Modified Atkins diet induces subacute selective ragged-red-fiber lysis in mitochondrial myopathy patients
Sofia Ahola1, Mari Auranen1,2, Pirjo Isohanni1
1Research Program of Molecular Neurology, Biomedicum Helsinki 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.
Insights
The modified Atkins diet (mAD) showed potential in treating mitochondrial myopathy (MM) by improving muscle strength, but also caused muscle damage in some patients. Further research is needed to understand its effects on mitochondrial disease progression.
Area of Science:
- Neurology
- Metabolic Disorders
- Mitochondrial Biology
Background:
- Mitochondrial myopathy (MM) with progressive external ophthalmoplegia (PEO) is a common adult mitochondrial disease with no cure.
- Ketogenic diets have shown promise in delaying MM progression in mouse models.
Purpose of the Study:
- To investigate the effects of a modified Atkins diet (mAD) on patients with PEO/MM.
- To analyze clinical, morphological, transcriptomic, and metabolomic changes associated with mAD intervention.
Main Methods:
- Pilot study involving five PEO/MM patients and control subjects.
- Intervention with a high-fat, low-carbohydrate modified Atkins diet (mAD).
- Follow-up assessments included clinical evaluations, muscle biopsy analysis (ultrastructure), transcriptomics, and metabolomics.
Main Results:
- Patients experienced subacute muscle pain and elevated muscle enzymes within 1.5-2 weeks, leading to diet discontinuation.
- Muscle ultrastructure analysis revealed selective damage, particularly in ragged-red-fibers (RRFs), a hallmark of MM.
- Two-year follow-up indicated improved muscle strength, suggesting muscle regeneration.
Conclusions:
- Nutrition can influence the progression of mitochondrial diseases.
- Dietary counseling should be integrated into MM patient care.
- Short-term mAD may serve as a tool for targeted RRF lysis but carries a risk of inducing muscle damage in susceptible individuals.
Related Concept Videos
01:48ATP Synthase: Mechanism
01:24Muscle Recovery and Fatigue