title: Long-term moderate calorie restriction inhibits inflammation without impairing cell-mediated immunity: a randomized controlled trial in non-obese humans.
abstract: Calorie restriction (CR) inhibits inflammation and slows aging in many animal species, but in rodents housed in pathogen-free facilities, CR impairs immunity against certain pathogens. However, little is known about the effects of long-term moderate CR on immune function in humans. In this multi-center, randomized clinical trial to determine CR's effect on inflammation and cell-mediated immunity, 218 healthy non-obese adults (20-50 y), were assigned 25% CR (n=143) or an ad-libitum (AL) diet (n=75), and outcomes tested at baseline, 12, and 24 months of CR. CR induced a 10.4% weight loss over the 2-y period. Relative to AL group, CR reduced circulating inflammatory markers, including total WBC and lymphocyte counts, ICAM-1 and leptin. Serum CRP and TNF-α concentrations were about 40% and 50% lower in CR group, respectively. CR had no effect on the delayed-type hypersensitivity skin response or antibody response to vaccines, nor did it cause difference in clinically significant infections. In conclusion, long-term moderate CR without malnutrition induces a significant and persistent inhibition of inflammation without impairing key in vivo indicators of cell-mediated immunity. Given the established role of these pro-inflammatory molecules in the pathogenesis of multiple chronic diseases, these CR-induced adaptations suggest a shift toward a healthy phenotype.
authors.affiliation: The Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA 02111, USA.
authors.forename: Simin N
authors.initials: SN
authors.lastname: Meydani
authors.affiliation: The Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA 02111, USA.
authors.forename: Sai K
authors.initials: SK
authors.lastname: Das
authors.affiliation: Duke University Medical Center, Durham, NC 27705, USA.
authors.forename: Carl F
authors.initials: CF
authors.lastname: Pieper
authors.affiliation: University of Vermont, Burlington, VT 05405, USA.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Lewis
authors.affiliation: Department of Medicine, Washington University School of Medicine, St Louis, MO 63110, USA.
authors.forename: Sam
authors.initials: S
authors.lastname: Klein
authors.affiliation: Comparative Medicine and Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06510, USA.
authors.forename: Vishwa D
authors.initials: VD
authors.lastname: Dixit
authors.affiliation: Pennington Biomedical Research Center, Baton Rouge, LA 70808, USA.
authors.forename: Alok K
authors.initials: AK
authors.lastname: Gupta
authors.affiliation: Baylor College of Medicine and Michael E DeBakey VA Medical Center, Houston, TX 77030, USA.
authors.forename: Dennis T
authors.initials: DT
authors.lastname: Villareal
authors.affiliation: Duke University Medical Center, Durham, NC 27705, USA.
authors.forename: Manjushri
authors.initials: M
authors.lastname: Bhapkar
authors.affiliation: Duke University Medical Center, Durham, NC 27705, USA.
authors.forename: Megan
authors.initials: M
authors.lastname: Huang
authors.affiliation: The Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA 02111, USA.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Fuss
authors.affiliation: The Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA 02111, USA.
authors.forename: Susan B
authors.initials: SB
authors.lastname: Roberts
authors.affiliation: Department of Medicine, Washington University School of Medicine, St Louis, MO 63110, USA.
authors.forename: John O
authors.initials: JO
authors.lastname: Holloszy
authors.affiliation: Department of Medicine, Washington University School of Medicine, St Louis, MO 63110, USA.|Department of Clinical and Experimental Sciences, Brescia University School of Medicine, Brescia, Italy.|CEINGE Biotecnologie Avanzate, Napoli, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Fontana
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D001823:Body Composition / Q000502:physiology*; D002097:C-Reactive Protein / Q000378:metabolism; D031204:Caloric Restriction; D004032:Diet; D002149:Energy Intake; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000178:diet therapy*; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D020738:Leptin / Q000097:blood; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D015415:Biomarkers; D020738:Leptin; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D002097:C-Reactive Protein
keywords: calorie restriction; cell-mediated immunity; familial longevity; human; inflammation; vaccine response