Effects of 12 Months of Caloric Restriction on Muscle Mitochondrial Function in Healthy Individuals.

Context: The effects of caloric restriction (CR) on in vivo muscle mitochondrial function in humans are controversial. Objective: We evaluated muscle mitochondrial function and associated transcriptional profiles in nonobese humans after 12 months of CR. Design: Individuals from an ancillary study of the CALERIE 2 randomized controlled trial were assessed at baseline and 12 months after a 25% CR or ad libitum (control) diet. Setting: The study was performed at Pennington Biomedical Research Center in Baton Rouge, LA. Participants: Study participants included 51 (34 female subjects, 25 to 50 years of age) healthy nonobese individuals randomized to 1 of 2 groups (CR or control). Intervention: This study included 12 months of a 25% CR or ad libitum (control) diet. Main Outcomes: In vivo mitochondrial function [maximal ATP synthesis rate (ATPmax), ATPflux/O2 (P/O)] was determined by 31P-magnetic resonance spectroscopy and optical spectroscopy, and body composition was determined by dual-energy X-ray absorptiometry. In a subset of individuals, a muscle biopsy was performed for transcriptional profiling via quantitative reverse transcription polymerase chain reaction and microarrays. Results: Weight, body mass index (BMI), fat, and fat-free mass (P < 0.001 for all) significantly decreased at month 12 after CR vs control. 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. A subgroup analysis according to baseline P/O demonstrated that a higher (vs lower) P/O was associated with notable improvements in ATPmax and P/O after CR. Conclusions: In healthy nonobese humans, CR has no effect on muscle mitochondrial function; however, having a "more coupled" (versus "less coupled") phenotype enables CR-induced improvements in muscle mitochondrial function.