Effects of 12 Months of Caloric Restriction on Muscle Mitochondrial Function in Healthy Individuals.
Level 2 - randomized trial
Individual randomized controlled trial
PubMed 27778643 · doi:10.1210/jc.2016-3211
What was done
An ancillary study of the CALERIE 2 randomized controlled trial evaluated 51 healthy, nonobese adults (34 females, aged 25 to 50 years) randomized to 12 months of 25% caloric restriction (CR) or an ad libitum control diet. In vivo muscle mitochondrial function—maximal ATP synthesis rate (ATPmax) and ATPflux/O2 (P/O)—was measured at baseline and 12 months using 31P-magnetic resonance spectroscopy and optical spectroscopy. Body composition was assessed by dual-energy X-ray absorptiometry. A subset of participants underwent muscle biopsies for targeted transcriptional profiling via quantitative RT-PCR and microarrays.
What was found
Weight, body mass index, fat mass, and fat-free mass significantly decreased at month 12 in the CR group compared with controls (P < 0.001 for all; exact numerical values not reported in abstract). Overall in vivo ATPmax and P/O were unaffected by 12 months of CR. Targeted transcriptional profiling showed no effects on pathways involved in mitochondrial biogenesis, function, or oxidative stress. In a subgroup analysis based on baseline coupling efficiency, higher baseline P/O was associated with notable improvements in ATPmax and P/O after CR compared to lower baseline P/O.
Why it matters
This trial demonstrates that sustained 25% caloric restriction in healthy, nonobese humans does not broadly enhance skeletal muscle mitochondrial function or biogenesis, challenging extrapolations from rodent models.
Limits
The sample size is relatively small (51 participants total), and muscle biopsy transcriptional data were restricted to a subset of unknown size. Specific effect sizes, point estimates, and confidence intervals are omitted from the abstract. Findings regarding the 'more coupled' baseline phenotype rely on subgroup analysis.
Cited by
- contradicts Eating 15% fewer calories has been shown in multiple randomized trials to have a major impact on boosting mitochondrial health.