The Annona fruits are staples throughout the neotropics. Every rural house in Puerto Rico, where I am currently compiling this, has a soursop or three. Annona squamosa & Annona reticulata are slightly less common. These fruits are planted widely, are varying degrees of domesticated, and are cherished by the peoples who grow them. Let us start by saying that yes, they all have some form & degree of annonaceous acetogenin (a potent neurotoxin — in a lab). Annonacin, bullaticin, squamocin, or one of the countless novel ones. This is a wide phytochemical family present throughout the Annonaceae — from the seed spices of West Africa (Xylopia, Monodora), to the Rollinias & Duguetias of Central America the Pond Apples of Florida & the Caribbean, to the autumn pawpaws of Ohio.

If you’ve been around the internet in fruit-growing circles you will have probably noticed a fair amount of people who readily warn you how these fruits are toxic, or potentially so. When you approach these fruits with a fear-based kilter, you unknowingly invoke the entire family Annonaceae (and Lauraceae too, which also contains acetogenins). This is problematic as humans have been eating from these families safely for a very long time. Words like "cytotoxic" and "neurotoxic" inspire fear, and fear is bias. Some people eat avocadoes, which contain cardiotoxic acetogenins, on a daily basis. So why don't they get sick? The answer, at least partly, is in how humans digest things.

I’m writing this to help address an important cultural discrepancy — and to show how people, piloted often by fear, have been misinformed by thier own biases. There’s a deep-seated fear of and distrust of the indigenous, the exotic, and it sometimes presents in the form of heightened, verging on obsessive "scientific" scrutiny with regard to food & food purity. This is especially prevalent in the western, English-speaking world. I have been keeping an eye on this “discussion” - in quotes as it scarcely changes - since 2008 or so when I became aware of it under the pretext of cherimoya and soursop (Annona cherimola & A. muricata respectively). It has since moved along into other Annonaceae fruits, including our beloved temperate pawpaws (Asimina triloba), which may contain 6-8x as much acetogenin (annonacin specifically) as a soursop. There are plenty of people afraid to eat tropical soursops, but the argument with pawpaws goes something like “If soursops made people sick at X amount, then pawpaws surely will at 8x that amount!?” Nature, of course, is hardly ever so straightforward. For now, let’s not get into the West African seed spices, laden with acetogenins, that’s a no man’s land.

Awhile back, there was a study referred to as “The Guadeloupe Study” (https://pubmed.ncbi.nlm.nih.gov/10440304/) which implicated consumption of boiled soursop leaf matter in neurodegeneration, observed in an isolated population of the French Guadeloupe. Then came another study from New Caledonia, with similar observations. The consumption was of a leaf tea, believed to provide health benefits and/or cancer treatment. Like many individual studies it has it’s limitations, and people who raise hysterics about the subject appear to be reading too far into it, into things the study never really said. Firstly, cooked leaf matter is an unconventional use of the plant - this is not how the plant has been consumed typically. Second, variable control — what were the other dietary, environmental, genetic factors involved? (Further studies have implicated a genetic factor to be likely involved. This is important to acknowledge - it may be a situation similar to celiac disease.) Third, were the participants drinking alcohol? Acetogenins are soluble in alcohol — not in water. And so on. The original study is a broad epidemiological observation of the effects of eating soursop leaves as tea, which identifies annonacin (*or it's immediate phytochemical family) as the culprit. Yes, there have also been further studies on soursop juice such as this one: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8175813/ — however, juices are concentrated and processed in a way involving heat and sterilization. Let’s not infer too much from power-feeding rodents an unnatural amount of something.

Note how the Guadeloupe Study does not concern consumption of the fresh fruit, or of heating / cooking the ingested fresh fruit material. That there is assumption being made based on the mere presence of said toxin, regardless of the form or part of plant consumed. Constituents of leaves and bark and fruit can vary, cooking changes chemistry, sometimes profoundly. Note also that there have been several studies since clarifying the activity of these compounds in living organism, not just in a laboratory. We don’t need comparatively vague epidemiology to understand the biochemical activity.

Oddly, or perhaps expectedly, the fearmongers among us do miss some basic things -- the absorption factors for acetogenins like annonacin are right around 3%. Yes, it was measured, in rodents at least. Despite how much neurotoxin the fruits may contain, only a small fraction is ultimately absorbed into the blood (https://www.thieme-connect.com/products/ejournals/abstract/10.1055/s-0034-1394993). In humans this is likely to be an even lower number, since their destruction takes place during the gastric phase (https://pubmed.ncbi.nlm.nih.gov/33096836), and humans have a lower stomach pH than rats do (though mean intestinal pH is higher). There is also the question of how humans metabolize it, which may differ from rodents — we have seen this before in the case of safrole. The cited study on bioavailability above came as a result of the Guadeloupe study, after. It's important to note also that the French Government (Agence française de sécurité sanitaire des produits de santé) did not conclude that consuming soursop leaf tea was harmful in and of itself, that there was more to it. They aren’t idiots, nor are they being negligent.

”But it still made people sick!”
A quick google will get you the approx. problematic annonacin dosage (one example -- 3.8 and 7.6 mg per kg per day for 28 days; from Wiki FWIW). This is something we know.

And how much each pawpaw fruit contains (or, in general, it's 6-8x that of soursop, circa 100-120mg) (bear in mind these numbers are tentative; inexact)

With an absorption/bioavailability circa 3% we aren't anywhere near the problem "dosages," at least in amounts people normally would eat-- in fact, much of the pharmaceutical study has been on how to increase the low absorption, via nanocarriers and such. There's some hope that it will be cancer medicine.

The math doesn’t add up in a basic way. This invokes genetics, diet and/or environment

It means there's some other variable(s) influencing the neurotoxicity first observed and documented in Guadeloupe and New Caledonia. Some part of it may the unconventional use of the plant (leaf tea) - but it also suggests there's some dietary, genetic, environmental element that's making people more susceptible -- either by increasing bioavailability, or by making people more sensitive to it. https://academic.oup.com/brain/article/130/3/816/277881

"About 50% of the atypical patients were not heavy consumers of annonaceaous products, suggesting that other factors, environmental or genetic, might affect the vulnerability of patients to the neurotoxins in Annonaceae."

The studies even pointed this out, too.

The less charitable among us have missed this part of it; instead they have conflated in-vitro toxicity (in a lab) with in-vivo digestion/absorption (in an organism). They flatly regard what you eat as the "dosage" and spread around a basic misunderstanding of human digestion, of science generally. Even the Wikipedia on soursop was guilty of this (until recently — it has been revised). Moreover, and on a principle, indigenous peoples aren't & weren't a bunch of ignoramuses poisoning themselves over & over during the domestication of all these different custard apples, which are staples all over the neotropics. These implied attitudes, and the quick-to-quarrel sort of people who seem to find them are exhibiting a kind of anti-indigenous perspective —- disheartening. This is the unfortunate cultural element I’m talking about, rooted in the separation of modern, insulated suburbanites from thier own past. Dare I point out how it’s mostly a provincial overconcern of white, English-speaking people? This is an observed aspect, not an overriding point. I only seem to encounter this “concern” in white-dominated spaces.

The charitable among us realize these fruits have a long history of safe consumption, at least when fresh, and realize the myriad of variables that come along with any discussions regarding their toxicity. They realize that in the wider context of nature there are many other fruits with similar (or different) toxicities (underripe commercial lychees, anyone? Ackee fruit?), of which we are simply unaware, or at which we barely bat an eye. After all, there is a hint of risk in everything, no? Some of us even seek out a potent neurotoxin, ethanol, on a daily basis.

The Annonas are no exception. Enjoy your fruits. Ignore the naysayers.