Birch

Birch (Betula spp.): A Comprehensive Reference on the Botanical, Traditional Uses, Phytochemistry, and Scientific Evidence

1. Identity and Botanical Classification

Birch belongs to the genus Betula L., which is the largest genus in the birch family, comprising more than 100 species widely distributed across the Northern Hemisphere. The family is Betulaceae. Among the numerous species, the two most widely used medicinally and pharmacopoeially recognised are:

• Betula pendula Roth — silver birch (synonyms: B. verrucosa Ehrh., B. alba in some older literature)
• Betula pubescens Ehrh. — downy birch (synonym: B. alba)

The folium of Betula pendula Roth and/or Betula pubescens Ehrh., as well as hybrids of both species, are approved in the European Union as a traditional herbal medicine to increase the amount of urine to achieve flushing of the urinary tract as an adjuvant in minor urinary complaints (EMA/HMPC/573241/2014).

Other medicinally documented species include Betula papyrifera Marshall (paper birch, common in North America), Betula lenta L. (sweet birch or black birch), and Betula utilis D.Don (Himalayan silver birch), the last of which is significant in Ayurvedic medicine. Although over a hundred Betula species are found distributed globally, about seven different species of Betula have been documented for their traditional uses.

Betula pendula Roth (Betulaceae) is well known as a birch tree widely distributed in the Northern Hemisphere from Canada to Japan. These trees can reach 30 m in height, and the white colour of their bark is due to betulin, its main constituent.

Pharmacopoeial Recognition

The monographs for "Birch leaf" are included in the State Pharmacopoeia of the Republic of Belarus (2007), in the European Scientific Cooperative on Phytotherapy (ESCOP, 2009), in the British Pharmacopoeia (2014), and the European Pharmacopoeia 10th edition (2020). The EMA's Committee on Herbal Medicinal Products (HMPC) has formally evaluated birch leaf preparations and established EU herbal monographs. The monograph of Betulae folium has been published in the European Pharmacopoeia (2005). Birch leaf is used in herbal medicine, particularly for urinary tract disorders.

2. Plant Parts Used and Common Forms of Preparation

Multiple parts of the birch tree have been applied medicinally. In herbal medicine, the birch primarily uses the young leaves, buds, bark, and sap, the latter collected in spring through small incisions in the trunk. The most important preparations include:

• Leaves (Betulae folium): Dried or fresh; prepared as aqueous infusion (herbal tea), hydroalcoholic tincture, powdered herbal substance, or standardised dry extract. By pharmacopoeial definition, this herbal drug consists of the whole or fragmented dried leaves of Betula pendula Roth and/or Betula pubescens Ehrh., as well as hybrids of both species.
• Bark: Birch bark flakes, powder, capsules, oil, sap, and liquid extracts are sold in herbal medicine shops and on the Internet. Birch bark is also the raw material for pharmaceutical-grade triterpene dry extracts.
• Sap: Birch sap consists of a natural water-based solution with valuable compounds such as minerals, sugars, organic acids, and phenolic compounds. It is consumed fresh or fermented, and is used in some traditional cultures as a spring tonic.
• Buds: Used in traditional preparations, particularly as cholagogues in Eastern European and Russian medicine.
• Essential oils: Distilled from bark; birch tar oil and sweet birch oil are known in several pharmacopoeias. Birch leaf oil has also been used. Birch tar oil and sweet birch oil are known in several pharmacopoeias (Martindale, 2007).
• Xylitol: Xylitol is a chemical that is naturally found in birch trees and some fruits. It is industrially extracted and used as a sugar substitute and dental health aid.
• Pharmaceutical preparations: Standardised triterpene oleogels from birch bark have reached regulatory approval for wound care applications (see Section 7).

Different formulations on the market incorporate birch extracts, either as standalone products or in combination with other herbal diuretics such as dandelion (Taraxacum officinale) and goldenrod (Solidago virgaurea).

3. Historical and Traditional Use

Prehistoric and Ancient Use

Birch boasts a millennia-old history of uses ranging from craftsmanship to traditional medicine. As early as the Middle Paleolithic, Neanderthals used birch pitch as an adhesive to bind arrowheads and harpoons, while Nordic populations exploited the bark, waterproof and resistant, to make clothing, footwear, containers, and even canoes.

Northern European and Russian Traditions

Birch trees have been used in traditional medicine for centuries, particularly for their purported anti-inflammatory and antiseptic properties. Various parts of the birch tree, including the bark, leaves, and buds, have been traditionally used to treat conditions such as rheumatism and inflammatory disorders, and, more recently, urinary tract infections.

Birch buds have been employed as cholagogues, particularly in Eastern Europe and Russia. In Russia, birch bark has been consumed since 1834. In Europe, birch sap was fermented into beer, wine, and other spirits.

The birch tree held deep cultural significance across the Northern Hemisphere. Often called the "mother tree" because it was the first to grow as the Ice Age retreated, it represents fertility. Birch is one of the quintessentially feminine trees of ancient European cultures, as well as Native American traditions. Birch is called "the Lady of the Forest" in Russian folklore.

Traditional European herbalism classified birch as primarily a diuretic herb. A tea brewed of the fresh or dried leaves was extensively used as a spring tonic, much needed in a season when fresh vegetables were not available. Birch tea contains some vitamin C and flavonoids as well as cleansing properties. The German Commission E and ESCOP indicate the use of birch as "therapeutic irrigation of the urinary tract in cases of inflammation and kidney stones; as an adjuvant in the treatment of bacterial infections of the urinary tract."

Native American Traditions

If we look at the traditional use of birch trees by indigenous peoples, at least in North America, we find that several groups used the bark to treat various skin disorders. Specific documented uses include: paper birch was used to treat skin rashes; the Cree used the outer bark to bandage burns; inner bark, added to pitch and grease, was used by the Cree as ointment for persistent scabs and rashes; and gray birch was used by the Maliseet and Mi'kmaq for infected cuts, while powdered wood from the downy birch was used by the Cree to treat chafed skin.

Among the Ojibwe, the root of the paper birch was used in medicines as a seasoner — its sweetish, aromatic, wintergreen flavour disguised less pleasant doses. The root bark and maple sugar cooked together made a soothing syrup to alleviate cramps in the stomach.

Himalayan and Ayurvedic Traditions

Betula utilis D. Don, commonly known as the Himalayan silver birch or Bhojpatra, holds significant value in traditional and folk medicine, particularly in Ayurvedic medicine, where its bark has been used to cure various illnesses, such as blood and ear infections, pneumonia, convulsions, skin ailments, and many more.

Traditional Uses Across Cultures — Summary

The available literature and information show that several Betula species have traditionally been used as medicine in different parts of the world. The most widespread use has been in the treatment of bone-related problems including arthritis, rheumatism, and gout as well as renal ailments. Birch sap has also been recommended against hepatitis, rash, intestinal worms, and scurvy. Besides medicinal uses, cosmetic applications have also been reported, mainly for hair growth and against freckles.

4. Key Constituents and Active Compounds

4.1 Bark — Triterpenes

The outer bark of Betula species is the richest source of pentacyclic triterpenes. Outer bark of birch (Betula alba cortex) contains pentacyclic triterpenes, mainly betulin (BE, up to 34%), but also betulinic acid (BA), oleanolic acid (OA), lupeol (LU), and erythrodiol (ER). The bark's white colour is itself attributable to betulin. The content of betulin in the bark is between 10–14%; there are also the glycoside gaultherine, saponins, and some essential oil, the principal component of which is the methyl ester of salicylic acid.

• Betulin (lup-20(29)-ene-3β,28-diol): The dominant triterpene. Birch tree bark-derived betulin has attracted scientific interest already for several centuries, being one of the first natural products identified from plants.
• Betulinic acid (3β-hydroxy-lup-20(29)-en-28-oic acid): Formed by oxidation of betulin. Betulinic acid is a well-known naturally occurring triterpenoid having a lupane-type pentacyclic structure. It is generally found in the bark of birch trees but can also be isolated from other plant sources.
• Lupeol, oleanolic acid, erythrodiol: Additional pentacyclic triterpenes with documented pharmacological activities.

Betulinic acid exhibits various pharmacological activities, such as anti-neoplastic, anti-inflammatory, anti-HIV, anti-diabetic, anti-malarial, antimicrobial, and hepatoprotective.

4.2 Leaves — Flavonoids, Phenolic Acids, and Minerals

Studies with birch leaf's main characteristic constituents — flavonol glycosides, principally hyperoside and other quercetin glycosides, together with glycosides of myricetin and kaempferol — are included in ESCOP's evaluation. The EMA's standardisation criterion requires that birch leaf preparations contain at least 1.5% flavonoids expressed as hyperoside.

A standardised B. alba leaf extract was characterised as containing: hyperoside (0.53%), quercetin glucuronide (0.36%), myricetin glucoside (0.32%), and chlorogenic acid (0.28%) as its main constituents.

Phenolic acids such as chlorogenic acid, vitamin C, various minerals (including potassium), salicylic acid, betulinic acid, tannins, and various sugars are also found in the sap. The potassium content of birch leaf may contribute to the diuretic effect. More specifically, the concentration of potassium in Betulae folium (B. pendula) is 8045 µg/g dry matter.

Previous studies found more than 26 polyphenol constituents in the methanol extract, including kaempferol and its derivatives. Non-flavonoid phenolic glycosides have also been identified as contributors to activity: the diuretic activity of a flavonoid-free birch leaves extract has been confirmed. The most abundant non-flavonoid constituent of the extract is 3-hydroxy-1-(4-hydroxyphenyl)-propan-1-one 3-O-β-D-glucoside (3,4′-DHPPG).

4.3 Bark — Additional Constituents

The bark contains mainly 4–5% tannins and essential oil; it is known as an antipyretic. Also betulin as the triterpene similar to lupeol, and the glycoside betuloside with aglycone betuligenol, are found in the bark.

4.4 Sap

Birch sap is used as a traditional drink and in traditional medicine in many countries in the Northern Hemisphere. The total amino acid concentration in birch sap ranges from 100–500 mg/L. Among the free amino acids, glutamine, citrulline, glutamic acid, isoleucine, valine, and asparagine are the most often detected, representing 92–96% of the total amino acid content. Birch sap also contains valuable minerals; calcium and potassium occur in the highest concentrations.

Birch sap contains a remarkable combination of minerals and trace elements: magnesium, calcium, potassium, manganese, zinc, vitamin C, flavonoids, and betulin.

4.5 Overall Phytochemical Profile

Phytochemical research on Betula species has led to the isolation of triterpenoids, diarylheptanoids, phenylbutanoids, lignans, phenolics, and flavonoids.

5. Mechanisms of Action

5.1 Diuretic Mechanism

It appears, based on animal studies, that the high potassium content of the leaves produces the diuretic effect, allowing an increase in urine volume and helping to address minor urinary disorders. The triterpenic saponins, flavonoid glucosides, and polysaccharides contained in the plant work synergistically to promote the elimination of excess fluids and metabolic waste. However, the precise mechanism remains unknown due to a lack of reliable information, and the justification for this use relies substantially on traditional medicine.

5.2 Anti-inflammatory Mechanisms

Betulin can exert important anticancer activities through modulation of diverse cellular pathways. Betulin-regulated molecular signalling has been analysed with a special focus on its participation in anti-inflammatory processes, especially by modulating nuclear factor-κB (NF-κB), prostaglandin/COX, and nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated cascades.

5.3 Anticancer Mechanisms

Anti-cancer agents such as betulin may exert therapeutic effects by targeting the modified membranes, owing to the high affinity of betulinic acid to the lipid monolayers present on the membranes. This mechanism may inhibit the growth and multiplication of cancerous cells.

5.4 Wound Healing Mechanisms

The active pharmaceutical ingredient of betulin-containing preparations modulates chemokines in the inflammation phase of wound healing and promotes the migration and differentiation of keratinocytes, thus accelerating re-epithelialisation and wound closure. More recently it was shown that fibroblasts too are stimulated by birch bark extract and its main constituents.

5.5 Biotransformation and Bioavailability

Experimental studies carried out on human and rat hepatic microsomes and cytosol indicated that two major biotransformation pathways for betulin are glucuronidation and sulfonation. The data obtained from studies in rat models showed that hUGT1A3 and 1A4 were the main hepatic enzymes responsible for the formation of possibly a C3-hydroxyl betulin glucuronide, while hSULT2A1 was the main isoform involved in sulfonation. In human systems, glucuronidation occurs hepatically and extra-hepatically (in the gastrointestinal tract).

A key limitation of the triterpene compounds is their poor water solubility. Betulin and its product of oxidation, betulinic acid, show poor aqueous solubility owing to their structure. Hence, various derivatives, such as amino acid esters, have been synthesised to improve bioavailability and delivery to target tissues.

6. Scientific Evidence by Area of Use

6.1 Urinary Tract / Diuretic Effects

Regulatory and pharmacopoeial status: Among its well-documented therapeutic effects, birch has been recognised for its mild diuretic properties. According to the European Pharmacopoeia, Betula pendula Roth (silver birch) and B. pubescens Ehrh. leaves, as well as hybrids of both species, are considered mild diuretics that can be used to promote urine flow in cases of lower urinary tract infections and renal gravel.

Clinical evidence: Although there are few clinical studies, including a study in 15 patients with urinary tract infections which suggested a positive effect on the urinary infection, data are too limited to be used as primary evidence. Hence, the HMPC conclusions on the use of birch leaf medicines to increase the production of urine are based on their long-standing use. A separately reported non-randomised clinical study found that the extract was administered at doses of 180–1080 mg/day during 2–4 weeks. About 56% of subjects with urinary tract infections additionally received antibiotic therapy. The symptoms disappeared in 75% of patients treated with birch leaf extract only and in 80% of patients who combined therapy with antibiotics.

ESCOP findings: In vitro experiments with birch leaf demonstrate diuretic, anti-inflammatory, and antioxidant properties. In vivo experiments with animals demonstrate diuretic and gastroprotective effects. Controlled and open clinical studies with birch leaf demonstrated its use as an anti-inflammatory and antimicrobial agent in patients suffering from urinary tract infections, cystitis, and other inflammatory complaints.

Preclinical (animal) evidence: Herbal extracts from Betula alba (birch) are traditionally used for their purported diuretic effects, but scientific evidence supporting these claims remains limited. In a pilot study, short-term effects of a standardised B. alba leaf extract (at two doses of 25 or 50 mg/kg) were evaluated in healthy adult rats. The extract contains hyperoside (0.53%), quercetin glucuronide (0.36%), myricetin glucoside (0.32%), and chlorogenic acid (0.28%) as its main constituents. After 3 days of treatment, the 24-hour urine output was measured. While no statistically significant changes were observed in the 24-hour urine volume or the urinary Na+ and K+ excretion, multivariate metabolomic analysis revealed treatment-induced alterations in the urinary metabolic profile.

Anti-adhesive effects: Anti-adhesive effects of a birch leaf hydroalcoholic extract against uropathogenic E. coli in human bladder cancer cells were reported (Rafsanjany et al., 2013). Though a reduction of E. coli motility was observed, biofilm inhibition was comparatively weak.

Evidence strength: Weak to moderate for traditional/pharmacopoeial indications. The European Medicines Agency's HMPC grants only "traditional use" status, not "well-established use," reflecting the insufficient body of controlled clinical trial data. Diuretic and urinary tract indications are supported by a long regulatory tradition, pharmacopoeial recognition (European Pharmacopoeia, British Pharmacopoeia, ESCOP), and limited clinical studies, but rigorous randomised controlled trials are absent.

6.2 Wound Healing and Skin Conditions — Betulin (Topical)

This is the area with the strongest and most directly clinical evidence for any birch constituent.

EMA approval: With central European approval in January 2016 for a betulin-oleogel (Episalvan), used to accelerate wound closure in partial thickness wounds, the herbal active ingredient triterpene dry extract (betulin) from birch bark was introduced into therapy for the first time. The active ingredient is new and its indication is for the first time clearly proven in studies.

Phase III clinical trial — burns: Oleogel-S10 (Episalvan) significantly accelerated the healing of superficial partial thickness burn wounds and was safe and well tolerated. A randomised phase III clinical trial investigating the re-epithelialisation of split-thickness skin graft wounds enrolled 219 patients; results showed the ability of this product to accelerate skin healing and re-epithelialisation.

Episalvan, a birch bark extract with Betulae cortex as the main active substance, received approval by the EMA for the treatment of superficial skin wounds and IIa-degree skin burn wounds in adults in 2016; however, it was withdrawn by the European Union as a medicine in 2022.

Fisuvez for epidermolysis bullosa: A new medicine, Fisuvez (a dry extract from birch bark using n-heptane as the extraction solvent), has recently been approved by the EMA for the treatment of epidermolysis bullosa. Triterpenes are known to improve scar formation for superficial lesions and have recently been approved by the EMA as agent for the treatment of epidermolysis bullosa dystrophica and junctionalis, suggesting a faster re-epithelialisation of wounds.

Systemic exposure from topical application: In three clinical studies with a total of 280 patients, application of Episalvan gel to open wounds did not lead to betulin plasma levels higher than natural background levels originating from nutrition. Since no biologically relevant levels of betulin were found in patients, no further studies related to distribution, biotransformation, and elimination were performed.

Evidence strength: Strong for topical wound healing. The Phase III trial data on partial-thickness burns and skin graft donor sites, along with EMA marketing authorisation for Episalvan and subsequent EMA approval of Fisuvez for epidermolysis bullosa, represent the highest level of clinical evidence attained for any birch-derived constituent.

6.3 Anti-inflammatory Effects

In vitro and animal data: Growth-inhibiting effects were measured in vitro on four malignant human cell lines: A431 (skin epidermoid carcinoma), A2780 (ovarian carcinoma), HeLa (cervix adenocarcinoma), and MCF7 (breast adenocarcinoma), by means of MTT assay. All of the prepared bark extracts exerted a pronounced antiproliferative effect against human cancer cell lines. In vivo studies involved the anti-inflammatory effect of birch extracts on TPA-induced model of inflammation in mice.

Because of the intense anti-inflammatory activity of betulin-enriched birch bark extract, the main conclusion which can be drawn is that betulin is a promising compound in this therapeutic field.

Evidence strength: Preliminary. Anti-inflammatory activity is well-documented in vitro and in animal models, and the NF-κB and COX-mediated mechanisms are supported mechanistically. Human clinical trials specifically targeting inflammation as a primary endpoint are absent for oral or systemic use. The anti-inflammatory effect for topical application is partly validated through the wound healing clinical trials referenced above.

6.4 Anticancer Properties

Pentacyclic triterpenes, mainly betulin and betulinic acid, are described as valuable anticancer agents found in the bark of the birch tree. This triterpene has gained a lot of attention as it exhibits various pharmacological activities, including anti-neoplastic properties.

The cellular events regulated by betulin and precise molecular mechanisms under these processes have only recently begun to be understood. Today we know that betulin can exert important anticancer activities through modulation of diverse cellular pathways.

Betulin exhibits enormous pharmacological potential, owing to its relatively small size and specific cytotoxic actions against tumour cells. This has encouraged research on the molecule, aiming to highlight its advantage as compared to conventional therapeutic agents.

Evidence strength: Preclinical only. Evidence for anticancer effects is confined to in vitro cell-line studies and animal models. No human clinical trials have been completed or published that demonstrate anticancer efficacy of betulin or betulinic acid as standalone treatments in cancer patients. Bioavailability limitations (poor water solubility) further constrain translational potential, and this remains an active area of pharmaceutical research.

6.5 Antioxidant Properties

A number of studies have found that the antioxidant activity of Betula pendula extracts correlates with the phenolic content, and thus the identification of the phenolic compounds in the plant extract may reveal compounds responsible for its antioxidant activity in various assays.

All extracts at tested concentrations reduced the production of hydrogen peroxide, superoxide anion radical, and 25% extract decreased malonic aldehyde formation in acetaldehyde-treated cells.

Evidence strength: Preliminary. Antioxidant activity is consistently demonstrated in vitro but has not been evaluated in clinical trials. The high flavonoid and polyphenol content of birch leaf extracts underpins this activity mechanistically.

6.6 Xylitol — Dental Health

Xylitol is used to reduce the risk of dental cavities because it can help slow down the growth of bacteria in the mouth. Xylitol is generally recognised as safe (GRAS) by the FDA. This is one of the most clinically robust applications of a birch-derived compound, though xylitol is now more commonly produced from other plant sources and is not subject to the same evidence questions as bark or leaf extracts.

6.7 Rheumatic Conditions / Musculoskeletal

Birch leaves (Betula pendula Roth, Betula pubescens Ehrh.) is a plant material traditionally used in gout, rheumatism, arthritis, and urinary tract conditions. The diuretic mechanism has been proposed to account for some of this benefit, since increased urine output may assist in the excretion of uric acid relevant to gout. Birch leaves act as an effective remedy for cystitis and other infections of the urinary system as well as removing excess water from the body. Perhaps because of this cleansing diuretic activity, the plant has been used for gout, rheumatism, and mild arthritic pain.

Evidence strength: Traditional use only. No controlled clinical trials exist examining birch preparations specifically for rheumatic or gouty conditions.

7. Body Systems and Health Areas

• Urinary / Renal system: Primary pharmacopoeial indication. Diuretic, irrigation of the urinary tract, adjuvant in lower urinary tract infections and renal gravel.
• Skin and wound healing: Topical betulin preparations are clinically validated for partial-thickness wound healing and burn care; Fisuvez has received EMA approval for epidermolysis bullosa.
• Musculoskeletal system: Traditional use for gout, rheumatism, and arthritis via diuretic and anti-inflammatory mechanisms; no direct clinical trial evidence.
• Oncology (preclinical interest): Betulin and betulinic acid show in vitro and in vivo anticancer activity but no completed human trials.
• Immune / Inflammatory system: NF-κB and Nrf2 pathway modulation documented in laboratory research; anti-allergic properties studied in animal models.
• Digestive system: Birch buds have been employed as cholagogues, particularly in Eastern Europe and Russia. Animal studies suggest gastroprotective effects.
• Oral health: Xylitol derived from birch is established for caries prevention.

8. Dosage Forms and Dosages Reported in Studies

The following dosages are reported directly in the cited sources and should not be interpreted as prescriptive recommendations.

Birch Leaf (Oral)

• Birch leaf medicines should only be used in adults and adolescents above 12 years of age. They are used over a period of 2 to 4 weeks (per EMA HMPC guidance).
• In the clinical study reviewed by the EMA, the extract was administered at doses of 180–1080 mg/day during 2–4 weeks.

Birch Bark (Topical — Pharmaceutical)

• There is an authorised prescription-only topical drug preparation, Episalvan gel (Amryt AG); 1 g gel contains 100 mg refined dry extract of birch bark (from B. pendula, B. pubescens, or hybrids), equivalent to 0.5–1 g birch bark, corresponding to 72–88 mg betulin.

Preclinical Doses (Not for Human Use — Reference Only)

• In the rat metabolomics pilot study: Two doses, 25 or 50 mg/kg, of a standardised B. alba extract were orally administered to rats.
• In a pharmacokinetic/toxicity study: At 300 mg/kg a maximum plasma concentration of 0.33 µg/mL betulin was detected after 28 daily applications in dogs.

9. Safety, Adverse Effects, and Interactions

9.1 General Safety Profile

Safety and toxicity data for birch are scant. The subchronic toxicity study showed no toxicity of triterpene extract (TE) in rats (i.p.) and dogs (s.c.). In conclusion, triterpene extract from birch bark is safe, its betulin is bioavailable, and TE provides high potential for further pharmaceutical and pharmacological research.

The birch triterpenes have known antiviral, antimicrobial, and hepatoprotective pharmacological activities. Betulinic acid, oleanolic acid, and betulin also have antitumour effects. These triterpenes show anti-inflammatory activities.

9.2 Reported Adverse Effects (Oral and Topical Use)

Side effects reported with birch leaf medicines include diarrhoea, feeling or being sick, and allergic reactions such as itching, rash, and stuffy and runny nose. Their frequency is unknown.

Clinical investigation of a birch leaf dry extract reported mild adverse events, including allergic systemic reactions and skin, gastrointestinal, and metabolic reactions.

Common side effects of xylitol may include bloating, gas, or loose stools.

9.3 Birch Pollen Allergy and Cross-Reactivity

Birch pollen is a significant and well-characterised aeroallergen. Pollen-allergic patients frequently present oral allergy-like symptoms after ingestion of several kinds of plant foods. The majority of these reactions are due to three distinct cross-reactive structures present in birch pollen. Proteins sharing common epitopes with Bet v 1, the major birch pollen allergen, occur in other kinds of tree pollen, apples, stone fruits, celery, carrots, and nuts. Approximately 70% of patients who are allergic to birch pollen may experience symptoms after consumption of foods from these groups.

Mal d 1, the major apple allergen, is 63% homologous to Bet v 1, the major birch pollen allergen. Other birch pollen-related proteins have been identified in hazelnuts (Cor a 1), celery (Api g 1), and potatoes.

This cross-reactivity is clinically important for individuals using birch preparations: birch sap, leaf, and pollen have caused allergic reactions. Birch pollen has been studied in extensive pre-clinical and clinical allergen research.

Separate from IgE-mediated pollen allergy, allergic contact dermatitis from the bark extract has also been documented in the literature. Allergic contact dermatitis caused by betulin-containing triterpene extract from the outer bark of birch (Betula alba) has been reported.

9.4 Contraindications

The EMA monograph notes that birch leaf preparations should not be used in cases of oedema due to reduced cardiac or renal function, or in cases of known allergy to birch pollen. No case of overdose has been reported for birch leaf preparations. None reported in terms of drug interactions with the leaf preparations assessed by EMA, though this reflects the limited data rather than confirmed absence of interactions.

9.5 Pregnancy, Lactation, and Paediatric Use

No fertility data are available from the EMA assessment of birch leaf preparations. The HMPC has not endorsed the use of birch leaf preparations in pregnant or breastfeeding women due to absence of safety data, and birch leaf medicines should only be used in adults and adolescents above 12 years of age per current EMA guidance.

9.6 Xylitol and Pets

Although beyond the scope of human supplementation, it is notable that xylitol, a birch-derived sugar alcohol, is well-established as toxic to dogs; this does not affect its human GRAS status.

9.7 Bioavailability Limitations

Betulin and its product of oxidation, betulinic acid, show poor aqueous solubility owing to their structure. Hence, various derivatives have been synthesised to improve bioavailability and delivery to target tissues. This constraint means that the promising preclinical data on anticancer and systemic anti-inflammatory properties may not translate directly to orally consumed dietary supplements without formulation-specific enhancement.

10. Summary of Evidence Quality by Use Area

• Topical wound healing (betulin oleogel): Strong — Phase III RCT data; EMA marketing authorisation (Episalvan, Fisuvez).
• Urinary tract support / diuretic (birch leaf): Moderate-low — Pharmacopoeial and regulatory traditional-use recognition by EMA, British Pharmacopoeia, ESCOP, and European Pharmacopoeia; very limited clinical trial data; classified as traditional use rather than well-established use.
• Anti-inflammatory effects: Preliminary — Mechanistic and preclinical evidence is substantial; human RCT evidence is absent.
• Anticancer effects: Preclinical only — Robust in vitro data; no completed human trials.
• Rheumatic / musculoskeletal: Traditional use only — No RCT evidence.
• Xylitol for dental caries prevention: Strong — Well-established, GRAS status.

References

• Investigating Systemic Metabolic Effects of Betula alba Leaf Extract in Rats via Urinary Metabolomics — PMC/NCBI (2025)
• Anti-Inflammatory and Anticancer Properties of Birch Bark-Derived Betulin: Recent Developments — PMC/NCBI (2021)
• Study of the Betulin Enriched Birch Bark Extracts Effects on Human Carcinoma Cells and Ear Inflammation — PMC/NCBI (2012)
• Evaluation of the Antioxidant Activity of Betula pendula Leaves Extract and Its Effects on Model Foods — PMC/NCBI (2018)
• A Preliminary Pharmacokinetic Study of Betulin, the Main Pentacyclic Triterpene from Extract of Outer Bark of Birch (Betulae alba cortex) — PMC/NCBI (2018)
• Antioxidative and Antimicrobial Evaluation of Bark Extracts from Common European Trees in Light of Dermal Applications — PMC/NCBI (2023)
• Evaluation of Antioxidative Mechanisms In Vitro and Triterpenes Composition of Extracts from Silver Birch and Black Birch Barks — PMC/NCBI (2021)
• Natural Therapeutics for Urinary Tract Infections — A Review — PMC/NCBI (2020)
• Oral Allergy Syndrome — PMC/NCBI
• Allergenic Cross-Reactivity, Food Allergy and Pollen — PubMed (2011)
• Betulin Wound Gel Accelerated Healing of Superficial Partial Thickness Burns: Results of a Randomized, Intra-Individually Controlled, Phase III Trial with 12-Months Follow-Up — PubMed (2018)
• The Wound Healing Properties of Betulin from Birch Bark from Bench to Bedside — PubMed/Planta Medica (2019)
• Betulae folium — Herbal Medicinal Product Page — European Medicines Agency (EMA)
• Final European Union Herbal Monograph on Betula pendula Roth; Betula pubescens Ehrh., folium — EMA (2014)
• Birch Leaf: Summary for the Public — EMA HMPC
• Assessment Report on Betula pendula Roth; Betula pubescens Ehrh., folium — EMA
• Betula pendula — ScienceDirect Topics Overview
• Betulae folium (Birch Leaf) — ESCOP Monograph (2015)
• Birch — Betula lenta, B. papyrifera, B. pendula and B. pubescens — Family Betulaceae (ResearchGate Review)
• Medicinal Plants of the Genus Betula — Traditional Uses and a Phytochemical-Pharmacological Review (Academia.edu / Journal of Ethnopharmacology, 2015)
• The Bioactive and Mineral Compounds in Birch Sap Collected in Different Types of Habitats (ResearchGate, 2017)
• Effect of Birch Sap as Solvent and Source of Bioactive Compounds in Casein and Gelatine Films — PMC/NCBI (2023)
• The Wound Healing Properties of Betulin from Birch Bark from Bench to Bedside — Planta Medica/Thieme (2019)
• Birch: Overview, Uses, Side Effects, Precautions, Interactions, Dosing — WebMD Natural Medicines
• Xylitol: Uses, Side Effects, Interactions — WebMD
• Plant Extracts and Natural Compounds for the Treatment of Urinary Tract Infections in Women — PMC/NCBI (2025)