Graviola

Graviola is native to tropical America and the Caribbean, and every part of the tree carries a traditional use somewhere in its range. The two main threads are parasitic infection and, in more recent folk practice, cancer ^{1Reference 1Moghadamtousi et al. · 2015ReviewAnnona muricata (Annonaceae): a review of its traditional uses, isolated acetogenins and biological activities — reviewView study →}.

The leaf is the principal medicine. It is taken for insomnia, headache, diabetes and cystitis, and a leaf decoction is drunk for rheumatic and neuralgic pain ^{1Reference 1Moghadamtousi et al. · 2015ReviewAnnona muricata (Annonaceae): a review of its traditional uses, isolated acetogenins and biological activities — reviewView study →}. It is also given for colic, dysentery and muscle aches. The darkest leaves were chosen as a sedative, and leaves were placed in a pillow or between the sheets as a sleep remedy. The usual preparation is a simple infusion or decoction.

The fruit is used for fever, diarrhoea, dysentery, malaria, worms and other parasites, and is eaten to increase a mother’s milk after childbirth. The crushed seeds are applied against external and internal worms, and cooked leaves are applied to abscesses and rheumatic joints ^{1Reference 1Moghadamtousi et al. · 2015ReviewAnnona muricata (Annonaceae): a review of its traditional uses, isolated acetogenins and biological activities — reviewView study →}.

Regional practice varies. In Brazil the leaves are decocted as a tea for liver complaints, and leaf oil and unripe fruit are applied for neuralgia and arthritis. In Peru the leaf is taken for excess catarrh, and the bark and root for diabetes, insomnia and muscle aches. In Guyana the leaf is taken as a heart tonic.

In tropical Africa the tree is used as an astringent, and for coughs, pain and skin diseases. It also serves as an insecticide and a fish poison. In Nigeria and elsewhere the leaves are used against tumours ^{1Reference 1Moghadamtousi et al. · 2015ReviewAnnona muricata (Annonaceae): a review of its traditional uses, isolated acetogenins and biological activities — reviewView study →}.

Graviola reached tropical Asia through cultivation. In India the fruit and flower are used for catarrh, and the root bark and leaves as an anti-inflammatory and against worms. In Malaysia a crushed-leaf mixture of A. muricata, A. squamosa and hibiscus is applied as a juice to the head to prevent fainting ^{1Reference 1Moghadamtousi et al. · 2015ReviewAnnona muricata (Annonaceae): a review of its traditional uses, isolated acetogenins and biological activities — reviewView study →}.

The acetogenins inhibit mitochondrial complex I and are cytotoxic to tumour cell lines. An ethyl acetate leaf extract induced mitochondrial apoptosis in A549 lung cancer cells ^{3Reference 3Moghadamtousi et al. · 2014In vitroAnnona muricata leaves induced apoptosis in A549 cells through the mitochondrial-mediated pathway — in vitroView study →}. In pancreatic cancer cells and in mice, a graviola extract reduced tumour growth and metastasis by disrupting cancer-cell metabolism ^{4Reference 4Torres et al. · 2012In vitroGraviola: a natural-derived drug that inhibits tumorigenicity and metastasis of pancreatic cancer cells in vitro and in vivo — animal modelView study →}.

The one human study is a randomised, double-blind, placebo-controlled trial in 28 colorectal cancer patients who had undergone tumour resection. After 8 weeks, serum from the leaf-extract group was more cytotoxic to colorectal cancer cell lines than serum from the placebo group ^{2Reference 2Indrawati et al. · 2017RCTThe effect of an Annona muricata leaf extract on nutritional status and cytotoxicity in colorectal cancer: a randomised controlled trialView study →}.

That is a laboratory readout, not a measure of tumour shrinkage, survival or recurrence, and the authors called for further work on clinical endpoints ^{2Reference 2Indrawati et al. · 2017RCTThe effect of an Annona muricata leaf extract on nutritional status and cytotoxicity in colorectal cancer: a randomised controlled trialView study →}. Most of the positive data remain at the cell and rodent level ^{1Reference 1Moghadamtousi et al. · 2015ReviewAnnona muricata (Annonaceae): a review of its traditional uses, isolated acetogenins and biological activities — reviewView study →}.

Gap: No trial has tested whether graviola changes any clinical cancer outcome; the human evidence is a single small study with a surrogate endpoint, and the active acetogenins are also neurotoxic.

Glucose lowering is the most consistently reproduced effect in animals.

A standardised leaf extract improved metabolic markers in alloxan–nicotinamide diabetic rats, and the lower dose reduced serum urea about as well as metformin ^{6Reference 6Zubaidi et al. · 2025AnimalDeciphering the mechanism of Annona muricata leaf extract in alloxan–nicotinamide-induced diabetic rats — animal modelView study →}. In type-2 diabetic mice, an extract lowered fasting glucose, HbA1c and insulin resistance and reduced liver damage ^{15Reference 15Son et al. · 2021AnimalAmeliorative effect of Annona muricata (Graviola) extract on hyperglycaemia-induced hepatic damage in STZ diabetic rats — animal modelView study →}.

In high-fat-fed mice, an aqueous leaf extract improved blood lipids and, at the highest dose, glucose tolerance, with no effect on fasting glucose ^{7Reference 7Sasso et al. · 2019AnimalUse of an extract of Annona muricata to prevent high-fat-diet-induced metabolic disorders — animal modelView study →}. In streptozotocin-diabetic rats, injected methanolic leaf extract increased the number and size of pancreatic β-cells ^{5Reference 5Adeyemi et al. · 2010AnimalHistomorphological and morphometric studies of the pancreatic islet cells of diabetic rats treated with Annona muricata — animal modelView study →}.

The effects appear across aqueous, ethanol and methanol preparations and several models of diabetes.

Gap: No adequately powered human trial; doses and extract standardization differ between studies, so an effective human regimen is unknown, and additive hypoglycemia with diabetes drugs is a real interaction risk.

An ethanol leaf extract given by mouth reduced pain responses and carrageenan paw swelling in rodents in a dose-dependent way. At 400 mg/kg it cut paw oedema by about 30–37% ^{8Reference 8De Sousa et al. · 2010AnimalAntinociceptive and anti-inflammatory activities of the ethanol extract of Annona muricata L. leaves in animal modelsView study →}.

A transdermal patch loaded with a flavonoid-rich leaf extract inhibited induced inflammation in animals for 6 hours, comparable to a commercial formulation ^{9Reference 9Araújo et al. · 2024AnimalDevelopment and pre-clinical anti-inflammatory efficacy of a transdermal ureasil–polyether Annona muricata formulation — in vivoView study →}.

All of this is preclinical and uses leaf extracts rather than the leaf tea most people drink. Neither the responsible constituent nor a human dose has been established.

This is the best-replicated infectious-disease finding. An aqueous leaf extract suppressed Plasmodium berghei in infected mice by 38%, 75% and 86% at 100, 500 and 1,000 mg/kg, and prolonged survival ^{10Reference 10Somsak et al. · 2016AnimalIn vivo antimalarial activity of Annona muricata leaf extract in mice infected with Plasmodium berghei — animal modelView study →}.

An ethanol leaf extract and its fractions reduced Toxoplasma gondii in cells and in infected mice ^{11Reference 11Miranda et al. · 2021In vitroAnti-parasitic activity of Annona muricata L. leaf ethanolic extract and its fractions against Toxoplasma gondii — in vitro and in vivoView study →}. A leaf extract reduced adult worm and larval counts of Trichinella spiralis in mice, and worked best combined with half-dose albendazole ^{12Reference 12El-Wakil et al. · 2021AnimalEvaluation of Annona muricata (Graviola) leaves activity against experimental trichinellosis — animal modelView study →}.

The activity spans protozoa and worms, matching the plant’s traditional antiparasitic use. The responsible fraction has not been identified.

Gap: All work is in infected animals or in vitro; there is no human antiparasitic trial, and efficacy relative to established antimalarial/anthelmintic drugs is untested.

In anaesthetised normotensive rats, an aqueous leaf extract given intravenously lowered blood pressure in a dose-dependent way without changing heart rate. The effect was not blocked by atropine, mepyramine, propranolol or L-NAME, and the authors attributed it to calcium antagonism rather than muscarinic, histamine, adrenergic or nitric oxide pathways ^{13Reference 13Nwokocha et al. · 2012AnimalPossible mechanisms of the hypotensive effect of Annona muricata (soursop) in normotensive rats — animal modelView study →}.

A second rat study found that aqueous leaf extracts of A. muricata and avocado (Persea americana), alone and combined, lowered blood pressure in normal and hypertensive rats ^{14Reference 14Sokpe et al. · 2020AnimalHypotensive and antihypertensive properties and safety for use of Annona muricata and Persea americana — animal modelView study →}.

These findings match the leaf’s traditional use as a heart tonic.

Gap: No human blood-pressure data; combining graviola with antihypertensive or hypoglycemic drugs could produce additive effects that have not been characterized.

Graviola preparations lowered liver enzymes and improved liver tissue in rodent models. An extract reduced liver damage in type-2 diabetic mice ^{15Reference 15Son et al. · 2021AnimalAmeliorative effect of Annona muricata (Graviola) extract on hyperglycaemia-induced hepatic damage in STZ diabetic rats — animal modelView study →}, and a stem-bark ethanol extract lowered ALT and AST in rats given toxic doses of paracetamol ^{16Reference 16Masykur et al. · 2023AnimalEffect of ethanol extract of soursop (Annona muricata L.) stem bark on rat liver function — animal modelView study →}.

The studies use different plant parts and different injury models, so no single preparation or dose has been shown to protect the liver.

Leaf extracts scavenge free radicals in vitro and shift tissue antioxidant markers (SOD, catalase, glutathione and lipid peroxidation) in many animal studies ^{1Reference 1Moghadamtousi et al. · 2015ReviewAnnona muricata (Annonaceae): a review of its traditional uses, isolated acetogenins and biological activities — reviewView study →}. This activity contributes to the liver and blood-sugar findings.

Most polyphenol-rich plants score well on these assays, and no clinical antioxidant endpoint has been measured.

Leaf, bark and seed extracts inhibit a range of bacteria and fungi in vitro, including Candida and Aspergillus species ^{1Reference 1Moghadamtousi et al. · 2015ReviewAnnona muricata (Annonaceae): a review of its traditional uses, isolated acetogenins and biological activities — reviewView study →}. A few animal Candida models support the laboratory results.

The activity is measured at concentrations reached in a dish, not at levels shown in a living host, and there are no human infection trials.

A 2018 study gave a hydroalcoholic leaf extract to mice by injection. It was sedative at 25–100 mg/kg and anxiolytic and anticonvulsant at 100 mg/kg, and these effects were partly reversed by flumazenil, which blocks the benzodiazepine site of the GABA-A receptor. The extract also lowered dopamine and noradrenaline in the striatum ^{17Reference 17Souza et al. · 2018AnimalPhytochemical analysis and central (sedative/anticonvulsant) effects of Annona muricata Linnaeus in mice — animal modelView study →}.

A 1979 report had described sedative effects of soursop earlier ^{18Reference 18Bourne et al. · 1979A preliminary study of the sedative effects of Annona muricata (soursop) — animal studyView study →}.

Gap: No human sleep or anxiety data; the sedative constituent(s) and any safe dose are unknown, and chronic use raises the acetogenin-neurotoxicity concern.

Neurotoxicity. The acetogenins, with annonacin as the marker compound, are mitochondrial complex I inhibitors. Annonacin killed dopaminergic neurons in culture at very low concentrations ^{20Reference 20Lannuzel et al. · 2003In vitroThe mitochondrial complex I inhibitor annonacin is toxic to mesencephalic dopaminergic neurons by impairment of energy metabolism — in vitroView study →}. Given to rats by continuous intravenous infusion for 28 days, it reached the brain, lowered brain ATP by 44% and caused a loss of dopaminergic neurons in the substantia nigra and of neurons in the striatum ^{21Reference 21Champy et al. · 2004AnimalAnnonacin, a lipophilic inhibitor of mitochondrial complex I, induces nigral and striatal neurodegeneration in rats — animal modelView study →}.

Parkinsonism. Heavy consumption of Annonaceae fruit and leaf teas is associated with an atypical, treatment-resistant parkinsonism in Guadeloupe and the wider Caribbean ^{22,23Reference 22Lannuzel et al. · 2006ReviewIs atypical parkinsonism in the Caribbean caused by the consumption of Annonaceae? — reviewView study →Reference 23Cleret de Langavant et al. · 2022ObservationalAnnonaceae consumption worsens disease severity and cognitive deficits in degenerative parkinsonism — observationalView study →}. In 180 Caribbean patients with parkinsonism, even low lifelong fruit or juice intake, or any use of Annonaceae herbal tea, was linked to more severe disease and cognitive decline ^{23Reference 23Cleret de Langavant et al. · 2022ObservationalAnnonaceae consumption worsens disease severity and cognitive deficits in degenerative parkinsonism — observationalView study →}. A registered multicentre study found more severe motor and cognitive symptoms in Caribbean Parkinson’s patients, nearly all of whom had eaten Annonaceae fruit, than in patients from mainland France ^{24Reference 24Ribeyron et al. · 2026The clinical effect of Annonaceae fruit consumption on Caribbean Parkinson’s disease severity — clinical multicentre study (NCT03368300)View study →}.

Dose. An adult who eats one fruit or drinks one can of nectar a day is estimated to take in, over a year, the amount of annonacin that caused brain lesions in rats given the purified compound intravenously ^{19Reference 19Champy et al. · 2005Quantification of acetogenins in Annona muricata linked to atypical parkinsonism in GuadeloupeView study →}. This is the basis for avoiding regular, long-term consumption.

Other neurodegenerative disease. In human neurons, annonacin and another complex I inhibitor increased the 4-repeat form of tau, the form that accumulates in progressive supranuclear palsy ^{25Reference 25Bruch et al. · 2014In vitroMitochondrial complex I inhibition increases 4-repeat isoform tau by SRSF2 upregulation — in vitroView study →}. The concern therefore extends beyond Parkinson’s disease. Graviola is best avoided altogether by people with Parkinson’s or any other neurodegenerative disorder.

Blood sugar and blood pressure. Graviola lowers blood glucose and blood pressure in animals, so additive effects with diabetes and blood-pressure medicines are possible ^{13,15Reference 13Nwokocha et al. · 2012AnimalPossible mechanisms of the hypotensive effect of Annona muricata (soursop) in normotensive rats — animal modelView study →Reference 15Son et al. · 2021AnimalAmeliorative effect of Annona muricata (Graviola) extract on hyperglycaemia-induced hepatic damage in STZ diabetic rats — animal modelView study →}.

Interactions. No human drug-interaction study has been done, and no effect on a named CYP450 enzyme has been shown. The cautions above are based on pharmacology. No WHO, ESCOP or EMA monograph covers graviola.