Piloting Novel Nutritional Interventions for Mechanistic Studies of Human Aging

TL;DR

This study tested adaptive versions of calorie restriction and time-restricted eating to see if they improve health and aging in humans.

Contribution

The study introduces adaptive versions of TRE and CR and evaluates their feasibility and effects on aging and healthspan.

Findings

Adaptive calorie restriction led to the greatest weight loss compared to control.

Adaptive interventions showed higher feasibility than traditional ones.

CR improved healthspan metrics more than TRE.

Abstract

Calorie restriction (CR) and time-restricted eating (TRE) have demonstrated efficacy for improving healthspan and biological age, yet long-term adherence remains problematic. Adaptive interventions may promote adherence in longer trials. This 24-week, parallel-arm, randomized controlled pilot trial compared adaptive and traditional versions of TRE and CR against a no-intervention control. Seventy (n = 70) healthy adults with body mass index 22.0-29.9 kg/m2 were randomized to one of five groups: control, traditional TRE with an 8-hour window, adaptive TRE, traditional CR targeting 25% energy restriction, or adaptive CR. The study aimed to examine intervention feasibility and effect sizes for primary aging and healthspan. Participants were 38±3 y (Mean+SD), 77% female, with mean BMI 26.0±2.6 kg/m2. The CR arms achieved 48% (traditional) and 77.6% (adaptive) of the CR target. TRE participants adhered to the 8-hour eating window on 74.5% (traditional) and 40.1% (adaptive) of days, respectively (86% adherence reflected the goal of following TRE 6 days per week). Weight change compared to control was greatest in adaptive CR (-8.8 kg, P < 0.001) followed by traditional CR (-5.8 kg, P < 0.001), traditional TRE (-2.3 kg, P = 0.05) and adaptive TRE (-1.4 kg, P = 0.15). Compared to control, biological age (Klemera-Doubal) effect sizes were modest over 24-weeks, with adaptive CR having the largest change (-1.8 y, P = 0.10; Cohen’s d = 0.24). Compared to control, healthspan (Metabolic Syndrome Score) improved in the CR arms (traditional -2.2, P < 0.01; adaptive -1.8, P = 0.02) but not in the TRE arms (traditional -0.6, P = 0.26; adaptive -0.7, P = 0.21). Intervention feasibility was highest in the adaptive groups.