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Cited by 969Dietary Effects on HealthGenetics, Aging, and Longevity in Model OrganismsExercise and Physiological Responses

Effect of 6-Month Calorie Restriction on Biomarkers of Longevity, Metabolic Adaptation, and Oxidative Stress in Overweight Individuals: A Randomized Controlled Trial

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Heilbronn, Leonie K., de Jonge, Lilian, Frisard, Madlyn I., DeLany, James P., Larson-Meyer, D. Enette, Rood, Jennifer, Nguyen, Tuong, Martin, Corby K. +8 more·2006·JAMA
DOI 10.1001/jama.295.13.1539PMC PMC2692623
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Abstract

CONTEXT: 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. DESIGN, SETTING, AND PARTICIPANTS: 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. INTERVENTION: 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). MAIN OUTCOME MEASURES: 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. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00099151.

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  1. Mates JM, Perez-Gomez C, Olalla L, Segura JM, Blanca M. Allergy to drugs: antioxidant enzymic activities, lipid peroxidation and protein oxidative damage in human blood. Cell Biochem Funct. 2000; 18:77-84.
  2. McCay CCM, Maynard LA. The effect of re- tarded growth upon the length of the lifespan and upon the ultimate body size. J Nutr. 1935;10:63-79.
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Authors
Heilbronn, L. K., de Jonge, L., Frisard, M. I., DeLany, J. P., Larson-Meyer, D. E., Rood, J., Nguyen, T., Martin, C. K., Volaufova, J., Most, M. M., Greenway, F. L., Smith, S. R., Deutsch, W. A., Williamson, D. A., Ravussin, E., & Pennington CALERIE Team, F. T.
Affiliations
Pennington Biomedical Research Center (US)
ORCID
Venue
JAMA
Publisher
American Medical Association (AMA)
Published
2006-04-05
Volume
295
Issue
13
Pages
1539
ISSN
  • 0002-9955 (ISSN-L)
  • 0098-7484
DOI
10.1001/jama.295.13.1539
PMC
PMC2692623
OpenAlex
W2117879192
Cited by
969
References
61
Citations by year
2026: 16 · 2025: 25 · 2024: 46 · 2023: 40 · 2022: 42 · 2021: 67 · 2020: 43 · 2019: 41 · 2018: 38 · 2017: 39 · 2016: 47 · 2015: 56 · 2014: 53 · 2013: 57 · 2012: 57
FWCI
41.20
Type
journal article
Language
en
Open access
Locations
  • JAMA (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion)
Funders
  • Louisiana State University
  • Ochsner Health
  • National Institutes of Health
  • National Institute on Aging (U01AG020478, U01-AG20478)
  • National Institute of Diabetes and Digestive and Kidney Diseases (P30DK072476)
Topics
  • Health Sciences › Medicine › Physiology › Dietary Effects on Health
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
  • Health Sciences › Medicine › Rehabilitation › Exercise and Physiological Responses
Keywords
caloric restriction, very low calorie diet, metabolic adaptation, oxidative stress, DNA damage, protein carbonyls, insulin, dehydroepiandrosterone sulfate, energy expenditure, core body temperature, body composition, weight loss, physical activity, overweight adults, sedentary lifestyle, aging, lifespan extension, metabolic rate, weight-maintenance diet
MeSH terms
Adult, Body Composition, Body Temperature, DNA Damage, Energy Metabolism, Female, Glucose, Humans, Insulin, Longevity, Male, Middle Aged, Rest, Exercise, Body Mass Index, Oxidative Stress, Dehydroepiandrosterone Sulfate, Caloric Restriction, Overweight, DNA Fragmentation

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