A 2-Year Randomized Controlled Trial of Human Caloric Restriction: Feasibility and Effects on Predictors of Health Span and Longevity.
Level 2 - randomized trial
Individual randomized controlled trial
PubMed 26187233 · doi:10.1093/gerona/glv057
What was done
A 2-year randomized controlled trial evaluated the feasibility, safety, and physiological effects of caloric restriction (CR) in 218 nonobese adults aged 21–51 years (mean baseline BMI 25.1 kg/m², range 21.9–28.0). Participants were randomized to an intervention designed to achieve 25% CR or to an ad libitum (AL) control diet. Primary endpoints were change from baseline resting metabolic rate adjusted for weight change (RMR residual) and core body temperature. Secondary endpoints were plasma triiodothyronine (T3) and tumor necrosis factor-α (TNF-α); exploratory physiological and psychological measures were also tracked.
What was found
Protocol completion was 82% in the CR group and 95% in the AL group. The CR group achieved 11.7 ± 0.7% restriction (mean ± SE) and maintained 10.4 ± 0.4% weight loss, whereas weight change in AL was negligible. RMR residual decreased significantly more in CR than AL at 12 months (p = .04) but not at 24 months. Core temperature change differed little between groups. T3 decreased significantly more in CR at month 12 and month 24 (p < .001), while TNF-α decreased significantly more in CR only at month 24 (p = .02). CR participants experienced greater decreases in cardiometabolic risk factors and weight-adjusted daily energy expenditure, without adverse effects on quality of life.
Why it matters
This study provides randomized evidence in humans that sustained, moderate caloric restriction (~12%) is feasible over two years and beneficially modifies physiological markers linked to longevity and cardiometabolic health.
Limits
The intervention achieved roughly half of its 25% CR target. The trial measured intermediate physiological and biomarker outcomes rather than direct disease incidence or longevity, and results from healthy, nonobese adults aged 21–51 may not generalize to older individuals or those with baseline metabolic disease.
Cited by
- supports The CALERIE trial showed that calorie restriction in humans improved health biomarkers with lasting effects, including on the epigenome.