Calorie restriction increases muscle mitochondrial biogenesis in healthy humans.
Level 2 - randomized trial
Individual randomized controlled trial
PubMed 17341128 · doi:10.1371/journal.pmed.0040076
What was done
Thirty-six young, overweight adults (mean age 36.8 ± 1.0 years, BMI 27.8 ± 0.7 kg/m²) were randomized to one of three 6-month interventions: Control (100% of energy requirements), CR (25% caloric restriction), or CREX (12.5% caloric restriction plus 12.5% increased energy expenditure via exercise). Investigators measured adjusted 24-hour energy expenditure, skeletal muscle mitochondrial gene expression, mitochondrial DNA content, mitochondrial enzyme activities, and DNA damage, alongside an in vitro study in primary human myotubes.
What was found
Adjusted 24-hour energy expenditure decreased in CR (-135 ± 42 kcal/d, p = 0.002) and CREX (-117 ± 52 kcal/d, p = 0.008), with no change in controls. Expression of genes involved in mitochondrial function (PPARGC1A, TFAM, eNOS, SIRT1, and PARL) increased in both CR and CREX (all p < 0.05). Muscle mitochondrial DNA content increased by 35% ± 5% in CR (p = 0.005) and 21% ± 4% in CREX (p < 0.004), while remaining unchanged in controls (2% ± 2%). Mitochondrial enzyme activities (citrate synthase, beta-hydroxyacyl-CoA dehydrogenase, cytochrome C oxidase II) were unchanged. DNA damage fell in CR (-0.56 ± 0.11 arbitrary units, p = 0.003) and CREX (-0.45 ± 0.12 arbitrary units, p = 0.011), but not in controls.
Why it matters
This study provides randomized evidence in humans that caloric restriction induces muscle mitochondrial biogenesis and decreases DNA damage, supporting mechanisms of metabolic adaptation previously seen mainly in animal models.
Limits
The sample size is small (n = 36 across three arms) and limited to young overweight adults over 6 months. Key mitochondrial enzyme activities did not increase despite higher mitochondrial DNA content, and clinical or lifespan endpoints were not evaluated.
Cited by
- supports Eating 15% fewer calories has been shown in multiple randomized trials to have a major impact on boosting mitochondrial health.