Symphytine (Comfrey Pyrrolizidine Alkaloid · Topical Context · PA Regulatory Reference)
| Compound | Symphytine |
| Chemical class | Alkaloid — Pyrrolizidine Alkaloid (Unsaturated macrocyclic PA; from comfrey) |
| CAS | 22257-23-4 |
| Primary source | Symphytum officinale (comfrey), Symphytum asperum (rough comfrey) |
| Key applications | Informational reference — primary comfrey hepatotoxic PA; topical comfrey context; regulatory compliance |
| Claim strength | Not applicable (regulatory and toxicological reference) |
| Typical form | Hepatotoxic contaminant in comfrey root extract; comfrey topical preparations (low-PA specification) |
| Buy from Herbuno | Browse HerbIQ Compound Index → |
Name origin: From Symphytum (comfrey genus). Symphytine is the primary hepatotoxic pyrrolizidine alkaloid of comfrey root — a macrocyclic unsaturated PA with the 1,2-unsaturated necine base structure responsible for hepatotoxic bioactivation. It co-occurs with echimidine, lycopsamine, and other PAs in comfrey root and leaf, with root having significantly higher PA content (0.5–3.0% PA by dry weight in root vs 0.01–0.3% in leaf). Traditional use context: Comfrey (Symphytum officinale, Knitbone, Blackwort) has centuries of traditional use in European herbal medicine for wound healing, bruise resolution, joint pain, and bone fractures — the traditional names “Knitbone” and “Boneset” reflect its traditional fracture-healing applications. Allantoin is the primary wound-healing constituent; pyrrolizidine alkaloids are toxicological contaminants rather than therapeutic actives. Regulatory history and current status: Germany restricted comfrey preparations for internal use in 1990 (later strengthening to prohibition for internal use). The EU, UK, US, and Australia have taken various regulatory actions restricting internal comfrey use. Topical comfrey preparations (allantoin-standardised, low-PA, short-duration use) retain EMA approval for wound healing and joint pain. Herbuno’s Comfrey Root Extract is primarily for topical formulation use — confirmation of PA content and compliance with applicable PA limits is required for any commercial formulation. Symphytine specifically is documented here as a regulatory and safety reference compound.
Symphytine — Regulatory and Toxicological Context
Comfrey hepatotoxicity mechanism — symphytine bioactivation: Symphytine and other comfrey PAs are bioactivated via CYP3A4 to pyrrolic esters — alkylating agents causing DNA cross-linking in hepatocytes and sinusoidal endothelial cells. The macrocyclic structure of symphytine makes it particularly prone to reactive pyrrole formation. Acute hepatic veno-occlusive disease from internal comfrey use has been documented — including fatal cases from prolonged internal comfrey root tea consumption. Critical safety reference.
Topical comfrey preparations — EMA-approved context: EMA Community Herbal Monograph (2011) approves topical comfrey root preparations standardised to allantoin (0.35% minimum in finished preparation) and with defined maximum PA content (<1 µg PA per daily topical dose in the EU). For wound healing, bruises, and joint pain applications, topical comfrey has positive RCT evidence for pain reduction and healing time. Herbuno’s Comfrey Root Extract — when formulated for topical use in compliance with EMA PA limits — is an appropriate commercial ingredient for these applications. Claim strength: Moderate (topical; EMA-approved traditional use).
PA content variation between root, leaf, and products: Comfrey root PA content: typically 0.5–3.0% dry weight (extremely high). Comfrey leaf PA content: typically 0.01–0.3% dry weight (lower but still concerning for internal use). Commercial comfrey oil (lipophilic extraction) has very low PA content (PAs are water-soluble; lipophilic extraction minimises PA co-extraction). For topical formulations, specified low-PA comfrey extract (processed to reduce PA below EMA limits) is the appropriate raw material. Request detailed PA panel by HPLC-MS/MS (covering symphytine, echimidine, lycopsamine, and all regulated PAs) on CoA. Formulator compliance reference.
This compound is documented for research and formulator education purposes. For commercially available botanical ingredients, explore the HerbIQ Compound Index →
Frequently Asked Questions — Symphytine
Is Herbuno’s Comfrey Root Extract suitable for internal supplement use?
No. Comfrey root preparations for internal use are banned or severely restricted in Germany, Austria, UK, and multiple other markets due to symphytine and other hepatotoxic PA content. The EMA Community Herbal Monograph does not support internal use of comfrey root. Herbuno’s Comfrey Root Extract products are intended for topical formulation use, where PA exposure via transdermal absorption is significantly lower and the EMA has established acceptable PA dose limits for short-term use. Any formulator considering internal use of comfrey root extract should seek regulatory advice in target markets.
What is the allantoin content of comfrey extract and what does it do?
Allantoin is the primary wound-healing active in comfrey — it promotes cell proliferation, reduces inflammation, and stimulates collagen synthesis in dermal fibroblasts. Comfrey root typically contains 0.6–1.0% allantoin (dry weight). The EMA monograph specifies minimum 0.35% allantoin in the finished topical preparation as the standardisation marker. Allantoin can also be synthesised (cosmetic-grade synthetic allantoin is available) — formulators seeking allantoin activity without PA contamination risk can use synthetic allantoin alongside other wound-healing actives rather than comfrey root extract.
What PA limits apply to topical comfrey formulations?
EMA Community Herbal Monograph (2011): maximum 1 µg total PA (as sum of all PAs) per day in finished topical preparation, calculated for the maximum daily applied dose. Maximum treatment duration: 4–6 weeks per year for adults (not to be applied to broken skin). The formulator must ensure that the comfrey extract used, at the intended use level in the finished formulation and at the maximum application dose per day, delivers <1 µg total PA. This requires HPLC-MS/MS PA quantification of the extract at the specified inclusion level.
Are there other wound-healing botanicals to consider alongside or instead of comfrey?
Yes. Alternatives and complements to comfrey for topical wound healing: Calendula (Calendula officinalis) — no PA concern, anti-inflammatory and re-epithelialising; Centella asiatica (TECA) — collagen-stimulating, high clinical evidence; Aloe vera — soothing, moisturising, modest wound-healing evidence; Hypericum perforatum (St John’s wort oil) — anti-inflammatory; Arnica — bruise resolution. For formulators with PA compliance concerns, these alternatives allow equivalent or superior wound-healing claims without the regulatory complexity of comfrey PA management.
Related compounds: Senecionine, Monocrotaline, Asiaticoside, Bisabolol
Claim-strength scale – High = multiple human RCTs; Moderate = limited trials or strong preclinical convergence; Emerging = early-stage lab or animal data.
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