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Interventions and public health nutrition

Changes in body weight, adherence, and appetite during 2 years of calorie restriction: the CALERIE 2 randomized clinical trial



The Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy Phase 2 (CALERIE) study showed that individuals who are nonobese were able to undergo significant calorie restriction (CR), yet the time course changes in adherence, weight, and appetite are unknown. This analysis aimed to investigate the time course changes in adherence, body weight, and appetite during the CALERIE study.


Overall, 143 participants (body mass index: 21.9–28.0 kg/m2) were randomized to a CR group that aimed to achieve 25% CR for 2 years. Throughout the intervention, body weight was measured, and appetite was assessed through visual analogue scales. Algorithms were utilized with body weight measurements to calculate adherence percentile score. Participants targeted an adherence percentile score of 50, though being between 80 (lowest acceptable adherence) and 10 (highest acceptable adherence) was adequate. Polynomial regression analyses were used to assess time course changes.


Polynomials indicated that adherence percentile score increased above 50 after approximately week 20, although adherence remained acceptable (adherence percentile score less than 80) (R2 = 0.89; P < 0.001). Weight loss occurred until approximately week 60 and then plateaued (R2 ≥ 0.92; P < 0.001). Hunger and thirst increased (R2 ≥ 0.30; P < 0.001), but the total increase in scale scores were <10 mm throughout the intervention.


In individuals who are nonobese, adherence to 25% CR declines after 20 weeks, but 2 years of CR that stimulates a meaningful reduction in weight, promotes aging-related benefits and negligibly affects appetite is viable.

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Fig. 1: Adherence and weight changes during CALERIE.
Fig. 2: Regression curves for adherence and weight loss during CALERIE.
Fig. 3: Appetite changes during CALERIE.
Fig. 4: Regression curves for appetite during CALERIE.

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We are indebted to the study participants. The efforts of the CALERIE data coordinating center (James Rochon, Kim Huffman, and William Krauss) are also acknowledged and greatly appreciated. CALERIE 2 data, including the data reported in this paper, can be accessed at


The research was supported by the National Institute on Aging and the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health (grants U01AG022132, U01AG020478, U01AG020487, and U01AG020480); National Obesity Research Center (grant P30 DK072476), sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases; and the National Institute of General Medical Sciences of the National Institutes of Health, which funds the Louisiana Clinical and Translational Science Center (grant 1 U54 GM104940). It was also supported by the American Heart Association Grant #20POST35210907 (James L. Dorling). The CALERIE data repository is supported by the CALERIE Research Network and contains an array of clinical, physiologic, and molecular data. More information about repository contents and how to request data and samples can be found at the following website:

CALERIE Study Members

Principal investigators (PIs), Coinvestigators (CIs), site intervention leaders (SILs), intervention counselors (ICs), study managers (SMs), project leaders (PLs), study coordinators (SCs), and other staff (OS) participating in the CALERIE study. Pennington Biomedical Research Center (clinical site)—PI: Eric Ravussin, PhD; CI: Catherine Champagne, RD, PhD; Alok Gupta, MD; Corby Martin, PhD; Leanne Redman, PhD; Steven Smith, MD; Donald Williamson, PhD; SIL: Corby Martin, PhD; Tiffany Stewart, PhD; IC: Michelle Begnaud, RD; Barbara Cerniauskas, RD; Allison Davis, MS; Jeanne Gabrielle, PhD; Heather Walden, MS; SM: Natalie Currier, RD; Mandy Shipp, RD; SC: Sarah Masters; Melody McNicoll; OS: Shelly Prince, MS, RD; Courtney Brock, RD; Renee Puyau, RD; Conrad Earnest, PhD; Jennifer Rood, PhD; Tiffany Stewart, PhD; Lillian Levitan, PhD; Crystal Traylor, WHNP; Susan Thomas, WHNP; Valerie Toups, LPN; Karen Jones, RN; Stephanie Tatum, RN; Celeste Waguespack, RN; Kimberly Crotwell, LPN; Lisa Dalfrey, LPN; Amy Braymer, LPN; Rhonda Hilliard, LPN; Onolee Thomas, RN; Jennifer Arceneaux, RN; Stacie LaPrarie, RN; Allison Strate, RN; Jana Ihrig, RN; Susan Mancuso, RN; Christy Beard, RN; Alicia Hymel; Desti Shepard; John Correa; Denise Jarreau; Brenda Dahmer; Grace Bella; Elizabeth Soroe; Bridget Conner; Paige McCown; Stephanie Anaya; Melissa Lupo. Tufts University (clinical site)—PI: Susan B. Roberts, PhD; CI: Sai Krupa Das, PhD; Simin Meydani, PhD; Roger Fielding, MD; Isaac Greenberg, PhD; Anastassios Pittas, MD; Edward Saltzman, MD; Tammy Scott, PhD; SIL: Cheryl Gilhooly, RD, PhD; IC: Kimberly Gerber, PhD; Isaac Greenberg, PhD; Marjory Kaplan, PhD; Christy Karabetian, MA; Russell Kennedy, PhD; Lisa Robinson, RD; OS: Assefa, Senait; Verona Bembridge; Maria Berlis; Scarlett Buer; Robert Carabello; Cherie Campbell; Lauren Collins, RN; Marybeth Doherty, RN; Alicia Freed, RD; Chervonte Hernandez; Gyna JeanBaptiste, RN; Mary Krasinski, RN; Marie Lim-Lucas, MPH, RD; Ekaterina Maslova; Barbara Maxwell, RN; Jean McShea, RN; Ann Muchowski, RN; Margaret Mulkerrin; Kerry Murphy; Carol Nelsen, RN; Megan O’Neill; Helen Rasmussen, RD, PhD; Brenda Roche; Eneida Roman; Gregory Sproull; Marie St. Victor, RN; Susan Storer, RN; Katherine Strissel, PhD; Stephanie Valliere; Margaret Vilme, RN; Justin Wheeler; Jill Wiley, RN; Fania Yangarber. Washington University (clinical site)—PI: John O. Holloszy, MD; CI: Luigi Fontana, MD; Sam Klein, MD; Charles Lambert, PhD; B. Selma Mohammed, MD, PhD; Susan Racette, PhD; Dennis Villareal, MD; SIL: Rick Stein, PhD; IC: Karen Cotton, Psy D; Margaret Hof, MS, RD, LD; Cherie Massmann, MA, LPC, NCC; Kathleen Obert, MS, RD, LD; Marni Pearlman, MA, PLPC; Tina M Reising, Psy D; Laura Weber, MSEd, RD, LD; SM: Mary Uhrich, MS; SC: Morgan Schram, MS; OS: Mel Meyer, RN, BSN, CRC; Chelsea Carlen, BS; Lisa Kee, DTR; Barbara Larson, DTR; Mary McFerson, BS, DTR; Rebecca Sabatino, BS; Bridgett Toennies, RRT. Duke Clinical Research Institute (coordinating center)—PI: James Rochon, PhD; CI: Connie W. Bales, PhD; Carl F. Pieper, DrPH; William Kraus, MD; PL: Katherine M. Galan, RN; OS: Richard Adrian, BS; Eleanor Law Allen, BA; William Blasko, BS; Manjushri Bhapkar, MS; Nikka Brown, BSN; Maria Butts, RN, BSN; Elaina K. Cossin, BS; Jennifer Curry, AAS; Jamie Daniel, BS, MS; Kathleen S. Diemer, RN; Lee Greiner, BS, MS; Darryl Johnson, BS; Cassandra Jones, BSEE; Lauren Lindblad, MS; Luanne McAdams, RN, MSN; Marty Mansfield, BA, PhD; Senthil Murugesan, MS; Lucy Piner, MS, ACSM CES; Christopher Plummer, BS; Mike Revoir, BS; Pamela Smith, RN, BSN; Monica Spaulding, MPH; James Topping, MS. Baylor College of Medicine (doubly labeled water laboratory)—PI: William W. Wong, PhD; OS: Lucinda L. Clarke, AA; Chun W. Liu, BS; J. Kennard Fraley, MPH. © 2016 American Medical Association. All rights reserved. 3 University of California at San Francisco (dual-energy x-ray absorptiometry reading center)—PI: Ann V. Schwartz, PhD; CI: John Shepherd, PhD; OS: Lisa Palermo, MS; Susan Ewing, MS; Michaela Rahorst; Caroline Navy. University of Vermont (biochemistry laboratory)—PI: Michael Lewis, MD, MBA; CI: Russell P. Tracy, PhD; OS: Rebekah Boyle, BS, MS; Elaine Cornell, BS; Patrick Daunais, BS; Dean Draayer, PhD; Melissa Floersch, BS; Nicole Gagne, BA; Florence Keating, BS; Angela Patnoad, BS. University of Cincinnati (nutrition reading center)—PI: Marcia Schmidt, MS, RD, LD; OS: Marcia Gavin BS, RD, LD; Frida Wiener MS, RD, LD; Ashley Hughes, DTR; Laura Benken. University of Pittsburgh (intervention counseling curriculum)—PI: Amy Otto, PhD. Data and safety monitoring board—Jeffrey Halter, MD (chair); David M. Buchner, MD, MPH; Patricia Elmer, PhD; Mark Espeland, PhD; Steven B. Heymsfield, MD; Xavier Pi-Sunyer, MD; Thomas Prohaska, MD; Sue Shapses, PhD; John Speakman, DSc; Richard Weindruch, PhD. National Institute on Aging (primary funding agency)—Evan C. Hadley, MD; Judy Hannah, PhD; Sergei Romashkan, MD. National Institute of Diabetes and Digestive and Kidney Diseases (cosponsor)—Mary Evans, PhD.

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JLD and CKM formulated the research question. CKM, JWA, SBR, SD, and CFP acquired, analyzed, or interpreted the data. DZ conducted the statistical analysis. JLD interpreted the data and wrote the paper. All authors read the paper and provided critical revisions.

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Correspondence to Corby K. Martin.

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The authors declare that they have no conflict of interest.

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Members of the CALERIE Study Group are listed below Acknowledgements.

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Dorling, J.L., Das, S.K., Racette, S.B. et al. Changes in body weight, adherence, and appetite during 2 years of calorie restriction: the CALERIE 2 randomized clinical trial. Eur J Clin Nutr 74, 1210–1220 (2020).

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