Abstract
Functional dyspepsia (FD) is a chronic upper gastrointestinal disorder marked by abdominal symptoms without a structural cause. It includes two subtypes: epigastric pain syndrome (EPS) and postprandial distress syndrome (PDS). FD affects up to 30% of adults worldwide, impairs quality of life (QoL), yet effective treatment options are limited, leaving many seeking alternative treatments. Mānuka honey has unique bioactive compounds, such as Lepteridine™(1), that may improve digestive symptoms. While used anecdotally for managing digestive disorders, its efficacy in FD has not been studied clinically. Seventy-five adults with mild-moderate symptoms of FD participated in a three-arm, randomised controlled feasibility trial. Participants consumed 10g of mānuka honey containing 10 (L10) or 25 (L25) mg/kg of Lepteridine™, or a honey-flavoured maple syrup control, twice daily for six weeks. Primary feasibility outcomes examined the initial effect of Lepteridine™ standardised mānuka honey on FD symptoms and QoL using the Nepean Dyspepsia Index (NDI)(2). Secondary outcomes included examining changes in Patient-Reported Outcomes Management Information System (PROMIS) scores for gastrointestinal symptoms, anxiety, and depression. Differences in changes in NDI and PROMIS scores between intervention groups were examined using general linear models that included baseline values. Prespecified subgroup analyses were performed in participants with EPS or PDS, using linear models that included main effect (with/without subtype), interaction term (treatment*subtype) and baseline values. Post-hoc pairwise comparisons were conducted to assess the effects of each intervention. After six weeks, compared with the control, FD symptom scores decreased by -7.01 (95%CI: -19.74, 5.72, p=0.275) and -7.04 (95%CI: -19.60, 5.51, p=0.267) points in L10 and L25 groups, respectively (overall treatment p=0.438). QoL scores increased by 3.72 (95%CI: -3.42, 10.85, p=0.302) and 2.01 (95%CI: -4.97, 8.99, p=0.568) points in L10 and L25 groups, respectively compared with the control (overall treatment p=0.586). There was a suggestion that participants with EPS had a greater treatment response in symptom scores (interaction p=0.062) and QoL scores (interaction p=0.036) than those without EPS. In participants with EPS, symptom scores decreased by -12.29 (-26.09, 1.51; p=0.080) and -16.99 (-31.09, -2.90, p=0.019) points and QoL scores increased by 7.99 (-0.12, 16.10; p=0.053) and 8.30 (0.65, 15.95, p=0.034) in L10 and L25 groups, respectively, compared to control. No significant differences were observed in PROMIS scores at week six (p>0.05). Although this feasibility study showed no statistically significant improvements in overall FD symptoms or QoL with Lepteridine™ standardised mānuka honey in the overall FD cohort, the confidence intervals of the differences in symptom severity include potentially clinically meaningful benefits. Subtype analyses suggest Lepteridine™ standardised mānuka honey may improve symptoms and QoL in participants with EPS subtype of FD. These feasibility data will support the design of future randomised controlled trials.