Effect of 6-Month Calorie Restriction on Biomarkers of Longevity, Metabolic Adaptation, and Oxidative Stress in Overweight Individuals

TLDR

Calorie restriction extends lifespan in rodents, but its impact on human longevity biomarkers and metabolic rate remains unstudied and requires longer trials. This study aimed to evaluate the effects of six months of calorie restriction, with or without exercise, on longevity and metabolic biomarkers in overweight adults. Forty‑eight sedentary overweight adults were randomized into four 6‑month interventions—weight‑maintenance diet, 25% calorie restriction, 25% restriction plus exercise, or very low‑calorie diet—and assessed for body composition, metabolic hormones, oxidative stress markers, energy expenditure, and core temperature. Six months of calorie restriction lowered fasting insulin and core body temperature, reduced DNA damage, and decreased energy expenditure beyond what would be expected from weight loss, indicating that CR improves two longevity biomarkers and lowers metabolic rate in overweight adults.

Abstract

ContextProlonged calorie restriction increases life span in rodents. Whether prolonged calorie restriction affects biomarkers of longevity or markers of oxidative stress, or reduces metabolic rate beyond that expected from reduced metabolic mass, has not been investigated in humans.ObjectiveTo examine the effects of 6 months of calorie restriction, with or without exercise, in overweight, nonobese (body mass index, 25 to <30) men and women.Design, Setting, and ParticipantsRandomized controlled trial of healthy, sedentary men and women (N = 48) conducted between March 2002 and August 2004 at a research center in Baton Rouge, La.InterventionParticipants were randomized to 1 of 4 groups for 6 months: control (weight maintenance diet); calorie restriction (25% calorie restriction of baseline energy requirements); calorie restriction with exercise (12.5% calorie restriction plus 12.5% increase in energy expenditure by structured exercise); very low-calorie diet (890 kcal/d until 15% weight reduction, followed by a weight maintenance diet).Main Outcome MeasuresBody composition; dehydroepiandrosterone sulfate (DHEAS), glucose, and insulin levels; protein carbonyls; DNA damage; 24-hour energy expenditure; and core body temperature.ResultsMean (SEM) weight change at 6 months in the 4 groups was as follows: controls, −1.0% (1.1%); calorie restriction, −10.4% (0.9%); calorie restriction with exercise, −10.0% (0.8%); and very low-calorie diet, −13.9% (0.7%). At 6 months, fasting insulin levels were significantly reduced from baseline in the intervention groups (all P<.01), whereas DHEAS and glucose levels were unchanged. Core body temperature was reduced in the calorie restriction and calorie restriction with exercise groups (both P<.05). After adjustment for changes in body composition, sedentary 24-hour energy expenditure was unchanged in controls, but decreased in the calorie restriction (−135 kcal/d [42 kcal/d]), calorie restriction with exercise (−117 kcal/d [52 kcal/d]), and very low-calorie diet (−125 kcal/d [35 kcal/d]) groups (all P<.008). These “metabolic adaptations” (~ 6% more than expected based on loss of metabolic mass) were statistically different from controls (P<.05). Protein carbonyl concentrations were not changed from baseline to month 6 in any group, whereas DNA damage was also reduced from baseline in all intervention groups (P <.005).ConclusionsOur findings suggest that 2 biomarkers of longevity (fasting insulin level and body temperature) are decreased by prolonged calorie restriction in humans and support the theory that metabolic rate is reduced beyond the level expected from reduced metabolic body mass. Studies of longer duration are required to determine if calorie restriction attenuates the aging process in humans.Trial RegistrationClinicalTrials.gov Identifier: NCT00099151