title: Effects of 2-year calorie restriction on circulating levels of IGF-1, IGF-binding proteins and cortisol in nonobese men and women: a randomized clinical trial.
abstract: Young-onset calorie restriction (CR) in rodents decreases serum IGF-1 concentration and increases serum corticosterone levels, which have been hypothesized to play major roles in mediating its anticancer and anti-aging effects. However, little is known on the effects of CR on the IGF-1 system and cortisol in humans. To test the sustained effects of CR on these key hormonal adaptations, we performed a multicenter randomized trial of a 2-year 25% CR intervention in 218 nonobese (body mass index between 22 and 27.8 kg m(-2) ) young and middle-aged (20-50 years age range) men and women. Average CR during the first 6 months was 19.5 ± 0.8% and 9.1 ± 0.7% over the next 18 months of the study. Weight loss averaged 7.6 ± 0.3 kg over the 2-years period of which 71% was fat mass loss (P < 0.0001). Average CR during the CR caused a significant 21% increase in serum IGFBP-1 and a 42% reduction in IGF-1:IGFBP-1 ratio at 2 years (P < 0.008), but did not change IGF-1 and IGF-1:IGFBP-3 ratio levels. Serum cortisol concentrations were slightly but significantly increased by CR at 1 year only (P = 0.003). Calorie restriction had no effect on serum concentrations of PDGF-AB and TGFβ-1. We conclude, on the basis of the present and previous findings, that, in contrast to rodents, humans do not respond to CR with a decrease in serum IGF-1 concentration or with a sustained and biological relevant increase in serum cortisol. However, long-term CR in humans significantly and persistently increases serum IGFBP-1 concentration.
authors.affiliation: Department of Medicine, Washington University School of Medicine, St Louis, MO, USA.|Department of Clinical and Experimental Sciences, University of Brescia Medical School, Brescia, Italy.|CEINGE Biotecnologie Avanzate, Napoli, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Fontana
authors.affiliation: Department of Medicine, Washington University School of Medicine, St Louis, MO, USA.|Center for Translational Research on Inflammatory Diseases (CTRID), Baylor College of Medicine, Michael E DeBakey VA Medical Center, Houston, TX, USA.
authors.forename: Dennis T
authors.initials: DT
authors.lastname: Villareal
authors.affiliation: Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA.
authors.forename: Sai K
authors.initials: SK
authors.lastname: Das
authors.affiliation: Pennington Biomedical Research Center, Baton Rouge, LA, USA.|Translational Research Institute for Metabolism and Diabetes, Florida Hospital, Sanford Burnham Medical Research Institute, Orlando, FL, USA.
authors.forename: Steven R
authors.initials: SR
authors.lastname: Smith
authors.affiliation: Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA.
authors.forename: Simin N
authors.initials: SN
authors.lastname: Meydani
authors.affiliation: Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA.
authors.forename: Anastassios G
authors.initials: AG
authors.lastname: Pittas
authors.affiliation: Department of Medicine, Washington University School of Medicine, St Louis, MO, USA.
authors.forename: Samuel
authors.initials: S
authors.lastname: Klein
authors.affiliation: Duke Clinical Research Institute, Durham, NC, USA.
authors.forename: Manjushri
authors.initials: M
authors.lastname: Bhapkar
authors.affiliation: Duke Clinical Research Institute, Durham, NC, USA.|Rho Federal Systems, Chapel Hill, NC, USA.
authors.forename: James
authors.initials: J
authors.lastname: Rochon
authors.affiliation: Pennington Biomedical Research Center, Baton Rouge, LA, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Ravussin
authors.affiliation: Department of Medicine, Washington University School of Medicine, St Louis, MO, USA.
authors.forename: John O
authors.initials: JO
authors.lastname: Holloszy
mesh_terms: D000328:Adult; D000375:Aging / Q000502:physiology*; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D031204:Caloric Restriction; D002149:Energy Intake / Q000502:physiology*; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood; D018969:Insulin-Like Growth Factor Binding Proteins / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D012727:Sex Characteristics; D013997:Time Factors
chemical_list: D001786:Blood Glucose; C583557:IGF1 protein, human; D018970:Insulin-Like Growth Factor Binding Protein 1; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I; D006854:Hydrocortisone
keywords: IGF-1; IGFBP-1; calorie restriction; cancer; cortisol; weight loss