PMID- 26187233 OWN - NLM STAT- MEDLINE DCOM- 20151102 LR - 20220330 IS - 1758-535X (Electronic) IS - 1079-5006 (Print) IS - 1079-5006 (Linking) VI - 70 IP - 9 DP - 2015 Sep TI - A 2-Year Randomized Controlled Trial of Human Caloric Restriction: Feasibility and Effects on Predictors of Health Span and Longevity. PG - 1097-104 LID - 10.1093/gerona/glv057 [doi] AB - 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-alpha (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-alpha 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. CI - Published by Oxford University Press on behalf of the Gerontological Society of America 2015. FAU - Ravussin, Eric AU - Ravussin E AD - Pennington Biomedical Research Center, Baton Rouge, Louisiana. ehadley@nih.gov. FAU - Redman, Leanne M AU - Redman LM AD - Pennington Biomedical Research Center, Baton Rouge, Louisiana. FAU - Rochon, James AU - Rochon J AD - Duke Clinical Research Institute and Duke University School of Medicine, Durham, North Carolina. Rho Federal Systems, Chapel Hill, North Carolina. FAU - Das, Sai Krupa AU - Das SK AD - Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts. FAU - Fontana, Luigi AU - Fontana L FAU - Kraus, William E AU - Kraus WE AD - Duke Clinical Research Institute and Duke University School of Medicine, Durham, North Carolina. FAU - Romashkan, Sergei AU - Romashkan S AD - National Institute on Aging, Bethesda, Maryland. FAU - Williamson, Donald A AU - Williamson DA AD - Pennington Biomedical Research Center, Baton Rouge, Louisiana. FAU - Meydani, Simin N AU - Meydani SN AD - Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts. FAU - Villareal, Dennis T AU - Villareal DT AD - Department of Medicine, Washington University School of Medicine, St. Louis, Missouri. FAU - Smith, Steven R AU - Smith SR AD - Pennington Biomedical Research Center, Baton Rouge, Louisiana. Translational Research Institute for Metabolism and Diabetes, Florida Hospital and Sanford Burnham Medical Research Institute, Orlando. FAU - Stein, Richard I AU - Stein RI AD - Department of Medicine, Washington University School of Medicine, St. Louis, Missouri. FAU - Scott, Tammy M AU - Scott TM AD - Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts. FAU - Stewart, Tiffany M AU - Stewart TM AD - Pennington Biomedical Research Center, Baton Rouge, Louisiana. FAU - Saltzman, Edward AU - Saltzman E AD - Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts. FAU - Klein, Samuel AU - Klein S AD - Department of Medicine, Washington University School of Medicine, St. Louis, Missouri. FAU - Bhapkar, Manju AU - Bhapkar M AD - Duke Clinical Research Institute and Duke University School of Medicine, Durham, North Carolina. FAU - Martin, Corby K AU - Martin CK AD - Pennington Biomedical Research Center, Baton Rouge, Louisiana. FAU - Gilhooly, Cheryl H AU - Gilhooly CH AD - Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts. FAU - Holloszy, John O AU - Holloszy JO AD - Department of Medicine, Washington University School of Medicine, St. Louis, Missouri. FAU - Hadley, Evan C AU - Hadley EC AD - National Institute on Aging, Bethesda, Maryland. FAU - Roberts, Susan B AU - Roberts SB AD - Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts. CN - CALERIE Study Group LA - eng SI - ClinicalTrials.gov/NCT00427193 GR - U24 AG047121/AG/NIA NIH HHS/United States GR - U01 AG020487/AG/NIA NIH HHS/United States GR - U01AG020480/AG/NIA NIH HHS/United States GR - U01AG020487/AG/NIA NIH HHS/United States GR - U01 AG020480/AG/NIA NIH HHS/United States GR - U01 AG022132/AG/NIA NIH HHS/United States GR - P30 DK072476/DK/NIDDK NIH HHS/United States GR - P30 DK098722/DK/NIDDK NIH HHS/United States GR - U01AG020478/AG/NIA NIH HHS/United States GR - U01AG022132/AG/NIA NIH HHS/United States GR - U01 AG020478/AG/NIA NIH HHS/United States PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, N.I.H., Extramural DEP - 20150717 PL - United States TA - J Gerontol A Biol Sci Med Sci JT - The journals of gerontology. Series A, Biological sciences and medical sciences JID - 9502837 RN - 0 (Blood Glucose) RN - 0 (Lipids) RN - 0 (Tumor Necrosis Factor-alpha) RN - 06LU7C9H1V (Triiodothyronine) RN - 9007-41-4 (C-Reactive Protein) SB - IM CIN - J Gerontol A Biol Sci Med Sci. 2015 Sep;70(9):1095-6. PMID: 26187232 EIN - J Gerontol A Biol Sci Med Sci. 2016 Jun;71(6):839-40. PMID: 27059599 MH - Adult MH - Basal Metabolism MH - Blood Glucose/analysis MH - Blood Pressure MH - Body Temperature MH - C-Reactive Protein/analysis MH - *Caloric Restriction MH - Energy Intake MH - Feasibility Studies MH - Female MH - Humans MH - Lipids/blood MH - *Longevity MH - Male MH - Middle Aged MH - Time Factors MH - Triiodothyronine/blood MH - Tumor Necrosis Factor-alpha/blood MH - Weight Loss MH - Young Adult PMC - PMC4841173 OTO - NOTNLM OT - Biomarkers OT - Caloric restriction OT - Metabolism OT - Nutrition OT - Risk factors FIR - Ravussin, Eric IR - Ravussin E FIR - Champagne, Catherine IR - Champagne C FIR - Gupta, Alok IR - Gupta A FIR - Martin, Corby IR - Martin C FIR - Redman, Leanne IR - Redman L FIR - Smith, Steven IR - Smith S FIR - Williamson, Donald IR - Williamson D FIR - Martin, Corby IR - Martin C FIR - Begnaud, Michelle IR - Begnaud M FIR - Cerniauskas, Barbara IR - Cerniauskas B FIR - Davis, Allison IR - Davis A FIR - Gabrielle, Jeanne IR - Gabrielle J FIR - Walden, Heather IR - Walden H FIR - Currier, Natalie IR - Currier N FIR - Shipp, Mandy IR - Shipp M FIR - Masters, Sarah IR - Masters S FIR - McNicoll, Melody IR - McNicoll M FIR - Prince, Shelly IR - Prince S FIR - Brock, Courtney IR - Brock C FIR - Puyau, Renee IR - Puyau R FIR - Earnest, Conrad IR - Earnest C FIR - Rood, Jennifer IR - Rood J FIR - Stewart, Tiffany IR - Stewart T FIR - Levitan, Lillian IR - Levitan L FIR - Traylor, Crystal IR - Traylor C FIR - Thomas, Susan IR - Thomas S FIR - Toups, Valerie IR - Toups V FIR - Jones, Karen IR - Jones K FIR - Tatum, Stephanie IR - Tatum S FIR - Waguespack, Celeste IR - Waguespack C FIR - Crotwell, Kimberly IR - Crotwell K FIR - Dalfrey, Lisa IR - Dalfrey L FIR - Braymer, Amy IR - Braymer A FIR - Hilliard, Rhonda IR - Hilliard R FIR - Thomas, Onolee IR - Thomas O FIR - Arceneaux, Jennifer IR - Arceneaux J FIR - LaPrarie, Stacie IR - LaPrarie S FIR - Strate, Allison IR - Strate A FIR - Ihrig, Jana IR - Ihrig J FIR - Mancuso, Susan IR - Mancuso S FIR - Beard, Christy IR - Beard C FIR - Hymel, Alicia IR - Hymel A FIR - Shepard, Desti IR - Shepard D FIR - Correa, John IR - Correa J FIR - Jarreau, Denise IR - Jarreau D FIR - Dahmer, Brenda IR - Dahmer B FIR - Bella, Grace IR - Bella G FIR - Soroe, Elizabeth IR - Soroe E FIR - Conner, Bridget IR - Conner B FIR - McCown, Paige IR - McCown P FIR - Anaya, Stephanie IR - Anaya S FIR - Lupo, Melissa IR - Lupo M FIR - Roberts, Susan B IR - Roberts SB FIR - Das, Sai Krupa IR - Das SK FIR - Meydani, Simin IR - Meydani S FIR - Fielding, Roger IR - Fielding R FIR - Greenberg, Isaac IR - Greenberg I FIR - Pittas, Anastassios IR - Pittas A FIR - Saltzman, Edward IR - Saltzman E FIR - Scott, Tammy IR - Scott T FIR - Gilhooly, Cheryl IR - Gilhooly C FIR - Gerber, Kimberly IR - Gerber K FIR - Greenberg, Isaac IR - Greenberg I FIR - Kaplan, Marjory IR - Kaplan M FIR - Karabetian, Christy IR - Karabetian C FIR - Kennedy, Russell IR - Kennedy R FIR - Robinson, Lisa IR - Robinson L FIR - Bembridge, Verona IR - Bembridge V FIR - Berlis, Maria IR - Berlis M FIR - Buer, Scarlett IR - Buer S FIR - Carabello, Robert IR - Carabello R FIR - Campbell, Cherie IR - Campbell C FIR - Collins, Lauren IR - Collins L FIR - Doherty, Marybeth IR - Doherty M FIR - Freed, Alicia IR - Freed A FIR - Hernandez, Chervonte IR - Hernandez C FIR - Jean-Baptiste, Gyna IR - Jean-Baptiste G FIR - Krasinski, Mary IR - Krasinski M FIR - Lim-Lucas, Marie IR - Lim-Lucas M FIR - Maslova, Ekaterina IR - Maslova E FIR - Maxwell, Barbara IR - Maxwell B FIR - McShea, Jean IR - McShea J FIR - Muchowski, Ann IR - Muchowski A FIR - Mulkerrin, Margaret IR - Mulkerrin M FIR - Murphy, Kerry IR - Murphy K FIR - Nelsen, Carol IR - Nelsen C FIR - O'Neill, Megan IR - O'Neill M FIR - Rasmussen, Helen IR - Rasmussen H FIR - Roche, Brenda IR - Roche B FIR - Roman, Eneida IR - Roman E FIR - Sproull, Gregory IR - Sproull G FIR - Victor, Marie St IR - Victor MS FIR - Storer, Susan IR - Storer S FIR - Strissel, Katherine IR - Strissel K FIR - Valliere, Stephanie IR - Valliere S FIR - Vilme, Margaret IR - Vilme M FIR - Wheeler, Justin IR - Wheeler J FIR - Wiley, Jill IR - Wiley J FIR - Yangarber, Fania IR - Yangarber F FIR - Holloszy, John O IR - Holloszy JO FIR - Fontana, Luigi IR - Fontana L FIR - Klein, Sam IR - Klein S FIR - Lambert, Charles IR - Lambert C FIR - Mohammed, B Selma IR - Mohammed BS FIR - Racette, Susan IR - Racette S FIR - Villareal, Dennis IR - Villareal D FIR - Stein, Rick IR - Stein R FIR - Cotton, Karen IR - Cotton K FIR - Hof, Margaret IR - Hof M FIR - Massmann, Cherie IR - Massmann C FIR - Obert, Kathleen IR - Obert K FIR - Pearlman, Marni IR - Pearlman M FIR - Reising, Tina M IR - Reising TM FIR - Weber, Laura IR - Weber L FIR - Uhrich, Mary IR - Uhrich M FIR - Schram, Morgan IR - Schram M FIR - Meyer, Mel IR - Meyer M FIR - Carlen, Chelsea IR - Carlen C FIR - Kee, Lisa IR - Kee L FIR - Larson, Barbara IR - Larson B FIR - McFerson, Mary IR - McFerson M FIR - Sabatino, Rebecca IR - Sabatino R FIR - Toennies, Bridgett IR - Toennies B FIR - Rochon, James IR - Rochon J FIR - Bales, Connie W IR - Bales CW FIR - Pieper, Carl F IR - Pieper CF FIR - Kraus, William IR - Kraus W FIR - Galan, Katherine M IR - Galan KM FIR - Adrian, Richard IR - Adrian R FIR - Allen, Eleanor Law IR - Allen EL FIR - Blasko, William IR - Blasko W FIR - Bhapkar, Manjushri IR - Bhapkar M FIR - Brown, Nikka IR - Brown N FIR - Butts, Maria IR - Butts M FIR - Cossin, Elaina K IR - Cossin EK FIR - Curry, Jennifer IR - Curry J FIR - Daniel, Jamie IR - Daniel J FIR - Diemer, Kathleen S IR - Diemer KS FIR - Greiner, Lee IR - Greiner L FIR - Johnson, Darryl IR - Johnson D FIR - Jones, Cassandra IR - Jones C FIR - Lindblad, Lauren IR - Lindblad L FIR - McAdams, Luanne IR - McAdams L FIR - Mansfield, Marty IR - Mansfield M FIR - Murugesan, Senthil IR - Murugesan S FIR - Piner, Lucy IR - Piner L FIR - Plummer, Christopher IR - Plummer C FIR - Revoir, Mike IR - Revoir M FIR - Smith, Pamela IR - Smith P FIR - Spaulding, Monica IR - Spaulding M FIR - Topping, James IR - Topping J FIR - Wong, William W IR - Wong WW FIR - Clarke, Lucinda L IR - Clarke LL FIR - Liu, Chun W IR - Liu CW FIR - Fraley, J Kennard IR - Fraley J FIR - Schwartz, Ann V IR - Schwartz AV FIR - Shepherd, John IR - Shepherd J FIR - Palermo, Lisa IR - Palermo L FIR - Ewing, Susan IR - Ewing S FIR - Rahorst, Michaela IR - Rahorst M FIR - Navy, Caroline IR - Navy C FIR - Lewis, Michael IR - Lewis M FIR - Tracy, Russell P IR - Tracy RP FIR - Boyle, Rebekah IR - Boyle R FIR - Cornell, Elaine IR - Cornell E FIR - Daunais, Patrick IR - Daunais P FIR - Draayer, Dean IR - Draayer D FIR - Floersch, Melissa IR - Floersch M FIR - Gagne, Nicole IR - Gagne N FIR - Keating, Florence IR - Keating F FIR - Patnoad, Angela IR - Patnoad A FIR - Schmidt, Marcia IR - Schmidt M FIR - Gavin, Marcia IR - Gavin M FIR - Wiener, Frida IR - Wiener F FIR - Hughes, Ashley IR - Hughes A FIR - Benken, Laura IR - Benken L FIR - Otto, Amy IR - Otto A FIR - Halter, Jeffrey IR - Halter J FIR - Buchner, David M IR - Buchner DM FIR - Elmer, Patricia IR - Elmer P FIR - Espeland, Mark IR - Espeland M FIR - Heymsfield, Steven B IR - Heymsfield SB FIR - Pi-Sunyer, Xavier IR - Pi-Sunyer X FIR - Prohaska, Thomas IR - Prohaska T FIR - Shapses, Sue IR - Shapses S FIR - Speakman, John IR - Speakman J FIR - Weindruch, Richard IR - Weindruch R FIR - Hadley, Evan C IR - Hadley EC FIR - Hannah, Judy IR - Hannah J FIR - Romashkan, Sergei IR - Romashkan S FIR - Evans, Mary IR - Evans M EDAT- 2015/07/19 06:00 MHDA- 2015/11/03 06:00 PMCR- 2016/09/01 CRDT- 2015/07/19 06:00 PHST- 2015/01/28 00:00 [received] PHST- 2015/04/05 00:00 [accepted] PHST- 2015/07/19 06:00 [entrez] PHST- 2015/07/19 06:00 [pubmed] PHST- 2015/11/03 06:00 [medline] PHST- 2016/09/01 00:00 [pmc-release] AID - glv057 [pii] AID - 10.1093/gerona/glv057 [doi] PST - ppublish SO - J Gerontol A Biol Sci Med Sci. 2015 Sep;70(9):1097-104. doi: 10.1093/gerona/glv057. Epub 2015 Jul 17.