2 years of calorie restriction and cardiometabolic risk (CALERIE): exploratory outcomes of a multicentre, phase 2, randomised controlled trial.
Level 2 - randomized trial
Individual randomized controlled trial evaluating exploratory physiological endpoints.
PubMed 31303390 · doi:10.1016/S2213-8587(19)30151-2
What was done
In a phase 2 multicentre randomized controlled trial (CALERIE) across three US centres, 218 healthy non-obese men and women (aged 21–50 years, BMI 22.0–27.9 kg/m²) were randomized 2:1 to a prescribed 25% calorie restriction diet (n=143) or an ad libitum control diet (n=75) for 2 years. Exploratory cardiometabolic outcomes—including blood pressure, plasma lipid profiles, high-sensitivity C-reactive protein (hs-CRP), metabolic syndrome score, and oral glucose tolerance measures—were analyzed on an intention-to-treat basis.
What was found
The calorie restriction group achieved a mean 11.9% reduction in calorie intake (2467 kcal down to 2170 kcal) versus 0.8% in controls, resulting in a sustained mean weight loss of 7.5 kg (71% fat mass) versus a 0.1 kg gain in controls. Calorie restriction led to significant reductions relative to control over 2 years in LDL cholesterol (p<0.0001), total-to-HDL cholesterol ratio (p<0.0001), systolic blood pressure (p=0.0011), and diastolic blood pressure (p<0.0001). Significant improvements were also observed for hs-CRP (p=0.012), insulin sensitivity index (p<0.0001), and metabolic syndrome score (p<0.0001), remaining robust after adjusting for relative weight loss.
Why it matters
This trial demonstrates that sustained moderate calorie restriction is achievable and confers substantial, multi-system cardiometabolic improvements even in healthy, young-to-middle-aged non-obese adults already within normal clinical ranges.
Limits
Participants achieved only ~12% calorie reduction rather than the target 25%. Cardiometabolic measures were exploratory endpoints, and the trial evaluated surrogate biomarkers over 2 years rather than hard cardiovascular outcomes or mortality. Findings may not generalize to older, obese, or medically complex populations.
Cited by
- supports The CALERIE study was a two-year randomized controlled trial evaluating a 25% caloric restriction intervention in humans.