Caloric Restriction (CR) — Diets
Sustained reduction in caloric intake below ad libitum levels while maintaining adequate nutrition, the most robustly studied longevity intervention across species.
Overview
Caloric restriction (CR) involves a sustained 15-25% reduction in energy intake relative to ad libitum consumption while maintaining adequate micronutrient status. CR is the most consistently reproduced longevity intervention across model organisms from yeast to primates. The landmark CALERIE trial demonstrated that 2 years of ~12% CR in healthy non-obese adults improved cardiometabolic risk factors, reduced oxidative stress, and slowed biological aging as measured by the DunedinPACE epigenetic clock. CR activates conserved nutrient-sensing pathways including AMPK, sirtuins, and autophagy while suppressing mTOR and IGF-1 signaling.
Indications
- Longevity and biological age reduction
- Cardiometabolic risk factor improvement
- Insulin sensitivity optimization
- Oxidative stress reduction
- Weight management
Mechanism of Action
Reduced caloric intake lowers circulating glucose and amino acids, activating AMPK and inhibiting mTORC1
Dosing
| Compound | Dose | Frequency | Notes |
|---|---|---|---|
| Caloric Restriction | 10-15% below maintenance | Daily | Moderate CR; best supported by CALERIE trial data |
| Caloric Restriction | 20-25% below maintenance | Daily | Aggressive CR; greater metabolic effects but higher adherence difficulty |
Evidence Grade
GRADE A
Safety & Contraindications
- Risk of sarcopenia and bone density loss, especially in older adults
- May impair immune function if micronutrient intake is inadequate
- Contraindicated in underweight individuals, eating disorder history, pregnancy, and growing children
- Can reduce thyroid hormone levels and reproductive hormones
- Requires careful nutritional planning to avoid deficiencies