title: A 2-Year Randomized Controlled Trial of Human Caloric Restriction: Feasibility and Effects on Predictors of Health Span and Longevity.
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.
authors.affiliation: Pennington Biomedical Research Center, Baton Rouge, Louisiana. ehadley@nih.gov.
authors.forename: Eric
authors.initials: E
authors.lastname: Ravussin
authors.affiliation: Pennington Biomedical Research Center, Baton Rouge, Louisiana.
authors.forename: Leanne M
authors.initials: LM
authors.lastname: Redman
authors.affiliation: Duke Clinical Research Institute and Duke University School of Medicine, Durham, North Carolina. Rho Federal Systems, Chapel Hill, North Carolina.
authors.forename: James
authors.initials: J
authors.lastname: Rochon
authors.affiliation: Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts.
authors.forename: Sai Krupa
authors.initials: SK
authors.lastname: Das
authors.forename: Luigi
authors.initials: L
authors.lastname: Fontana
authors.affiliation: Duke Clinical Research Institute and Duke University School of Medicine, Durham, North Carolina.
authors.forename: William E
authors.initials: WE
authors.lastname: Kraus
authors.affiliation: National Institute on Aging, Bethesda, Maryland.
authors.forename: Sergei
authors.initials: S
authors.lastname: Romashkan
authors.affiliation: Pennington Biomedical Research Center, Baton Rouge, Louisiana.
authors.forename: Donald A
authors.initials: DA
authors.lastname: Williamson
authors.affiliation: Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts.
authors.forename: Simin N
authors.initials: SN
authors.lastname: Meydani
authors.affiliation: Department of Medicine, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Dennis T
authors.initials: DT
authors.lastname: Villareal
authors.affiliation: Pennington Biomedical Research Center, Baton Rouge, Louisiana. Translational Research Institute for Metabolism and Diabetes, Florida Hospital and Sanford Burnham Medical Research Institute, Orlando.
authors.forename: Steven R
authors.initials: SR
authors.lastname: Smith
authors.affiliation: Department of Medicine, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Richard I
authors.initials: RI
authors.lastname: Stein
authors.affiliation: Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts.
authors.forename: Tammy M
authors.initials: TM
authors.lastname: Scott
authors.affiliation: Pennington Biomedical Research Center, Baton Rouge, Louisiana.
authors.forename: Tiffany M
authors.initials: TM
authors.lastname: Stewart
authors.affiliation: Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts.
authors.forename: Edward
authors.initials: E
authors.lastname: Saltzman
authors.affiliation: Department of Medicine, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Samuel
authors.initials: S
authors.lastname: Klein
authors.affiliation: Duke Clinical Research Institute and Duke University School of Medicine, Durham, North Carolina.
authors.forename: Manju
authors.initials: M
authors.lastname: Bhapkar
authors.affiliation: Pennington Biomedical Research Center, Baton Rouge, Louisiana.
authors.forename: Corby K
authors.initials: CK
authors.lastname: Martin
authors.affiliation: Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts.
authors.forename: Cheryl H
authors.initials: CH
authors.lastname: Gilhooly
authors.affiliation: Department of Medicine, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: John O
authors.initials: JO
authors.lastname: Holloszy
authors.affiliation: National Institute on Aging, Bethesda, Maryland.
authors.forename: Evan C
authors.initials: EC
authors.lastname: Hadley
authors.affiliation: Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts.
authors.forename: Susan B
authors.initials: SB
authors.lastname: Roberts
mesh_terms: D000328:Adult; D001481:Basal Metabolism; D001786:Blood Glucose / Q000032:analysis; D001794:Blood Pressure; D001831:Body Temperature; D002097:C-Reactive Protein / Q000032:analysis; D031204:Caloric Restriction; D002149:Energy Intake; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D008055:Lipids / Q000097:blood; D008136:Longevity; D008297:Male; D008875:Middle Aged; D013997:Time Factors; D014284:Triiodothyronine / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D015431:Weight Loss; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D008055:Lipids; D014409:Tumor Necrosis Factor-alpha; D014284:Triiodothyronine; D002097:C-Reactive Protein
keywords: Biomarkers; Caloric restriction; Metabolism; Nutrition; Risk factors