Graviola supplement research studies, benefits, risks, side effects, how well does it benefit cancer treatment or prevention? What is the right dosage? by Ray Sahelian, M.D.

Graviola tree, also known as soursop, is found in the Amazon jungle and some of the Caribbean islands. The Annona muricata tree 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 are used in traditional medicine for their tranquillizing and sedative properties.

What does the research say
As of 2011, 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 it to have anti-viral, anti-parasitic and potent anti- cancer properties. However we do not know if it has the same benefits or risks if ingested as a supplement in humans.

My opinion
Until human trials are done, it is difficult to make any recommendations with certainty. Does it work well when taken as a supplement? What is the ideal dosage? How often should it 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, for instance two days off each week. one full week off each month, and one full month off every three months.

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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.

What's in the fruit, seed and leaf?
The pulp contains 81% moisture, 3% titratable acidity and 24% non-reducing sugar. Graviola seed contains 8% moisture, 2% crude protein, 13% ash, 8% crude fiber, 20% fat and 47% carbohydrate. The seed also contains 0.2% water soluble ash, 0.8% titratable acidity and 17 mg calcium / 100 grams.
   There are quite a number of compounds in the fruit with exotic names. Some of these include acetogenins, muricins, annomuricine and muricapentocin, muricatocins A and B, and many others including annopentocins A, B, and C. The leaves contain monotetrahydrofuran acetogenins such as annomuricins A and B, gigantetrocin A, annonacin-10-one, muricatetrocins A and B, annonacin, and goniothalamicin.

Cancer prevention or treatment
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, its role in cancer prevention or treatment in humans in unclear. 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.

My father involve with adenocarcinoma of colon and metastatic complication to liver. He is under chemotherapy from 5 weeks ago. Please send me some information about graviola and it's anticancer effect. Will this herbal product help him?
    It is not possible to know since human studies are lacking.

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.

My wife has breast cancer and is taking graviola along with her chemo treatments. The herbal product has worked miracles, it's taken away the pain in the sternum and the tumors on her liver have shrunk in size.
   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?

If you had cancer would you, personally, use graviola herb as a treatment?
   There are many types of cancer and for some, modern medicine has a good treatment option. It depends on the type of cancer, the stage, what kind of therapy modern medicine offered, and what kind of available laboratory, animal, or human research was available at the time regarding the potential benefits of the herbal option.

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.
   We searched Medline in May 2009 and did not find any human graviola cancer studies mentioned in JAMA.

Five novel mono-tetrahydrofuran ring acetogenins from the seeds of Annona muricata
J Nat Prod. 1996.
Cis-annonacin, cis-annonacin-10-one, cis-goniothalamicin, arianacin, and javoricin were isolated. Cis-annonacin was selectively cytotoxic to colon adenocarcinoma cells (HT-29) in which it was 10,000 times the potency of adriamycin.

Depression
Isoquinoline derivatives isolated from the fruit of Annona muricata as 5-HTergic 5-HT1A receptor agonists in rats: unexploited antidepressive (lead) products.
J Pharm Pharmacol. 1997.
Extracts of the graviola plant have been shown to inhibit binding of [3H]rauwolscine to 5-HTergic 5-HT1A receptors in calf hippocampus, including three alkaloids, annonaine, nornuciferine and asimilobine. Our results imply that the fruit of graviola possesses anti-depressive effects, possibly induced by compounds annonaine, nornuciferine and asimilobine.

Herpes simplex
Effect of the extract of Annona muricata and Petunia nyctaginiflora on Herpes simplex virus.
J Ethnopharmacol. 1998.
Annona muricata and Petunia nyctaginiflora were screened for their activity against Herpes simplex virus-1 (HSV-1). The minimum inhibitory concentration of ethanolic extract of graviola and aqueous extract of P. nyctaginiflora was found to be 1 mg/ml.

Prostate gland
I am a 58 year old man, who has had a PSA elevated, benign for years, it has continually gone higher and higher, it went to 13. I went through all the biopsies, non cancerous. I went on a 3 capsules graviola herb per morning, 3 capsules per evening for 3 months went and retested and it was almost undetectable. I went off it now for approx two years, and now the PSA is back to 10, so starting again the herbal product, just wanted you to know, I did not take other peoples word and this is not something someone else said they did. It did cause some nausea and loose bowels, but I know it works. I used 3 capsules of Gravola Max, AM, PM, for three months, took my rising PSA from from 13 to 0.01, almost undetectable, and THAT is the ONLY thing that did it, it was rising for 5 years till then, just info only for your benefit.

Graviola extract
I have heard that some companies sell a graviola extract, but whether an 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.

The mitochondrial complex I inhibitor annonacin is toxic to mesencephalic dopaminergic neurons by impairment of energy metabolism.
Neuroscience. 2003.
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,. When added to mesencephalic cultures, annonacin was much more potent than MPP(+) and as effective as rotenone in killing dopaminergic neurons.

Graviola fruit concerns, potential toxicity, danger
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. Laboratory of Pharmacognosy, UMR 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, 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.

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.
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 graviola, to rats. Annonacin inhibited complex I in brain homogenates in a concentration-dependent manner, and, when administered systemically, entered the brain parenchyma and decreased brain ATP levels. In the absence of evident systemic toxicity, we observed neuropathological abnormalities in the basal ganglia and brainstem nuclei. There was loss of dopaminergic neurones in the substantia nigra, and cholinergic and dopamine neurons in the striatum, accompanied by a significant increase in the number of astrocytes and microglial cells. The distribution of the lesions was similar to that in patients with atypical parkinsonism.

I noticed you mention potential toxicity. If studies have been done over years spanning lifetimes, did these Parkinsonian graviola eaters die of cancer ever? Do you think death likelihood from colon adenocarcinoma has greater morbidity over Parkinson's? What is the morbidity window for persons with pancreatic, lung, bone, bladder cancer versus Parkinson's of the lifepsans of persons studied leading to your 'potential toxicity' report? Is the toxicity of cancer less or greater than the toxicity of the plant? If you had cancer, would you consume graviola?
    These are good questions and there are no easy answers since there is little research addressing these issues. Different cancers have different causes and treatments. If I had a form of cancer that had no good pharmaceutical options, I would certainly explore the use of graviola or other herbal and plant remedies.

Emails
Q. 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 dot 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.

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." Your research has saved me alot of valuable time. 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 it 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.

Near the beginning of this year, I had a PSA of 11 after being followed for 4 or 5 years with a PSA in the range of 5 to 6.8 by my personal urologist who retired a full year before the PSA of 11 was obtained. I had been seeing him for regular checkups every 6 months prior to his retirement; however, after his retirement it was a full year before I had the next one obtained by my family physician. I saw another urologist, a much younger man, who had much difficulty in listening to anything I said and so when he began to talk about a biopsy and the possibility of surgery without answering any of my questions, I went to the Univ of Chicago Center for Advanced Medicine, where I have received excellent services of other kinds in the past. This lead to a biopsy in April with a negative finding for cancer; however, there were "markers" present suggesting a need for further biopsy and that there would be a 50% chance of finding the presence of cancer. So during the ensuing 6 to 7 weeks, I initially set and did nothing other than my usual activity and then, I decided to take a look at the internet discussions relative to alternative methods of treatment other than surgery and radiation. I discovered that which you had to say about graviola and ordered a 100 capsule supply. This arrived on June 19, 2009 and I began taking it on that day using the minimum dosage you recommended of 1 per day for 5 days each week with one week off during the month and 1 month after each 3 months. Meanwhile, on July 9, which meant I had been taking the graviola for about 3 weeks, I had the 2nd biopsy. The results were made available to me on July 16 with a finding that I was cancer free and although there were a very few "markers" present, they were not significant at this time. A follow up in 6 months, as usual, was recommended. Also, I was invited to participate in a preventive study using green tea which the nurse would explain to me in a later call back to me. I received that call and in the ensuing discussion, I told the nurse about the use of graviola. She responded with immediate surprise, as judged by the sound of her voice and things she said, that she wondered why there was such a significant difference between the April biopsy and the most recent biopsy here in July, stating that of the 12 essays (???) or samples I would assume, only one of them had a couple of markers whereas before 4 of the samples each had several markers. Of course, she could not equate this difference to have anything to do with the graviola; nor, having been a researcher in the social sciences myself, would I expect for her to say so. I do, however, pay attention to potential clinical evidence that might help as long as it does not interfere with things that are known to help and offers no apparent negative side effects. So, in this situation if I were asked if taking the graviola helped me in my fight to ward off cancer I would say, I don't know if it helped or not. It does not seem to have caused any negative side effects, it is inexpensive and easy to take and I don't have cancer at this point in time. Will I continue to take it as recommended in the minimum dosage? I would answer with a resounding, Yes! Thank you for your time and patience in reading this letter.
    This is interesting, please keep me updated on your future results and I wish you the best outcome.

My uncle is afflicted with squamous cell lung cancer which has also spread to other parts of the body. He is currently undergoing chemotherapy which is not helping him much. The toxicity is so high that his WBC count reaches dangerous levels after every chemo session. Where could I purchase Graviola online? I wanted your recommendation on using Graviola to help him survive longer. I have read the standard dosage on your webpage. 1 per day for 5 days each week with one week off during the month and 1 month after each 3 months. Would you recommend a similar dosage? I would appreciate any help, and of course, I understand that you are not making any guarantees.
    It is not possible to predict how this supplement will interact with chemotherapy drugs and or whether it will offer any help in treating lung cancer since human studies are not available. I am not in a position to offer individual advice, but if his doctor approves this herbal product can be used.

I live in Uruguay, and I have an hepatic carcinoma. I have been drinking graviola leaf infusions (using 4 leaves per cup of water) once a day for seven months. Although I completely trust its healing properties, I do not know about its administration quantities, how often should I consume it, if I should take brakes in between its usage, etc. and would appreciate if you could guide me on this. The leaves I am using are brought to me directly from Brazil.
    Unfortunately there is not enough research on this topic to know the answers to any of these questions. Also, most of the studies I have seen in a laboratory have been done with the fruit rather than with the leaf.

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