"The little apple of death"

A little look into the manchineel tree- considered to be one of the deadliest trees on Earth.

Consider this my Halloween, nature-be-scary style post. A bit fitting given that this is the perfect time to indulge in apples. So why not visit an apple-like fruit that is extremely toxic? Best of both worlds!

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With fall comes apple season. This means apple pie, candied apples, caramel apples, and all other things apples.

As beloved as apples can be, there is one apple-like fruit in particular that has been considered so toxic that the Guinness Book of World Records labeled the tree bearing these “apples” the “most dangerous tree” in 2011.

This horrifying, deadly tree is called the manchineel tree, or Hippomane mancinella, apparently being named by taxonomist Carl Linnaeus meaning “horse madness”.

Image from Warner Tree Services. Manchineel trees with their green, apple-like fruits.

The manchineel tree belongs to the spurge, or Euphorbiaceae, family of plants, and partially bears its name due to the fruits that resemble apples. But the tree also goes by many names, such as poison guava or beach apple due to where the trees tend to be found, as they are native to the Caribbean and Gulf of Mexico, and can usually be found along beach shores. In fact, the trees are native to Florida- how many of you Floridians knew that?

However, the name that may fit the tree most comes from descriptions from Spanish conquistadors who referred to the fruit from the manchineel trees as manzanillas de la muerte, or little apples of death.

Some of the apple-like fruits from the manchineel trees which have fallen on the sand. Image from Best Facts.

Indeed, the manchineel has had a rather long history of being highly poisonous, being known to poison shipwrecked crew members who stumble upon these trees and being none the wiser to their toxicity, being used by natives for medicinal purposes as well as poisonous agents in their arrows and water against the Spaniards, and up to modern day where beach goers and tourists may unknowingly eat the fruit and be in for a rude awakening.

One well-circulated account of such modern poisonings comes from Dr. Nicola Strickland¹, who told of visiting the island of Tobago with a non-medical friend. While perusing the beaches, she came across various fallen fruits such as mangoes and coconuts, as well as the curious apple-like manchineel fruit, which she unfortunately chose to partake in (while also encouraging the friend as well).

What followed was an initial mouthful of sweetness, which took a quick downturn:

I rashly took a bite from this fruit and found it pleasantly sweet. My friend also partook (at my suggestion). Moments later we noticed a strange peppery feeling in our mouths, which gradually progressed to a burning, tearing sensation and tightness of the throat. The symptoms worsened over a couple of hours until we could barely swallow solid food because of the excruciating pain and the feeling of a huge obstructing pharyngeal lump. Sadly, the pain was exacerbated by most alcoholic beverages, although mildly appeased by pina coladas, but more so by milk alone.

The symptoms, unfortunately, persisted the next few hours:

Over the next eight hours our oral symptoms slowly began to subside, but our cervical lymph nodes became very tender and easily palpable.

When recounting the tale to locals it became quite obvious that Dr. Strickland and her friend consumed the toxic fruits of the manchineel tree.

This anecdotal report is rather frightening, even more so when one considers the fact that the initial bite of sweetness may lull unsuspecting people into eating more before the onset of the pain and swelling. Dr. Strickland warns of children on vacation who may unknowingly consume these fruit, as she notes that the taste is similar to that of a ripe plum.

Typical signs of manchineel poisoning included the burning, blistering sensation in the mouth which may be accompanied by difficulty breathing. Ulcerations, hemorrhages, gastrointestinal problems, vomiting, and diarrhea are also common. In some instances, cardiovascular complications may manifest, with one alleged case of manchineel poisoning leading to bradyarrhythmia and the need for a pacemaker in one individual.

In the case of Dr. Strickland and her friend the outcome was rather fortunate, likely due to their limited consumption of the fruit.

In contrast, probably one of the best reported cases of death by the manchineel tree comes from the death of Spanish explorer/conquistador Juan Ponce de León. Juan Ponce de León explored Florida during the early 1500s searching for a supposed fountain of youth. In his return around 1521 to colonize Florida, he and his crew were allegedly attacked by the indigenous people of the Calusa tribe. As the story goes, Ponce de León was hit in the leg by an arrow dipped in the white, milky sap of the manchineel tree. Ponce de León was then brought to Cuba where he eventually succumbed to his wounds. It’s been difficult to find any details on his symptoms, and given the time it’s not too difficult to assume that a deep wound to the leg may prove fatal.

Nonetheless, nearly all parts of the manchineel tree are dangerous. Consuming the fruits may be one of the quickest ways of becoming poisoned, but even the sap and wax (called latex) are highly poisonous.

In fact, even standing below a manchineel tree during a downpour can prove dangerous, as the toxic agents from the tree can wash onto you, leading to severe cases of swelling, inflammation, and contact dermatitis. A WebMD article on manchineel toxicity even suggests that people may have been tied to the tree and left during a storm as a form of torture, although I haven’t been able to corroborate this remark.

One reported case series² of basking in the manchineel toxins comes from 4 Americans who decided to stand beneath the trees during rain storm while in the Caribbean, becoming doused in the trees toxins and unfortunately experiencing serious problems soon thereafter.

One of these cases includes the following description of events:

A 23‐year‐old Caucasian female had direct contact with the bark and leaves of the Manchineel while repairing from the rain, leaning against the tree trunk, and touching the leaves. She was wearing a bikini and strapless dress during her exposure of 1 hour. She did not have a brimmed cap during that time. Twelve hours after her exposure she noted the onset of severe pain, erythema, and swelling of her eyelids and face. This extended rapidly to all of her exposed skin including chest, arms, and legs with accompanying burning and irritation. The lesions progressed with conjunctivitis and blisters including the eyelids (Figure 1) and several of her body surfaces. Healing occurred in about 5 days with mild scarring of the left upper eyelid. She was treated with oral corticosteroid and bathing of the skin to remove remaining toxin.

From Blue, et al. Remnants of contact dermatitis following exposure to manchineel tree toxins are shown on this individual, where pustules still appear on this individual’s eye.

Suffice it to say, you should try avoiding every bit of this tree as much as possible. Even burning of parts of the tree can be extremely dangerous, as inhalation of the fumes may lead to pulmonary edemas as well as running the possibility of causing blindness.³

Because of these dangers most areas where manchineel trees reside are labeled with signs warning beachgoers and travelers of their toxicity, such as the ones below:

Image from Britannica

Image from Express.co.uk

In addition, the trees are generally labeled with some sort of red mark, usually a ring or an “X” noting that the tree is dangerous and must be avoided:

Red rings signifying manchineel trees. Image from A Renaissance Writer.

In instances where no defining signs or visible markings are available try looking for certain features, as noted in the WebMD article:

Although these trees carry the moniker of being the most dangerous trees on Earth, their existence is not all bad. The bark and wood of the trees have been used as furniture for centuries by the natives. The trees are also pivotal in preventing erosion near beaches as the large root systems help during times of heavy downpours and flooding. Unfortunately, due to the toxic nature of these trees they have been removed from many beaches, causing the manchineel tree to become an endangered species.

More importantly, the tree is a habitat for some species who are apparently immune to its poisons, such as the garrabo (also goes by striped iguana, black iguana, and black spiny-tailed iguana) which consume the fruit and are known to live among its branches. Removal of these trees, unfortunately, comes with the price of removing a natural habitat for these iguanas, as well as other animals who rely on the trees for their fruit and shade.

Ctenosaura similis, or the black spiny-tailed iguana. These animals are one of a select few who appear to be immune to the toxins from the manchineel tree, and in fact are known to both eat the fruit as well as relax on the branches of the tree. Image from STSW Media.

It’s a reminder that things that may be highly toxic may also serve other uses. Care should be taken to understand the role something plays within a habitat before choosing to outright remove them.

The phorbol of my eyes

Several agents have been implicated in the manchineel’s toxicity, but the prime agent of concern is a class of compounds called Phorbols. More distinctly, it’s the esterified forms of phorbol that are argued to be highly toxic.

Phorbols are a rather complex ring structure, resembling the diterpenoid Tigliane with additional hydroxylations (addition of -OHs) on various carbons:

From Goel, et al. Comparative structures of Tigliane to Phorbol. note that the main difference is the addition of various hydroxyl groups on Phorbol. TPA is shown on the bottom and is a commonly researched phorbol ester. Note that the phorbol ester form is argued to be more bioactive, as the esters (boxed in red) mimic the effects of diacylglycerol and induce protein kinase C activation.

Again, the main toxic form of phorbols are the forms bearing the esters (boxed in red above) called…phorbol esters.

Allegedly, the phorbol esters act as potent protein kinase C (PKC)⁴ activators, likely owed to the ester portions which mimic the structure of diacylglycerols, which are common endogenous activators of PKC

Protein kinase C are a class of membranous enzymes responsible for lipid hydrolysis, phosphorylation of serine and threonine residues, and are critical for various cellular processes and signaling pathways, including cell division.

Both diacylglycerol, as well as phorbol esters, induce translocation of protein kinase C to the surface of cells, likely by acting as anchors which sit on the surface and lead to recruitment of these enzymes.

Goel, et al.⁵ details some of the downstream effects from PKC recruitment below:

The primary action of phorbol esters is on biological membranes. The phorbol esters are amphiphillic molecules and have tendency to bind to phospholipid membrane receptors. These receptors are usually the primary targets for the phorbol esters. The initial membrane effects include modification in activities of cell receptors, enhanced intake of 2-deoxyglucose and other nutrients, altered cell adhesion, induction of arachidonic acid release and prostaglandin synthesis, inhibition of binding of epidermal growth factor to cell surface receptors, and altered lipid metabolism (Weinstein et al. 1979). The most investigated activity of the phorbol is its binding and activation of PKC, which plays a critical role in signal transduction pathway and regulate cell growth and differentiation (Clemens, Trayner, and Menaya 1992; Nishizuka 1992). It has been proposed that the phorbol esters convert PKC into a constitutive active form that is irreversibly inserted into the membrane (Mosior and Newton 1995). During normal signal transduction, the enzyme is activated by DAG (diacylglycerol), which is then rapidly hydrolyzed. DAG is responsible for activating PKC function by increasing its affinity for phospahtidylserine (PS)-containing membranes. Upon activation, PKC enzymes are translocated to the plasma membrane by RACK (receptor for activated C-kinase) proteins (membrane-bound receptor protein for activated PKC) to conduct various other signal transduction pathways.

The direct end result of inflammation, ulceration, and other symptoms aren’t fully detailed in the literature, although it’s suspected that these alterations to PKC signaling may be responsible for these adverse effects. However, bear in mind that other agents are argued to also be toxic, and so it’s likely a mix of different agents that are responsible for manchineel’s toxicity.

What’s rather shocking is that phorbol esters have been looked into for their ability to act as tumor promotors due to this association with PKC activation. In particular, phorbol esters have been designated as co-carcinogens as they are known to enhance the effects of carcinogens:

The phorbols themselves do not induce tumors but promote tumor growth following exposure to a subcarcinogenic dose of a carcinogen. They can thus be designated as cocarcinogens. The cocarcinogenic property of compounds produced by Euphorbiaceae came to light when Berenblum (1941) found that croton oil (Croton tiglium) was capable of enhancing tumor formation when applied to mouse skin, either together with, or separately from, a subeffective dose of the carcinogenic hydrocarbon 3,4-bezpyrene.Berebblum and Shubik (1947) found that increased tumor production was only observed when croton oil treatment followed, not preceded, the application of a carcinogen.

But this effect isn’t all-too clear, as phorbol esters are argued to be anti-cancer agents as well due to their ability to induce apoptosis of cancer cells.

More specifically, phorbol esters are being examined for their possible therapeutic effects when it comes to various leukemias.⁶ They are also being investigated for their anti-HIV properties as well.⁷

In fact, it’s been suggested that plants similar to the manchineel tree were used to aid those with edema, so there may be some therapeutic benefits to phorbol esters, and researchers continue to balance the possible toxicity of these agents while also finding therapeutic uses.

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In years past the manchineel tree likely lived up to its namesake of bearing “little apples of death”. However, this moniker likely doesn’t work today, as there doesn’t appear to be any recent cases of people succumbing to exposure to the tree, possibly due to proactive measures to warn individuals.

That being said, be careful in assuming that trees which bear fruit may be safe to consume.⁸ If you happen to travel to the Caribbean islands, or if you’re a new visitor Florida be mindful to not accidentally eat these fruits, lest you want to fall into a world of pain!

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1. Strickland N. H. (2000). Eating a manchineel "beach apple". BMJ (Clinical research ed.), 321(7258), 428. https://doi.org/10.1136/bmj.321.7258.428

2. Lauren M. Blue, Christopher Sailing, Christopher DeNapoles, Jordan Fondots, Edward S. Johnson, Manchineel Dermatitis in North American Students in the Caribbean, Journal of Travel Medicine, Volume 18, Issue 6, 1 November 2011, Pages 422–424, https://doi.org/10.1111/j.1708-8305.2011.00568.x

3. Pitts, J. F., Barker, N. H., Gibbons, D. C., & Jay, J. L. (1993). Manchineel keratoconjunctivitis. The British journal of ophthalmology, 77(5), 284–288. https://doi.org/10.1136/bjo.77.5.284

4. Newton A. C. (2018). Protein kinase C: perfectly balanced. Critical reviews in biochemistry and molecular biology, 53(2), 208–230. https://doi.org/10.1080/10409238.2018.1442408

5. Goel G, Makkar HPS, Francis G, Becker K. Phorbol Esters: Structure, Biological Activity, and Toxicity in Animals. International Journal of Toxicology. 2007;26(4):279-288. doi:10.1080/10915810701464641

6. Wang Y, Shan Y, Feng R, et al. Synthesis and anti-leukemia activity of phorbol 13,20-diesters and phorbol 12,13,20-triesters. Journal of Chemical Research. 2023;47(3). doi:10.1177/17475198231180835

7. Li, Q. R., Cheng, Y. Y., Zhao, L., Huang, X. L., Jiang, X. G., Cui, Y. D., Morris-Natschke, S. L., Goto, M., Chen, C. H., Lee, K. H., Chen, D. F., & Zhang, J. (2021). New phorbol ester derivatives as potent anti-HIV agents. Bioorganic & medicinal chemistry letters, 50, 128319. https://doi.org/10.1016/j.bmcl.2021.128319

8. One paradox of the manchineel tree is the fact that its fruit is both highly toxic while also being sweet, creating an evolutionary conundrum for why this may be the case. A report from STSTW Media seems to suggest that the fruit of the manchineel tree follow a similar pattern as coconuts, such that the fruit fall into the neighboring water, have their outer shell removed while in the water, and eventually land onshore where they grow. Again, it raises a question as to why a tree may spend so much energy making a fruit sweet when the animals that eat it may not be able to transport the seeds before dying.