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Calorie Restriction May Improve Biomarkers of Longevity

  • Authors: News Author: Laurie Barclay, MD
    CME Author: Désirée Lie, MD, MSEd
  • CME Released: 4/4/2006
  • Valid for credit through: 4/4/2007
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Target Audience and Goal Statement

This article is intended for primary care clinicians and specialists who care for overweight patients.

The goal of this activity is to provide medical news to primary care clinicians and other healthcare professionals in order to enhance patient care.

Upon completion of this activity, participants will be able to:

  • Describe the effect of caloric restriction with and without exercise on weight, fat mass, fasting glucose, insulin, and DHEAS levels in overweight individuals.
  • Describe the effect of caloric restriction with and without exercise on metabolic adaptation and markers of aging in overweight individuals.


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  • Laurie Barclay, MD

    Laurie Barclay is a freelance reviewer and writer for Medscape.


    Disclosure: Laurie Barclay, MD, has disclosed no relevant financial relationships.


  • Gary Vogin, MD

    Senior Medical Editor, Medscape


    Disclosure: Gary Vogin, MD, has disclosed no relevant financial relationships.

CME Author(s)

  • Désirée Lie, MD, MSEd

    Clinical Professor of Family Medicine; Director, Division of Faculty Development, University of California, Irvine School of Medicine, Irvine, California


    Disclosure: Désirée Lie, MD, MSEd, has disclosed no relevant financial relationships.

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Calorie Restriction May Improve Biomarkers of Longevity

Authors: News Author: Laurie Barclay, MD CME Author: Désirée Lie, MD, MSEdFaculty and Disclosures

CME Released: 4/4/2006

Valid for credit through: 4/4/2007


April 4, 2006 -- Calorie restriction improves biomarkers of longevity, according to the results of a randomized trial reported in the April 5 issue of JAMA. However, the authors and editorialist recommend studies of longer duration.

"Prolonged calorie restriction increases life span in rodents," write Leonie K. Heilbronn, PhD, from the Pennington Biomedical Research Center and Louisiana State University in Baton Rouge, and colleagues from the Pennington CALERIE (Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy) Team. "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."

Between March 2002 and August 2004, 48 healthy, sedentary men and women 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); or very low-calorie diet (890 kcal/day until 15% weight reduction, followed by a weight maintenance diet). At baseline, participants were overweight but nonobese (body mass index, 25 to 30 kg/m 2). Primary endpoints were body composition; dehydroepiandrosterone sulfate (DHEAS), glucose, and insulin levels; protein carbonyls; DNA damage; 24-hour energy expenditure; and core body temperature.

Mean weight change at 6 months was -1.0% ± 1.1% for controls, -10.4% ± 0.9% for calorie restriction, -10.0% ± 0.8% for calorie restriction with exercise, and -13.9% ± 0.7% for very low-calorie diet. Fasting insulin levels were reduced from baseline to 6 months in all 3 intervention groups (all P <.01), but 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 adjusting for body composition changes, sedentary 24-hour energy expenditure was unchanged in controls, but decreased in the calorie restriction (-135 ± 42 kcal/day), calorie restriction with exercise (-117 ± 52 kcal/day), and very low-calorie diet (-125 ± 35 kcal/day) groups (all P < .008). These "metabolic adaptations" in the intervention groups were statistically different than in the control group ( P < .05), and they were about 6% greater than expected based on loss of metabolic mass. None of the groups had changes in protein carbonyl concentrations from baseline to month 6, but all intervention groups had a reduction in DNA damage ( P < .005).

"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," the authors write. "Studies of longer duration are required to determine if calorie restriction attenuates the aging process in humans."

The National Institutes of Health supported this study. The authors have disclosed no relevant financial relationships.

In an accompanying editorial, Luigi Fontana, MD, PhD, from Washington University School of Medicine in St Louis, Mo, notes several limitations in the CALERIE study design. The study was of insufficient duration to detect changes in biomarkers of longevity such as serum DHEAS and glucose concentrations, and sample size was small.

"Measuring tissue-specific effects of calorie restriction using genomic, proteomic, and metabolomic techniques will foster the development of an understanding of the complex biological processes involved in the antiaging effects of calorie restriction," Dr. Fontana writes. "Although is it not likely that many individuals would adopt a calorie-restricted diet, the value of these studies is that they suggest possible mechanisms of aging in humans and points of intervention to modify the effects of aging. Further elucidating the mechanisms that control longevity will be a major step in understanding the age dependency of a range of chronic human diseases and will help to improve the quality of life in old age."

Dr Fontana has disclosed no relevant financial relationships.

JAMA. 2006;295:1539-1548, 1577-1578

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