Unveiling the safety, tolerability, and herb-drug interaction concerns of Hibiscus Sabdariffa L. (Roselle): A systematic scoping review of current evidence

Background Hibiscus sabdariffa L. (Hs) is widely consumed worldwide for multiple health benefits. Despite its use, the overall safety profile of Hs as a therapeutic natural product is still not established. This review aims to collate evidence on the safety, tolerability, and herb-drug interactions of Hs, and establish safety levels for Hs-based products from human and animal studies. Methods A systematic search was conducted (PubMed, Web of Science, CENTRAL, Embaseand CINAHL) from inception to February 2024. Human interventional, animal toxicology,and herb-drug interaction studies were included. Spontaneous ADR reports were obtained from local and international pharmacovigilance databases. Articles were analysed on reporting of safety parameters and adverse outcomes. The CONSORT guideline for herbal intervention was used to evaluate the quality of included RCTs. Results A total of 51 clinical, 53 preclinical and 14 herb-drug interaction articles were included for descriptive analysis.Reports acquired from the WHO (n = 4) and MADRAC database (n = 16), involved polyherbal Hs preparations. Overall, Hs intervention was well tolerated in 25.5% (n = 13) of the clinical trials identified. The most frequent ADRs were mild and self-limiting gastrointestinal disturbances. The reporting quality of included RCTs (n = 30) was low to moderate. Preclinical studies reported on kidney (n = 3), liver (n = 2), developmental (n = 5), and reproductive (n = 5) toxicity findings. Hs interactions were clinically evident in altering plasma concentrations of certain drugs (e.g. chloroquine, acetaminophen), affecting bioavailability. Discussion/conclusions Our review suggests Hs extracts have a favourable safety profile in humans at doses below 32.3 mg/kg BW/day, and 500 mL/day of tea with concentrations below 30 g/L for up to 6 months. Insufficient evidence on longer duration of consumption still raises concern, as indicated by preclinical toxicity studies assessing the liver, kidneys, and male reproductive organs. Evidence of interactions with modern drugs should be strongly considered. Further validation in large, controlled clinical trials or safety cohort studies on standardised Hs preparations, and rigorous post-marketing surveillance are warranted.