DNC News

Graviola and Parkinsons

August 28, 2005

Subject: New study links the herb Graviola to Parkinson-like disease

I had a bad day at the office today.  For the first time I can remember I had someone walk out on me during an office visit.
I had expressed my dismay about using Graviola as a primary treatment for breast cancer. 

You may recall an article by Ralph Moss on Graviola sent out a few months ago.
http://www.denvernaturopathic.com/news/graviola.html

I generally have little concern about people using unproven therapies. What I did have a problem with was the patient's husband adamant claim that his wife's choice was well validated by scientific research.  I expressed my opinion of the research rather abruptly in less than tactful words, and that was the end of the appointment.

Having a free morning on my hands I took a few minutes to see if I could find the volumes of research on Graviola that I had spoken so ill of. What I found was disturbing.

Recall from Moss's article that a PubMed search on Graviola provides scanty research listings, today I found only a single study characterizing the aromas of various plants using a gas chromatograph.  On the other hand, Google generates 76,200 hits on the single word Graviola. A great many people want to sell you Graviola. Raintree.com, the top hit on the list gives quite a bit of interesting information, including the plants scientific name, Annona muricata.  Plugging this term into PubMed generated more studies, five hits on the terms, Graviola and cancer.

Keep in mind that in comparison a PubMed search today on the terms green tea and cancer produces 753 listings or, pulling a random term out of the air, onions and cancer produces 75 listings; finding five hits on graviola and cancer did not impress me greatly.

It seems the active chemicals from Graviola being studied are called annonaceous acetogenins and a PubMed search using this tongue twister produced more information.  Linking annonaceous acetogenins and cancer on PubMed yields 28 hits.  This is starting to look interesting.

PubMed lists these studies in reverse chronological order so the first study I looked at was very recent and unfortunately disturbing. The study, published in Movement Disorders, on August 2, 2005, quantified the amounts of annonaceous acetogenins found in commercial food products, mostly fruit juices, sold in Guadeloupe.  These chemicals interfere with mitochondrial chemical pathways and may be why Graviola has an inhibitory effect on cancer cells.

These chemical may also be why there is a higher than expected incidence of Parkinson-like disease in Guadeloupe. In January, 2004 the Journal of Neurochemistry published an article that examined a theory that consumption of juices and teas made from Annona muricata was causing a higher then expected number of Parkinson-like symptoms in the area.  When given to rats these chemicals cause lesions in the brain that look similar to those caused by Parkinson Disease.

While Graviola may have a long history of use as both food and medicine, it possibly causes brain damage resulting in  Parkinson-like symptoms.  This month's study suggests that the amount found in beverages can accumulate over a year's time and reach the concentrations proven to cause brain damage in rats.

 While few people in the United States consume appreciable amounts of Graviola as food, many people respond to website promotions and consume large amounts of concentrated Graviola as medicine.  In the past I've considered this herb in the "we don't know if it helps but it probably won't hurt" category; these studies suggest that we now consider it potentially toxic. If we follow Hippocrates primary injunction to 'first do no harm', Gaviola is off the list of possible treatments until proven otherwise.

I have also been practicing tactful phrases, repeating them like mantras:
"It is interesting you think that, let's look at the research."
"When I last checked, the research was actually rather scanty, weak, minimal, etc."
"Some websites may exaggerate what the research actually said."

 I may be too old to learn tact, but I at least I can try.



References:


Mov Disord. 2005 Aug 2; [Epub ahead of print]
Quantification of acetogenins in Annona muricata linked to atypical parkinsonism in guadeloupe.

Champy P, Melot A, Guerineau Eng V, Gleye C, Fall D, Hoglinger GU, Ruberg M, Lannuzel A, Laprevote O, Laurens A, Hocquemiller R.

Laboratory of Pharmacognosy, UMR 8076 Centre National de la Recherche Scientifique (CNRS) BioCIS, Faculte de Pharmacie Paris XI, Chatenay-Malabry, France.

Atypical parkinsonism in Guadeloupe has been associated with the consumption of fruit and infusions or decoctions prepared from leaves of Annona muricata L. (Annonaceae), which contains annonaceous acetogenins, lipophilic inhibitors of complex I of the mitochondrial respiratory chain. We have determined the concentrations of annonacin, the major acetogenin in A. muricata, in extracts of fruit and leaves by matrix-assisted laser desorption-ionization mass spectrometry. An average fruit is estimated to contain about 15 mg of annonacin, a can of commercial nectar 36 mg, and a cup of infusion or decoction 140 mug. As an indication of its potential toxicity, an adult who consumes one fruit or can of nectar a day is estimated to ingest over 1 year the amount of annonacin that induced brain lesions in rats receiving purified annonacin by intravenous infusion. (c) 2005 Movement Disorder Society.

PMID: 16078200 [PubMed - as supplied by publisher]

J Neurochem. 2004 Jan;88(1):63-9.
Annonacin, a lipophilic inhibitor of mitochondrial complex I, induces nigral and striatal neurodegeneration in rats: possible relevance for atypical parkinsonism in Guadeloupe.

Champy P, Hoglinger GU, Feger J, Gleye C, Hocquemiller R, Laurens A, Guerineau V, Laprevote O, Medja F, Lombes A, Michel PP, Lannuzel A, Hirsch EC, Ruberg M.

Experimental Neurology and Therapeutics, INSERM U289, Hopital de la Salpetriere, Paris, France.

In Guadeloupe, epidemiological data have linked atypical parkinsonism with fruit and herbal teas from plants of the Annonaceae family, particularly Annona muricata. These plants contain a class of powerful, lipophilic complex I inhibitors, the annonaceous acetogenins. To determine the neurotoxic potential of these substances, we administered annonacin, the major acetogenin of A. muricata, to rats intravenously with Azlet osmotic minipumps (3.8 and 7.6 mg per kg per day for 28 days). Annonacin inhibited complex I in brain homogenates in a concentration-dependent manner, and, when administered systemically, entered the brain parenchyma, where it was detected by matrix-associated laser desorption ionization-time of flight mass spectrometry, and decreased brain ATP levels by 44%. In the absence of evident systemic toxicity, we observed neuropathological abnormalities in the basal ganglia and brainstem nuclei. Stereological cell counts showed significant loss of dopaminergic neuro
 nes in
the substantia nigra (-31.7%), and cholinergic (-37.9%) and dopamine and cyclic AMP-regulated phosphoprotein (DARPP-32)-immunoreactive GABAergic neurones (-39.3%) in the striatum, accompanied by a significant increase in the number of astrocytes (35.4%) and microglial cells (73.4%). The distribution of the lesions was similar to that in patients with atypical parkinsonism. These data are compatible with the theory that annonaceous acetogenins, such as annonacin, might be implicated in the aetiology of Guadeloupean parkinsonism and support the hypothesis that some forms of parkinsonism might be induced by environmental toxins.

PMID: 14675150 [PubMed - indexed for MEDLINE]


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