Effect of 6-month calorie restriction on biomarkers of longevity, metabolic adaptation, and oxidative stress in overweight individuals: a randomized controlled trial.
BACKGROUND
Prolonged 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.


OBJECTIVE
To 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.


METHODS
Randomized 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.


METHODS
Participants 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).


METHODS
Body composition; dehydroepiandrosterone sulfate (DHEAS), glucose, and insulin levels; protein carbonyls; DNA damage; 24-hour energy expenditure; and core body temperature.


RESULTS
Mean (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).


CONCLUSIONS
Our 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.


BACKGROUND
ClinicalTrials.gov Identifier: NCT00099151.
Heilbronn
Leonie K
LK
Pennington Biomedical Research Center, Louisiana State University, Baton Rouge 70808, USA.
de Jonge
Lilian
L
Frisard
Madlyn I
MI
DeLany
James P
JP
Larson-Meyer
D Enette
DE
Rood
Jennifer
J
Nguyen
Tuong
T
Martin
Corby K
CK
Volaufova
Julia
J
Most
Marlene M
MM
Greenway
Frank L
FL
Smith
Steven R
SR
Deutsch
Walter A
WA
Williamson
Donald A
DA
Ravussin
Eric
E
D000328:Adult; D001823:Body Composition; D015992:Body Mass Index; D001831:Body Temperature; D031204:Caloric Restriction; D004249:DNA Damage; D053938:DNA Fragmentation; D019314:Dehydroepiandrosterone Sulfate / Q000378:metabolism; D004734:Energy Metabolism; D015444:Exercise; D005260:Female; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism; D008136:Longevity / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D050177:Overweight / Q000502:physiology*; D018384:Oxidative Stress / Q000502:physiology*; D012146:Rest
D007328:Insulin; D019314:Dehydroepiandrosterone Sulfate; D005947:Glucose