Parkinson's in the setting of PawPaw consumption (and other Annonaceaes) article

[pagnr]

It is interesting that the Annonas seem to have evolved chemicals that possibly act as insecticides against one group of creatures that would eat the fruit, but not at levels to deter the animals that it needs to eat its fruit and distribute its seeds.

[Pouteria_fan]

The "Determination of Neurotoxic Acetogenins in Pawpaw (Asimina triloba) Fruit by LC-HRMS" study linked really is impressive. The NMR and Mass Spect brings back good college memories. If only I had the interest in tropical fruits back then, could have made for a very interesting project with more annonaceaes.

Would be great to see similar research on Rollinia and others. A particularly motivated person, with access to fresh fruit, could possibly partner with local chemistry department at a collegiate level for such a project. Anyone interested?

Of note, Memorial Slone Kettering has an interesting page on the pawpaws, stating:
(https://www.mskcc.org/cancer-care/integrative-medicine/herbs/american-pawpaw)

"Pawpaw fruit contains high concentrations of annonacin, which is toxic to nerve cells. In addition there have been case reports of possibly related nerve toxicity. Therefore, chronic use should be avoided."

[greg_D]

Noticed today that the company "Miami Fruit," popular on TikTok, is selling soursop tea and telling people to drink it every day.

https://miamifruit.org/collections/dry-canned-goods/products/soursop-leaf-tea

https://miamifruit.org/collections/dry-canned-goods/products/dried-mountain-soursop-leaves

[ben mango]

So they are promoting something they are selling ? Truly shocking 

[Draak]

I went down the rabbit hole on this a few years ago, and posted my findings. You can find most post if you search for it.

If you look at the incidence rate of Parkinson’s in the population that the document studied, the incidence rate of Parkinson’s on the island is not higher than the incidence rate of Parkinson’s in mainland USA. Therefore, the consumption of annona fruits does not cause Parkinson’s.

HOWEVER, if you do have Parkinson’s, it will make it worse! You will develop a “parkinsonism”, which is a more severe and less treatable version of Parkinson’s. The incidence rate of parkinsonisms in that island is much higher than in mainland USA. That said, there is some evidence that if you stop eating annona, you downgrade back to regular Parkinson’s.

As for how it affects other forms of illness, nobody knows! But, all fruits and veggies make their own insecticides to some degree, so we throw those dice anytime we eat anything plant based.

[pagnr]

I think the studies do make some big leaps, from directly injecting/ingesting  rats with Annonacin toxin, to applying the same chemical to extracted neurons in a petri dish. Then connecting this to Annona fruit use.
In the study I looked at from Guadeloupe, the use of Annona fruit and teas was determined by a usage questionnaire to the patients as I remember.
Not sure how accurate that would be, people could easily exaggerate their use to explain their symptoms or downplay their use to avoid responsibility.
Certainly hard to gauge how much Annona people are using on a daily basis.
The presence of a disease cluster was a rate of disease different to the "normal" rate of disease incidence, sometimes in other populations or worldwide.
Otherwise it is known that some plants in the group have insecticidal properties. ( Annona Squamosa and Annona Muricata seed ).

[crucianella]

I essentially avoid any Annonaceae for my own consumption, there's not enough research in the metabolism of it in the body, whether or not it can accumulate in the tissues. Similar issues were found with unrelated compound BMAA in cycads and that indeed was bioaccumulating in the bats who in turn gradually poisoned the people. This is ignoring the fact that nerve damage does not repair well in general.

A very big concern I have though is with rotenoids found in a fair few fabids, like Tephrosia, Derris, Amorpha and most concerningly Pachyrhisus (jicama) which I see showing up in the markets lately. And a rare couple non fabids like Verbascum (mullein) and Mirabilis. all these definitely have cumulative nerve damaging effects that effectively DO NOT resolve in your lifespan.

[Acetogenin]

So….does anyone else have tingling feeling in their tongue days after eating annonas?  I’ve noticed if I start stripping flesh off the seeds with my tongue, get a tingling/prickly feeling in my tongue…same feeling like when foot falls asleep.  Just me…? Lol

[Draak]

I essentially avoid any Annonaceae for my own consumption, there's not enough research in the metabolism of it in the body, whether or not it can accumulate in the tissues. Similar issues were found with unrelated compound BMAA in cycads and that indeed was bioaccumulating in the bats who in turn gradually poisoned the people. This is ignoring the fact that nerve damage does not repair well in general.

A very big concern I have though is with rotenoids found in a fair few fabids, like Tephrosia, Derris, Amorpha and most concerningly Pachyrhisus (jicama) which I see showing up in the markets lately. And a rare couple non fabids like Verbascum (mullein) and Mirabilis. all these definitely have cumulative nerve damaging effects that effectively DO NOT resolve in your lifespan.

This is fascinating!

[CeeJey]

If you look at the incidence rate of Parkinson’s in the population that the document studied, the incidence rate of Parkinson’s on the island is not higher than the incidence rate of Parkinson’s in mainland USA. Therefore, the consumption of annona fruits does not cause Parkinson’s.

The incidence rate of standard Parkinson's (what you're referring to here) doesn't matter in the case of the studies, since they were expressly looking at atypical Parkinson's/ atypical parkinsonism: that is, Parkinson's-adjacent symptoms and degenerative disease progression that don't have the same cause or response to the same treatments as standard Parkinson's. The American Parkinson Disease Association has a decent explanation of the difference on their website: https://www.apdaparkinson.org/article/atypical-parkinsonism/ So does John Hopkins: https://www.hopkinsmedicine.org/health/conditions-and-diseases/parkinsons-disease/atypical-parkinsonian-disorders .

The studies in Guadeloupe used MRI and testing to exclude normal Parkinson's (see https://pubmed.ncbi.nlm.nih.gov/17303592/), and all of the relevant studies refer to "atypical parkinsonism" in the title. The guy who ate 30 lbs. of paw paws a year in the study linked originally at the top of this thread also had atypical Parkinson's/ parkinsonism.

"Parkinsonism", which just means "the symptoms of Parkinson's regardless of cause", is generally the result of damage to or loss of functioning of dopamine neurons. Multiple studies in vitro and in vivo have shown that chemicals in annona plants can damage dopamine neurons, which is why this research/discussion is even happening.

(Also the US is a poor benchmark even for standard Parkinson's as we have a slightly-above-global-average rate of standard-Parkinson's deaths anyway, if we were going to look at that. But again it doesn't matter, even if deaths to atypical Parkinsons get folded into the WHO numbers, because the studies screened for that. there is some confusion since some of the other countries that have or had high atypical parkinsonism, like Guam, also have or had high rates of standard Parkinson's.)

HOWEVER, if you do have Parkinson’s, it will make it worse! You will develop a “parkinsonism”, which is a more severe and less treatable version of Parkinson’s. The incidence rate of parkinsonisms in that island is much higher than in mainland USA. That said, there is some evidence that if you stop eating annona, you downgrade back to regular Parkinson’s.

This seems to be a misunderstanding about what "parkinsonism" means."Parkinsonism" just means "disease with Parkinson's symptoms", it's not something extra on top of Parkinson's. The incidence of atypical parkinsonism is what was being studied in regards to the annonas. Not standard levadopa-responsive Parkinson's. The studies looked at people who did NOT have Parkinson's but instead had atypical Parkinson's.

EDIT: I can't find any indication that excludes people with Parkinson's also having MORE dopamine neuron damage from a different source than pre-existing Parkinson's, but again that wasn't what was being studied.

But, all fruits and veggies make their own insecticides to some degree, so we throw those dice anytime we eat anything plant based.

The various insecticides found in fruit and vegetables are wildly different in physical effects and many are better-studied than acetogenins. The glucosinolates that make broccoli bitter are an insecticide (and safe for human consumption in amounts found in broccoli), while solanine is also an insecticide (which is NOT safe for human consumption). Eating food that has under-studied nerve-damaging chemicals in clinically relevant amounts from normal consumption (like the annonans) is more of a potential risk to most people than eating a chili pepper containing some capscacin, despite both of those containing "insecticides to some degree".

I think the studies do make some big leaps, from directly injecting/ingesting  rats with Annonacin toxin, to applying the same chemical to extracted neurons in a petri dish. Then connecting this to Annona fruit use.

That's how they study what chemicals do, though. We apply them to cells in a petri dish and then apply them to animals, and then if it is safe and ethical to do so we apply them to humans to be sure. In this case we can't do that last one (humans) because it wouldn't be safe or ethical based on the results of the animal studies.

Anyway, in both cases studied (in vitro and in animals), annonacin causes damage to the cells in a way that could cause atypical Parkinson's. The study on asminia triloba also confirmed that it wasn't just the purified annonacin but the raw fruit extract that can cause the damage.

There doesn't appear to be a debate at the research level, at all, about whether annonacin can cause damage to neurons. The only question is whether or not enough of it gets into the bloodstream from achievable ingestion to cause the pathology. EDIT: Sorry, I think on re-read I misunderstood that this was what you were specifically referring to, that you feel it's a leap to assumptions about ingested effects. I'd agree except that you've got these cases/clusters of atypical parkinsonism popping up and that we know that IF the chemical gets into the bloodstream then it can damage neurons (from the rat studies).

In the study I looked at from Guadeloupe, the use of Annona fruit and teas was determined by a usage questionnaire to the patients as I remember.
Not sure how accurate that would be, people could easily exaggerate their use to explain their symptoms or downplay their use to avoid responsibility.

I went back and checked the main Guadeloupe study, and they had a double-blind and a similar-demographics-but-no-Parkinson's control group on the questionnaire to prevent that kind of bias (they also included a screen for the control group for Parkinson's). Food questionnaires are pretty unreliable, sure, but if you have a proper control and double-blind then a relative difference can still be seen if you have a big enough number of participants.

Otherwise it is known that some plants in the group have insecticidal properties. ( Annona Squamosa and Annona Muricata seed ).

Those insecticidal chemicals (the acetogenins which include annonacin) are also found in the fruit and other plant parts of muricata, squamosa, a. triloba, and mucosa per a couple of different studies linked in this thread.

[Julie]

Am I understanding correctly that they are saying the man ate 30lbs of paw paw fruit per year and that caused parkinsons?  A mature fruit tree will produce like 100+lbs of fruit in one season so it would be very easy to eat way more than that. 

I planted a San Pablo Red Custard Apple at my house because the fruit is so good.  Right now it hasn't started producing yet but now I'm worried.

[Julie]

The only experience I have with something similar is that over the summer I grew a jicama plant from seed, trying to test different plants that can be grown here in the summer.  The plant successfully produced a huge root over the summer.  When eating it I soon felt really hot all over and had a feeling like I was intoxicated.  Knowing that the plants have toxins "in the leaves/seeds only" I got worried that there probably was toxin in the roots too so I stopped eating it and I felt better soon.  I don't know if it was psychological/anxiety related but I'm not going to grow it again.

[pagnr]

Am I understanding correctly that they are saying the man ate 30lbs of paw paw fruit per year and that caused parkinsons?

Or you could say a man with Parkinsons ate 30lbs of paw paw fruit per year and that was possibly a factor, considering overseas studies  ?

In my mind the "Jurian" is still out on that, especially in a one off case, as above, of one elderly person.

[Julie]

Am I understanding correctly that they are saying the man ate 30lbs of paw paw fruit per year and that caused parkinsons?

Or you could say a man with Parkinsons ate 30lbs of paw paw fruit per year and that was possibly a factor, considering overseas studies  ?

In my mind the "Jurian" is still out on that, especially in a one off case, as above, of one elderly person.

I'm just pointing out 30 lbs is not a lot at all of a single tropical fruit if you have a mature tree.  Most mature fruit trees will produce 100+lbs per season and you're going to be eating a lot of it if it's in your backyard.. So if I buy a 2 lb bunch of bananas at Costco, and eat 15 of those bunches in an entire year, I've at 30 lbs of bananas.  Am I misunderstanding what is going on?

[K-Rimes]

Am I understanding correctly that they are saying the man ate 30lbs of paw paw fruit per year and that caused parkinsons?

Or you could say a man with Parkinsons ate 30lbs of paw paw fruit per year and that was possibly a factor, considering overseas studies  ?

In my mind the "Jurian" is still out on that, especially in a one off case, as above, of one elderly person.

"Nursery owner with pawpaw patch was diagnosed with Parkinson's. Man reportedly ate 30lb of fruit annually for 10 years and this may have contributed."

I think a lot of us are trying to find a way around the fact that Annonacin is a neurotoxin and the Guadeloupe study shows negative health outcomes after eating it over a lifetime. I certainly am looking for an alternative reasoning for the atypical Parkinsonism in Guadeloupe, but reasonably I think the truth is there for all to see if you combine all the studies in this thread that annonacin in large amounts of a long period of time will probably produce negative health outcomes. Seeing the concentrations in pawpaw certainly takes it up a notch and I wonder if 10 years of pawpaw is roughly the same as 50 years of soursop.

Being that I still like to eat bacon, smoked meats, and sugar - I'll risk a bit of annonacin here and there, but still, I guess I should slow down on planting it...

[pagnr]

So if I buy a 2 lb bunch of bananas at Costco, and eat 15 of those bunches in an entire year, I've at 30 lbs of bananas.  Am I misunderstanding what is going on?

From that point no, I probably eat 25 bunches of Bananas per year.
As you say it is not going to be hard to reach 30 lbs of Annona fruit per year, especially from your own trees.
On the other hand a San Pablo Red Custard Apple is not an Asimina paw paw.
Some people I know, fruitarian fanatics in Nth Qld, must be well over that amount of Annona fruit per year over the previous 20 years I have known them.
30 lbs could be a far lower amount than what some people actually eat ?

[CeeJey]

Am I understanding correctly that they are saying the man ate 30lbs of paw paw fruit per year and that caused parkinsons?  A mature fruit tree will produce like 100+lbs of fruit in one season so it would be very easy to eat way more than that. 

I planted a San Pablo Red Custard Apple at my house because the fruit is so good.  Right now it hasn't started producing yet but now I'm worried.

He got atypical parkinsonism, which there is evidence can be caused by chemicals in annona fruit in large long-term amounts.

The amount of the chemical that concerns most researchers varies from species to species; paw paws and soursops seem to have higher concentrations in particular depending on the batch tested. One study (it's linked higher up and in some earlier forum threads) found paw paws specifically to have a LOT of the chemical, more per serving than the high dose they were using intravenously in the rat studies.

I've been posting a lot in this thread since I enjoy sorting through and reading research studies, and I've seen enough evidence for ME that I believe annonacin can cause some of the brain damage seen in clusters (or one-offs, as with this nursery owner) with high consumption. BUT I haven't seen enough to make me personally give up annonas totally. Many, many people eat these around the world without apparent incident.

I've got a couple of small annona trees (custard apple, cherimoya, atemoya) myself that I'm working on adapting to the climate out here, and I'm not planning on throwing them out. I'm just going to keep the fruit intake down when and if they do fruit, and I'm still going to have the occasional grocery store fruit once in a while until then. I'm just not going to eat a ton of them, and focus on really enjoying the good ones as a treat. I'm also probably going to be careful about soursop and especially paw paw consumption until I see more research since those had the highest tested values and are the ones potentially linked to real-world brain damage rather than hypothetical. That's where my risk tolerance is based on the evidence so far.

Edit: Oh yeah and the seeds are still bad for all of them, apparently.

[Julie]

I'm just shocked that the amount is only 30 lbs.  A single mango is like 1 lb, so that's only the equivalent of eating 30 mangoes in an entire year.  That seems like a very low threshold.  I'm glad I read this though, since I have a small tree, I won't be eating tons of them once it's a large tree.  For example I eat like 2-3 passionfruits (with seeds) per day, pretty much every day, since I have tons.  If my trees get a good harvest of mango or lychee I could eat like 100 lbs a year between fresh and frozen fruit.  Had I not read this I could have eaten like 50 red custard apples a year.

Two years ago I ate probably 10 red custard apples in a year, which could be like 15-20 lbs.

[Julie]

Are there any other tropical crops that are unhealthy to eat a lot of?  What about yuca, I eat a lot of that both from my yard & the cassava flour tortillas & pastas?

[Galatians522]

According to the table on the first page of this discussion, paw paw has approximately 2,000 times the annonacin content of atemoya. Presuming this was indeed the causitive factor,  I would need to consume over 600,000 lbs of atemoya pulp in 10 years to get the same effect. Put another way, that is  167 pounds a day for 10 years. I think I'm safe.

[Galatians522]

Are there any other tropical crops that are unhealthy to eat a lot of?  What about yuca, I eat a lot of that both from my yard & the cassava flour tortillas & pastas?

Because the protein is essential to the detoxification of cassava, most of the issues I remember happen only in diets that are extremely low in protein (or that involve improperly cooked cassava). Here's a good article I found:

https://www.google.com/url?sa=t&source=web&rct=j&url=https://journals.sagepub.com/doi/pdf/10.1177/156482650202300418&ved=2ahUKEwjs7KCQgZH7AhUVZTABHVg-D-0QFnoECB0QAQ&usg=AOvVaw3c38djpxXFehp9YNyNC1hQ

[pagnr]

Are there any other tropical crops that are unhealthy to eat a lot of? 

Taro and Monstera deliciousa come to mind ( oxalic acid ). Not a problem if prepared properly.
Both Cashew and Mango fruit have irritating sap, many for fruit pickers.
Durian and Jackfruit directly kill a bunch of people ever year, heavy fruit falling on their heads.
Apples have cyanide in the seed, can cause problems if not removed before brewing Scrumpy Cider.

[fruit nerd]

We eat rollina fairly often but otherwise I'm not a huge fan of soursops, sugar apples and atemoya. I knew the seeds were toxic but wasn't aware that small amounts are also present in the flesh. I've planted lots of mangoes, durian, artocarpus and pouteria.....Happy I didn't go crazy planting annonas, ha.

[CeeJey]

Are there any other tropical crops that are unhealthy to eat a lot of?  What about yuca, I eat a lot of that both from my yard & the cassava flour tortillas & pastas?

In addition to what others said:

chaya when it isn't cooked enough (hydrogen cyanide content that breaks down with cooking)
katuk in huge amounts: https://www.eattheweeds.com/edible-katuk-sauropus-androgynus-2/
bitter melon in huge amounts (common story with anti-diabetic stuff, anything that helps with blood sugar seems to be rough on the liver in large volume)
monkey orange/strychnos spinosa when the fruit isn't ripe

I've come across more, but those off the top of my head.

According to the table on the first page of this discussion, paw paw has approximately 2,000 times the annonacin content of atemoya. Presuming this was indeed the causitive factor,  I would need to consume over 600,000 lbs of atemoya pulp in 10 years to get the same effect. Put another way, that is  167 pounds a day for 10 years. I think I'm safe.

Yeah, atemoya and biriba seemed to have the lowest amounts tested in every study so far. I really wish somebody would test cherimoya.

[Gulfcoastgardening]

Both of my grandparents, and several of their friends that lived in Guam for a period of time on the base developed Parkinsonism/PSP. None of them were genetically related. My relatives never knowingly consumed pawpaw or annona fruits. We did a fair bit of research regarding cause when my second grandparent was diagnosed and it seems like it would be very difficult to unwind all of the potential causes. I'd be curious too, and I haven't looked, but about the overall increase in instances of Parkinsonism across the world and its territories and how much could be assigned to better testing, more awareness, or just overall greater case load. (before demonizing pawpaw)

I just want to add, pesticides like paraquat have been shown to cause Neurodegenerative diseases at elevated rates also. In Guam, there was excessive pesticide use, and nowhere for it to really go when my grandparents (and mother) lived there for a period of time. My mother is 68 today, and has no signs of degeneration, thankfully. I don't know about Guadalupe, but it would be worth looking into also.

Undoubtedly, consuming an enormous amount of pawpaw, or anything, could have health consequences; and it would be valuable to know at what rate it's more toxic, or toxic enough to be highly concerned. Breathing city air is probably doing more harm than the occasional pawpaw, atemoya, or soursop.

Are there a lot of studies on long-term consumption of soursop/guanabana shakes and things like that? For certain there's groups of folks in tropical areas that drink shakes almost daily and would cause an uptick in neurodegenerative diseases. (if it was causative)

Man, I've edited this a bunch, just spoke with a friend of mine from the DR, he says that when they drink shakes they blend the seeds and fruit together.

Daniel

There is a similar Parkinsons type syndrome in Guam and other Islands.
It was first linked to Cycad seed consumption, then Fruit Bat Consumption, then consumption of Fruit Bats that eat Cycad seeds.

Guadeloupe has a unique population, founded on imported slaves. There could be inherited factors in the Parkinsons syndrome, but as I remember from when this topic came up on another fruit forum, the studies didn't show family member inheritance.
They did seem to have low samples of patient numbers.

It would be interesting to note if the same type of Parkinsons syndrome appears in other Annona fruit eating countries.
They must also be heavily consumed elsewhere in South America, Caribbean etc.
Soursop drinks are pretty popular in SE Asia, Phillipines, etc. Canned versions are available at my local supermarket and Asian grocery.