Modified Atkins diet induces subacute selective ragged‐red‐fiber lysis in mitochondrial myopathy patients. Issue 11 (19th September 2016)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: EMBO molecular medicine. Volume 8:Issue 11(2016)
• Page Start: 1234
• Page End: 1247
• Publication Date: 2016-09-19
• Subjects: mitochondrial myopathy -- modified Atkins diet -- PEO -- ragged‐red‐fibers; Molecular biology -- Periodicals; Medical genetics -- Periodicals; Pathology, Molecular -- Periodicals; 616.04205
• DOI: 10.15252/emmm.201606592
• Languages: English
• ISSNs: 1757-4676

Abstract

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. Synopsis: High‐fat, low‐carbohydrate modified Atkins diet (mAD) is a common weight‐loss method, found to ameliorate mitochondrial myopathy in mice. In human patients, mAD induces muscle damage, especially of ragged‐red fibers, the most affected by the disease. mAD causes subacute lysis of respiratory chain‐deficient fibers in mitochondrial myopathy. All mitochondrial myopathy patients experienced similar muscle symptoms, independently of their disease mutation. Ragged‐red fibers (RRFs) are unable to use fuels other than glucose. Short dietary intervention could be a tool to reduce RRF amount. The Atkins diet may thus cause muscle damage to a population subgroup with subclinical mitochondrial disease. Abstract : High‐fat, low‐carbohydrate modified Atkins diet (mAD) is a common weight‐loss method, found to ameliorate mitochondrial myopathy in mice. In human patients, mAD induces muscle damage, especially of ragged‐red fibers, the most affected by the disease.