol and 14-hydroxy-4,5-dihydro-β-caryophyllene are present in oil from Turkey,76 but α-copaene, germacrene D, and δ-cadinene are present in German birch bud oil.

Oral administration of birch leaf preparations has been shown to increase the volume of urine excretion in rabbits and mice,78 dogs,79 and rats80-83 in a dose-dependent manner. The impact of an aqueous birch leaf extract on E. coli biofilm formation was investigated by Wojnicz et al (2012).84 Rafsanjany et al (2013) reported anti-adhesive effects of a birch leaf hydroalcoholic extract against uropathogenic E. coli in human bladder cancer cells.85 Though a reduction of E. coli motility was observed, biofilm inhibition was comparatively weak. Adhesion inhibition, however, was shown to be significant (IC50 = 415 µg/mL). An acetone extract of birch leaf showed significant in vitro effects against Staphylococcus aureus but not against other bacteria or fungi.86 Virostatic (virus-inhibiting) and cytostatic (cell-inhibiting) effects of birch leaf preparations were reported by Petkov (1988).87 These results support the traditional use of birch leaf preparations as a mild aquaretic (an agent that promotes excretion of water), while antiallergic, anti-inflammatory, antimicrobial, antioxidant, antiproliferative, antirheumatoid, antiviral, gastroprotective, and uteroprotective activities have been shown for various isolates.64,88,89

Safety and toxicity data for birch are scant. No signs of dermal irritation or sensitization from a decoction of birch leaves in a cream base were detected in rabbits, rats, and mice.90 Quercetin was suspected to be responsible for a very weak mutagenic response in the Ames test.91 However, quercetin showed no carcinogenicity in other investigations.92 Birch sap, leaf, and pollen have caused allergic reactions.93 Birch pollen has been studied in extensive pre-clinical and clinical allergen research (see below). Clinical investigation of a birch leaf dry extract reported mild adverse events, including allergic systemic reactions and skin, gastrointestinal, and metabolic reactions.94 Other than birch’s allergenic potential, no immediate risks are expected from any known birch (leaf) constituent.

Few clinical trials have investigated endpoints related to the traditional use of birch leaf. Of the approximately 1,100 registered medicinal birch products (not counting homeopathics) in the German market (Arzneimittelinformationssystem [AMIS] German Drug Information System Database, accessed December 2019), close to 1,000 are medicinal teas (mono-preparations and combinations), with the remaining products being mostly anti-allergens, topical products in combination, and a handful of solid dosage forms (capsules, tablets, and granules), all using the same aqueous birch leaf dry extract (DER 4-8:1) at varying dosages. Sublivac Fix (HAL Allergy B.V.; Leiden, the Netherlands), a liquid oral preparation of B. pendula pollen extract for sublingual immunotherapeutic treatment of allergic rhinitis/rhinoconjuctivitis induced by birch pollen, has gone through phase I, II, and III clinical trials. Other prominent manufacturers that have sponsored clinical research in that segment include ALK-Abelló A/S (Denmark), Lofarma S.p.A. (Italy), and Allergopharma GmbH & Co. KG (Germany).

To date, no published clinical trials affirm the effects of birch leaves and preparations thereof, other than two early 20th-century reports,95,96 which failed to demonstrate increased diuresis after administrations of a 1:10 infusion of birch leaf. The first report described a small randomized, double-blind, placebo-controlled pilot study97 in which three out of seven patients with urinary tract infections (UTIs) were symptom-free after 20 days of four cups of birch leaf tea per day vs. one out of six in the control group. The second report described a non-interventional study98 with 1,066 subjects suffering from UTIs, cystitis or other inflammations, irritable bladder, stones, and other complaints. All subjects received aqueous birch leaf dry extract at varying doses (180-1,080 mg), 56% of the UTI group received additional antibiotic treatment, and the treatment period averaged two to four weeks. Symptoms subsided in all groups (in 80% of subjects co-treated with antibiotics and in 75% without co-treatment). A 2002 dissertation reported on a pilot study with 14 healthy subjects comparing urine volumes after administration of birch leaf tea and water, respectively. No increase in urine volume could be shown.99

Apart from birch products based on traditional use claims, Episalvan gel is a licensed new drug in Europe. The public assessment report of the EMA lists three phase III trials treating split-thickness skin graft wounds (two trials) and grade 2 burn wounds (one trial). A total of 217 skin graft patients received treatment and wound dressing on one half of the wound and dressing only on the other half. Wound closure occurred significantly faster with Episalvan (average time from surgery to wound closure was 17.1 days for the wounds treated with standard wound dressing only and 15.5 days for the wounds also treated with Episalvan). In 57 subjects with partial-thickness burn wounds, using the same methodology, wound closure occurred in 7.6 days vs. 8.8 days.56 Some data from these studies were published subsequently.100-102 Furthermore, more than 2,500 papers have been published on the pharmacological actions of selected triterpene compounds (e.g. betulin, betulinic acid, and lupeol), extracted and isolated from the outer bark of Betula species, for a wide range of human health applications (Brian Garhofer [president and CEO of The Actives Factory] email to T. Smith, January 16, 2020).

ADULTERATION

Adulteration of official Betulae folium in Europe is rare.103 Occasional confusion with the leaves of Populus tremula (Salicaceae) has been reported.104 According to Flora of ChinaB. pendula may easily be confused with B. platyphylla (now considered to be B. pendula subsp. mandshurica). The branches of B. platyphylla, however, are not pendulous (do not hang down). The name B. alba (syn. B. pubescens) is also reported to be persistently misapplied to B. pendula.1 Betula pubescens trees also differ from B. pendula because their branches usually stand upright (are not pendulous).105

SUSTAINABILITY AND FUTURE OUTLOOK

All Betula species discussed in this article have been assigned to the conservation category of Least Concern (LC), as assessed according to the International Union for Conservation of Nature (IUCN) Red List categories and criteria. The assessment of LC is based on their widespread distribution with no known significant threats in the foreseeable future.3-6 Climate change, however, is expected to extirpate the two North American species, B. lenta and B. papyrifera, at the southernmost part of their distribution, but it is believed that this may be offset with an expansion of their northern range limits in Quebec and Ontario.5,6 Wild B. pendula is, however, a protected species in some regions, such as North Macedonia.106 Wild B. pubescens is also classified as LC overall, even though it is considered threatened in some areas. For example, the species is classified as Critically Endangered in Croatia, Vulnerable in Hungary and Bosnia and Herzegovina, and Near Threatened in Luxembourg.4

Estimates of birch leaf wild-collected annually range from one to five tons in Finland,22 five tons in Croatia,20 80 to 100 tons in Bosnia and Herzegovina, and 200 tons in Romania.20 For the five-year period 2001-2005, Bulgaria’s Ministry of Environment and Water reported an average annual export of 72,760 kg of Betulae folium (both cultivated and wild – collected) and 802 kg of Betulae cortex.21 In 2005, an estimated 1,668,700 hectares (6,443 square miles) were registered for certified organic wild-collection of B. pendula leaves globally.107

Given the expansive distribution area of birch trees, their conservation status as not threatened at this time, coupled with evidence that collection is occurring increasingly under organic wild-crop harvesting rules (especially in Belarus, North Macedonia, Poland, and Ukraine), and that some of the supply is also being cultivated, the continued use of birch ingredients in natural products appears to be sustainable if monitored and managed.

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