Graviola: The Next Big Cancer Remedy?

What if there was an anti-cancer compound found in a tropical fruit called graviola?  You’d eat it, right?  But what if you had to eat two backpacks full of that fruit to have any meaningful effect?   


One of the biggest problems in the search for new anti-cancer compounds from plants is that the effective dose is usually far too large to ingest in its natural plant form.  Graviola is an interesting exception.  Ingesting just a few capsules or a few cups of tea per day might offer surprising benefits such as longer survival, decreased tumor sizes, decreased metastasis, and so on. 


A second problem with most plant compounds is that they actually get broken down in the digestive system and no longer have the same benefits once they reach the cancer cells.  This is why so much research testing products directly on cancer cell lines in the lab never bears fruit.  But that's not the case with this plant, either!


Graviola (also known as Annonum muricatum, soursop, gyanabana) contains over a hundred anti-cancer compounds called acetogenins.  Acetogenins are only found in the Annonaceae family, and graviola is a member of this family.  The acetogenins occur in surprisingly effective doses in their natural form, particularly within the leaves and stems.


This tropical plant grows in Central and South America, Africa, and southern Florida.  Scientists have been studying it since the 1940s.  So far, eight clinical studies have been conducted on the acetogenin compounds showing that they selectively kill cancer cells.


Hundreds of acetogenins have been isolated and tested, from dozens of Annonaceae species. At least half of these compounds are bioactive.

How Does Graviola Work?

Investigators at Purdue University have conducted much of the research on acetogenins.  The research has been funded by The National Cancer Institute and/or the National Institutes of Health.  


  • Acetogenins target many biochemical pathways that regulate the control, metabolism, division, survival, and spread of cancer cells (1, 2).  
  • Acetogenins negatively affect certain enzymes that cancer cells rely on for energy production (3). 
  • Acetogenins regulate the immune system and reduce inflammation in the cancer (4).  
  • Acetogenins reduce the expression of estrogen growth factor receptor in breast cancer cells (5).
  • Finally, acetogenins target multi-drug resistant cancer cells. 


About 2% of cancer cells have a biochemical pump in their membrane that expels chemotherapy drugs before they can kill the cancer cell.  While chemotherapy may kill the rest of the cancer, this small number of resistant cells can eventually grow out of control.  Unfortunately, this pump works against additional chemotherapy drugs, too.  This is what we call multi-drug resistance. 


Purdue researchers have reported that approximately a dozen acetogenins are more effective against multi-drug resistant cancer cells than standard chemotherapy drugs! (1)


So, to summarize, compounds in soursop can affect many biochemical pathways in the physiology of cancer cells.  If you’ve seen my Nutrition and Cancer section, you’ll have learned that one of the things that makes dietary interventions so effective in cancer treatment is that they target multiple biochemical pathways, in ways that drugs are often unable to do.

Why Don't We Use Graviola?

So, why doesn’t this information ever get translated into practical application in cancer treatment centers?  Very simply, it’s been difficult to develop acetogenins into patented drugs.  Because of technical difficulty alone, the main active acetogenin, annonacin, took ten years just to be made in a lab!


But let’s say these acetogenins could all be easily isolated or made in a lab.  Then what?  The next step for a pharmaceutical company would be to change the chemical just enough without losing its anti-cancerous properties, so that it could be patented.  


After this, clinical trials would have to be carried out, at a potential expense of hundreds of millions of dollars.  The well-known breast cancer drug, taxol, was developed in a similar manner from the yew tree.


When we hear about “miracle cancer cures” on the nightly news, this is why those cures may disappear from public view for decades in the United States. 


So, why not just use the natural compounds themselves?  That’s possible if the drug doesn’t get metabolized or huge doses don’t need to be ingested.  And — good news — that seems to be the case with this plant!  In fact, it’s already used in mainstream medicine in many places in South America where the plant grows.


But as with all natural substances, the FDA prohibits that it be marketed as a cancer therapy until it undergoes the requisite clinical trials, which are very expensive.  There’s simply very little financial incentive to perform this research on the unaltered soursop plant itself.  Therefore, large-scale, double-blind clinical trials will probably never be done in order to prove that it's an effective cancer treatment.

How Do I Use Graviola?

There are a few ways to use acetogenins that have some limited support in the scientific literature.  These are: Paw Paw Cell Reg capsules, Raintree capsules, and leaves.

Paw Paw Cell Reg Capsules

Dr. Forsythe at Century Wellness Clinic (Reno, NV) found that Paw Paw Cell-Reg,  when  given  one  capsule  four times per day,  stabilized  a  number  of patients  with  advanced  breast, lung, prostate, lymphatic, and colorectal cancers.  The  patients  showed no abnormalities in liver, kidney, electrolyte, blood sugar, or bone marrow functions. (1)


Patients experienced the following: 

  • reductions in the blood levels of tumor antigens
  • measurable decreases in tumor sizes
  • inhibition of further metastases
  • weight gain
  • increased mobility
  • enhanced energy
  • increased duration of survival

Paw Paw Cell Reg was introduced to the market in spring 2003. As a dietary supplement, it cannot be advertised as a treatment in the United States, and the company (Nature’s Sunshine Products) makes no such claims for the product. (1)

Raintree Graviola Capsules

Raintree capsules consist of 100% pure, finely milled graviola leaf/stem powder.  They have been shown to be effective against transplanted pancreatic and prostate tumors in mice. (6, 7)  In the prostate tumor study, the dose that was effective in mice, if extrapolated to human weights, would be between 350-700 mg. Raintree capsules per 150 lb. person. (6) 


It is important to note that this product has not been tested in humans in a clinical trial.  It has only been tested in animals.  However, it is one option available for those who want to ingest this plant, and this particular brand is known for producing high quality, unadulterated products.

Graviola Leaf Tea

Finally, an intriguing case study was published of a woman with breast cancer achieved stable disease using graviola and Xeloda after progressing on a number of therapies.  It was consumed by making a tea from the leaves (10 - 12 dry leaves boiled in 8 oz. water for 5 - 7 minutes). (8)  


Unfortunately, there appears to be little guidance for those who want to use leaves bought on the internet, and fraud is a problem in the supplement market.  In the reviews for many leaf products available for purchase on Amazon, one may frequently find people in the comments section claiming that the plant does not taste like soursop.  


NalLife leaves get good reviews on Amazon and appear to be authentic, but I think the best choices for products with acetogenins are Paw Paw Cell Reg or Raintree capsules as they have actually undergone some clinical testing. 

Warnings

Soursop can lower blood pressure and heart rate.  It may interfere with MAO-inhibitor drugs.  It also has uterine stimulant activity.  This means that if you are on any blood pressure or heart medications, or you are pregnant, you should not consume it.  Large doses may cause nausea or vomiting. (3) 


Soursop has anti-bacterial properties, so long-term use may lead to die-off of beneficial bacteria in the digestive tract.  Soursop also can cause changes in the neurotransmitters dopamine, norepinephrine, and serotonin, and can cause drowsiness at high dosages. (3)


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References

1) McLaughlin JL. 2008. Paw paw and cancer: annonaceous acetogenins from discovery to commercial products. J Nat Prod. 71(7):1311-21. doi: 10.1021/np800191t

2) Deep, G., Kumar, R., Jain, A. K., Dhar, D., Panigrahi, G. K., Hussain, A., … Agarwal, R. 2016. Graviola inhibits hypoxia-induced NADPH oxidase activity in prostate cancer cells reducing their proliferation and clonogenicity. Scientific Reports, 6, 23135. http://doi.org/10.1038/srep23135 

3) Graviola.  Raintree Tropical Plant Database.  Copyrighted 1996 to present by Leslie Taylor, Milam County, TX 77857. Last updated 12-28-2012, http://www.rain-tree.com/graviola.htm#.WYeep9OGOu4

4) Syed Najmuddin, S. U. F., Romli, M. F., Hamid, M., Alitheen, N. B., & Nik Abd Rahman, N. M. A. 2016. Anti-cancer effect of Annona Muricata Linn Leaves Crude Extract (AMCE) on breast cancer cell line. BMC Complementary and Alternative Medicine, 16(1), 311. http://doi.org/10.1186/s12906-016-1290-y  

5) Dai Y, Hogan S, Schmelz EM, Ju YH, Canning C, Zhou K. 2011. Selective growth inhibition of human breast cancer cells by graviola fruit extract in vitro and in vivo involving downregulation of EGFR expression. Nutr Cancer. 63(5):795-801. doi: 10.1080/01635581.2011.563027.

6) Torres, M. P., Rachagani, S., Purohit, V., Pandey, P., Joshi, S., Moore, E. D., … Batra, S. K. 2012. Graviola: A Novel Promising Natural-Derived Drug That Inhibits Tumorigenicity and Metastasis of Pancreatic Cancer Cells In Vitro and In Vivo Through Altering Cell Metabolism. Cancer Letters, 323(1), 29–40. http://doi.org/10.1016/j.canlet.2012.03.031 

7) Yang, C., Gundala, S. R., Mukkavilli, R., Vangala, S., Reid, M. D., & Aneja, R. 2015. Synergistic interactions among flavonoids and acetogenins in Graviola (Annona muricata) leaves confer protection against prostate cancer. Carcinogenesis, 36(6), 656–665. http://doi.org/10.1093/carcin/bgv046  

8) Hansra, D. , Silva, O. , Mehta, A. and Ahn, E. (2014) Patient with Metastatic Breast Cancer Achieves Stable Disease for 5 Years on Graviola and Xeloda after Progressing on Multiple Lines of Therapy. Advances in Breast Cancer Research, 3, 84-87. doi: 10.4236/abcr.2014.33012  

Disclaimer

The ideas in this website are not intended as a substitute for the advice of a trained health professional. All matters regarding your health require medical supervision. Consult your physician and/or health care professional before adopting any nutritional, exercise, or medical protocol. Consult your physician about any condition that may require diagnosis or medical attention. Statements regarding certain products and services represent the views of the author alone, and do not constitute a recommendation or endorsement or any product or service.