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

> **NIH NIH R01** · UNIVERSITY OF HAWAII AT MANOA · 2022 · $1,110,521

## Abstract

PROJECT SUMMARY/ABSTRACT
Intermittent energy restriction (IER) has been suggested to have important advantages over daily ER (DER) in
producing sustained weight loss and reducing cancer risk. While IER is already being promoted in the general
population to improve health and longevity, supportive evidence is urgently needed from rigorously conducted
randomized trials. We propose a six-month randomized trial to demonstrate the superiority of IER over DER in
reducing ectopic fat and total fat mass, and in improving cancer-related biomarkers and gut microbiome
functions. Our previous work strongly suggests that ectopic fat, independently of total adiposity, plays an
important role in the etiology of, and in the racial/ethnic disparities in, obesity-related cancers. We reported
striking racial/ethnic differences in the strength of the association between body mass index (BMI) and risk of
obesity-related cancers in the Multiethnic Cohort (MEC). We observed corresponding disparities in the
propensity to accumulate visceral and liver fat among the same five ethnic groups in a recent MRI-based study
and demonstrated an independent association of a robust biomarker-based visceral fat score with incident breast
cancer in MEC. Additionally, we adapted an IER protocol combined with a Mediterranean dietary pattern
(IER+MED) and demonstrated its feasibility, safety and greater efficacy over an active comparator (a heart-
healthy DER approach) in reducing total and ectopic adiposity and improving beneficial gut microbiome functions
in a 12-week randomized trial among 60 middle-aged adults of various Asian ethnicities with visceral obesity.
We now propose the Healthy Diet and Lifestyle Study II, a 24-week randomized trial of IER+MED vs. MED/DER
among 260 middle-aged Oahu adults of East-Asian, Pacific Islander or white ethnicity with VAT greater than the
population median. The intervention will be delivered through 16 focused and customized consultations with
research dietitians and will consist of an IER+MED (IER is 70% energy restriction on two consecutive days and
a euenergetic MED diet for the other five days of the week) or the MED with a 20% daily energy restriction
(MED/DER). Dietitians will monitor dietary compliance using the mobile food record (mFR) and compliance to a
common physical activity recommendation using interviews and actigraphy throughout the intervention. We will
compare IER+MED vs. MED/DER for reduction in MRI-measured visceral and liver fat and DXA-measured total
adiposity (Aim 1) and for improvement in cancer-related biomarkers (IGF-1, IGFBP3, insulin, HOMA-IR, leptin,
adiponectin, S HBG, hsCRP) and fecal metagenomic markers of microbial metabolite production (Aim 2). We
will also investigate behavioral predictors of adherence to the prescribed IER, including psychosocial measures
of self-efficacy and outcome expectancies, and dietary patterns based on timing and frequency of eating
episodes (Aim 3). This study will provide robust effect...

## Key facts

- **NIH application ID:** 10492506
- **Project number:** 5R01CA258179-02
- **Recipient organization:** UNIVERSITY OF HAWAII AT MANOA
- **Principal Investigator:** LOIC LE MARCHAND
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $1,110,521
- **Award type:** 5
- **Project period:** 2021-09-22 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10492506

## Citation

> US National Institutes of Health, RePORTER application 10492506, Effects of Intermittent Energy Restriction on Intra-Abdominal Fat and the Gut Microbiome: A Randomized Trial (5R01CA258179-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10492506. Licensed CC0.

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