Impact of Mānuka Honey on Symptoms and Quality of Life in Individuals with Functional Dyspepsia: a Feasibility Study Protocol. (Preprint)

Functional dyspepsia is a common gastrointestinal condition characterised by symptoms such as epigastric pain or burning, early satiety, or postprandial fullness, that negatively impacts quality of life, work productivity and healthcare costs. A lack of well-defined causes for the condition limits effective treatment options. Consumers around the world report using mānuka honey as a treatment for gastrointestinal symptoms, including dyspepsia, although clinical evidence supporting such use is limited. Pre-clinical studies indicate that unique compounds in mānuka honey may have bioactive properties that could prevent gastrointestinal inflammation. Recently, a 3,6,7 trimethyllumazine (Lepteridine™), a natural pteridine compound in mānuka honey, was shown to inhibit enzymes involved in gastrointestinal inflammation in in vitro studies. Therefore, Lepteridine™ standardised mānuka honey may deliver digestive health benefits. The aim of this feasibility study is to gather data required to estimate sample size and support study logistics to design future trials. The primary objective will be preliminary assessments of the impact of Lepteridine™ standardised mānuka honey on digestive symptom severity and quality of life in subjects with mild to moderate functional dyspepsia. Other feasibility objectives include assessing the biological responses to mānuka honey standardised to medium and high levels of Lepteridine™, and concentrations of mānuka honey-derived metabolites in blood and urine following consumption. This is a three-arm, parallel, controlled, double-blind, randomised feasibility study. Seventy-five healthy adults with symptoms of functional dyspepsia (Rome IV Criteria) and mild-to-moderate severity of dyspepsia (Short Form Leeds Dyspepsia Questionnaire) were recruited between October 2022 and September 2023. Participants were randomised into one of three groups: 1) mānuka honey standardised to contain 10 mg/kg Lepteridine™; 2) mānuka honey standardised to contain 40 mg/kg Lepteridine™; or 3) honey maple flavoured syrup control. After a two-week lead-in period, participants consumed 10 g of their respective intervention twice daily for six weeks. Throughout the study, participants completed daily bowel movement diaries and validated weekly questionnaires about their gastrointestinal symptoms and quality of life. Three-day diet records and stool samples were collected at baseline and end of the intervention. Blood samples were collected at baseline, weeks two and four, and at the end of the intervention. In addition, six healthy participants without symptoms of functional dyspepsia were recruited to undergo an acute five-hour assessment for the appearance of Lepteridine™ and related metabolites in plasma and urine following consumption of Lepteridine™ standardised mānuka honey. The study was approved by the Northern B Health and Disability Ethics Committee. At the time of writing, laboratory and data analyses are being undertaken. The results of the primary and secondary outcomes will be published in peer-reviewed journals. This study will provide essential information on the potential efficacy and suitability of Lepteridine™ standardised mānuka honey to design future clinical trials investigating the effect of Lepteridine™ standardised mānuka honey for the treatment of symptoms of functional dyspepsia. Australian New Zealand Clinical Trials Registry, Trial Number ACTRN12622001140741p