Caloric restriction: what CALERIE showed in humans, and what it costs

What it means

Caloric restriction (CR) means eating 10–30% fewer calories than needed to maintain weight, indefinitely, while keeping protein, vitamins and minerals adequate. It is distinct from time-restricted eating (which restricts when) and from dieting to a target (which ends). The proposed mechanisms run through lower mTOR and IGF-1, higher AMPK and sirtuin activity, and more autophagy.

In the lab, 20–40% restriction extends rodent lifespan by up to 50%; in rhesus monkeys the two long-running studies disagreed on lifespan but agreed on less disease.

Why it matters for longevity

CR is the reason longevity biology exists as a field: it proved that ageing is modifiable. For humans the practical question is how much of the benefit comes from leanness and low insulin — obtainable without hunger — and how much from restriction itself, with its costs in muscle, bone, libido and cold tolerance.

What the evidence says

CALERIE 2 (Ravussin 2015, Kraus 2019): 218 healthy non-obese adults randomised to 25% CR or usual diet for two years. The CR group achieved about 12% restriction and lost 7.5 kg; they improved blood pressure, LDL, insulin sensitivity and hs-CRP, slowed DunedinPACE by 2–3%, and lowered core temperature and metabolic rate. They also lost lean mass and bone density, and about a third of the intended restriction proved unachievable.

The Wisconsin monkey study (Colman 2009, 2014) found longer lifespan and less disease on CR; the NIA study (Mattison 2012) found less disease but no lifespan gain — the control monkeys were already eating a healthier diet, which suggests avoiding overfeeding captures much of the benefit.

How to measure or use it

• The humane version: a modest energy deficit until body fat and HOMA-IR are in range, then maintenance at a lean weight — most of CALERIE's marker improvements, without the bone and muscle cost.
• Protein at 1.6 g/kg and resistance training are non-negotiable during any restriction; a DEXA every six months tracks lean mass and bone.
• The markers CALERIE moved — blood pressure, LDL/ApoB, fasting insulin, hs-CRP — are the ones to watch.

Related

• Fasting and time-restricted eating — CR in context with the other patterns
• Biomarkers of ageing — the markers CALERIE tracked
• Muscle mass and ageing — the cost side