The Healthy Diet and Lifestyle Study II

Summary

Intermittent energy restriction (IER) may have important advantages over daily energy restriction (DER) in producing sustained weight loss and reducing cancer risk. IER is already being promoted with limited evidence, thus, additional evidence is urgently needed from rigorously conducted clinical trials. IER has been proposed to invoke a greater metabolic shift to fat metabolism than DER and preferentially reduce central obesity. The Investigators adapted the IER and the Mediterranean diet (MED) approach which have been recommended as a healthy weight-loss diet in the management of non-alcoholic fatty liver disease, for an ethnically diverse population. The effectiveness was compared to an active comparator (DASH diet) in reducing overall and visceral adiposity in a randomized trial among 60 middle-aged adults with visceral obesity. This 12-week pilot demonstrated the feasibility and safety of IER and the culturally-adapted MED \[NCT03639350\]. The six-month randomized trial will demonstrate the superiority of IER over DER in reducing fat and total fat mass, and in improving cancer-related biomarkers and gut microbiome functions. This longer trial, to confirm safety and superiority of IER over DER in reducing VAT and liver fat will expand our understanding of adherence to IER and its effect on the gut microbiome as a possible mediator of systemic inflammation. The Investigators will conduct a 24-week randomized trial of IER+MED vs. MED/DER among 260 middle-aged adults of East-Asian, Native Hawaiian and other Pacific Islanders or White ethnicity with high VAT. The primary research question is whether a diet plan combining IER and the MED dietary pattern will be superior to MED/DER in reducing abdominal MRI-measured visceral and liver fat and dual-energy X-ray absorptiometry (DXA) measured total adiposity. The Healthy Diet and Lifestyle Study II (HDLS2) will 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 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. With an expected attrition rate of \~16% (10% in Pilot), the investigators expect 130 participants per group to complete the study.

Conditions

• Intra-Abdominal Fat

Interventions

BEHAVIORAL

IER+MED

Over a 6 month period follow a euenergetic Mediterranean diet 5 days per week and a 20% energy restriction over 2 contiguous days as a 70% energy restriction using the same macronutrient distribution of 45% carbohydrate, 25% energy from protein, and 30% energy from fat. For each participant a tailored diet plan is created based on sex, weight, height, and age. Complete a 1 hour walk five days per week.

BEHAVIORAL

MED/DER

Over a 6 month period follow a Mediterranean diet 7 days per week with a 20% energy restriction 7 days a week using the macronutrient distribution of 45% carbohydrate, 25% energy from protein, and 30% energy from fat. For each participant a tailored diet plan is created based on sex, weight, height, and age. Complete a 1 hour walk five days per week.

Sponsors & Collaborators

• National Institutes of Health (NIH)

  collaborator NIH

• University of Hawaii Cancer Research Center

  collaborator OTHER

• National Cancer Institute (NCI)

  collaborator NIH

• University of Hawaii

  lead OTHER

Principal Investigators

• Loic Le Marchand, MD, PhD · University of Hawaii Cancer Research Center

Study Design

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

TRIPLE

Model

PARALLEL

Eligibility

Min Age

35 Years

Max Age

69 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2022-01-20

Primary Completion

2026-09-30

Completion

2026-09-30

Countries

• United States

Study Locations