R01CA258179

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

Intermittent energy restriction (IER) has been suggested to have important advantages over daily energy restriction (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 visceral adipose tissue (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, SHBG, 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 effectiveness data for IER on lowering cancer-related risk factors and inform future translational and dissemination research to reduce cancer risk in various US populations.

University Of Hawaii

NOT APPLICABLE

93.393 - Cancer Cause and Prevention Research

National Cancer Institute (NCI) [HHS - NIH]

Honolulu, Hawaii 968135515 United States

Single Zip Code

Research Answers to National Cancer Institute's (NCI) Provocative Questions (R01 Clinical Trial Optional) (RFA-CA-20-004)

Amendment Since initial award the End Date has been extended from 08/31/26 to 08/31/27 and the total obligations have increased 396% from $1,104,814 to $5,478,236.