Graviola tree, also known as soursop, is found in the Amazon jungle and some of the Caribbean islands. The graviola tree (Annona muricata) produces a delicious fruit which is widely consumed by indigenous peoples. (There seems to be some confusion regarding calling the graviola fruit Brazilian pawpaw or papaw since fruits from other plant species may also be called pawpaw, such as the tropical fruit papaya (Carica papaya).) The fruit and the leaves of graviola are used in traditional medicine for their tranquillizing and sedative properties.

What does the research say about Graviola
As of October 2008, I cannot find any research with graviola supplements done with humans, or even animals. There are dozens of laboratory tests done in test tubes. Some of these studies show graviola to have anti-viral, anti-parasitic and potent anti- cancer properties. However we do not know if graviola has the same benefits or risks if ingested as a supplement in humans.

Dr. Sahelian's opinion on graviola supplement
Until human trials are done, it is difficult to make any recommendations regarding graviola. Does graviola work well when taken as a supplement? What is the ideal dosage? How often should graviola be taken and for how long? Does graviola have side effects that we are not aware of if taken daily for many months or years? These are questions that still need to be answered through rigorous research.  However, some of the studies regarding graviola's anti-cancer potential are intriguing and certainly worthwhile to further explore. In the meantime, it is prudent to take breaks from use of graviola, for instance two days off each week. one full week off each month, and one full month off every three months.

Graviola supplement, 500 mg

This graviola product is 100% pure ground natural plant material.

Supplement Facts:
Graviola - 500 mg *
   (Annona muricata) leaf and stem         

Click here to buy Graviola supplement product, or to subscribe to a FREE and very popular newsletter
Subscribe to a FREE Supplement Research Update newsletter. Twice a month you will receive an email with a discussion of several studies on various supplements and natural medicine topics, and their practical interpretation by Ray Sahelian, M.D. We will discuss graviola cancer research as more information becomes available.

Suggested Use:  As a dietary supplement, take 1 graviola capsule daily or as directed by a health care professional. Take breaks from use, for instance tow days off a week and one week off per month.
* Graviola daily value not established

What's in Graviola fruit?
There are quite a number of compounds in graviola fruit with exotic and long names. Some of these include acetogenins, muricins, and many others.

Graviola and Cancer
Although laboratory research with graviola and cancer looks promising, little is known about the role graviola supplements would play in human cancer prevention or treatment. Therefore, at this point, the role of graviola and cancer in humans in unclear.

Graviola Extract
I have heard that some companies sell a graviola extract, but whether a graviola extract offers benefits beyond that of regular graviola whole powder is not known.

Graviola and atypical Parkinson's disease symptoms, side effects, caution, safety and toxicity
There have been a few reports that regular ingestion of graviola fruit for decades by residents of Guadeloupe and other Caribbean countries may lead to atypical Parkinsonian type symptoms. Until this is clarified, it is a good idea to follow the suggestions of frequent breaks from the use of graviola supplements as suggested earlier in this article.

Graviola Research Update
Proximate composition and selected physicochemical properties of the seed, pulp and oil of sour sop (Annona muricata - graviola ).
Plant Foods Hum Nutr. 2002 Spring;57(2):165-71.
Proximate composition and physicochemical analyses were carried out on the seed, pulp and extracted oil of sour sop ( graviola ). The results showed that the graviola seed contained 8.5% moisture, 2.4% crude protein, 13.6% ash, 8.0% crude fiber, 20.5% fat and 47.0% carbohydrate. The graviola seed also contained 0.2% water soluble ash, 0.79% titratable acidity and 17.0 mg calcium/100 g. The graviola pulp was found to contain 81% moisture, 3.43% titratable acidity and 24.5% non-reducing sugar. Selected physicochemical characteristics included refractive indices of 1.335 for the graviola seed and 1.356 for the pulp, pH values of 8.34 for the graviola seed and 4.56 for the pulp, and soluble solids contents of 1.5 degrees Brix for the graviola seed and 15 degrees Brix for the pulp.

Effect of the extract of Annona muricata ( graviola extract ) and Petunia nyctaginiflora on Herpes simplex virus.
J Ethnopharmacol. 1998 May;61(1):81-3.
Annona muricata (graviola) and Petunia nyctaginiflora (Solanaceae) were screened for their activity against Herpes simplex virus-1 (HSV-1) and clinical isolate (obtained from the human keratitis lesion). We have looked at the ability of extract(s) to inhibit the cytopathic effect of HSV-1 on vero cells as indicative of anti-HSV-1 potential. The minimum inhibitory concentration of ethanolic extract of graviola and aqueous extract of P. nyctaginiflora was found to be 1 mg/ml.

Annonacin, a lipophilic inhibitor of mitochondrial complex I, induces nigral and striatal neurodegeneration in rats: possible relevance for atypical parkinsonism in Guadeloupe.
J Neurochem. 2004 Jan;88(1):63-9.
In Guadeloupe, epidemiological data have linked atypical parkinsonism with fruit and herbal teas from plants of the Annonaceae family, particularly Annona muricata ( graviola ). 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 graviola, 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 neurones 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.

The mitochondrial complex I inhibitor annonacin is toxic to mesencephalic dopaminergic neurons by impairment of energy metabolism.
Neuroscience. 2003;121(2):287-96.
The death of dopaminergic neurons induced by systemic administration of mitochondrial respiratory chain complex I inhibitors such as 1-methyl-4-phenylpyridinium (MPP(+); given as the prodrug 1-methyl-1,2,3,6-tetrahydropyridine) or the pesticide rotenone have raised the question as to whether this family of compounds are the cause of some forms of Parkinsonism. We have examined the neurotoxic potential of another complex I inhibitor, annonacin, the major acetogenin of Annona muricata ( graviola ), a tropical plant suspected to be the cause of an atypical form of Parkinson disease in the French West Indies (Guadeloupe). When added to mesencephalic cultures for 24 h, annonacin was much more potent than MPP(+) (effective concentration [EC(50)]=0.018 versus 1.9 microM) and as effective as rotenone (EC(50)=0.034 microM) in killing dopaminergic neurons. The uptake of [(3)H]-dopamine used as an index of dopaminergic cell function was similarly reduced. Toxic effects were seen at lower concentrations when the incubation time was extended by several days whereas withdrawal of the toxin after a short-term exposure (<6 h) arrested cell demise. Unlike MPP(+) but similar to rotenone, the acetogenin also reduced the survival of non-dopaminergic neurons. Neuronal cell death was not excitotoxic and occurred independently of free radical production. Raising the concentrations of either glucose or mannose in the presence of annonacin restored to a large extent intracellular ATP synthesis and prevented neuronal cell demise. Deoxyglucose reversed the effects of both glucose and mannose. Other hexoses such as galactose and fructose were not protective. Attempts to restore oxidative phosphorylation with lactate or pyruvate failed to provide protection to dopaminergic neurons whereas idoacetate, an inhibitor of glycolysis, inhibited the survival promoting effects of glucose and mannose indicating that these two hexoses acted independently of mitochondria by stimulating glycolysis. In conclusion, our study demonstrates that annonacin promotes dopaminergic neuronal death by impairment of energy production. It also underlines the need to address its possible role in the etiology of some atypical forms of Parkinsonism in Guadeloupe.

Toxicity of Annonaceae for dopaminergic neurons: potential role in atypical parkinsonism in Guadeloupe.
In the French West Indies there is an abnormally high frequency of levodopa-resistant parkinsonism, suggested to be caused by consumption of fruit and infusions of tropical plants, especially Annona muricata ( graviola ). To determine whether toxic substances from this plant can cause the neuronal degeneration or dysfunction underlying the syndrome, we exposed mesencephalic dopaminergic neurons in culture to the total extract (totum) of alkaloids from Annona muricata root bark and to two of the most abundant subfractions, coreximine and reticuline. After 24 hours, 50% of dopaminergic neurons degenerated with 18 microg/ml totum, 4.3 microg/ml (13 microM) coreximine, or 100 microg/ml (304 microM) reticuline. The effects of the alkaloid totum were not restricted to the population of dopaminergic cells since GABAergic neurons were also affected by the treatment. Nuclei in dying neurons showed DNA condensation or fragmentation, suggesting that neuronal death occurred by apoptosis. Cell death was not excitotoxic and did not require toxin uptake by the dopamine transporter. Neurodegeneration was attenuated by increasing the concentration of glucose in the culture medium, which also reduced the effect of the dopaminergic neurotoxin MPP+, a mitochondrial respiratory chain inhibitor. Toxin withdrawal after short-term exposure arrested cell death. Acute treatment with totum, coreximine, or reticuline reversibly inhibited dopamine uptake by a mechanism that was distinct from that causing neuronal death. GABA uptake was not reduced under the same conditions. This study suggests that alkaloids from graviola can modulate the function and the survival of dopaminergic nerve cells in vitro. It is therefore conceivable that repeated consumption could cause the neuronal dysfunction and degeneration underlying the West Indian parkinsonian syndrome.

Cytotoxicity and antileishmanial activity of Annona muricata pericarp - graviola.
Fitoterapia. 2000 Apr;71(2):183-6.
Hexane, ethyl acetate and methanol extracts of Annona muricata pericarp ( graviola ) were tested in vitro against Leishmania braziliensis and L. panamensis promastigotes, and against cell line U-937. The ethyl acetate graviola extract was more active than the other extracts and even of Glucantime used as reference substance. Its fractionation led to the isolation of three acetogenins--annonacin, annonacin A and annomuricin A.

Two new mono-tetrahydrofuran ring acetogenins, annomuricin E and muricapentocin, from the leaves of Annona muricata - graviola.
J Nat Prod. 1998 Apr;61(4):432-6.
Bioactivity-directed fractionation of the leaf extract of Annona muricata L. (graviola) has resulted in the isolation of two new Annonaceous acetogenins, annomuricine (1) and muricapentocin (2). Compounds 1 and 2 are monotetrahydrofuran ring acetogenins bearing two flanking hydroxyl groups; however, each has three additional hydroxyl groups. Compound 1 has an erythro 1,2-diol, and 2 has a 1,5,9-triol moiety. Both 1 and 2 showed significant cytotoxicities against six types of human tumors, with selectivities to the pancreatic carcinoma (PACA-2) and colon adenocarcinoma (HT-29) cell lines. Graviola research.

Isoquinoline derivatives isolated from the fruit of Annona muricata ( graviola ) as 5-HTergic 5-HT1A receptor agonists in rats: unexploited antidepressive (lead) products.
J Pharm Pharmacol. 1997 Nov;49(11):1145-9.
Extracts of the graviola plant have been shown to inhibit binding of [3H]rauwolscine to 5-HTergic 5-HT1A receptors in calf hippocampus, and three alkaloids, annonaine (1), nornuciferine (2) and asimilobine (3), isolated from the fruit have been shown to have IC50 values of 3 microM, 9 microM and 5 microM, respectively, although in ligand-binding studies it was not possible to determine whether interaction of these ligands with the receptor was agonistic or antagonistic. These results imply that the fruit of graviola possesses anti-depressive effects, possibly induced by compounds 1, 2 and 3, and that in the past potent leads for the development of anti-depressive therapeutics have not been used.

Five new monotetrahydrofuran ring acetogenins from the leaves of Annona muricata - graviola.
J Nat Prod. 1996 Nov;59(11):1035-42.
Bioactivity-directed fractionation of the leaves of Annona muricata ( graviola ) resulted in the isolation of annopentocins A (1), B (2), and C(3), and cis- and trans-annomuricin-D-ones (4, 5). Compounds 1-3 are the first acetogenins reported bearing a mono-tetrahydrofuran (THF) ring with one flanking hydroxyl, on the hydrocarbon side, and another hydroxyl, on the lactone side, that is one carbon away from the THF ring. Compounds 4 and 5 from graviola were obtained in a mixture and are new mono-THF ring acetogenins bearing two flanking hydroxyls and an erythro-diol located between the THF and the ketolactone rings. Compound 1 was selectively cytotoxic to pancreatic carcinoma cells (PACA-2), and 2 and 3 were selectively cytotoxic to lung carcinoma cells (A-549); the mixture of 4 and 5 was selectively cytotoxic for the lung (A-549), colon (HT-29), and pancreatic (PACA-2) cell lines with potencies equal to or exceeding those of Adriamycin. Graviola anti-cancer benefits.

Five novel mono-tetrahydrofuran ring acetogenins from the seeds of Annona muricata ( graviola ).
J Nat Prod. 1996 Feb;59(2):100-8.
Bioactivity-directed fractionation of the seeds of Annona muricata L. ( graviola ) resulted in the isolation of five new compounds: cis-annonacin (1), cis-annonacin-10-one (2), cis-goniothalamicin (3), arianacin (4), and javoricin (5). Three of these (1-3) are among the first cis mono-tetrahydrofuran ring acetogenins to be reported. NMR analyses of published model synthetic compounds, prepared cyclized formal acetals, and prepared Mosher ester derivatives permitted the determinations of absolute stereochemistries. Bioassays of the pure graviola compounds, in the brine shrimp test, for the inhibition of crown gall tumors, and in a panel of human solid tumor cell lines for cytotoxicity, evaluated relative potencies. Compound 1 from graviola was selectively cytotoxic to colon adenocarcinoma cells (HT-29) in which it was 10,000 times the potency of adriamycin.

Muricatocins A and B, two new bioactive monotetrahydrofuran Annonaceous acetogenins from the leaves of Annona muricata (graviola).
J Nat Prod. 1995 Jun;58(6):902-8.
The leaves of Annona muricata (graviola) have yielded the novel monotetrahydrofuran Annonaceous acetogenins, muricatocins A [1] and B [2]. Each compound possesses five hydroxyl groups, with two hydroxyl groups at the C-10 and C-12 positions. The absolute configurations of 1 and 2 (except for positions C-10 and C-12) were determined by Mosher ester methodology. The C-10, C-12 acetonides (1c, 2c) suggested relative stereochemistry and significantly enhanced cytotoxicity against the A-549 human lung tumor cell line. Three known monotetrahydrofuran acetogenins, annonacin A, (2,4-trans)-isoannonacin, and (2,4-cis)-isoannonacin, were also found from graviola.

Two new cytotoxic monotetrahydrofuran Annonaceous acetogenins, annomuricins A and B, from the leaves of Annona muricata ( graviola ).
J Nat Prod. 1995 Jun;58(6):830-6.
The leaves of graviola have yielded eight monotetrahydrofuran Annonaceous acetogenins. Two of them, annomuricins A [1] and B [2], whose chemical structures were deduced by ms, nmr, ir, and uv spectral and chemical methods, are novel and unusual. Compounds 1 and 2 each possess five hydroxyl groups; two hydroxyl groups are vicinal, with the vicinal group of 1 threo and that of 2 erythro. The absolute configurations of 1 and 2 were determined by Mosher ester methodology. Six monotetrahydrofuran acetogenins, previously described in the graviola seeds, were found in the graviola leaves; these are gigantetrocin A, annonacin-10-one, muricatetrocins A and B, annonacin, and goniothalamicin.

Graviola fruit concerns
As you can read in detail in the research updates above, there is a concern that consuming the graviola fruit for prolonged periods (many years in a row or perhaps a lifetime) may increase the risk for a form of Parkinson's Disease. This is not known for certain at this time but to be cautious, it would be best to take holidays from use of graviola and not eat the fruit for months at a time without a break.

Quantification of acetogenins in Annona muricata linked to atypical parkinsonism in guadeloupe.
Mov Disord. 2005 Dec;20(12):1629-33. Laboratory of Pharmacognosy, UMR 8076 Centre National de la Recherche Scientifique BioCIS, Faculté de Pharmacie Paris XI, Châtenay-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. 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 microg. 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.

Graviola Emails
Q. Two years ago my nephew was scheduled for surgery after a positive biopsy for prostrate cancer. While awaiting surgery he took graviola supplements for two months. His tumors disappeared and his PSA dropped to 2 and his surgery was cancelled. His checkups remain fine. His PSA is now less than 2.Thanks for your excellent site detailing reliable information about many complementary health supplements. I have benefited by reading many articles that you publish.

Q. I came across your entry about graviola. In March of 2003 I met Dr. Jerry McLaughlin, emeritus professor of pharmacognosy of Purdue. Dr. McLaughlin lectured about his work with the Annonaceous acetogenins. Among these are the molecules from Annona muricata ( graviola ) and Asimina triloba ( paw paw ). He distinguished these species mainly because of the difference in bioassay activity and the difference in tumor inhibition in mice. He reported on a human trial in the US of an extract from Asimina triloba ( paw paw ) that had 94 participants with diagnosed cancer. Later that year, I videotaped his lecture. I then posted the parts on an educational website called pawpaw.tv. Although he is the former editor of the Journal of Natural Products and has published 70 papers in peer-reviewed journals concerning Annonaceous acetogenins, he has not had success thus far in finding a publisher. I wanted you to be aware that there is a significant difference in activity levels of the double ring compounds (e.g. bullatacin) found in Asimina triloba, and the single ring compounds found in Annona muricata ( annonacin ). Much of the popular writing from sources on the internet fails to distinguish the difference. This causes a misleading information to be put forward about the biological use of the two herbs. You may with to refer to his published review of Annonaceous acetogenins found in the 1999 Journal of Natural Products. My website
www.pawpaw.tv has his lecture and some written information about his research.

Q. I was reading up on one of the herbs and came across this explanation Graviola, also known as soursop, is a small tree from the Amazon jungle and some of the Caribbean islands. The graviola tree ( Annona muricata ) produces a delicious fruit commonly called paw-paw, which is widely consumed by indigenous peoples'. I was reading up on products concerning the immune system and came across this write up and was abit confused as you say in the above that the soursop is a small tree and produces fruit commonly called paw-paw but they are both different fruits are you aware of that? I live in Australia and we grow both fruit trees the soursop tree similar to the custard apple fruit and the paw-paw tree which has a few varieties both grown in Queensland.
   A. We're not completely sure about this since we are not botanists but rather focus on the clinical effects of herbs and plant extracts, but it appears that in Brazil the graviola fruit is called Brazilian paw paw, and in Australia paw-paw is distantly related to soursop (Annona muricata), and in Australia the tropical papaya, Carica papaya, is also known as pawpaw. The main point is that the plant we are focused on this page is graviola, annona muricata. If there are botanists familiar with this topic who would like to enlighten us, we would appreciate it.

Q.  I have relied on your website to help me decide on whether or not to use many products. I constantly refer to your book "Mind Boosting Secrets." My health totally depends on use of natural products. Your research has saved me alot of valuable time. I appreciate all your hard work. I am a little confused by your statements on your site about graviola being/not being tested in animals. You state that after a thorough Medline search you could not find research with animals. Then a little later in the dissertation you present the J Neurochem 2004 research that actually does administer annonacin intravenously to rats. This looks like research with animals to my understanding. I have done a further Medline search and rats are being tested. Please preserve the credibility of your site by correcting this error. Please check all your research disclaimer statements for all your product evaluations accordingly.
   Please find the following attached excerpts from your site: What does the research say about Graviola: I did a thorough Medline search and could not find any research with graviola done with humans, or even animals. There are dozens of laboratory tests done in test tubes. Some of these studies show graviola to have anti-viral, anti-parasitic and potent anti- cancer properties. However we do not know if graviola has the same properties if ingested as a supplement in humans. "Annonacin, a lipophilic inhibitor of mitochondrial complex I, induces nigral and striatal neurodegeneration in rats: possible relevance for atypical parkinsonism in Guadeloupe."
   A. You bring up important issues that deserve a response. Firstly, never completely rely on any nutritional (or on any topic) information from any source, whether this information is on a medical website, major news website, a medical textbook, official government website, medical university web site, etc., or even my website. Nutritional research is in its infancy, and many varied opinions exist on a number of nutritional topics. Secondly, it is impossible to update the thousands of pages on a website to keep them always current. Thirdly, there could be misspellings or wrong interpretations. Fourthly, some sources may purposely provide false information in order to sell a product or damage the reputation of a competitor. There are no guarantees that any information printed anywhere is correct. Every consumer and reader should keep this in mind. There is no such thing as infallibility.
   As to the specific question your address, there is a difference researching the effect of a specific extract versus the effects from the whole herb. Every herb has dozens or hundreds of chemical substances in it. For instance, graviola has, among other substances, acetogenins, muricins, and many others. Using annonacin by itself does not mean that the same effect would be elicited by giving the whole graviola herb. There could be other substances within the graviola herb that could modify, enhance or counteract the effects of annonacin.

Q. I am a journalist from Brazil, and I am very much interested in knowing about graviola extract use to cure cancer.
   A. Since I am not aware of any human trials that have been reported in medical journals available to western medical doctors regarding the use of graviola extract for the treatment of cancer, it is difficult to say whether graviola herb or extract is effective, what the appropriate dosage would be, how long treatment would be needed, which cancers it is suited for, and how it combines with pharmaceutical anti-cancer drugs. When the dosage of graviola herb exceeds 500 mg a day, some individuals feel sedated and sleepy.

Q. My wife has breast cancer and is taking graviola along with her chemo treatments. The graviola has worked miracles, it's taken away the pain in the sternum and the tumors on her liver have shrunk in size.
   A. I would be very happy if graviola was the natural treatment that is actually helping with the pain and liver tumor shrinkage, but since she is taking chemotherapy treatments at the same time, how do we know it is the graviola supplement use that is responsible for the liver tumor shrinkage?

Q. I was told by what I believe is a reliable person that JAMA had an article in it about the benefits of graviola extract for cancer. He didn't know the date of the Journal. I can't find any info on the article, etc. Do you or your staff have any information regarding a JAMA article on graviola plant for cancer?
   A. We searched Medline in May 2008 and did not find any human graviola cancer studies mentioned in JAMA.

Q. I have heard it reported at various places on the internet that graviola herb has anti tumor properties and can be used to treat cancer and tumors in the human body. As far as I know there is still no graviola herb research done on this besides anecdotal reports from consumers. Do you have any further information you could share?
   A. As of October 2008, I have not seen such human graviola research.

Q. I am an epidemiologist and was hoping you may know if there are currently any clinical trials under-way looking at annona muricata graviola and any contact information of the Investigators. I am interested in knowing the possible interaction of this herb.
   A. As of December 2008 I am not aware of any human clinical trials with graviola herbal supplements.

Graviola research - Soursops (Annona muricata L.) are highly aromatic fruits with white juicy flesh and are native to tropical North and South America.