Objectives
Annona muricata, also known as graviola, soursop and guanabana, has been widely utilised for the treatment of a range of cancers. The mechanism of action and the efficacy of A. muricata and its constituents in the treatment of cancer have been comprehensively reviewed. The aim of this systematic review was to summarise the available literature that reports on factors related to the safety and tolerability of A. muricata leaf extract and its acetogenins.
Methods
In‐vitro, preclinical animal studies and human studies of any design written in any language were included. Studies that evaluated A. muricata leaf extract and its constituents were searched through the databases Pubmed, Medline and Embase from inception to April 2019. The elaborated item 4 of Consolidated Standards of Reporting Trials statement and Animals in Research: Reporting In vivo Experiments guidelines were used to evaluate the quality of the studies.
Key findings
The results suggest that A. muricata and its constituents have hepatoprotective, neurotoxic, antinociceptive, anti‐ulcerative and chemopreventive effects. The dose and duration used in animal studies demonstrating toxicity may not directly translate into the effects in humans. Studies included in this review were judged to be of medium to high quality.
Conclusions
The overall outcome of the current review suggests that A. muricata has a favourable safety and tolerability profile. Future studies investigating its use in people diagnosed with a range of cancers are warranted.
Natural products, also referred to as dietary supplements, complementary and alternative medicines, and health or food supplements are widely used by people living with cancer. These products are predominantly self-selected and taken concurrently with cancer treatments with the intention of improving quality of life, immune function and reducing cancer symptoms and treatment side effects. Concerns have been raised that concurrent use may lead to interactions resulting in adverse effects and unintended treatment outcomes. This review provides an overview of the mechanisms by which these interactions can occur and the current evidence about specific clinically important natural product–drug interactions. Clinical studies investigating pharmacokinetic interactions provide evidence that negative treatment outcomes may occur when Hypericum perforatum, Grapefruit, Schisandra sphenanthera, Curcuma longa or Hydrastis canadensis are taken concurrently with common cancer treatments. Conversely, pharmacodynamic interactions between Hangeshashinto (TJ-14) and some cancer treatments have been shown to reduce the side effects of diarrhoea and oral mucositis. In summary, research in this area is limited and requires further investigation.
Background: Annona muricata, also known as graviola, soursop and guanabana is a herbal product used by people living with cancer. Anecdotal clinical evidence suggests this herb has potential anti-cancer activity. There are numerous pre-clinical studies detailing Annona muricata’s main bioactive constituents. To date, clinical studies evaluating the efficacy, safety and tolerability are limited. This study aims to investigate the safety and tolerability of Annona muricata leaf in people living with advanced malignancy.
Methods: This open label pilot study will involve people living with stage III and IV cancers of any type, who are not undergoing chemotherapeutic treatment. The primary outcome is safety and tolerability of an Annona muricata leaf product in this population assessed by participants’ self-reporting of adverse effects experienced and the proportion of participants completing the study. Secondary outcomes include biomarkers of inflammation and immune function, disease status and self-reported quality of life scores. Participants (n = 24) will be allocated to one of two groups for 12 weeks. Participants will commence at different timepoints and be assigned to either 530 mg or 1060 mg of Annona muricata daily. The study has been approved by the Human Research Ethics Committee Bellberry (2022-04-420) and will be conducted in compliance with the SPIRIT statement.
Discussion: The results of this study will provide safety and tolerability data for clinicians involved in the care of people living with cancer who choose to use Annona muricata products as an integrative approach to their healthcare. The results of this study will inform further research about the potential role of Annona muricata in cancer.
Trial registration: This study has been registered with the Australian New Zealand Clinical Trials Register (ACTRN 12622001288718)
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