May's heart-stopping flower: Lily of the Valley
This unassuming birth flower of May also bears a rather strong heart toxin.
I’ll strangely admit that within the past few years I’ve grown to appreciate flowers to a greater degree. There’s something about seeing the world come to life, reawakening from a winter slumber with such vibrancy and diversity.
However, underneath some of nature’s beauties exists some of the strongest toxins out there.
A good friend described one of her favorite flowers, Lily of the Valley, which is also the birth flower for the month of May.
This connection isn’t coincidental, as it appears that Lily of the Valley blooms around this time of the year; roughly in late spring. Lily of the Valley are perennial flowers found throughout the Eastern US as well as in Europe and Asia. They are recognized by their small bell-shaped flowers pointing downward and surrounded by large leaves. One can find Lily of the Valley in shady areas, and they may also bear red berries as their fruits. Strangely, the flower is not actually a lily, but rather is related to the asparagus family (Asparagaceae), and strangely being the only species within the Convallaria family of asparagus.
The flower carries cultural significance, with its inclusion within a bouquet being rather common among British royal families, and was featured within Queen Elizabeth II’s coronation bouquet.
Evidence of Lily of the Valley can be found in many places. This comes as no surprise, as the flower symbolizes happiness, prosperity, and luck.
The flower also likely bears its name from religious text. Farmer’s Almanac makes note of some lore associated with Lily of the Valley, including where its name is derived from, as well as associations to Virgin Mary:
The flower’s association with the month of May comes in part from a bit of traditional lore that nightingales won’t sing until the lily of the valley blooms each May.
The plant takes its name common from a passage in the Biblical Song of Solomon, which reads, “I am the rose of Sharon and the lily of the valley.” It was probably named because it tends to grow in valleys.
This is not the flower’s only religious association. A popular nickname for lily of the valley is “Our Lady’s Tears.” The plant’s downcast posture reminds some of teardrops in the same way a weeping willow’s sweeping branches do. Those of a poetic mindset say the plant is a reminder of the Virgin Mary’s tears at the foot of the cross. Others say the tears were Eve’s, after being cast out of Eden.
Deadly toxins come in small packages
Irrespective of where its name comes from, Lily of the Valley is widely enjoyed and adored throughout the world.
But we wouldn’t be hear discussing pretty flowers if there wasn’t something else going on.
What alerted me to another aspect of Lily of the Valley was when my friend sent me a text, detailing how this rather unassuming flower also contains an extremely deadly heart toxin.
Indeed, there’s a lot of evidence online warning of the possible toxicity from ingesting Lily of the Valley.
The toxin in question is a cardiac glycoside aptly called Convallotoxin, which is found throughout the entire Lily of the Valley plant.
Convallotoxin is a glycoside, meaning that the toxin’s structure is made up of a sugar molecule (rhamnose) bound to a steroid molecule (Strophanthidin) via a glycosidic bond.
Convallotoxin’s mechanism of action is similar to that of digitalis-like cardiac glycosides found in other plants such as foxgloves, in that it inhibits the Na+/K+/ATPase pump1 of the heart and vascular tissue. This pump utilizes the energy-containing molecule ATP in order to maintain intracellular sodium/potassium levels, which are critical for many cellular processes:
The sodium and potassium move against the concentration gradients. The Na+ K+-ATPase pump maintains the gradient of a higher concentration of sodium extracellularly and a higher level of potassium intracellularly. The sustained concentration gradient is crucial for physiological processes in many organs and has an ongoing role in stabilizing the resting membrane potential of the cell, regulating the cell volume, and cell signal transduction.[2] It plays a crucial role on other physiological processes, such as maintenance of filtering waste products in the nephrons (kidneys), sperm motility, and production of the neuronal action potential.[5] Furthermore, the physiologic consequences of inhibiting the Na+-K+ ATPase are useful and the target in many pharmacologic applications.
Ingestion of Lily of the Valley leads to widespread inhibition of this crucial pump. The end result is ion imbalance, including imbalance in intracellular calcium levels. Calcium is critical, as the alterations in intracellular calcium leads to a cellular response in which extra calcium gets released and leads to alterations in heart contractions (Ershad, et al.2, context added):
CAS [cardiac steroids- similar name for cardiac glycosides] primarily serve as inotropic agents in therapeutic settings. Apart from myocytes, they also have effects on vascular smooth muscle and sympathetic nervous system. The primary mechanism of action is the reversible inhibition of the sodium-potassium ATPase pump, which leads to increased intracellular sodium and decreased intracellular potassium levels, leading to the inactivation of sodium-calcium anti-porter pump, which in turn causes an accumulation of calcium intracellularly. This accumulation of intracellular calcium consequently triggers further calcium release from the sarcoplasmic reticulum and finally causes increased myocardial contractility. Besides increased inotropy, CAS causes increased vagal tone in SA and AV nodes decreasing conduction in the nodes with a decreased duration of the refractory period, which increases the risk of automaticity and arrhythmias.
Additional readings on the effects of cardiac glycosides can be found in the following review:
El-Mallakh, et al.3: Cardiac Glycosides in Human Physiology and Disease: Update for Entomologists.
Signs of cardiac glycoside poisoning generally include arrhythmias and chest pain, and usually comes with gastrointestinal problems such as nausea and vomiting. However, in higher doses these compounds can lead to heart failure and death. Thus, the planting of flowers such as Lily of the Valley comes with concerns over pets and children who may accidentally ingest the plants.
An interesting case report4 was noted in which two elderly Chinese individuals accidentally consumed foxglove (the husband mistook it for the kale they were growing) and led to their hospitalization. It should be noted that foxglove cardiac glycosides (Digoxin in particular) is considered more toxic than Convallotoxin.
They provide another overview of symptoms to look out for in relation to cardiac glycoside consumption:
Why be toxic?
There’s an obvious question as to why such unassuming plants would require such a deadly toxin. It’s not as if humans are out and about constantly making foxglove salads to consume, so why have such a defense mechanism?
That may be due to other predators, in this case insects, who may want to snack on the leaves of these plants.
Indeed, it appears that the evolutionary principle behind these cardiac glycosides is for them to act as botanical insecticides- such a tiny dose of cardiac glycosides is likely to be sufficient enough to down and deter any fly or beetle while keeping the plant relatively unharmed.
This has been validated in various convergent evolution studies, in which it was found that different species of insects which may consume cardiac glycoside-containing plants may evolve to have mutations within their Na+/K+/ATPase pumps that make them more resistant to these toxic effects.5,6
Thus, the toxicity in humans is likely carryover from the insecticidal nature of these compounds.
The balance between toxicity and therapy
Although cardiac glycosides can be very dangerous if accidentally ingested, there’s evidence that plants containing these compounds have been used extensively in medicine spanning several centuries and countries, with some evidence of its used being traced back to Japan, China, and parts of Europe.
A piece from Haas, L. F.7 published in 1995 provides a brief reference to the use of Lily of the Valley as a therapeutic agent:
Other accounts of cardiac glycosides being used for medicine has been difficult to find on my end, although the use of these compounds should not come as a surprise.
Cardiac glycosides have been isolated from plants, and are prescribed under specific circumstances for people suffering from arrhythmias and congestive heart failure, usually when other medications haven’t been considered effective.
And in recent years, research into cardiac glycosides have expanded in order to examine them for multiple therapeutic routes8 including looking at them cardiac glycosides for their antiviral9 and anticancer properties10.
This is an example of striking a balance between a compound being a therapeutic agent or becoming toxic. In this case, the therapeutic window for cardiac glycosides is rather narrow, as it is easy for these compounds to become toxic when not used in strictly controlled environments.
Keep in mind that although these compounds have been recognized as a centuries-old remedy, we don’t have any account of the people who may have died from accidental overdoses- that tends to be left out of history books. Be very careful when examining these plants for their therapeutic uses, as an uneducated, intentional use of these plants can easily lead to severe cardiac complications.
Like with everything else, the information here is intended to be informative and not prescriptive.
So when out on a stroll during these warm, late Spring days take some time and enjoy the bounty nature has to offer. Take a gander and see if you can find some Lily of the Valley for yourself- just be careful not to eat any!11
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Pirahanchi Y, Jessu R, Aeddula NR. Physiology, Sodium Potassium Pump. [Updated 2023 Mar 13]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK537088/
Ershad M, Meredith A, Shah N, et al. Cardioactive Steroid Toxicity. [Updated 2022 Sep 12]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK536963/
El-Mallakh, R. S., Brar, K. S., & Yeruva, R. R. (2019). Cardiac Glycosides in Human Physiology and Disease: Update for Entomologists. Insects, 10(4), 102. https://doi.org/10.3390/insects10040102
Janssen, R. M., Berg, M., & Ovakim, D. H. (2016). Two cases of cardiac glycoside poisoning from accidental foxglove ingestion. CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne, 188(10), 747–750. https://doi.org/10.1503/cmaj.150676
Georg Petschenka, Vera Wagschal, Michael von Tschirnhaus, Alexander Donath, and Susanne Dobler
The American Naturalist 2017 190:S1, S29-S43
Dobler, S., Dalla, S., Wagschal, V., & Agrawal, A. A. (2012). Community-wide convergent evolution in insect adaptation to toxic cardenolides by substitutions in the Na,K-ATPase. Proceedings of the National Academy of Sciences of the United States of America, 109(32), 13040–13045. https://doi.org/10.1073/pnas.1202111109
Haas L. F. (1995). Convallari majalis (lily of the valley) (also known as Our Lady's tears, ladder to heaven). Journal of neurology, neurosurgery, and psychiatry, 59(4), 367. https://doi.org/10.1136/jnnp.59.4.367
Kytidou, K., Artola, M., Overkleeft, H. S., & Aerts, J. M. F. G. (2020). Plant Glycosides and Glycosidases: A Treasure-Trove for Therapeutics. Frontiers in plant science, 11, 357. https://doi.org/10.3389/fpls.2020.00357
Škubník, J., Bejček, J., Pavlíčková, V. S., & Rimpelová, S. (2021). Repurposing Cardiac Glycosides: Drugs for Heart Failure Surmounting Viruses. Molecules (Basel, Switzerland), 26(18), 5627. https://doi.org/10.3390/molecules26185627
Bejček, J., Jurášek, M., Spiwok, V., & Rimpelová, S. (2021). Quo vadis Cardiac Glycoside Research?. Toxins, 13(5), 344. https://doi.org/10.3390/toxins13050344
Note that the toxicity of cardiac glycosides are derived from ingesting the plants, and not from sniffing them, so huff away at nature!
Cool plant! We inherited a bed of Lily of the valley from the ancestors. It's been with the farmhouse forever. When we did a post on invasive plants a couple weeks ago, we touched on this weed along with Star of Bethlehem, Ornithogallum umbellatum, which has similar convallotoxin, and spreads much more aggressively. That one could be confused by some with wild onions, but the taste isn't the same.
Very interesting thank you. The comment of defining between what is toxic or therapeutic is very poignant.