Lycopsamine (Pyrrolizidine Alkaloid · Hepatotoxic · Food Safety Reference)

Compound	Lycopsamine ((+)-Lycopsamine; Trachelanthamine; 7-Angeloylretronecine)
Class	Alkaloid — Pyrrolizidine (Monoester, retronecine type)
CAS	10285-07-1
Molecular formula	C₁₅H₂₃NO₅
Primary sources	Borago officinalis (borage), Cynoglossum officinale (hound's tongue), Echium spp.
Plant part	Aerial parts, seeds, leaves
Claim strength	Emerging (toxicology)
Key applications	EFSA priority PA; borage safety reference; food supplement regulatory reference; informational-only
Buy from Herbuno	Informational reference — see HerbIQ Compound Index →

Name origin: Lycopsamine is named after Lycopsis arvensis (now Anchusa arvensis — bugloss), from which it was first isolated. It belongs to the retronecine-type monoester PAs — unlike the hepatotoxic macrocyclic and open-chain diester PAs, lycopsamine has a monoester structure, which gives it lower intrinsic hepatotoxic potency than lasiocarpine or retrorsine. However, it remains a significant food safety concern in borage products due to the volumes consumed. Traditional context: Borago officinalis (borage) has extensive traditional use in European herbal medicine for adrenal support, mood, and as a diuretic. Borage seed oil (rich in GLA — gamma-linolenic acid) is a mainstream supplement. However, borage leaf and flower preparations contain lycopsamine and other PAs, creating a safety-benefit balance challenge. Research trajectory: Lycopsamine is one of the six EFSA priority PAs requiring monitoring in food and herbal products. Its relative hepatotoxic potency is lower than macrocyclic PAs, but its presence at detectable concentrations in borage aerial part preparations and honey from borage-growing regions creates meaningful regulatory exposure. Safety context: Lycopsamine is hepatotoxic at sufficiently high exposures and genotoxic by class-based assessment. The key regulatory concern is cumulative exposure from multiple dietary sources (borage tea, pollen, honey).

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Toxicological Profile of Lycopsamine

Relative hepatotoxic potency: Lycopsamine, as a monoester PA, has lower in vivo hepatotoxic potency than macrocyclic diester PAs (retrorsine, senecionine) or open-chain diester PAs (lasiocarpine, heliotrine). Rodent LD₅₀ values for monoester PAs are generally 3–10-fold higher (less acutely toxic) than equivalent macrocyclic types. However, chronic low-dose exposure may still cause sinusoidal obstruction syndrome and genotoxic effects. Claim strength: Moderate (toxicology).

EFSA priority status: Lycopsamine is designated as one of six EFSA priority PAs for food monitoring because of its ubiquity in borage (a widely consumed herb and seed oil), its presence in honey from borage-growing regions, and the large number of European consumers with potential exposure. EFSA's 2016 opinion used MOE analysis to conclude concern for human health at observed dietary exposure levels, particularly for children and high-consuming adults. Claim strength: High (regulatory).

Borage-specific considerations: Borage seed oil (GLA source) derived from seeds contains lower PA concentrations than aerial parts — seed oil production typically reduces PA content due to PA preferential retention in aqueous/protein fractions. However, refined borage seed oil is not guaranteed PA-free; quality specifications require testing. Borage leaf, flower, and herbal tea preparations have higher PA content requiring full monitoring. Claim strength: High (food safety).

Honey contamination: Borage (Borago officinalis) is a major bee forage plant in Mediterranean and UK agriculture. Borage honey carries lycopsamine from nectar; European honey monitoring surveys find lycopsamine in 15–40% of UK and Mediterranean honey samples. Blended honeys may dilute concentrations; monofloral borage honey has the highest risk. Claim strength: High (food safety).

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Regulatory and Safety Context for Formulators

The regulatory framework for lycopsamine in food products is established and enforced in the EU. EU Regulation 2020/2040 sets lycopsamine limits (combined with its epimer intermedine) in honey (0.1 μg/kg), dried herbs (400 μg/kg for borage flowers), herbal infusions (0.35 μg/kg finished beverage), and food supplements containing borage (1.0 μg/kg for adults).

Formulators using borage seed oil should ensure supplier CoAs include PA analysis (LC-MS/MS, EFSA 28-PA panel). Refined, certified-low-PA borage seed oil is commercially available; demand for this specification is growing in quality supplement manufacturing. Borage leaf or aerial part use in supplements is not recommended without rigorous PA monitoring.

Importantly, Herbuno's borage-sourced products (Borage Oil) should be assessed for PA compliance with supplier documentation. This is not a Herbuno-specific concern — it is industry-wide for any borage-derived ingredient — but transparency in CoA documentation for PA results is a key quality indicator.

Consumer communication: supplement labels in markets with PA regulations (EU, Australia) may require disclosure or restricted claims for borage-containing products. The European Herbal Practitioner's Association guidance for PA-containing herbs recommends maximum daily intake of 1 μg total PAs per day for adults from all sources.

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Frequently Asked Questions — Lycopsamine

Is borage seed oil (GLA) safe to supplement with regarding PA exposure?
Refined borage seed oil contains significantly lower PA concentrations than borage aerial part preparations, because lycopsamine and other PAs are primarily water-soluble and preferentially partition into aqueous and protein fractions during oil extraction. However, "refined" does not guarantee PA-free status; quality-tested borage seed oil with documented PA analysis (LC-MS/MS, <0.1 μg/kg or below detection limit) is commercially available. Formulators and consumers should verify CoA documentation for PA content in borage GLA supplements.

How does lycopsamine differ from other borage PAs like thesinine?
Borage contains several PAs including lycopsamine, its N-oxide, intermedine (the epimer), thesinine, and amabiline. Thesinine is a retronecanol-based monoester (differing necine base from lycopsamine's retronecine) with similar but lower hepatotoxic potency. EFSA monitors lycopsamine and intermedine as a combined indicator for borage PA load; thesinine is in the full 28-PA monitoring panel. All are hepatotoxic by class and must be controlled within established limits.

What is the difference between N-oxide and free-base forms of lycopsamine?
Lycopsamine N-oxide co-occurs with free-base lycopsamine in plants — typically at higher concentrations than the free base. N-oxides were historically considered less toxic (requiring reduction to free base for CYP-mediated activation). However, gut bacterial reduction of N-oxides can convert them to free base in the GI tract, and EFSA's current risk assessment treats N-oxide and free-base PA equivalently for total PA burden calculations.

What should formulators specify when sourcing borage seed oil to comply with EU PA limits?
Specify: (1) refined borage seed oil with documented GC analysis for GLA content (typically ≥19%); (2) PA analysis by LC-MS/MS using the EFSA 28-PA panel with detection limits below the EU maximum levels; (3) CoA issued by an accredited third-party laboratory; (4) traceability to agricultural origin for geographic contamination risk assessment. Borage oil produced under Good Agricultural and Collection Practices (GACP) with documented PA monitoring provides the highest quality assurance for supplement manufacture.

Related compounds: Lasiocarpine, Retrorsine, Senkirkine, Platyphylline

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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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