Effect of 6-mo. calorie restriction on biomarkers of longevity, metabolic adaptation and oxidative stress in overweight subjects
Prolonged calorie restriction (CR) increases lifespan in rodents. Whether prolonged CR affects biomarkers of longevity, markers of oxidative stress, and reduces metabolic rate, beyond that expected from reduced metabolic mass, has not previously been tested in humans.
To examine the effects of 6 months of calorie restriction, with or without exercise in nonobese (25≤BMI<30) humans.
Design, Setting, and Participants
Healthy, sedentary men and women (n=48) were randomized to one of four groups for 6-mo; Control=100% of energy requirements; CR=25% diet restriction; CREX=12.5%CR+12.5% increase in energy expenditure; LCD=low calorie diet until 15% weight reduction followed by weight maintenance.
Main Outcome Measures
Body composition, dehydroepiandrosterone sulfate (DHEAS), glucose, insulin, protein carbonyls, DNA damage, 24h energy expenditure (24h-EE, metabolic chamber) and core body temperature.
Weight change at M6 was -1.0(1.1)% (Control), -10.4(0.9)% (CR), -10.0(0.8)% (CREX), -13.9(0.7)% (LCD). At M6, fasting insulin was reduced from baseline in CR, CREX and LCD groups (all, p<0.01), whereas DHEAS and glucose were unchanged. Core temperature was reduced in CR by 0.2(0.05)°C and by 0.3(0.08)°C in CREX (both, p<0.05). After adjustment for changes in body composition, sedentary 24h-EE was unchanged in controls (-18(52) kcal/d; p>0.05), but decreased in CR (-135(42)kcal/d), CREX (-117(52)kcal/d) and LCD (-125(35)kcal/d, (all, p<0.008). These “metabolic adaptations” (~6% more than expected based on loss of metabolic mass) were statistically different from controls (p<0.05). DNA damage was also reduced from baseline in CR, CREX and LCD groups at M6 (p≤ 0.002).
These results show that two previously reported biomarkers of longevity (fasting insulin and body temperature) are reduced by prolonged CR in humans and support the theory that metabolic rate is reduced beyond the level expected for reduced metabolic body size. Studies of longer duration are now required to determine if CR attenuates the aging process in humans.
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