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Cited by 407Dietary Effects on HealthNutritional Studies and DietDiabetes, Cardiovascular Risks, and Lipoproteins

2 years of calorie restriction and cardiometabolic risk (CALERIE): exploratory outcomes of a multicentre, phase 2, randomised controlled trial

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Kraus, William E, Bhapkar, Manjushri, Huffman, Kim M, Pieper, Carl F, Krupa Das, Sai, Redman, Leanne M, Villareal, Dennis T, Rochon, James +4 more·2019·The Lancet Diabetes & Endocrinology
DOI 10.1016/s2213-8587(19)30151-2PMC PMC6707879
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Abstract

Background For several cardiometabolic risk factors, values considered within normal range are associated with an increased risk of cardiovascular morbidity and mortality. We aimed to investigate the short-term and long-term effects of calorie restriction with adequate nutrition on these risk factors in healthy, lean, or slightly overweight young and middle-aged individuals. Methods CALERIE was a phase 2, multicentre, randomised controlled trial in young and middle-aged (21-50 years), healthy non-obese (BMI 22·0-27·9 kg/m 2) men and women done in three clinical centres in the USA. Participants were randomly assigned (2:1) to a 25% calorie restriction diet or an ad libitum control diet. Exploratory cardiometabolic risk factor responses to a prescribed 25% calorie restriction diet for 2 years were evaluated (systolic, diastolic, and mean blood pressure; plasma lipids; high-sensitivity C-reactive protein; metabolic syndrome score; and glucose homoeostasis measures of fasting insulin, glucose, insulin resistance, and 2-h glucose, area-under-the curve for glucose, and insulin from an oral glucose tolerance test) analysed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT00427193. Findings From May 8, 2007, to Feb 26, 2010, of 238 participants that were assessed, 218 were randomly assigned to and started a 25% calorie restriction diet (n=143, 66%) or an ad libitum control diet (n=75, 34%). Individuals in the calorie restriction group achieved a mean reduction in calorie intake of 11·9% (SE 0·7; from 2467 kcal to 2170 kcal) versus 0·8% (1·0) in the control group, and a sustained mean weight reduction of 7·5 kg (SE 0·4) versus an increase of 0·1 kg (0·5) in the control group, of which 71% (mean change in fat mass 5·3 kg [SE 0·3] divided by mean change in weight 7·5 kg [0·4]) was fat mass loss. Calorie restriction caused a persistent and significant reduction from baseline to 2 years of all measured conventional cardiometabolic risk factors, including change scores for LDL-cholesterol (p<0·0001), total cholesterol to HDL-cholesterol ratio (p<0·0001), and systolic (p<0·0011) and diastolic (p<0·0001) blood pressure. In addition, calorie restriction resulted in a significant improvement at 2 years in C-reactive protein (p=0·012), insulin sensitivity index (p<0·0001), and metabolic syndrome score (p<0·0001) relative to control. A sensitivity analysis revealed the responses to be robust after controlling for relative weight loss changes. Interpretation 2 years of moderate calorie restriction significantly reduced multiple cardiometabolic risk factors in young, non-obese adults. These findings suggest the potential for a substantial advantage for cardiovascular health of practicing moderate calorie restriction in young and middle-aged healthy individuals, and they offer promise for pronounced long-term population health benefits. Funding National Institute on Aging and National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health.

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  • CALERIE Phase 2 calorie restriction group participants accomplished 14% of the intended calorie restriction.

    “CR group participants accomplished 14% of CR.”

    From Taurine lowers inflammaging by regulating the NLRP3 inflammasome in macrophages (2026) · cites this paper as [66]

    The Results section (“Intervention adherence, body weight and composition”; page unavailable) reports that the CR group averaged 11.7% calorie restriction over the two-year intervention, not 14%. The Methods state that the prescribed target was 25%. (LLM, conf=0.90)

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  • 238 metabolically healthy adults (BMI 22.0-27.9 kg/m2, age 25-45) were enrolled in CALERIE Phase 2 and randomized to a 25% calorie restriction intervention versus an ad-libitum control group.

    “238 metabolically healthy adults (BMI: 22.0– 27.9 kg/m2, Age: 25–45) were enrolled in the study from Pennington Biomedical Research Center (PBRC, Baton Rouge, LA), Washington University (St. Louis, MO) and Tufts University (Boston, MA) (NCT00427193)”

    From Taurine lowers inflammaging by regulating the NLRP3 inflammasome in macrophages (2026) · cites this paper as [66]

    The Results report that 238 participants began baseline assessments, but only 220 were randomized; the claim overstates the number randomized. Methods > Study population supports the BMI range and three clinical centers, and Methods > Treatment assignment and intervention supports the 25% calorie-restriction and ad-libitum arms. The stated age range of 25–45 is not supported: the paper describes men aged 21–50 and women aged 21–47. (LLM, conf=0.92)

    Experimental — accuracy not yet measured

  • CALERIE Phase 2 is a multi-center, parallel-group, randomized controlled trial recruiting non-obese healthy individuals.

    “CALERIE Phase 2 is a multi-center, parallel group, randomized controlled trial recruiting non-obese healthy individuals.”

    From Taurine lowers inflammaging by regulating the NLRP3 inflammasome in macrophages (2026) · cites this paper as [66]

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Authors
Kraus, W. E., Bhapkar, M., Huffman, K. M., Pieper, C. F., Krupa Das, S., Redman, L. M., Villareal, D. T., Rochon, J., Roberts, S. B., Ravussin, E., Holloszy, J. O., & Fontana, L.
Affiliations
  • Duke University (US)
  • Pennington Biomedical Research Center (US)
  • Michael E. DeBakey VA Medical Center (US)
  • Rho (United States) (US)
  • Tufts University (US)
  • Washington University in St. Louis (US)
  • The University of Sydney (AU)
Corresponding author
Kraus, William E
ORCID
Venue
The Lancet Diabetes & Endocrinology
Publisher
Elsevier BV
Published
2019-09
Volume
7
Issue
9
Pages
673-683
ISSN
2213-8587 (ISSN-L)
DOI
10.1016/s2213-8587(19)30151-2
PMC
PMC6707879
OpenAlex
W2958408897
Cited by
407
References
55
Citations by year
2026: 52 · 2025: 62 · 2024: 73 · 2023: 61 · 2022: 56 · 2021: 54 · 2020: 41 · 2019: 8
FWCI
27.27
Type
journal article
Language
en
Open access
Licence
Locations
  • The Lancet Diabetes & Endocrinology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • Institutional Research Information System (Università degli Studi di Brescia) (submittedVersion)
Funders
  • National Institute on Aging (NIA)
  • National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (U01AG022132, U01AG020478, U01AG020487, U01AG020480)
  • NIH General Clinical Research Center (RR00036)
  • Diabetes Research Training Center (DK20579)
  • NIH Clinical Nutrition Research Unit (DK56341)
Topics
  • Health Sciences › Medicine › Physiology › Dietary Effects on Health
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Nutritional Studies and Diet
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
Keywords
caloric restriction, cardiometabolic risk factors, weight loss, fat loss, LDL cholesterol, triglycerides, HDL cholesterol, blood pressure, C-reactive protein, metabolic syndrome, insulin resistance, glucose homeostasis, young and middle-aged adults, long-term dietary intervention, cardiovascular risk reduction, overweight individuals
MeSH terms
Adult, Blood Pressure, Cardiovascular Diseases, Female, Glucose Tolerance Test, Humans, Cholesterol, LDL, Male, Metabolic Diseases, Middle Aged, Prospective Studies, Time Factors, Weight Loss, Treatment Outcome, Caloric Restriction, Overweight, Young Adult

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