title: A Diet Mimicking Fasting Promotes Regeneration and Reduces Autoimmunity and Multiple Sclerosis Symptoms.
abstract: Dietary interventions have not been effective in the treatment of multiple sclerosis (MS). Here, we show that periodic 3-day cycles of a fasting mimicking diet (FMD) are effective in ameliorating demyelination and symptoms in a murine experimental autoimmune encephalomyelitis (EAE) model. The FMD reduced clinical severity in all mice and completely reversed symptoms in 20% of animals. These improvements were associated with increased corticosterone levels and regulatory T (Treg) cell numbers and reduced levels of pro-inflammatory cytokines, TH1 and TH17 cells, and antigen-presenting cells (APCs). Moreover, the FMD promoted oligodendrocyte precursor cell regeneration and remyelination in axons in both EAE and cuprizone MS models, supporting its effects on both suppression of autoimmunity and remyelination. We also report preliminary data suggesting that an FMD or a chronic ketogenic diet are safe, feasible, and potentially effective in the treatment of relapsing-remitting multiple sclerosis (RRMS) patients (NCT01538355).
authors.affiliation: Longevity Institute, School of Gerontology, and Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: In Young
authors.initials: IY
authors.lastname: Choi
authors.affiliation: Department of Neurology and Neurosurgery and Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Piccio
authors.affiliation: Global Medicine Program, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: Patra
authors.initials: P
authors.lastname: Childress
authors.affiliation: Department of Neurology and Neurosurgery and Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Bryan
authors.initials: B
authors.lastname: Bollman
authors.affiliation: Department of Neuroscience, Dana and David Dornsife College of Letters, Arts and Sciences, University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: Arko
authors.initials: A
authors.lastname: Ghosh
authors.affiliation: Longevity Institute, School of Gerontology, and Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Brandhorst
authors.affiliation: Longevity Institute, School of Gerontology, and Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: Jorge
authors.initials: J
authors.lastname: Suarez
authors.affiliation: Institute of Social Medicine, Epidemiology and Health Economics, Charité University Medicine Berlin, 10117 Berlin, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Michalsen
authors.affiliation: Department of Neurology and Neurosurgery and Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Anne H
authors.initials: AH
authors.lastname: Cross
authors.affiliation: Longevity Institute, School of Gerontology, and Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: Todd E
authors.initials: TE
authors.lastname: Morgan
authors.affiliation: Longevity Institute, School of Gerontology, and Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Wei
authors.affiliation: NeuroCure Clinical Research Center and Clinical and Experimental Multiple Sclerosis Research Center, Department of Neurology, Charité University Medicine Berlin, 10117 Berlin, Germany; Experimental and Clinical Research Center, a joint cooperation between the Charité Medical Faculty and the Max-Delbrueck Center for Molecular Medicine, 10117 Berlin, Germany.
authors.forename: Friedemann
authors.initials: F
authors.lastname: Paul
authors.affiliation: NeuroCure Clinical Research Center and Clinical and Experimental Multiple Sclerosis Research Center, Department of Neurology, Charité University Medicine Berlin, 10117 Berlin, Germany; Experimental and Clinical Research Center, a joint cooperation between the Charité Medical Faculty and the Max-Delbrueck Center for Molecular Medicine, 10117 Berlin, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Bock
authors.affiliation: Longevity Institute, School of Gerontology, and Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA; Department of Neuroscience, Dana and David Dornsife College of Letters, Arts and Sciences, University of Southern California, Los Angeles, CA 90089, USA; Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA; IFOM, FIRC Institute of Molecular Oncology, 20139 Milan, Italy. Electronic address: vlongo@usc.edu.
authors.forename: Valter D
authors.initials: VD
authors.lastname: Longo
mesh_terms: D000818:Animals; D000941:Antigens / Q000276:immunology; D017209:Apoptosis; D015551:Autoimmunity; D004032:Diet; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000178:diet therapy* / Q000276:immunology*; D005215:Fasting; D005260:Female; D006801:Humans; D018655:Lymphocyte Count; D008214:Lymphocytes / Q000473:pathology; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D009103:Multiple Sclerosis / Q000178:diet therapy* / Q000276:immunology*; D009186:Myelin Sheath; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000276:immunology; D009836:Oligodendroglia / Q000473:pathology; D010446:Peptide Fragments / Q000276:immunology; D012038:Regeneration; D013116:Spinal Cord / Q000276:immunology / Q000473:pathology; D013154:Spleen / Q000473:pathology
chemical_list: D000941:Antigens; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; C445081:myelin oligodendrocyte glycoprotein (35-55)