Colchicine - lethal confusion with wild garlic
Colchicine is a lethal tropolone alkaloid of autumn crocus, often confused with the edible wild garlic.
Collecting wild food in nature is popular, and especially the collection of wild garlic (Allium ursinum L.) has seen a dramatic increase in several countries in the last decade. Though not containing any significant toxins itself, the popularity of wild garlic has caused mortalities through the confusion with autumn crocus (Colchicum autumnale L.) and Lily of the valley (Convallaria majalis L.). The toxins of Convallaria majalis has already been treated in the toxin of the week: Convallatoxin.
This article is on the toxins of Colchicum autumnale L., specifically colchicine.
Colchicum autumnale L. sounds several names: autumn crocus, meadow saffron and naked ladies. It is in the order of Liliales, while the - from appearance - similar Allium ursinum and Convallaria majalis are from the order of Asparagales. As the name implies, it is autumn-blooming, and though the blossoms are distinct, the leaves can be confused with Allium ursinum before this stage (Figure 2).
Figure 1: From left to right: Allium ursinum, Convallaria majalis and Colchicum autumnale (Pilegaard 2012)
Cases of intoxication with Colchicum autumnale appears every year in spring. In a German investigation based on occurrences reported at the poison centers in Freiburg(2000-2004) and Münich (1994-2004), 32 cases were identified (Hermanns-Clausen et al. 2006). Of these 6 cases – 18.75% - were lethal. In the cases of lethal intoxication, the patients died within 1-4 days after ingestion. Symptoms include vomiting, diarrhea, pulmonary edema and rhabdomyolyses (breakdown of damaged skeleton muscle).
Colchicine is a tropolone alkaloid (tropolone=hydroxyderivate of tropone, a non-benzenoid aromatic) with a stereocenter, giving rise to S and R enantiomers (Figure 2). Only the S-enantiomer occurs in nature.
Figure 3: Colchicine 3D structure
Upon digestion and absorption, colchicine binds to the intracellular protein tubulin and thereby inhibits the polymerization of microtubuli, causing a changed protein composition in the Golgi apparatus, reduced endocytosis, changed cell shape and mobility, and inhibition of mitosis in the early cell cycle. The pharmacological characteristics have been used for beneficial purposes through time and at present to treat gout (inflammatory arthritis) and Behçet's disease (inflammatory disorder). It thus manifests the basic principle of toxicology: “The dose makes the poison”. Intoxication symptoms appear at 0.5 mg per kg bodyweight, and death at ingestion above 0.8 mg per kg bodyweight. This means there is a risk of death, when a person of 60 kg eats a portion of lettuce of 60g.
- Ghawanmeh, Abdullah A., Hussein M. Al-Bajalan, Mukram Mohamed Mackeen, Feras Q. Alali, and Kwok Feng Chong. 2020. “Recent Developments on (−)-Colchicine Derivatives: Synthesis and Structure-Activity Relationship.” European Journal of Medicinal Chemistry 185 (January): 111788. https://doi.org/10.1016/j.ejmech.2019.111788.
- Hermanns-Clausen, Maren, U. Stedtler, F. Schindler, T. Zilker, and N. Felgenhauer. 2006. “Warnen Sie Ihre Patienten vor dem tödlichen Salat!: Verwechslungsgefahr im Frühjahr: Bärlauch und Herbstzeitlose.” MMW - Fortschritte der Medizin 148 (12): 45–47. https://doi.org/10.1007/BF03364609.
- Pilegaard, Af Kirsten. 2012. “Ramsløg kan forveksles med giftige planter,”
- Pubchem, CID:6167, https://pubchem.ncbi.nlm.nih.gov/compound/6167 (accessed 10:30, January 10, 2020)
- Teuscher, E.; Lindequist, U. (2010) Biogene Gifte: Biologie-Chemie-Pharmakologie-Toxikologie. Wissenschaftliche Verlagsgesellschaft GmbH, Stuttgart, 3 Auflage.
Sarah Stierch - Own work, CC BY 4.0, https://commons.wikimedia.org/w/index.php?curid=16519103
Enrico Blasutto - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=7778495
Chromolithograph by Portail after Auguste Faguet - Dictionnaire de botanique by Henri Ernest Baillon and others, volume 3., Public Domain, https://commons.wikimedia.org/w/index.php?curid=3493546
CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=134698
ESR4 Bettina Gro Sørensen