Modified Atkins diet induces subacute selective ragged-red-fiber lysis in mitochondrial myopathy patients
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- 作者：Sofia Ahola ; Mari Auranen ; Pirjo Isohanni ; Satu Niemisalo ; Niina Urho ; Jana Buzkova ; Vidya Velagapudi ; Nina Lundbom ; Antti Hakkarainen ; Tiina Muurinen ; Pä ; ivi Piirilä ; Kirsi H Pietilä ; inen and Anu Suomalainen
- 刊名：EMBO Molecular Medicine
- 出版年：2016
- 出版时间：November 2016
- 年：2016
- 卷：8
- 期：11
- 页码：1234-1247
- 全文大小：5682K
- ISSN：1757-4684
文摘
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.