Toxicology expert raises alarm over potential neurotoxins in graviola/soursop

Dr Alex Schauss is senior research director at AIBMR Life Sciences, which specializes in toxicological/safety testing, nutraceutical research, managing clinical trials, and regulatory compliance.

He contacted NutraIngredients-USA after seeing new ads for dietary supplements containing extracts from the fruit and leaves of graviola, which, he says, contain a neurotoxin called annonacin.​

Epidemiological, in vitro and animal data all indicate that chronic consumption could be risky, he said.

“I did nutrition research in Guam in the early 1980s on behalf of a legislative committee on the island over a span of three years and we found an association between chronic fruit consumption and atypical Parkinson's disease ​[that was] shocking. 67% of Parkinson's cases were of the atypical form, compared to less than 5% in Europe.”​

‘I was somewhat shocked given what I knew of its neurotoxicity’​

He added: “What worries me is the appearance of the fruit in products of late given that it contains isoquinoline alkaloids that have been linked to the development of atypical Parkinson's.”​

The recent interest in graviola appeared to be on the back of research suggesting it has anti-cancer properties, he said.  

“I received inquiries on these ​[anti-cancer] claims… I was somewhat shocked given what I knew of its neurotoxicity when one caller mentioned that they were considering bringing it out as a juice.”​

Why is this not better known in the supplements trade?​

He added: “I spoke at a recent international symposium on the safety of natural products and mentioned soursop. Quite a number of scientists in the audience came from tropical/sub-tropical countries and recognized the fruit immediately when shown on a slide, but did not know about the associated neurotoxic compounds it contains. ​

“During lunch, one of the attendees did a PubMed search and confirmed my comments earlier that morning and asked why this was not better known.”​

Concerns about graviola were first raised several years ago, said Schauss. “But people forget. So when given the opportunity to co-author with Professor Badrie ​[a professor at the University of the West Indies] on the subject ​[in 2009] we agreed that recapping the toxicology of the fruit was important.”​

A. muricata and other plants of Annonaceae contain potential neurotoxins​

In chapter 39 of the book Bioactive Foods in Promoting Health​ edited by Ronald Ross Watson and Victor R. Preedy (Oxford: Academic Press, 2009) Schauss and Badrie write:

“​​The aqueous extract of leaves and the extract of the root bark of Annona muricata and infusions and decoctions of the fruit have been shown in both in vitro and in vivo experiments to be a potentially toxic inhibitor of the mitochondrial respiratory chain.​

“Experimental studies have confirmed annonacin, an isoquinoline derivative, the major acetogenin found in soursop, as the toxic agent responsible for this effect. A. muricata and other plants of Annonaceae contain potential neurotoxins, particularly the isoquinolinic alkaloids and acetogenins, structurally homogenous fatty acid derivatives known as polyketides specific to Annonaceae. ​

“This class of polyketides are among the most potent inhibitors of complex I of the mitochondrial respiratory chain known in nature, some 50-fold more potent than the class complex I inhibitor MPP + and two times more potent than rotenone in inducing neuronal death.”​

Epidemiological evidence​

The significance of these findings relates to the abnormally high rate of atypical parkinsonism found on islands such as Guam in the Northern Mariana islands, New Caledonia, western New Guinea, the Kii peninsula of Japan, and the French West Indian island of Guadeloupe in the Caribbean, where epidemiological evidence “suggests a close association of the disease with regular consumption of soursop fruit, infusions, and decoctions”, ​they observe.

“What is interesting is the virtual disappearance over the years of the disproportionate incidence of atypical parkinsonism previously reported in Guam and New Guinea. ​

“It has been suggested that the significant reduction in incidences may be due to changes in diet in New Guinea and in Guam, in particular owing to the adoption of Western diets and the abandonment of native foods, such as soursop.”​

Fruit and​ leaves represent potential risk​

Conerns have been raised about the leaf as well as the fruit, he added, citing papers by Champy et al (click here​ , here​ and here​). A phenomenologic study of parkinsonism by Caparros-Lefebvre in The Lancet​ also raises concerns about herbal teas, he added. Click here​.

NutraIngredients-USA has contacted several firms selling graviola supplements for comment including Raintree Nutrition, Swanson​ and Vitabase​ but has not had any feedback to date.

However, NOW Foods technical director Dr Michael Lelah said: "NOW Foods is aware of the potential safety concerns about graviola. We use a leaf extract which contains annonacin levels many times lower than the safe level.  ​

"Additionally, no adverse events have been reported for our product. On the other hand, high concentrations of annonacin are found in the fruits or seeds, which are consumed by Caribbean populations." ​

American Botanical Council (ABC) founder Mark Blumenthal was unavailable for comment.