CALERIE: Comprehensive Assessment of Long-Term Effects of Reducing Intake of Energy

NCT00427193 | Completed Results DMC

• 6 other identifiers: Pro00016876PBRC U01-AG0204878Tufts U01-AG020480WashU U01-AG020487DCRI/Duke U01-AG022132AG0078
• Study Type: interventional
• Target: 238
• Locations: 1 country
• Sites: 3

Brief Summary

The purpose of this study is to test the hypothesis that two years of sustained 25% caloric restriction (CR) in men age 21-50 (inclusive) and women age 21-47 (inclusive) will slow aging and protect against age-related disease processes.

Conditions

Aging

Keywords

dietary restriction; disease /disorder prevention /control; nutrition of aging; bioenergetics; cardiovascular function; disease /disorder proneness /risk; insulin sensitivity / resistance

Outcome Measures

Primary Outcomes (4)

• Change in Core Body Temperature, Baseline to 12 Months

  Baseline to 12 months

• Change in Core Temperature, Baseline to 24 Months

  Baseline to 24 months

• Change in Resting Metabolic Rate (RMR) Corrected for Changes in Body Composition, Baseline to 12 Months

  Baseline, 12 months

• Change in Resting Metabolic Rate (RMR) Corrected for Changes in Body Composition

  Baseline, 24 months

Secondary Outcomes (1)

• Change in Tumor Necrosis Factor-α (TNF-α), Baseline to 12 Months

  change baseline to 12 months

Other Outcomes (2)

• Change in Fat Mass

  change 0 to 24 months

• Change in Fat Mass

  baseline, 12 months

Study Arms (2)

Caloric Restriction (CR)

EXPERIMENTAL

25% caloric restriction

Behavioral: Caloric Restriction (CR)

Control, Ad libitum (AL)

ACTIVE COMPARATOR

Ad libitum energy intake

Behavioral: Control

Interventions

Caloric Restriction (CR) BEHAVIORAL

Participants follow a diet with 25% fewer calories than calculated at baseline over a period of 24 months

Caloric Restriction (CR)

Control BEHAVIORAL

Participants continue their current diet for 24 months

Control, Ad libitum (AL)

Eligibility Criteria

• Age: 21 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Age must be between 21-50 (inclusive) for men and 21-47 (inclusive) for women
• Body mass index (BMI) must be greater than or equal to 22 and less than 28
• Female participants must use acceptable forms of contraception (barrier method, oral contraceptive, intra-uterine device, or similar) and be willing to continue using such a method while enrolled in the study

You may not qualify if:

• History or clinical manifestation of cardiovascular disease or an elevated blood pressure (greater than 140/90 mm Hg)
• Abnormal resting ECG
• History or clinical manifestation of diabetes
• History or clinical manifestation of cholelithiasis (the presence or formation of gallstones in the gallbladder or bile ducts)
• History of anaphylaxis, severe allergies, or asthma
• History or clinical manifestation of any other significant metabolic, hematologic, pulmonary, cardiovascular, gastrointestinal, neurologic, immune, hepatic, renal, urologic disorders, or cancer that, in opinion of the investigator, would make the candidate ineligible for the study
• History of stomach or intestinal surgery (except appendectomy) or major abdominal, thoracic or non-peripheral vascular surgery within one year prior to the randomization date
• Any disease or condition that seriously affects body weight and/or body composition
• Potassium level above the upper limit of normal at the screening visit confirmed by a test repeated within two weeks
• Hemoglobin, hematocrit, RBC, or iron level below the lower limit of normal at the screening visit confirmed by a test repeated within two weeks
• Evidence of active liver disease or ALT levels above 1.5 times the upper limit of normal
• Practice a vegan dietary lifestyle
• History or clinical manifestation of any eating disorder
• Any history of pharmacologic treatment for a psychiatric disorder within one year prior to the randomization date or a history of more than one episode of a pharmacologic treatment for a psychiatric disorder within lifetime
• History of drug or alcohol abuse (up to 14 drinks a week are allowed) within the past two years

Sponsors & Collaborators

• Duke University: lead

Study Sites (3)

Pennington Biomedical Research Center

Baton Rouge, Louisiana, 70808, United States

Location

Jean Mayer Human Nutrition Research Center on Aging at Tufts University

Boston, Massachusetts, 02111, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Publications (25)

• Ravussin E, Redman LM, Rochon J, Das SK, Fontana L, Kraus WE, Romashkan S, Williamson DA, Meydani SN, Villareal DT, Smith SR, Stein RI, Scott TM, Stewart TM, Saltzman E, Klein S, Bhapkar M, Martin CK, Gilhooly CH, Holloszy JO, Hadley EC, Roberts SB; CALERIE Study Group. A 2-Year Randomized Controlled Trial of Human Caloric Restriction: Feasibility and Effects on Predictors of Health Span and Longevity. J Gerontol A Biol Sci Med Sci. 2015 Sep;70(9):1097-104. doi: 10.1093/gerona/glv057. Epub 2015 Jul 17.

  PMID: 26187233 RESULT

• Rochon J, Bales CW, Ravussin E, Redman LM, Holloszy JO, Racette SB, Roberts SB, Das SK, Romashkan S, Galan KM, Hadley EC, Kraus WE; CALERIE Study Group. Design and conduct of the CALERIE study: comprehensive assessment of the long-term effects of reducing intake of energy. J Gerontol A Biol Sci Med Sci. 2011 Jan;66(1):97-108. doi: 10.1093/gerona/glq168. Epub 2010 Oct 5.

  PMID: 20923909 RESULT

• Racette SB, Rochon J, Uhrich ML, Villareal DT, DAS SK, Fontana L, Bhapkar M, Martin CK, Redman LM, Fuss PJ, Roberts SB, Kraus WE. Effects of Two Years of Calorie Restriction on Aerobic Capacity and Muscle Strength. Med Sci Sports Exerc. 2017 Nov;49(11):2240-2249. doi: 10.1249/MSS.0000000000001353.

  PMID: 29045325 RESULT

• Belsky DW, Huffman KM, Pieper CF, Shalev I, Kraus WE. Change in the Rate of Biological Aging in Response to Caloric Restriction: CALERIE Biobank Analysis. J Gerontol A Biol Sci Med Sci. 2017 Dec 12;73(1):4-10. doi: 10.1093/gerona/glx096.

  PMID: 28531269 RESULT

• Martin CK, Bhapkar M, Pittas AG, Pieper CF, Das SK, Williamson DA, Scott T, Redman LM, Stein R, Gilhooly CH, Stewart T, Robinson L, Roberts SB; Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE) Phase 2 Study Group. Effect of Calorie Restriction on Mood, Quality of Life, Sleep, and Sexual Function in Healthy Nonobese Adults: The CALERIE 2 Randomized Clinical Trial. JAMA Intern Med. 2016 Jun 1;176(6):743-52. doi: 10.1001/jamainternmed.2016.1189.

  PMID: 27136347 RESULT

• Racette SB, Silver RE, Barry VG, DeGraff JJ, Gunning JA, Kebbe M, Gilhooly CH, Das SK. Diet quality and nutritional adequacy during a 2-year calorie restriction intervention: the Comprehensive Assessment of Long-Term Effects of Reducing Intake of Energy 2 trial. Am J Clin Nutr. 2025 Dec 29;123(3):101182. doi: 10.1016/j.ajcnut.2025.101182. Online ahead of print.

  PMID: 41475553 DERIVED

• Ryan CP, Corcoran DL, Banskota N, Eckstein Indik C, Floratos A, Friedman R, Kobor MS, Kraus VB, Kraus WE, MacIsaac JL, Orenduff MC, Pieper CF, White JP, Ferrucci L, Horvath S, Huffman KM, Belsky DW. The CALERIE Genomic Data Resource. Nat Aging. 2025 Feb;5(2):320-331. doi: 10.1038/s43587-024-00775-0. Epub 2024 Dec 13.

  PMID: 39672986 DERIVED

• Glasbrenner C, Hochsmann C, Pieper CF, Wasserfurth P, Dorling JL, Martin CK, Redman LM, Koehler K. Prediction of individual weight loss using supervised learning: findings from the CALERIETM 2 study. Am J Clin Nutr. 2024 Nov;120(5):1233-1244. doi: 10.1016/j.ajcnut.2024.09.003. Epub 2024 Sep 11.

  PMID: 39270937 DERIVED

• Ryu S, Spadaro O, Sidorov S, Lee AH, Caprio S, Morrison C, Smith SR, Ravussin E, Shchukina I, Artyomov MN, Youm YH, Dixit VD. Reduction of SPARC protects mice against NLRP3 inflammasome activation and obesity. J Clin Invest. 2023 Oct 2;133(19):e169173. doi: 10.1172/JCI169173.

  PMID: 37781916 DERIVED

• Silver RE, Roberts SB, Kramer AF, Chui KKH, Das SK. No Effect of Calorie Restriction or Dietary Patterns on Spatial Working Memory During a 2-Year Intervention: A Secondary Analysis of the CALERIE Trial. J Nutr. 2023 Mar;153(3):733-740. doi: 10.1016/j.tjnut.2023.01.019. Epub 2023 Jan 14.

  PMID: 36805108 DERIVED

• Dorling JL, Ravussin E, Redman LM, Bhapkar M, Huffman KM, Racette SB, Das SK, Apolzan JW, Kraus WE, Hochsmann C, Martin CK; CALERIE Phase 2 Study Group. Effect of 2 years of calorie restriction on liver biomarkers: results from the CALERIE phase 2 randomized controlled trial. Eur J Nutr. 2021 Apr;60(3):1633-1643. doi: 10.1007/s00394-020-02361-7. Epub 2020 Aug 14.

  PMID: 32803412 DERIVED

• Thomas DM, Clark N, Turner D, Siu C, Halliday TM, Hannon BA, Kahathuduwa CN, Kroeger CM, Zoh R, Allison DB. Best (but oft-forgotten) practices: identifying and accounting for regression to the mean in nutrition and obesity research. Am J Clin Nutr. 2020 Feb 1;111(2):256-265. doi: 10.1093/ajcn/nqz196.

  PMID: 31552422 DERIVED

• Dorling JL, Bhapkar M, Das SK, Racette SB, Apolzan JW, Fearnbach SN, Redman LM, Myers CA, Stewart TM, Martin CK; CALERIE Study Group. Change in self-efficacy, eating behaviors and food cravings during two years of calorie restriction in humans without obesity. Appetite. 2019 Dec 1;143:104397. doi: 10.1016/j.appet.2019.104397. Epub 2019 Aug 6.

  PMID: 31398376 DERIVED

• Kraus WE, Bhapkar M, Huffman KM, Pieper CF, Krupa Das S, Redman LM, Villareal DT, Rochon J, Roberts SB, Ravussin E, Holloszy JO, Fontana L; CALERIE Investigators. 2 years of calorie restriction and cardiometabolic risk (CALERIE): exploratory outcomes of a multicentre, phase 2, randomised controlled trial. Lancet Diabetes Endocrinol. 2019 Sep;7(9):673-683. doi: 10.1016/S2213-8587(19)30151-2. Epub 2019 Jul 11.

  PMID: 31303390 DERIVED

• Broskey NT, Marlatt KL, Most J, Erickson ML, Irving BA, Redman LM. The Panacea of Human Aging: Calorie Restriction Versus Exercise. Exerc Sport Sci Rev. 2019 Jul;47(3):169-175. doi: 10.1249/JES.0000000000000193.

  PMID: 30998529 DERIVED

• Guo J, Brager DC, Hall KD. Simulating long-term human weight-loss dynamics in response to calorie restriction. Am J Clin Nutr. 2018 Apr 1;107(4):558-565. doi: 10.1093/ajcn/nqx080.

  PMID: 29635495 DERIVED

• Redman LM, Smith SR, Burton JH, Martin CK, Il'yasova D, Ravussin E. Metabolic Slowing and Reduced Oxidative Damage with Sustained Caloric Restriction Support the Rate of Living and Oxidative Damage Theories of Aging. Cell Metab. 2018 Apr 3;27(4):805-815.e4. doi: 10.1016/j.cmet.2018.02.019. Epub 2018 Mar 22.

  PMID: 29576535 DERIVED

• Das SK, Roberts SB, Bhapkar MV, Villareal DT, Fontana L, Martin CK, Racette SB, Fuss PJ, Kraus WE, Wong WW, Saltzman E, Pieper CF, Fielding RA, Schwartz AV, Ravussin E, Redman LM; CALERIE-2 Study Group. Body-composition changes in the Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE)-2 study: a 2-y randomized controlled trial of calorie restriction in nonobese humans. Am J Clin Nutr. 2017 Apr;105(4):913-927. doi: 10.3945/ajcn.116.137232. Epub 2017 Feb 22.

  PMID: 28228420 DERIVED

• Rochon J, Bhapkar M, Pieper CF, Kraus WE. Application of the Marginal Structural Model to Account for Suboptimal Adherence in a Randomized Controlled Trial. Contemp Clin Trials Commun. 2016 Dec 15;4:222-228. doi: 10.1016/j.conctc.2016.10.005. Epub 2016 Nov 3.

  PMID: 27900372 DERIVED

• Sparks LM, Redman LM, Conley KE, Harper ME, Yi F, Hodges A, Eroshkin A, Costford SR, Gabriel ME, Shook C, Cornnell HH, Ravussin E, Smith SR. Effects of 12 Months of Caloric Restriction on Muscle Mitochondrial Function in Healthy Individuals. J Clin Endocrinol Metab. 2017 Jan 1;102(1):111-121. doi: 10.1210/jc.2016-3211.

  PMID: 27778643 DERIVED

• Meydani SN, Das SK, Pieper CF, Lewis MR, Klein S, Dixit VD, Gupta AK, Villareal DT, Bhapkar M, Huang M, Fuss PJ, Roberts SB, Holloszy JO, Fontana L. Long-term moderate calorie restriction inhibits inflammation without impairing cell-mediated immunity: a randomized controlled trial in non-obese humans. Aging (Albany NY). 2016 Jul;8(7):1416-31. doi: 10.18632/aging.100994.

  PMID: 27410480 DERIVED

• Sanghvi A, Redman LM, Martin CK, Ravussin E, Hall KD. Validation of an inexpensive and accurate mathematical method to measure long-term changes in free-living energy intake. Am J Clin Nutr. 2015 Aug;102(2):353-8. doi: 10.3945/ajcn.115.111070. Epub 2015 Jun 3.

  PMID: 26040640 DERIVED

• Wong WW, Roberts SB, Racette SB, Das SK, Redman LM, Rochon J, Bhapkar MV, Clarke LL, Kraus WE. The doubly labeled water method produces highly reproducible longitudinal results in nutrition studies. J Nutr. 2014 May;144(5):777-83. doi: 10.3945/jn.113.187823. Epub 2014 Feb 12.

  PMID: 24523488 DERIVED

• Redman LM, Kraus WE, Bhapkar M, Das SK, Racette SB, Martin CK, Fontana L, Wong WW, Roberts SB, Ravussin E; CALERIE Study Group. Energy requirements in nonobese men and women: results from CALERIE. Am J Clin Nutr. 2014 Jan;99(1):71-8. doi: 10.3945/ajcn.113.065631. Epub 2013 Nov 20.

  PMID: 24257721 DERIVED

• Huffman KM, Redman LM, Landerman LR, Pieper CF, Stevens RD, Muehlbauer MJ, Wenner BR, Bain JR, Kraus VB, Newgard CB, Ravussin E, Kraus WE. Caloric restriction alters the metabolic response to a mixed-meal: results from a randomized, controlled trial. PLoS One. 2012;7(4):e28190. doi: 10.1371/journal.pone.0028190. Epub 2012 Apr 16.

  PMID: 22523532 DERIVED

Related Links

• CALERIE website

MeSH Terms

Conditions

Disease Susceptibility; Insulin Resistance

Interventions

Caloric Restriction

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Diet Therapy; Nutrition Therapy; Therapeutics; Energy Intake; Diet; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena

Limitations and Caveats

1. The Caloric Restriction (CR) group fell short of achieving the 25% CR goal specified in the protocol. 2. The completion rates differed between groups.

Results Point of Contact

• Title: William E. Kraus, Director of Clinical Research, Duke Center for Living
• Organization: Duke University Medical Center

william.kraus@duke.edu

919-681-6733

Study Officials

• William Kraus, MD

  Duke Clinical Research Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: all lab based assays were masked due to de-identified person and time interval measured. All physical measures were masked to intervention group status.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 24, 2007
• First Posted: January 26, 2007
• Study Start: May 1, 2007
• Primary Completion: November 1, 2012
• Study Completion: November 1, 2012
• Last Updated: March 16, 2022
• Results First Posted: December 6, 2018

Record last verified: 2022-03

Locations

US (3)