Efficacy of a Culturally-adapted Mediterranean Diet Intervention on Depression in Relation to the Gut Microbiome

Efficacy of a Culturally-adapted Mediterranean Diet Intervention on Depression in Relation to the Gut Microbiome: A Randomised Controlled Trial Using the Experience Sampling Methodology

The objective of this study is to investigate the efficacy of a culturally-adapted Mediterranean diet, in accordance with clinical guidelines and research evidence, in reducing depressive symptoms among Hong Kong Chinese adults. Additionally, this study will also explore the potential underlying role of the gut microbiome in the relationship between the Mediterranean diet and depression. This study serves as a pioneering attempt to examine the efficacy and intervention acceptability of a culturally-adapted Mediterranean diet in managing depressive symptoms.

Several studies have demonstrated the relationship between diet and mood, while existing studies suggest that consistently adhering to the Mediterranean diet may yield a more pronounced antidepressant effect. Considering that depression is often associated with low motivation, dietary interventions that require active participation may encounter implementation challenges and potentially impact the adherence rate. To address this issue, our study proposes using ecological momentary assessment (EMA), which involves sending frequent reminders to participants, allowing us to examine diet quality and adherence as well as changes in depressive symptoms at various time points. This approach also minimizes potential recall bias and enhances data collection accuracy. If the hypothesis is supported, dietary intervention could emerge as a promising therapeutic strategy for alleviating depressive symptoms. Furthermore, this study could provide insights into the role of the gut microbiome as a potential underlying mechanism between diet and depressive symptoms. The findings could have significant implications for clinical practice.

Study Overview

• Status: Not yet recruiting
• Conditions: Depression
• Intervention / Treatment: Dietary supplement: Mediterranean Diet

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Hong Kong
  • Shatin, Hong Kong
    • The Chinese University of Hong Kong

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Hong Kong residents aged 18-65 years;
2. Able to read Chinese and type in Chinese or English;
3. Have a Patient Health Questionnaire-9 (PHQ-9) score of 10 or higher, indicating at least a moderate level of depressive symptoms;
4. Meet the Diagnostic and Statistical Manual of Mental Disorders (DSM) diagnostic criteria for current MDD according to the Mini International Neuropsychiatric Interview (MINI);
5. Have a Mediterranean Diet Index (KIDMED 2.0) score less than 3, indicating very-low-quality diet;
6. Possess an Internet-enabled iOS- or Android-operated mobile device; and
7. Willing to provide informed consent and comply with the trial protocol.

Exclusion Criteria:

1. The presence of other current psychiatric disorders as assessed by the MINI (bipolar disorder, posttraumatic stress disorder, personality disorders, eating disorders, psychotic disorders, or substance abuse disorder);
2. Have a medical condition or neurocognitive disorder that may prevent dietary changes as recommended by physicians or dietitians;
3. Current serious suicidal risk (non-fleeting intent or plan) as assessed by a PHQ-9 Item 9 score >2 (referral information to professional mental health services will be provided);
4. Involvement in dietary changes (self-initiated/supervised by professionals) in the past 2 weeks;
5. Involvement in any psychological treatment specifically for depression in the past 6 months;
6. A change in medication within 2 weeks prior to the baseline assessment/during the study;
7. Pregnancy and hospitalization;
8. Current participation in any other trial(s); and
9. Unwilling to change their diet if being allocated to the MediDiet group or food allergies or intolerances preventing diet adherence (specifically allergies to seafood, soy, nuts, yogurt, or dairy products).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Mediterranean diet (MediDiet) group; Participants in MediDiet group will receive a culturally adapted Mediterranean diet prepared by the research team on a daily basis. This diet is designed by a certified dietitian based on clinical guidelines and research evidence. Participants will follow the intervention for a duration of four consecutive weeks.	Dietary supplement: Mediterranean Diet; This group will adhere to the meals (meal delivery, excluding weekends and holidays) prepared by the research team and report their mood and diet quality and adherence using EMA with push notifications four times a day. In addition, photographic food records will also be used to record planned or unplanned meals or snacks. Pre-recorded sessions covering topics such as general dietetic advice, nutrition education on the Mediterranean diet and food components, SMART goal setting will be provided to the participants before the initiation of the MediDiet intervention. Moreover, a brief weekly phone call will be conducted to assess participant adherence, provide encouragement, and address any issues or challenges that may arise.
No Intervention: Care-as-usual (CAU) group; Participants in the CAU group will be instructed to maintain their usual dietary habits throughout the study period and will not receive any specially prepared Mediterranean diet from the research team. In addition, they will have access to care based on their needs and preferences, such as pharmacological interventions, psychological interventions, and complementary and alternative medicine. An intervention tracking log will be used to monitor the care the participants received to prevent violations of the study protocol. The CAU group will be given lifestyle-based self-help materials after the completion of follow-up assessments.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the Patient Health Questionnaire-9 (PHQ-9)	The PHQ-9 is a 9-item questionnaire used for screening, diagnosing, monitoring and measuring the severity of depression, which scores each of the nine DSM-IV criteria from "0" (not at all) to "3" (nearly every day).	Baseline, immediate post-intervention, and 12-week follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the Generalized Anxiety Disorder 7-item Scale (GAD-7)	The GAD-7, a 7-item self-report questionnaire, was used to measure generalized anxiety symptoms. Each item is rated on a 4-point Likert scale, with response categories ranging from 'not at all' (0) to 'nearly every day' (3). The total score is the sum of the 7 items, with a range of 0 to 21.	Baseline, immediate post-intervention, and 12-week follow-up
Change in the adapted version of the Modified Mediterranean Diet Score (ModiMedDiet Score)	The ModiMedDiet Score is a 12-item criterion-based diet quality index ranging from 0-120, with higher scores indicating greater adherence to the Mediterranean diet pattern promoted in the SMILES dietary intervention trial. It assesses intake of 12 food groups based on recommended intakes. Scores were calculated for both intervention and control groups to measure compliance and dietary changes over time. An adherence level of ≥55.62 was defined as highest, and ≤33.65 as lowest. Extras intake (sweets, processed foods, fast food, sugary drinks) was also reported separately due to their less healthy profiles. An adapted version will be designed based on the original ModiMedDiet to reflect the food groups delivered to the MediDiet group in the current study.	Baseline, immediate post-intervention, and 12-week follow-up
Change in the Seven-day Food Record (7dFR)	The 7dFR is a self-reported record of all foods and beverages consumed over a consecutive 7-day period. Participants record descriptions of food/drink items, amounts consumed, brands, preparation methods and portion sizes for every eating occasion over the 7 days. Intakes are then analyzed using nutrition software to derive daily nutrient intakes.	Baseline, immediate post-intervention, and 12-week follow-up
Change in the International Physical Activities Questionnaire-Chinese version (IPAQ-C)	The IPAQ-C is a 5-item self-report tool that measures time spent sitting, walking, in moderate activity, and vigorous exercise in the last 7 days. Responses are converted to minutes and reported as a continuous metabolic equivalent task (MET) minutes per week variable, with the exception of sitting time reported in hours. MET is a quantitative indicator of energy expenditure, with walking assigned 3.3 METs, moderate activity 4 METs, and vigorous activity 8 METs. A total physical activity score is calculated as the sum of walking and moderate to vigorous exercise MET-minutes. Higher total scores represent greater physical activity levels.	Baseline, immediate post-intervention, and 12-week follow-up
Change in the Short Form (Six-Dimension) Health Survey (SF-6D)	HRQoL will be evaluated using the Short Form (Six-Dimension) Health Survey (SF-6D; Lam et al., 2008). The participants select the levels (up to 4 or 6 levels) that best describe their physical functioning, role limitation, social functioning, bodily pain, mental health, and vitality. A preference-based single index measure is calculated by adding the scores of the 6 dimensions using a scoring algorithm. The total SF-6D score ranges from 0.315 (the worst HRQoL) to 1 (full health).	Baseline, immediate post-intervention, and 12-week follow-up
Change in the Sheehan Disability Scale (SDS)	SDS is a brief, 5-item self-report tool that assesses functional impairment in work/school, social life, and family life.	Baseline, immediate post-intervention, and 12-week follow-up
Change in the Treatment Acceptability Scale (TAS)	TAS is a 15-item self-report measure used to assess parents' and caregivers' acceptability and willingness to implement a proposed treatment for their child. Respondents rate their level of agreement with statements about the treatment on a 7-point Likert scale ranging from 1 (strongly disagree) to 7 (strongly agree). Example items address the treatment's effectiveness, appropriateness, risks, and consent requirements. Scores are summed with higher total scores indicating greater treatment acceptability. The TAS provides a standardized tool for clinicians to evaluate parents' perceptions of interventions as part of the treatment selection process.	Baseline and immediate post-intervention
Change in the Credibility-Expectancy Questionnaire (CEQ)	The 6-item CEQ yielded ratings of treatment credibility, acceptability/satisfaction, and expectations for success.	Baseline and immediate post-intervention
Change in the Insomnia Severity Index (ISI)	The ISI is a 7-item scale designed to evaluate perceived insomnia severity. Ratings on the 5-point Likert scale are obtained on the perceived severity of sleep-onset, sleep-maintenance, early morning awakening problems, satisfaction with current sleep pattern, interference with daily functioning, noticeable of impairment attributed to the sleep problem, and level of distress caused by the sleep problem.	Baseline, immediate post-intervention, and 12-week follow-up
Change in gut microbiome	Fresh stool samples will be collected by participants using the gut microbiome test kit developed by BioMed Technology, Hong Kong.	Baseline and immediate post-intervention
Self-developed Survey	The self-developed survey will collect basic demographic information such as age, gender, level of education, occupation, relationship status, height, weight, waist circumference, and body mass index (BMI).	Baseline

Collaborators and Investigators

• Sponsor: Chinese University of Hong Kong

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2026
• Primary Completion (Estimated): February 28, 2027
• Study Completion (Estimated): June 30, 2027

Study Registration Dates

• First Submitted: February 24, 2026
• First Submitted That Met QC Criteria: February 24, 2026
• First Posted (Actual): March 2, 2026

Study Record Updates

• Last Update Posted (Actual): March 3, 2026
• Last Update Submitted That Met QC Criteria: March 1, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Depression; Randomised controlled trial; Mediterranean diet; Ecological momentary assessment; The Microbiota-Gut-Brain Axis
• Additional Relevant MeSH Terms: Behavioral Symptoms; Behavior; Depression; Therapeutics; Diet, Food, and Nutrition; Physiological Phenomena; Nutritional Physiological Phenomena; Diet, Plant-Based; Diet Therapy; Nutrition Therapy; Diet; Diet, Mediterranean
• Other Study ID Numbers: PSY035

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No