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EMBO Mol Med. 2016 Nov 2;8(11):1234-1247. doi: 10.15252/emmm.201606592. Print 2016 Nov.

Modified Atkins diet induces subacute selective ragged-red-fiber lysis in mitochondrial myopathy patients.

Author information

1
Research Program of Molecular Neurology, Biomedicum Helsinki University of Helsinki, Helsinki, Finland.
2
Clinical Neurosciences, Neurology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
3
Obesity Research Unit, Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland.
4
Metabolomics Unit, Institute for Molecular Medicine Finland FIMM University of Helsinki, Helsinki, Finland.
5
Department of Radiology, University of Helsinki and HUS Radiology Helsinki Medical Imaging Center, Helsinki, Finland.
6
Department of Clinical Physiology and Nuclear Medicine, Laboratory of Clinical Physiology, Helsinki University Hospitals, Helsinki, Finland.
7
Department of Medicine, Division of Endocrinology, Helsinki University Central Hospital, Helsinki, Finland.
8
Research Program of Molecular Neurology, Biomedicum Helsinki University of Helsinki, Helsinki, Finland anu.wartiovaara@helsinki.fi.
9
Neuroscience Center, University of Helsinki, Helsinki, Finland.

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.

KEYWORDS:

PEO; mitochondrial myopathy; modified Atkins diet; ragged‐red‐fibers

PMID:
27647878
PMCID:
PMC5090657
DOI:
10.15252/emmm.201606592
[Indexed for MEDLINE]
Free PMC Article

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