Effects of Intermittent Energy Restriction on Intra-Abdominal Fat and the Gut Microbiome: A Randomized Trial

Goal: This study proposes a 24-week randomized trial of intermittent energy restriction (IER) and the Mediterranean diet (MED), IER+MED, compared to daily energy restriction (MED/DER) among 260 middle-aged adults of East-Asian, Native Hawaiian and other Pacific Islanders or white ethnicity with high visceral fat (VAT) and liver fat.

1. To investigate whether a diet plan combining IER+MED will be superior to MED/DER in reducing abdominal visceral and liver fat and total adiposity among a multiethnic, at-risk, adult population. The Healthy Diet and Lifestyle Study II (HDLS2) plans to recruit 312 men and women from the general population with VAT at or above the population-median (men: ≥90 cm2; women ≥80 cm2) and randomize them to the IER+MED or MED/DER diet (156 per group). The IER+MED group will follow IER for two consecutive days (70% energy restriction) and a total energy MED diet for the other five days of the week, reaching an overall 20% energy restriction. The MED/DER group will be prescribed a 20% daily energy restriction. The expected attrition rate is ~16%, thus 130 participants per group are expected to complete the study.
2. To determine if the IER+MED compared to the MED/DER influences intermediate markers: cancer-related blood biomarkers and the gut microbial community structure and function.
3. To assess behavioral predictors of adherence to the prescribed IER+MED and DER/MED. To test modifications to psychosocial constructs being associated with adherence differently between IER+MED and MED/DER.

Design: The HDLS2 is a parallel, randomized, trial to compare the effects of two diets over 24-weeks: the IER+MED diet pattern vs. the MED/DER daily energy restriction diet pattern. For randomization, biostatisticians will prepare a blocked randomization schedule, stratified by men/women, the three ethnic groups, age <50 and 50+ y for men, menopausal status for women (based on any periods in the last 12 months), and two VAT groups (high, 80-150 cm2 or very high, ≥150 cm2). The randomization procedure will be conducted using opaque, sealed, sequentially numbered envelopes each containing assignment with equal probability to one of the two dietary interventions. The participants and measurement staff will be masked from the moniker of the assigned dietary intervention. The dietitians will coordinate and conduct the intervention activities using four face to face meetings (or an alterative if needed), and 12 remote meetings using phones or communication platforms (eg. Zoom). Every effort will be made for each participant to stay with the same dietitian. Enrollment of 156/study arm and completion of the intervention activities will take place over 3.5 years.

The research will be carried out in the University of Hawaii Cancer Center (UHCC) Translational Research Clinic, Nutrition Education Center, and Metabolic Kitchen, as well as the University of Hawaii (UH) Magnetic Resonance Imaging (MRI) Research Center. Each of these units have approved common guidelines addressing specific guidance for the coronavirus disease (COVID-19) screening of staff and research participants prior to the visit, upon arrival to the clinic, entry to the clinic, and post appointment guidelines.

Recruitment, clinic, and imaging staff will be blinded to randomization and intervention activities. Likewise, other than baseline demographic information, the intervention staff (dietitians) will be blinded to assessment measures of the study participants (with the exception of body weight, which is needed for the dietary prescriptions). Volunteers will be recruited among Oahu residents using advertising, media exposure, community and workplace presentations, and referrals from clinical partners. Main eligibility criteria were informed by the pilot study. Assuming a ~16% drop-out rate to yield 260 participants completing the 6-month intervention. The first recruits will start in October 2021, with the goal of recruiting 16 participants/month (except mid Nov through first week of Jan).