Ombasa Laura, Miller Jody, Ware Lara, Abbotts-Holmes Holly, Tang Jeffry, Gasser Olivier, Fraser Karl, Bayer Simone, Kemp Roslyn, Costello Rory, Highton Andrew, Evans Jackie, Merry Troy, Schultz Michael, Frampton Chris, Gearry Richard, McNabb Warren, Roy Nicole
Department of Human Nutrition, University of Otago, Dunedin, New Zealand.
Riddet Institute, Massey University, Palmerston North, New Zealand.
JMIR Res Protoc. 2025 May 21;14:e66417. doi: 10.2196/66417.
Functional dyspepsia is a common gastrointestinal condition that reduces the quality of life and increases health care costs. The lack of well-defined causes limits effective treatments. Consumers report using mānuka honey to treat gastrointestinal symptoms, although clinical evidence supporting such use is limited. Preclinical studies suggest its unique bioactive compounds may reduce gastrointestinal inflammation. Recently, 3,6,7-trimethyllumazine (Lepteridine), a natural pteridine in mānuka honey, was shown to inhibit enzymes involved in gastrointestinal inflammation in in vitro studies. Therefore, Lepteridine-standardized mānuka honey may deliver digestive health benefits.
The aim of this feasibility study is to gather the 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-standardized mānuka honey on symptom severity and the quality of life in participants with mild-to-moderate functional dyspepsia. Other feasibility objectives include assessing the biological responses to mānuka honey standardized to medium and high levels of Lepteridine and measuring mānuka honey-derived metabolites in blood and urine.
This is a 3-arm, parallel, controlled, double-blind, randomized feasibility study. A total of 75 healthy adults with symptoms of functional dyspepsia (Rome IV criteria) and mild-to-moderate dyspepsia severity (Short Form Leeds Dyspepsia Questionnaire) were recruited between October 2022 and September 2023. Participants were randomized into one of three groups: (1) mānuka honey standardized to contain 10 mg/kg Lepteridine, (2) mānuka honey standardized to contain 40 mg/kg Lepteridine, or (3) honey maple flavored syrup control. After a 2-week lead-in period, participants consumed 10 g of allocated intervention twice daily for 6 weeks. Throughout the study, participants completed daily bowel movement diaries and validated weekly questionnaires about their gastrointestinal symptoms and quality of life. Stool samples and 3-day diet records were collected at baseline and the end of the intervention. Blood samples were collected at baseline, weeks 2 and 4, and at the end of the intervention. In addition, 6 healthy participants without symptoms of functional dyspepsia were recruited to undergo an acute 5-hour assessment for the appearance of Lepteridine and related metabolites in plasma and urine following consumption of Lepteridine-standardized mānuka honey. The study was approved by the Northern B Health and Disability Ethics Committee.
Initial analysis includes 68 participants, with laboratory and data analyses being undertaken as of March 2024. 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-standardized mānuka honey for designing future clinical trials investigating its effect in treating symptoms of functional dyspepsia.
Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12622001140741p; https://anzctr.org.au/Trial/Registration/TrialReview.aspx?id=384094.
INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/66417.
功能性消化不良是一种常见的胃肠道疾病，会降低生活质量并增加医疗保健成本。由于缺乏明确的病因，限制了有效的治疗方法。消费者报告称使用麦卢卡蜂蜜来治疗胃肠道症状，尽管支持这种用法的临床证据有限。临床前研究表明，其独特的生物活性化合物可能会减轻胃肠道炎症。最近，在体外研究中发现，麦卢卡蜂蜜中的天然蝶啶3,6,7-三甲基蝶嗪（Lepteridine）可抑制参与胃肠道炎症的酶。因此，标准化为含有Lepteridine的麦卢卡蜂蜜可能对消化健康有益。
本可行性研究的目的是收集估计样本量所需的数据，并为设计未来试验的研究后勤工作提供支持。主要目标将是对标准化为含有Lepteridine的麦卢卡蜂蜜对轻度至中度功能性消化不良参与者的症状严重程度和生活质量的影响进行初步评估。其他可行性目标包括评估对标准化为中等和高水平Lepteridine的麦卢卡蜂蜜的生物学反应，以及测量血液和尿液中源自麦卢卡蜂蜜的代谢物。
这是一项三臂、平行、对照、双盲、随机可行性研究。在2022年10月至2023年9月期间，共招募了75名有功能性消化不良症状（符合罗马IV标准）且消化不良严重程度为轻度至中度（利兹消化不良问卷简表）的健康成年人。参与者被随机分为三组之一：（1）标准化为含有10 mg/kg Lepteridine的麦卢卡蜂蜜，（2）标准化为含有40 mg/kg Lepteridine的麦卢卡蜂蜜，或（3）枫糖浆口味的蜂蜜对照。在为期2周的导入期后，参与者每天分两次食用10 g分配的干预物，持续6周。在整个研究过程中，参与者完成每日排便日记，并每周填写经过验证的关于其胃肠道症状和生活质量的问卷。在基线和干预结束时收集粪便样本和3天饮食记录。在基线、第2周和第4周以及干预结束时采集血样。此外，招募了6名没有功能性消化不良症状的健康参与者，在食用标准化为含有Lepteridine的麦卢卡蜂蜜后，对其血浆和尿液中Lepteridine及相关代谢物的出现情况进行5小时的急性评估。该研究已获得北B卫生与残疾伦理委员会的批准。
初步分析纳入了68名参与者，截至2024年3月正在进行实验室和数据分析。主要和次要结果将发表在同行评审期刊上。
本研究将为标准化为含有Lepteridine的麦卢卡蜂蜜在设计未来临床试验以研究其治疗功能性消化不良症状的效果方面的潜在疗效和适用性提供重要信息。
澳大利亚新西兰临床试验注册中心（ANZCTR）ACTRN12622001140741p；https://anzctr.org.au/Trial/Registration/TrialReview.aspx?id=384094。
国际注册报告标识符（IRRID）：DERR1-10.2196/66417。
