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A 2-Year Randomized Controlled Trial of Human Caloric Restriction: Feasibility and Effects on Predictors of Health Span and Longevity.

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26187233
PMC4841173
The journals of gerontology. Series A, Biological sciences and medical sciences
Sept. 1, 2015
Eric Ravussin8, Leanne M Redman6, James Rochon3, Sai Krupa Das4, Luigi Fontana, William E Kraus2, Sergei Romashkan5, Donald A Williamson6, Simin N Meydani4, Dennis T Villareal1, Steven R Smith7, Richard I Stein1, Tammy M Scott4, Tiffany M Stewart6, Edward Saltzman4, Samuel Klein1, Manju Bhapkar2, Corby K Martin6, Cheryl H Gilhooly4, John O Holloszy1, Evan C Hadley5, Susan B Roberts4, CALERIE Study Group, Eric Ravussin, Catherine Champagne, Alok Gupta, Corby Martin, Leanne Redman, Steven Smith, Donald Williamson, Corby Martin, Michelle Begnaud, Barbara Cerniauskas, Allison Davis, Jeanne Gabrielle, Heather Walden, Natalie Currier, Mandy Shipp, Sarah Masters, Melody McNicoll, Shelly Prince, Courtney Brock, Renee Puyau, Conrad Earnest, Jennifer Rood, Tiffany Stewart, Lillian Levitan, Crystal Traylor, Susan Thomas, Valerie Toups, Karen Jones, Stephanie Tatum, Celeste Waguespack, Kimberly Crotwell, Lisa Dalfrey, Amy Braymer, Rhonda Hilliard, Onolee Thomas, Jennifer Arceneaux, Stacie LaPrarie, Allison Strate, Jana Ihrig, Susan Mancuso, Christy Beard, Alicia Hymel, Desti Shepard, John Correa, Denise Jarreau, Brenda Dahmer, Grace Bella, Elizabeth Soroe, Bridget Conner, Paige McCown, Stephanie Anaya, Melissa Lupo, Susan B Roberts, Sai Krupa Das, Simin Meydani, Roger Fielding, Isaac Greenberg, Anastassios Pittas, Edward Saltzman, Tammy Scott, Cheryl Gilhooly, Kimberly Gerber, Isaac Greenberg, Marjory Kaplan, Christy Karabetian, Russell Kennedy, Lisa Robinson, Verona Bembridge, Maria Berlis, Scarlett Buer, Robert Carabello, Cherie Campbell, Lauren Collins, Marybeth Doherty, Alicia Freed, Chervonte Hernandez, Gyna Jean-Baptiste, Mary Krasinski, Marie Lim-Lucas, Ekaterina Maslova, Barbara Maxwell, Jean McShea, Ann Muchowski, Margaret Mulkerrin, Kerry Murphy, Carol Nelsen, Megan O'Neill, Helen Rasmussen, Brenda Roche, Eneida Roman, Gregory Sproull, Marie St Victor, Susan Storer, Katherine Strissel, Stephanie Valliere, Margaret Vilme, Justin Wheeler, Jill Wiley, Fania Yangarber, John O Holloszy, Luigi Fontana, Sam Klein, Charles Lambert, B Selma Mohammed, Susan Racette, Dennis Villareal, Rick Stein, Karen Cotton, Margaret Hof, Cherie Massmann, Kathleen Obert, Marni Pearlman, Tina M Reising, Laura Weber, Mary Uhrich, Morgan Schram, Mel Meyer, Chelsea Carlen, Lisa Kee, Barbara Larson, Mary McFerson, Rebecca Sabatino, Bridgett Toennies, James Rochon, Connie W Bales, Carl F Pieper, William Kraus, Katherine M Galan, Richard Adrian, Eleanor Law Allen, William Blasko, Manjushri Bhapkar, Nikka Brown, Maria Butts, Elaina K Cossin, Jennifer Curry, Jamie Daniel, Kathleen S Diemer, Lee Greiner, Darryl Johnson, Cassandra Jones, Lauren Lindblad, Luanne McAdams, Marty Mansfield, Senthil Murugesan, Lucy Piner, Christopher Plummer, Mike Revoir, Pamela Smith, Monica Spaulding, James Topping, William W Wong, Lucinda L Clarke, Chun W Liu, J Kennard Fraley, Ann V Schwartz, John Shepherd, Lisa Palermo, Susan Ewing, Michaela Rahorst, Caroline Navy, Michael Lewis, Russell P Tracy, Rebekah Boyle, Elaine Cornell, Patrick Daunais, Dean Draayer, Melissa Floersch, Nicole Gagne, Florence Keating, Angela Patnoad, Marcia Schmidt, Marcia Gavin, Frida Wiener, Ashley Hughes, Laura Benken, Amy Otto, Jeffrey Halter, David M Buchner, Patricia Elmer, Mark Espeland, Steven B Heymsfield, Xavier Pi-Sunyer, Thomas Prohaska, Sue Shapses, John Speakman, Richard Weindruch, Evan C Hadley, Judy Hannah, Sergei Romashkan, Mary Evans
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  • 1
    Department of Medicine, Washington University School of Medicine, St. Louis, Missouri.
  • 2
    Duke Clinical Research Institute and Duke University School of Medicine, Durham, North Carolina.
  • 3
    Duke Clinical Research Institute and Duke University School of Medicine, Durham, North Carolina. Rho Federal Systems, Chapel Hill, North Carolina.
  • 4
    Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts.
  • 5
    National Institute on Aging, Bethesda, Maryland.
  • 6
    Pennington Biomedical Research Center, Baton Rouge, Louisiana.
  • 7
    Pennington Biomedical Research Center, Baton Rouge, Louisiana. Translational Research Institute for Metabolism and Diabetes, Florida Hospital and Sanford Burnham Medical Research Institute, Orlando.
  • 8
    Pennington Biomedical Research Center, Baton Rouge, Louisiana. ehadley@nih.gov.
Triiodothyronine, Young Adult, Basal Metabolism, Longevity, Caloric Restriction, Body Temperature, Tumor Necrosis Factor-alpha, Feasibility Studies, Blood Glucose, Energy Intake, C-Reactive Protein, Weight Loss, Male, Lipids, Blood Pressure, Time Factors, Adult, Middle Aged, Humans, Female
P30 DK098722, U24 AG047121, U01 AG020480, U01 AG022132, U01AG020487, U01AG020478, U01AG020480, U01AG022132, U01 AG020487, U01 AG020478
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. The journals of gerontology. Series A, Biological sciences and medical sciences 2015 Sep.

Abstract

BACKGROUND: Caloric restriction (CR), energy intake reduced below ad libitum (AL) intake, increases life span in many species. The implications for humans can be clarified by randomized controlled trials of CR. METHODS: To determine CR's feasibility, safety, and effects on predictors of longevity, disease risk factors, and quality of life in nonobese humans aged 21-51 years, 218 persons were randomized to a 2-year intervention designed to achieve 25% CR or to AL diet. Outcomes were change from baseline resting metabolic rate adjusted for weight change ("RMR residual") and core temperature (primary); plasma triiodothyronine (T3) and tumor necrosis factor-α (secondary); and exploratory physiological and psychological measures. RESULTS: Body mass index averaged 25.1 (range: 21.9-28.0 kg/m(2)). Eighty-two percent of CR and 95% of AL participants completed the protocol. The CR group achieved 11.7±0.7 %CR (mean ± standard error) and maintained 10.4±0.4% weight loss. Weight change in AL was negligible. RMR residual decreased significantly more in CR than AL at 12 months (p = .04) but not 24 months (M24). Core temperature change differed little between groups. T3 decreased more in CR at M12 and M24 (p < .001), while tumor necrosis factor-α decreased significantly more only at M24 (p = .02). CR had larger decreases in cardiometabolic risk factors and in daily energy expenditure adjusted for weight change, without adverse effects on quality of life. CONCLUSIONS: Sustained CR is feasible in nonobese humans. The effects of the achieved CR on correlates of human survival and disease risk factors suggest potential benefits for aging-related outcomes that could be elucidated by further human studies.