Open AccessModified Atkins diet induces subacute selective ragged‐red‐fiber lysis in mitochondrial myopathy patients
Author(s) -
Ahola Sofia,
Auranen Mari,
Isohanni Pirjo,
Niemisalo Satu,
Urho Niina,
Buzkova Jana,
Velagapudi Vidya,
Lundbom Nina,
Hakkarainen Antti,
Muurinen Tiina,
Piirilä Päivi,
Pietiläinen Kirsi H,
Suomalainen Anu
Publication year - 2016
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.15252/emmm.201606592
Subject(s) - myopathy , mitochondrial myopathy , fiber , lysis , medicine , biology , pathology , chemistry , endocrinology , biochemistry , mitochondrial dna , gene , organic chemistry
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 ( RRF s), 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.