CALERIE — Caloric Restriction in Non-Obese Humans

Design

CALERIE (Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy) Phase 2 enrolled 218 non-obese (BMI 22–28) adults aged 21–50 and randomised 2:1 to ~25% caloric restriction or ad libitum control for 2 years.

Achieved CR averaged ~12% (less than the 25% target — sustaining strict restriction over 2 years is hard).

Findings

• Significant reductions in body weight (~10%), fat mass, blood pressure, total and LDL cholesterol, triglycerides.
• Improved insulin sensitivity and inflammatory markers.
• Slower rate of biological aging by DunedinPACE (Belsky 2023).
• Modest reduction in epigenetic-age acceleration by some clocks.
• Quality of life and mood maintained.
• Bone mineral density loss in lumbar spine (mostly attributable to weight loss).
• Modest decline in lean mass (relevant trade-off in older adults).

Why it matters

CALERIE is the only long-term RCT of caloric restriction in humans. It demonstrates that meaningful biological-age modification by lifestyle is detectable in 2 years, and that CR is tolerable in motivated non-obese adults.

Limitations

• Achieved restriction less than planned.
• Younger, mostly white, healthy cohort — not generalisable to older adults where CR may be harmful.
• No hard clinical endpoints (event rates) over 2 years.

Related entries

Caloric restriction, DunedinPACE, Daniel Belsky.