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White Hellebore

Scientific Name(s): Veratrum album L., Veratrum californicum Dur., Veratrum fimbriatum A. Gray., Veratrum frigidum Schltdl. and Cham., Veratrum nigrum L., Veratrum viride Ait.
Common Name(s): Black false hellebore, California false hellebore, False hellebore, Fringed false hellebore, Green hellebore, Indian poke, Itchweed, Langwort, Western hellebore, White hellebore

Clinical Overview

Use

Historically, false hellebore was evaluated for use in hypertension; however, toxicity precludes its widespread use. Research reveals no clinical trials regarding the use of veratrum for any condition.

Dosing

White hellebore is toxic; however, doses of 0.02 to 0.1 g of the powdered root have been traditionally used.

Contraindications

No longer considered safe for use.

Pregnancy/Lactation

Avoid use. Documented adverse effects.

Interactions

None well documented.

Adverse Reactions

GI irritation, hypersalivation, vomiting, headache, visual disturbances, paresthesia, dizziness, bradycardia, atrioventricular block, hypotension, and syncope have been reported.

Toxicology

Numerous nonfatal poisonings have been reported.

Botany

The genus Veratrum comprises multiple recognized false hellebore species, including the archetypical V. album or white false hellebore. Veratrum should not be confused with the genus Helleborus (buttercup family). False hellebore is a perennial that is widely distributed throughout Europe, northern Asia, and North America. The plant grows 1.5 to 2.5 m in height and is characterized by a hairy stem and large, oval, yellow-green leaves that alternate around the stem and have a slightly hairy undersurface, with the plant's lower leaves reaching up to 0.3 m in length. Its greenish flowers bloom in June and July, producing a capsule-like fruit. The rhizome has an acrid taste and onion-like odor.Chevallier 2001, USDA 2016

History

The term "veratrum" is derived from the Latin words "vere" meaning "truly" and "ater" meaning "black." Historical use of V. album centers on its toxic potential. In Roman times, V. album was used as a poison and an extract of the plant was used as an arrow tip poison; there is some thought that poisoning with V. album extract was the cause of death for Alexander the Great.Schep 2014 Small doses were used to treat symptoms of cholera, often with less than desirable effects. White hellebore was used in place of Colchicum for the treatment of gout, to aid in the treatment of hypertension, and to treat herpetic lesions externally, but use has been limited by its toxicity. White hellebore was listed in the French pharmacopeia as a treatment for hypertension, toxemia of pregnancy, and cardiac failure until 1982; however, current use in herbal medicines is rare, except in homeopathy.Chevallier 2001, Quatrehomme 1993, Van Wassenhoven 2004

Chemistry

Reviews of the alkaloidal content of false hellebore species have been published, especially concerning that of veratrum extracts for use in the management of hypertension prior to being superseded by safer, more effective medications.Heretsch 2015, Li 2006, Schep 2006

More than 200 alkaloids have been described, including the toxicologically relevant cevadine and veratridine, as well as a mixture of alkaloids collectively referred to as "veratrine."Duke 1992, Heretsch 2015, Schep 2006 The entire plant contains toxic alkaloids.Schep 2006 Potential chemotherapeutic applications of the toxic alkaloids, including the jervanine alkaloid cyclopamine, have been investigated.Heretsch 2015, Li 2006, Wilson 2010 A method for identifying toxic alkaloids in cases of poisoning has been described.Gaillard 2001, Grobosch 2008

Uses and Pharmacology

Veratrum alkaloids act by binding to sodium voltage–gated channels in skeletal muscle and cardiac and nerve cells, which delays repolarization and allows prolonged conduction of impulses.Schep 2006

Cardiovascular effects

Animal data

Older animal studies verified cardiovascular effects of Veratrum spp.Schep 2006

Clinical data

Veratrum extracts were used historically in the management of hypertension. However, research reveals no current clinical data regarding the use of false hellebore for cardiovascular use, in part due to the plant’s recognized toxicity.Quatrehomme 1993, Schep 2006

Other uses

Potential chemotherapeutic applications of the toxic alkaloids, including the jervanine alkaloid cyclopamine, have been investigated.Heretsch 2015, Li 2006, Wilson 2010

Dosing

Veratrum extract is toxic. The powdered root of the plant has been traditionally dosed at 0.02 to 0.1 g.Greunwald 2002

Pregnancy / Lactation

Avoid use. No longer considered safe for use. Teratogenic effects have been reported in animals.Schep 2006

Interactions

None well documented. Interactions could theoretically occur with cardiovascular drugs.

Adverse Reactions

GI irritation, salivation, vomiting, headache, visual disturbances, paresthesia, dizziness, bradycardia, atrioventricular block, hypotension, and syncope have been reported.Gilotta 2010, Grobosch 2008

Toxicology

Poisoning has been reported, commonly due to mistaking the plant for wild garlic or other species. Symptoms, including vomiting that may minimize absorption of the toxic principles, can appear 30 minutes following ingestion.Gilotta 2010, Grobosch 2008, Pfab 2016, Rauber-Lüthy 2010, Schep 2006, Zagler 2005 Treatment is aimed at achieving hemodynamic stability with the use of fluids, atropine, and vasopressor agents; with prompt supportive care, recovery is typical (although fatalities have been reported).Schep 2006 Children can be managed in the same manner.Rauber-Lüthy 2010 Teratogenic effects (including congenital tracheal stenosis) have been reported in fetuses of animals grazing on V. californicum.Schep 2006

References

Chevallier A. Encyclopedia of Medicinal Plants. New York, NY: DK Publishing; 2001.
Duke J. Handbook of Biologically Active Phytochemicals and Their Activities. Boca Raton, FL: CRC Press, Inc; 1992.
Gaillard Y, Pepin G. LC-EI-MS determination of veratridine and cevadine in two fatal cases of Veratrum album poisoning. J Anal Toxicol. 2001;25(6):481-485.11550825
Gilotta I, Brvar M. Accidental poisoning with Veratrum album mistaken for wild garlic (Allium ursinum). Clin Toxicol (Phila). 2010;48(9):949-952.21171854
Greunwald J, Brendler T, Jaenicke C, eds. PDR for Herbal Medicines. 4th ed. Montvale, NJ: Medical Economics Co; 2002.
Grobosch T, Binscheck T, Martens F, Lampe D. Accidental intoxication with Veratrum album. J Anal Toxicol. 2008;32(9):768-773.19021933
Heretsch P, Giannis A. The Veratrum and Solanum alkaloids. Alkaloids Chem Biol. 2015;74:201-232.25845062
Li HJ, Jiang Y, Li P. Chemistry, bioactivity and geographical diversity of steroidal alkaloids from the Liliaceae family. Nat Prod Rep. 2006;23(5):735-752.17003907
Pfab R, Hohe M, Pietsch J, Eyer F. Accidental poisoning with pulverized Veratrum: a case report with analytical confirmation. Clin Toxicol. 2016;54:499.
Quatrehomme G, Bertrand F, Chauvet C, Ollier A. Intoxication from Veratrum album. Hum Exp Toxicol. 1993;12(2):111-115.8096707
Rauber-Lüthy C, Halbsguth U, Kupferschmidt H, et al. Low-dose exposure to Veratrum album in children causes mild effects—a case series. Clin Toxicol (Phila). 2010;48(3):234-237.20170391
Schep LJ, Schmierer DM, Fountain JS. Veratrum poisoning. Toxicol Rev. 2006;25(2):73-78.16958554
Schep LJ, Slaughter RJ, Vale JA, Wheatley P. Was the death of Alexander the Great due to poisoning? Was it Veratrum album? Clin Toxicol (Phila). 2014;52(1):72-77.24369045
Van Wassenhoven M. Towards an evidence-based repertory: clinical evaluation of Veratrum album. Homeopathy. 2004;93(2):71-77.15139090
Veratrum album. USDA, NRCS. 2016. The PLANTS Database (http://plants.usda.gov, September 2016). National Plant Data Team, Greensboro, NC 27401-4901 USA. Accessed September 2016.
Wilson SR, Strand MF, Krapp A, et al. Hedgehog antagonists cyclopamine and dihydroveratramine can be mistaken for each other in Veratrum album. J Pharm Biomed Anal. 2010;53(3):497-502.20646889
Zagler B, Zelger A, Salvatore C, Pechlaner C, De Giorgi F, Wiedermann CJ. Dietary poisoning with Veratrum album—a report of two cases. Wien Klin Wochenschr. 2005;117(3):106-108.15773425

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