Even though edible fruits are an important part of a healthy diet, at least one has caused an atypical form of Parkinson’s disease when over consumed on the islands of Guadeloupe, Guam and New Caledonia, as well as the Afro-Caribbean and Indian population in London 1. This is based on epidemiology, or evidence of epidemics in real people (in vivo). Recently, Martinique has been added to this list 2.
The fruit that caused it and continues to do so grows on a tree called soursop in English, graviola in Portuguese, guanábana in Spanish and Laxmanphal in India. Even though graviola is the Brazilian Portuguese word for A. muricata, this word has become quite popular in English. Moreover, the top five the most frequently searched herbs in 2008 in the Memorial Sloan-Kettering Cancer Center (MSKCC) “AboutHerbs” web site include graviola and not soursop 3. Its scientific name is Annona muricata. The fruits are used to make both a juice and a nectar that are quite popular in Puerto Rico in the USA, Mexico, Brazil, Malaysia, China, India and other many other countries. However, the public has been misled and misinformed.
There are many more websites, magazine articles and even at least one book that claim that graviola can prevent or cure cancer. So, some people may succumb to this atypical form of Parkinson’s disease when they think they are preventing or curing cancer. This is sad because there are many clinically tested and FDA-approved treatments and cures for many types of cancer. Moreover, a person (especially a child) could increase their risk of getting atypical parkinsonism by taking a dietary supplement that is not only ineffective, but can have serious harmful side effects. The goal of this article is to explain how the misinformation about the alleged anticancer effects happened and why people (especially children) should not over consume fruits from the graviola tree or other trees in the same botanical family (Annonaceae).
Graviola and other fruits in the Annonaceae family contain a class of neurotoxins called acetogenins 4. These neurotoxins are also present in other fruits in this family, including the North American pawpaw (Asimina triloba) 5. However, many articles have been published that describe the anticancer effects that are seen in cells grown in laboratories (in vitro). Unfortunately, extracts of both graviola and the pawpaw are widely available as dietary supplements 6. They are marketed as being able to kill cancer cells, but supposedly do not affect healthy cells, such as neurons in the brain 7. Unfortunately, one book stated that “Medicine only works as a palliative.
The cure never cames [sic] because it is focused on DISEASE INDUSTRY” 8. The author wrote the following: “The FDA supports the claim that the smell of soursop fruit is very similar to that of chemotherapy drugs and there are several reports that it is a powerful weapon against cancer whereby it kills the damaging cells up to 10,000 times more efficiently than chemotherapy drugs because graviola is known to attack cancer cells without harm to the healthy cells” 8. The author cited reference 41 and said that it was the FDA website on Inspections, Compliance, Enforcement, and Criminal Investigations.
If you search that website for graviola and cancer, you will find two warning letters to organizations that sell a graviola extract. These letters do NOT support the claim that the FDA thinks that graviola is known to attack cancer cells without harm to the healthy cells. They support just the opposite – that such claims are not just false, but also illegal. This author went on to claim that physicians don’t want people to know that a class of compounds called acetogenins (that are in fruits, seeds, stems and leaves of graviola and other members of the Annonaceae family) can cure cancer and are more effective than the first line treatment for many types of cancer (Adriamycin) 8, which has saved hundreds of millions of lives 9. So, the FDA issued a warning letter to companies that sold a graviola extract and claimed on their website that it was intended for use in the cure, mitigation, treatment, or prevention of disease 10.
For example, on the webpage titled “Graviola Extract” under the Benefits tab it was claimed that “Graviola extract is the best alternative supplement to support the cancer tratments [sic] and to help with the cure of the following types of cancer: Prostate cancer, (Also help with the Prostatitis) Breast cancer Lung cancer Colon cancer, (Rectume [sic] Cancer) Uterus Cancer Non-Hodgkin Melanoma Skin cancer Kidney Cancer Ovary Cancer. Another webpage titled “Graviola Extract Benefits” claimed that it “Kills cancer cells without harming healthy cells”. Still another webpage titled “Is Graviola a Cancer Cure?” claimed that “Comparative studies were done in vitro by comparing the effect with adriamycin (known chemotherapy). It was found that it (graviola leaves) is 10,000 times more powerful, and that kills cancer cells without harming healthy cells as with chemotherapy (chemotherapy causes nausea, weight loss and hair)…” 10.
This last falsehood has been spread extensively through the popular and scientific literature. One article that was published in a peer reviewed scientific article claimed that one particular acetogenin has a “potency of over 100 million times that of Adriamycin” 11. However, neither the original authors nor the scientists who reviewed it had any experience in properly preparing or analyzing very dilute solutions. If they had, they would have realized that it is impossible to prepare very dilute solutions in an ordinary laboratory. It is possible to prepare very dilute solutions of sodium chloride (salt) that are needed to analyze very pure deionized water if it is done in a facility that is as clean as the rooms used to manufacture electronic devices. Even then, it is essential that the dilute solutions be analyzed to ensure their proper dilution. Such precautions were not taken and analyses of the allegedly dilute solutions were never done in the study that compared graviola to adriamycin 11.
The FDA subsequently issued another warning letter to a company that sold a graviola extract 12. It indicated that, “Your product is not generally recognized as safe and effective for the above referenced uses and, therefore, the product is a “new drug” under section 201(p) of the Act [21 U.S.C. § 321(p)]. New drugs may not be legally introduced or delivered for introduction into interstate commerce without prior approval from FDA, as described in section 505(a) of the Act [21 U.S.C. § 355(a)]; see also section 301(d) of the Act [21 U.S.C. § 331(d)]. FDA approves a new drug on the basis of scientific data submitted by a drug sponsor to demonstrate that the drug is safe and effective. Furthermore, your product Graviola Extract is offered for conditions that are not amenable to self-diagnosis and treatment by individuals who are not medical practitioners; therefore, adequate directions for use cannot be written so that a layperson can use this drug safely for its intended purposes. Thus, this drug is misbranded within the meaning of section 502(f)(1) of the Act, in that its labeling fails to bear adequate directions for use [21 U.S.C. § 352(f)(1)]. The introduction of a misbranded drug into interstate commerce is a violation of section 301(a) of the Act [21 U.S.C. § 331(a)]” 12. So, the FDA and similar agencies in other countries realize that graviola and the North American pawpaw should not be marketed as cures for cancer.
Papaya is NOT the same as pawpaw
Unfortunately, the very healthy and nontoxic papaya fruit has been confused with the pawpaw 13-15. The papaya is in a different family (Caricaceae), and has a completely different genus and species, Carica papaya Linn. 16. The fruit contains many antioxidants, vitamins and minerals, as well as enzymes (papain and lipase) that help digestion as well as chitinase, which has antibacterial activity 17. It also has relatively few calories (32 Calories/100 g of ripe fruit). The health benefits include being hypertensive (helps prevent high blood pressure) and is hepatoprotective (beneficial to the liver). The fruit also has antibacterial, antihelminthic (helminths are worms that are intestinal parasites), antifungal and antimalarial properties. Fermented papaya fruits also support the immune system. The antioxidants in the fruit can help prevent heart disease, stroke, cancer and neurodegenerative diseases (such as Alzheimer’s disease and Parkinson’s disease). An extract of the seeds is marketed as being able to rejuvenate the body and increases one’s energy 17. So, the fruit of the papaya tree is quite different than the fruit of the North American pawpaw. Papaya fruits are very healthy.
In conclusion, graviola, the North American pawpaw and other fruits in the Annonaceae family can cause an atypical form of Parkinson’s disease that does not respond to the standard therapy (L-DOPA). Moreover, there is much misinformation and confusion in not just the popular literature, but also in some peer reviewed articles that have been published in scientific journals.
1 Lannuzel, Annie et al. Atypical parkinsonism in Guadeloupe: a common risk factor for two closely related phenotypes?, Brain. volume 130, 2007, pages 816-827.
2 Lannuzel, Annie et al. Further evidence for a distinctive atypical degenerative parkinsonism in the Caribbean: A new cluster in the French West Indian Island of Martinique. Journal of the Neurological Sciences, volume 388, 15 May 2018, pages 214-219.
3 Cassileth, Barrie R et al. The public health impact of herbs and nutritional supplements. Pharmaceutical Biology, volume 47, 2009, pages 761–767. 4 Smith, Robert E et al. Bioactive Annonaceous Acetogenins. Studies in Natural Products Chemistry, Chapter 4, Volume 41, 2014, pages 93-117.
5 Levine, Robert A et al. Determination of neurotoxic acetogenins in pawpaw (Asimina triloba) fruit by LC-HRMS. Journal of Agricultural and Food Chemistry, volume 63, 2015, pages 1053-1056.
6 Höllerhage, Matthias et al. Neurotoxicity of dietary supplements from Annonaceae species. International Journal of Toxicology, volume 36, 2015, pages 543-550.
7 BeatCancer.org Graviola (Soursop): Anti-Cancer Superfood?
8 Vianna N. Acetogenins: A New Vision Against Cancer. DIGITAL; FIRST EDITION REVISION 1, 2015. 9 Smith Robert E. Medicinal Chemistry – Fusion of Traditional and Western Medicine, 2nd ed. Bentham Science, Sharjah, U.A.E. 2014.
10 FDA, Inspections, Compliance, Enforcement, and Criminal Investigations. Graviola Group.
11 Hopp, D Craig. Squamotacin: An Annonaceous Acetogenin with Cytotoxic Selectivity for the Human Prostate Tumor Cell Line (PC-3). Journal of Natural Products. Volume 59, 1996, pages 97-99.
12 FDA, [Inspections, Compliance, Enforcement, and Criminal Investigations. Majopa Industries Corporation]. (https://www.fda.gov/ICECI/EnforcementActions/WarningLetters/2016/ucm485275.htm1/20/16, 2016).
14 Fresh Basket. Papaya.
15 Adeoye IB, Umeh UC, Ajetunmobi T. Prospects and problems of marketing pawpaw in the urban environment of Ibadan, Nigeria. Libyan Agricultural Research Center Journal International. Volume 3, 2012, pages 80−84.
16 United States Department of Agriculture. Classification for Kingdom Plantae Down to Species Carica papaya L..
17 Krishna, KL et al. Review on nutritional, medicinal and pharmacological properties of Papaya (Carica papaya Linn.). Natural Products Radiance. Volume 7(4), 2008, pages 364-373.