title: Safety of two-year caloric restriction in non-obese healthy individuals.
abstract: BACKGROUND
  The extent to which sustained caloric restriction (CR) in healthy non-obese adults is safe has not been previously investigated.
  
  
  OBJECTIVE
  Assess the safety and tolerability of sustained two-year CR intervention in healthy, non-obese adults.
  
  
  METHODS
  A multi-center, randomized controlled trial. Participants were randomized using a 2:1 allocation in favor of 25% CR vs. Ad-Libitum intake (AL). Adverse and serious adverse events (AE, SAE), safety laboratory tests, and other safety parameters were closely monitored.
  
  
  RESULTS
  Three participants were withdrawn from the CR intervention because of the safety concerns. No deaths and one SAE was reported by participants in the CR group. Although the difference in AE between AL and CR groups was not significant, within the CR group, the incidence of nervous system (p = 0.02), musculoskeletal (p = 0.02) and reproductive system (p = 0.002) disorders was significantly higher in the normal-weight than in the overweight participants. At months 12 and 24, bone mineral densities at the lumbar spine, total hip, and femoral neck of participants in the CR group were significantly lower than in those in the AL group.
  
  
  CONCLUSIONS
  Two-years of CR at levels achieved in CALERIE was safe and well tolerated. Close monitoring for excessive bone loss and anemia is important.
authors.affiliation: National Institute on Aging, Bethesda, MD, USA.
authors.forename: Sergei V
authors.initials: SV
authors.lastname: Romashkan
authors.affiliation: Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA.
authors.forename: Sai Krupa
authors.initials: SK
authors.lastname: Das
authors.affiliation: Washington University School of Medicine, St Louis, MO, USA.|Baylor College of Medicine and Michael E DeBakey VA Medical Center, Houston, TX, USA.
authors.forename: Dennis T
authors.initials: DT
authors.lastname: Villareal
authors.affiliation: Pennington Biomedical Research Center, Baton Rouge, LA, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Ravussin
authors.affiliation: Pennington Biomedical Research Center, Baton Rouge, LA, USA.
authors.forename: Leanne M
authors.initials: LM
authors.lastname: Redman
authors.affiliation: Rho Federal Systems, Chapel Hill, NC, USA.|Duke Clinical Research Institute and Duke University School of Medicine, Durham, NC, USA.
authors.forename: James
authors.initials: J
authors.lastname: Rochon
authors.affiliation: Duke Clinical Research Institute and Duke University School of Medicine, Durham, NC, USA.
authors.forename: Manjushri
authors.initials: M
authors.lastname: Bhapkar
authors.affiliation: Duke Clinical Research Institute and Duke University School of Medicine, Durham, NC, USA.
authors.forename: William E
authors.initials: WE
authors.lastname: Kraus
mesh_terms: D000328:Adult; D000740:Anemia / Q000175:diagnosis / Q000209:etiology; D001823:Body Composition; D001835:Body Weight; D015519:Bone Density; D031204:Caloric Restriction / Q000009:adverse effects / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008991:Monitoring, Physiologic / Q000379:methods; D018570:Risk Assessment / Q000379:methods / Q000706:statistics & numerical data; D012307:Risk Factors; D055815:Young Adult
keywords: Gerotarget; calorie restriction; dietary energy restriction; humans; safety