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Author Topic: Annonacin, Toxicity, Parkinsons, and a general review of the literature  (Read 743 times)

Draak

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As a new homeowner and a newbie starting my subtropical fruit collection, I am eagerly awaiting all of the fruits I will finally get try try. I'm particularly eager to try the annona fruits, and am happy to have 4 sapling pawpaws of good varietals in my collection. Then, browsing the forum, I found a post warning of pawpaw neurotoxicity. As a scientist, I then spent the next 5 hours of my life fervorously searches in google scholar learning everything I could learn about the subject. There is a good synthesis of all the data available, but it definitely takes a LOT of time digging up this information from obscure places, and some knowledge of pharmacy and bioavailability. I would like to share my findings here for anyone who would like to know. For those who do not wish to read: Cherimoya, Atemoya, Sugar Apple, and Biriba *flesh* is rather benign, consuming soursop leaf tea from *dry* leaves is probably benign, annonacins will not give you Parkinsons (but if you have parkinsons, it may make your symptoms MUCH worse), and think critically about how much risk you're willing to take to eat this fruit.

All plants have some mechanism for preventing themselves from being eaten by undesirable things, and bugs are particularly pestilent. Natural pesticides are found in nearly all plants. Annona plants have evolved annonacins and similar groups of chemicals as their chosen pesticides. Pawpaw extract was a hot topic for a little while for being the next natural & organic pesticide, with patents granted http://www.pawpawresearch.com/botanical-2002.html. However, these plants generally also want us mammals to eat their fruits, and us mammals have managed to be quite tolerant of natural pesticides in reasonable doses.

Simon put together an EXCELLENT review of the literature on his parkinsonís blog: https://scienceofparkinsons.com/2017/12/16/paq/comment-page-1/?unapproved=24905&moderation-hash=e85986022f83b02e21abe8bad7b2ffa3#comment-24905. He provides links to all of the scientific literature, and I encourage you all to read it (he is a fun writer!). You can also see my reply to Simon at the bottom of that page. Iíll be summarizing some of his blog and my response here.

The dilemma with annonacins and human health was first conceived in the 1999 paper by Caparros-Lefebvre, where they found that 80% of people in their study with Parkinsons in Guatemala had a very bad form of it, which doesnít respond to treatment. Compared to USA and Europe, these bad form of Parkinsons were relatively unlikely among those with Parkinsons (only ~30% of people). They hypothesized a reason for this was due to consumption of Soursop fruit and tea. It was then found that these toxins are surprisingly good at killing neurons when directly applied to nervous tissue compared to common lab standard toxins.

Simon continues on with his article about positive effects of other Annona chemicals for parkinsons. However, there is more to the annonacin story.

Pomper et al. looked at the toxicity of soursop, cherimoya, pawpaw varietals, peach, and banana: https://pubs.acs.org/doi/abs/10.1021/jf9018239. They measured toxicity by finding the amount of extract needed to kill 50% of a brine shrimp population. Among many things, they found:

1)   that cherimoya flesh was 100x less toxic than soursop, and is almost as benign as peaches (yay!).
2)   that some pawpaws were 100x more toxic than soursop, and that some pawpaws were about as toxic as soursop.
3)   Drying the pawpaw fruit reduced the toxicity by ~100x. They did not comment on why (nor did they interpret their results correctlyÖugh). If it is real that this toxicity reduction occurs, a *guess* at this mechanism are that the toxins crystallized and became significantly less bioavailable (a routine scenario in pharmacology).

Thanks to Nullzero for finding this awesome science poster by Smith et al. on Annona neurotoxin concentrations! https://www.scribd.com/document/314499988/FDA-Annona. There is indeed ~100x more total ug/g concentration of annonacin+squamocin in soursop compared to Atemoya and Sugar apple (presumably, cherimoya has a similar concetration to atemoya and sugar apple). They used overlese pawpaws in this study (https://pubs.acs.org/doi/full/10.1021/jf504500g?src=recsys), which was found to have ~10x more annonacin in this case. So, Pomperís methodology, measurements, and conclusions seem to generally agree to the measured annonacin by Smith et al.

The amount of annonacin in some pawpaws is truly staggering! But, itís this dramatic figure which likely proves the point that this is rather well tolerated by much of the population. A homeowner binge-eating fruit from their pawpaw tree could end up eating ~3lbs of pawpaw in a day (or 3~5 pawpaw fruits). Assuming a typical soursop weighs 6lbs, thatís roughly like eating 50 soursop fruits in a single day! A single tree could yield 30~80 pounds of fruit, so that could amass to eating the equivalent of 500~1300 soursops per tree. Thatís a dose higher than eating a full 6lbs of soursop every day *and* drinking the soursop leaf tea every day for a year, but administered all in 1~2 months! If thatís the case, fruit fanatics and pawpaw lovers in the american midwest should be suffering just as much or more than the people of french west indies due to the Indiana banana!

One of the concluding points of that paper was that there have not yet been any links between consumption of pawpaw and the incidence rates of Parkinsons vs. Parkinsonisms. They point to another paper in the concluding remarks, and suggest that people who seem to be affected by this toxin are likely genetically predisposed. This is perhaps backed up during a presentation by the same authors with an acknowledgement of Caparros-Lefebvre et al, who estimated in 2005 that there are approximately 640 cases of parkinsons and parkinsonisms combined in Guadeloupe out of a population of 420,000, which is an incidence rate that is identical to the united states and europe. http://www.pawpaw.kysu.edu/PDF/AcetoUpdate3.pdf. That is, there werenít more people with Parkinsonís in the countries of concern, simply those that had Parkinsonís were worse. That paper amazingly also found that younger folks who had parkinsonism symptoms managed to reverse symptoms (presumably down to regular parkinsons) when they stopped annona products. It seems that this toxin doesnít cause parkinsons, but it seems like there is clear evidence that it could make existing parkinsons worse.

It is extremely concerning that Champy found in 2004 that *injecting* rats for 1 month with annonacin induced neurodegeneration of basal ganglia and mesencephalon. However, it is again pointed out by the authors that this does not investigate bioavailability upon digestion http://www.pawpaw.kysu.edu/PDF/AcetoUpdate3.pdf; 1 month is really dramatic, and I would imagine that people would have quite a bad reaction if it damaged their nervous system that hard every month.

As for Soursop tea, the concentration of annonacin is ~300ug/g: https://www.sciencedirect.com/science/article/pii/S0102695X15002331. A typical serving of dry leaf tea is ~2g, providing a dose of 600ug. If this is dried tea, and assuming that the dried tea is 100x less toxic than fresh tea due to the relationship seen in Pomperís data remaining true, thatís roughly equivalent to consuming 6ug. Thatís a trivial dose.

For getting sick from an acute dose (ingesting seeds), I note that the fruit flesh of soursop and pawpaws seem to have more ug/g of annonacin than an atemoya seed, but atemoya seeds have a MASSIVE concentration of squamocin (14,200ug/g), whereas squamocin concentrations are low in the flesh (<200ug/mg) https://www.scribd.com/document/314499988/FDA-Annona.

All that said, I believe that there is enough evidence to say that this can make certain people with parkinsons develop worse symptoms. Further, it is not known if there are other neurological conditions that this could negatively affect. How about people who have a genetic predisposition to alzheimers or dementia? What about just simple anxiety? Fibromyalgia? Schizophrenia?

Unlike twilight plea on the Parkinsonís blog, Iíve decided for myself that I have enough health problems, and pawpaw is unfortunately too risky to grow and consume. :'( This may be a conservative approach, and I suspect that most could tolerate annonacin without any problem. I may partake on occasion, but Iíll be giving my trees away. However, I will be enjoying cherimoya, atemoya, sugar apple, and biriba without worry  :D. Iíll just have to figure out how in the world Iíll GROW those thingsÖ

SeaWalnut

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Paw paws are not good for ipohondriacs but i think they are safer for humans to eat than lets say a fruit that evolved for a bird ,iet we eat manny of those too in high quantity.
I dont think annonacin is the problem on that island and these studyes are just supositions .Keep in mind that no scientist had prooven the exact relation between a famous plant that kills humans,tobacco.There is no death certificate that says ,,killed by tobacco,, or ,,killed by the X alcaloid found in tobacco,,. .Sunflower its a low annonacin paw paw and more interesting than ,,causing,, parkinson is the curing effect on cancer of annonacin.
Also,on that island with high parkinson rate ,paw paws dont grow and what if there is another alkaloid wich causes parkinson and not the annonacin? Like tobacco ,each plant has manny alkaloids and harmfull substances not just one.
What if the culprit is a non discovered substance thats found more in somme tropical annonaceae than in the temperate paw paws?
« Last Edit: July 23, 2019, 08:04:52 AM by SeaWalnut »


SeaWalnut

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https://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=11&cad=rja&uact=8&ved=2ahUKEwiBptTyh8vjAhUPnlkKHdOhBJ8QFjAKegQIAhAB&url=https%3A%2F%2Fgrist.org%2Ffood%2Fplants-are-poison-and-that-just-may-be-why-they-keep-us-healthy%2F&usg=AOvVaw0MV67er1b6xikpU7h5lbg7

Toxins (may} help
Its like geting Toxoplasmosis from a pet cat or from eating raw or semi raw meat .It strenghtens your immune sistem and is a good disease to have.
Or like eating bee pollen.In case you eat it and have to do a blood test,you have to tell your doctor about it or else he will think your severely ill because of high anticorps numbers.

shot

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His theory is that toxins in fruits and vegetables help turn over damaged mitochondria cells

K-Rimes

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Fascinating thread and research which makes me question my similar 5 paw-paw seedlings. I had been quite excited to try them in the future, and probably will still dabble even with the risk.

A thought about soursop is that it's frequently consumed in smoothie and juice form in equatorial countries - which I would presume means blending the seeds, too? Could this relation be more seed related than fruit related (even if the PawPaw does have xx% more toxicity)?

Draak

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Fascinating thread and research which makes me question my similar 5 paw-paw seedlings. I had been quite excited to try them in the future, and probably will still dabble even with the risk.

A thought about soursop is that it's frequently consumed in smoothie and juice form in equatorial countries - which I would presume means blending the seeds, too? Could this relation be more seed related than fruit related (even if the PawPaw does have xx% more toxicity)?

Plants may want you to eat their fruit, and some plants would like you to swallow their seeds whole.  However, no plant wants you to destroy their seeds. You can search this forum and find several people who have accidentally blended a seed with their Annona fruit, and have gotten extremely sick because of it.

K-Rimes

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Fascinating thread and research which makes me question my similar 5 paw-paw seedlings. I had been quite excited to try them in the future, and probably will still dabble even with the risk.

A thought about soursop is that it's frequently consumed in smoothie and juice form in equatorial countries - which I would presume means blending the seeds, too? Could this relation be more seed related than fruit related (even if the PawPaw does have xx% more toxicity)?

Plants may want you to eat their fruit, and some plants would like you to swallow their seeds whole.  However, no plant wants you to destroy their seeds. You can search this forum and find several people who have accidentally blended a seed with their Annona fruit, and have gotten extremely sick because of it.

I had heard of their toxic nature, but wasn't sure how extreme it would be. Doesn't sound fun.

Guanabanus

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Nature's Sunshine Products sells "Paw Paw CellReg", a standardized PawPaw twig extract.  This was developed for them by Dr. Jerry McGloughlin, after his long career in pharmacognosy research at Purdue University.  Some of his papers are displayed on the Nature's Sunshine website.

At his lectures during the International Pawpaw conferences that I attended, he showed that soursop leaves from some trees have substantial amounts of annonaceous acetogenins (alkaloids such as annonacin, asiminicin, bullatacin...), while leaves from other sousop trees had negligible or undetectable amounts.  [Research in Mayaguez, Puerto Rico showed extreme variation in the many components of soursop pulp aroma.]  Purveyors of sousop leaves for tea, honestly have no idea that they are providing a total crapshot for their customers.

Caribbean-Islander home-remedy practitioners drink teas of fresh leaves of sousop and custard-apple (Annona reticulata), and apparently of mountain-soursop, and also head-washes with hot tea and the hot leaves from the tea.  Some smash the seeds to apply to hair roots to kill head lice.  Any annonaceous acetogenins ingested by eating the pulp of these fruits would be additional to that in the herbal medicines;  but just eating the fruits without also practicing herbalism would, at least from a majority of the trees, involve negligible amounts of the alkaloids. 

When I was inter-breeding Annona species, I was taste-evaluating more than a dozen hybrids per day, most days, for about 4 months each year, for nearly a decade.  No parkinsonism.  None of the hybrids that fruited, though, included soursop or pawpaw.
Har

Draak

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Re: Annonacin, Toxicity, Parkinsons, and a general review of the literature
« Reply #9 on: August 20, 2019, 01:48:46 PM »
Nature's Sunshine Products sells "Paw Paw CellReg", a standardized PawPaw twig extract.  This was developed for them by Dr. Jerry McGloughlin, after his long career in pharmacognosy research at Purdue University.  Some of his papers are displayed on the Nature's Sunshine website.

At his lectures during the International Pawpaw conferences that I attended, he showed that soursop leaves from some trees have substantial amounts of annonaceous acetogenins (alkaloids such as annonacin, asiminicin, bullatacin...), while leaves from other sousop trees had negligible or undetectable amounts.  [Research in Mayaguez, Puerto Rico showed extreme variation in the many components of soursop pulp aroma.]  Purveyors of sousop leaves for tea, honestly have no idea that they are providing a total crapshot for their customers.

Caribbean-Islander home-remedy practitioners drink teas of fresh leaves of sousop and custard-apple (Annona reticulata), and apparently of mountain-soursop, and also head-washes with hot tea and the hot leaves from the tea.  Some smash the seeds to apply to hair roots to kill head lice.  Any annonaceous acetogenins ingested by eating the pulp of these fruits would be additional to that in the herbal medicines;  but just eating the fruits without also practicing herbalism would, at least from a majority of the trees, involve negligible amounts of the alkaloids. 

When I was inter-breeding Annona species, I was taste-evaluating more than a dozen hybrids per day, most days, for about 4 months each year, for nearly a decade.  No parkinsonism.  None of the hybrids that fruited, though, included soursop or pawpaw.

Thank you for sharing that! The pieces of the story that I have tracked down so far are mainly talking about Annonacin and squamocin, it’s good to know that other components of the complex mix have been identified. I also hadnt heard about the high variability among leaves! I wonder if that has to do with whether the leaf had been chomped on by a pest or not, inducing the production of pesticides. Did he offer any hypotheses or mechanisms on the high variability among leaves?

From the literature, I have concluded so far that consuming these Annona pesticides will not induce Parkinson’s or parkinsonisms. However, if you do have Parkinson’s, it will cause you to develop an untreatable Parkinsonism. From the data available, only people with parkinsons  should not consume these fruits, and everyone else should be ok.

That said, we don’t have any information on how this neurotoxic pesticide affects other neurological problems. For example, I have fibromyalgia, which can be debilitating and disabling when untreated. It is poorly understood, but is believed to have a neuropathic component to it. Given how horrible it was, I don’t want to risk worsening my condition in any way. Would eating a few pawpaws cause irreversible problems? Perhaps not, and I’ll likely try a couple some day. Should I eat a hundred pounds per year from my four pawpaw trees? Probably not. I’ll just have to be satisfied with cherimoya, atemoya, sugar apple, and deliciosa.

FlyingFoxFruits

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Re: Annonacin, Toxicity, Parkinsons, and a general review of the literature
« Reply #10 on: August 20, 2019, 07:58:08 PM »
this junk study, everyone references, has some key issues that are overlooked by almost everyone who shares it.

1st, the study was conducted on an island population...

2nd, the population had been exposed to harmful chemicals via the agricultural industry in their area, chemicals which can cause parkinsons like symptoms....

so put that in your pipe and smoke it...

and be very afraid to eat homegrown fruits, especially those damn Annonas...

they are the devil's dessert...   ;)

Guanabanus

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Re: Annonacin, Toxicity, Parkinsons, and a general review of the literature
« Reply #11 on: August 21, 2019, 09:53:16 AM »
Draak, the difference in Soursop leaf samples was not from leaves of the same tree;  it was from  leaves of different Soursop trees--- so it was about genetic variation among indiviual trees.  Growing conditions, time of year, and sun or shade placement of a branch certainly CAN influence leaf concentrations, but that wasn't being checked on during the study referenced.  [However, the Pawpaw twig extract is from branches pruned off in the month of May, due to the much higher alkaloid concentrations in the Spring, than at any other time of year.]

Flying Fox, interesting info about the agri-toxics!

Additionally, any population engaged in traditional herbalism is using rather large numbers of plants:  roots, bark, leaves, flowers, fruits, seeds, fish, insects, etc.;  eating them, using them in baths, washes, inhalations of fresh smells or steams or smokes, drinking teas, applying poultices....   Latching immediately onto one or two of these as the likely cause of a physical issue in a population is imaginative at best--- or simplistic.
Har

FlyingFoxFruits

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Re: Annonacin, Toxicity, Parkinsons, and a general review of the literature
« Reply #12 on: August 21, 2019, 03:11:44 PM »
yea Annonas are dangerous to eat, but the chems they spray all over Guadalupe had no effect on the population who probably ate loads of locally grown fruit, laden with all sorts of pesticides...

https://www.theguardian.com/environment/2013/may/07/guadeloupe-economy-theatened-pesticides-pollution

FlyingFoxFruits

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Re: Annonacin, Toxicity, Parkinsons, and a general review of the literature
« Reply #13 on: August 21, 2019, 03:14:35 PM »
how about this article?

still ready to blame one of God's gifts to mankind for this disease?

or one of Satan's scourges?

http://drrickschwartz.com/art-Parkinson.html
« Last Edit: August 21, 2019, 03:17:27 PM by FlyingFoxFruits »

Draak

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Re: Annonacin, Toxicity, Parkinsons, and a general review of the literature
« Reply #14 on: September 10, 2019, 03:22:00 AM »
Draak, the difference in Soursop leaf samples was not from leaves of the same tree;  it was from  leaves of different Soursop trees--- so it was about genetic variation among indiviual trees.  Growing conditions, time of year, and sun or shade placement of a branch certainly CAN influence leaf concentrations, but that wasn't being checked on during the study referenced.  [However, the Pawpaw twig extract is from branches pruned off in the month of May, due to the much higher alkaloid concentrations in the Spring, than at any other time of year.]

Flying Fox, interesting info about the agri-toxics!

Additionally, any population engaged in traditional herbalism is using rather large numbers of plants:  roots, bark, leaves, flowers, fruits, seeds, fish, insects, etc.;  eating them, using them in baths, washes, inhalations of fresh smells or steams or smokes, drinking teas, applying poultices....   Latching immediately onto one or two of these as the likely cause of a physical issue in a population is imaginative at best--- or simplistic.


Thank you for your very insightful comments about the variations of samples! I'm trying to understand where in my post you were referencing; were you commenting on the dried fruit samples vs. the fresh fruit samples? They used "NC-1" fruit for both. They also looked at "NC-1" dried twig, and found that it was approximately as toxic as the non-dried fruit. I'm not sure what a fresh twig would be like.

There are indeed quite a lot of factors that could be contributing to the aggravation of these parkinsons symptoms, and thank you for making this point. What was particularly compelling about the evidence presented was that stopping the consumption of soursop products resulted in a reversal of symptoms: http://www.pawpaw.kysu.edu/PDF/AcetoUpdate3.pdf (see slide 14). I unfortunately don't have access to the original publication where this was observed, and in the worst case scenario, it could just be a noisy case study. That person (or persons?) could have done quite a lot of other things to reduce their exposure to environmental aggravators of Parkinsons.

But again, the overwhelming evidence says that the vast majority of people should probably be fine. People in the midwest don't seem to get neuropathies from oral consumption of NC-1 pawpaws which should be 100x worse than soursop.

Draak

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Re: Annonacin, Toxicity, Parkinsons, and a general review of the literature
« Reply #15 on: September 10, 2019, 03:56:38 AM »
how about this article?

still ready to blame one of God's gifts to mankind for this disease?

or one of Satan's scourges?

http://drrickschwartz.com/art-Parkinson.html


Quite sorry if I've offended you. Back when I didn't know that more than 10 kinds of fruit existed in the world, trying a sugar apple in Taiwan was what got me hooked on interesting fruits. Squamosa still remains my favorite fruit (until my next amazing experience, perhaps). I of course love annonas, and if it wasn't clear from my post, I'm rather upset that I have concluded it would probably not be in my best interest to eat copious amounts of pawpaw. There's a darn good chance it could otherwise end up being my next favorite fruit!  :'(.

I have a condition (fibromyalgia) that is debilitating at its worst, and eating certain foods is known to aggravate it. You and 99% of others will almost certainly be fine eating whatever annona you wish, but it may be risky for me. I'll probably try pawpaw (and maybe other annonas outside of squamosa & cherimola) one day, but it would be a questionable decision for me to eat incredible amounts of it.

If it makes you feel better, the evidence available suggests that soursop *is not* causing Parkinsons in the general population. I can say this because the incidence rate of Parkinsons on the island in question is not higher than Parkinsons anywhere else.

edzone9

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Re: Annonacin, Toxicity, Parkinsons, and a general review of the literature
« Reply #16 on: September 10, 2019, 06:55:42 AM »
How many of the islanders was on Statin Drugs that are proven to cause neurological issues ?
I have no fear eating Gods Fruits! ..

The study smells of the pharmaceutical industrial complex trying to steer a study on a fruit that potentially could be life saving VS Mustard Gas Treatment..

Ed
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Re: Annonacin, Toxicity, Parkinsons, and a general review of the literature
« Reply #17 on: September 10, 2019, 07:28:50 AM »
I enjoyed your post Draak. Very interesting, thank you for sharing.

 

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