title: Modified Atkins diet induces subacute selective ragged-red-fiber lysis in mitochondrial myopathy patients.
abstract: Mitochondrial myopathy (MM) with progressive external ophthalmoplegia (PEO) is a common manifestation of mitochondrial disease in adulthood, for which there is no curative therapy. In mice with MM, ketogenic diet significantly delayed progression of the disease. We asked in this pilot study what effects high-fat, low-carbohydrate "modified Atkins" diet (mAD) had for PEO/MM patients and control subjects and followed up the effects by clinical, morphological, transcriptomic, and metabolomic analyses. All of our five patients, irrespective of genotype, showed a subacute response after 1.5-2 weeks of diet, with progressive muscle pain and leakage of muscle enzymes, leading to premature discontinuation of the diet. Analysis of muscle ultrastructure revealed selective fiber damage, especially in the ragged-red-fibers (RRFs), a MM hallmark. Two years of follow-up showed improvement of muscle strength, suggesting activation of muscle regeneration. Our results indicate that (i) nutrition can modify mitochondrial disease progression, (ii) dietary counseling should be part of MM care, (iii) short mAD is a tool to induce targeted RRF lysis, and (iv) mAD, a common weight-loss method, may induce muscle damage in a population subgroup.
authors.affiliation: Research Program of Molecular Neurology, Biomedicum Helsinki University of Helsinki, Helsinki, Finland.
authors.forename: Sofia
authors.initials: S
authors.lastname: Ahola
authors.affiliation: Research Program of Molecular Neurology, Biomedicum Helsinki University of Helsinki, Helsinki, Finland.|Clinical Neurosciences, Neurology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
authors.forename: Mari
authors.initials: M
authors.lastname: Auranen
authors.affiliation: Research Program of Molecular Neurology, Biomedicum Helsinki University of Helsinki, Helsinki, Finland.
authors.forename: Pirjo
authors.initials: P
authors.lastname: Isohanni
authors.affiliation: Obesity Research Unit, Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland.
authors.forename: Satu
authors.initials: S
authors.lastname: Niemisalo
authors.affiliation: Clinical Neurosciences, Neurology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
authors.forename: Niina
authors.initials: N
authors.lastname: Urho
authors.affiliation: Research Program of Molecular Neurology, Biomedicum Helsinki University of Helsinki, Helsinki, Finland.
authors.forename: Jana
authors.initials: J
authors.lastname: Buzkova
authors.affiliation: Metabolomics Unit, Institute for Molecular Medicine Finland FIMM University of Helsinki, Helsinki, Finland.
authors.forename: Vidya
authors.initials: V
authors.lastname: Velagapudi
authors.affiliation: Department of Radiology, University of Helsinki and HUS Radiology Helsinki Medical Imaging Center, Helsinki, Finland.
authors.forename: Nina
authors.initials: N
authors.lastname: Lundbom
authors.affiliation: Department of Radiology, University of Helsinki and HUS Radiology Helsinki Medical Imaging Center, Helsinki, Finland.
authors.forename: Antti
authors.initials: A
authors.lastname: Hakkarainen
authors.affiliation: Department of Clinical Physiology and Nuclear Medicine, Laboratory of Clinical Physiology, Helsinki University Hospitals, Helsinki, Finland.
authors.forename: Tiina
authors.initials: T
authors.lastname: Muurinen
authors.affiliation: Department of Clinical Physiology and Nuclear Medicine, Laboratory of Clinical Physiology, Helsinki University Hospitals, Helsinki, Finland.
authors.forename: Päivi
authors.initials: P
authors.lastname: Piirilä
authors.affiliation: Clinical Neurosciences, Neurology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.|Department of Medicine, Division of Endocrinology, Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Kirsi H
authors.initials: KH
authors.lastname: Pietiläinen
authors.affiliation: Research Program of Molecular Neurology, Biomedicum Helsinki University of Helsinki, Helsinki, Finland anu.wartiovaara@helsinki.fi.|Clinical Neurosciences, Neurology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.|Neuroscience Center, University of Helsinki, Helsinki, Finland.
authors.forename: Anu
authors.identifier: 0000-0003-4833-5195
authors.initials: A
authors.lastname: Suomalainen
mesh_terms: D000328:Adult; D050528:Diet, Carbohydrate-Restricted / Q000009:adverse effects* / Q000379:methods*; D005260:Female; D006801:Humans; D007625:Kearns-Sayre Syndrome / Q000178:diet therapy*; D008297:Male; D009132:Muscles / Q000473:pathology*; D063806:Myalgia; D010865:Pilot Projects; D017211:Treatment Failure; D055815:Young Adult
keywords: PEO; mitochondrial myopathy; modified Atkins diet; ragged‐red‐fibers