Dataset Information

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

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.

SUBMITTER: Ahola S

PROVIDER: S-EPMC5090657 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Ahola Sofia S Auranen Mari M Isohanni Pirjo P Niemisalo Satu S Urho Niina N Buzkova Jana J Velagapudi Vidya V Lundbom Nina N Hakkarainen Antti A Muurinen Tiina T Piirilä Päivi P Pietiläinen Kirsi H KH Suomalainen Anu A

EMBO molecular medicine 20161102 11

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 analys ...[more]

PMID: 27647878

Similar Datasets

Project description:ImportanceThe ketogenic diet (KD) has been used successfully to treat children with drug-resistant epilepsy. Data assessing the efficacy of the modified Atkins diet (MAD) and low glycemic index therapy (LGIT) diet compared with the KD are scarce.ObjectiveTo determine whether the MAD and LGIT diet are noninferior to the KD among children with drug-resistant epilepsy.Design, setting, and participantsOne hundred seventy children aged between 1 and 15 years who had 4 or more seizures per month, had not responded to 2 or more antiseizure drugs, and had not been treated previously with the KD, MAD, or LGIT diet were enrolled between April 1, 2016, and August 20, 2017, at a tertiary care referral center in India.ExposuresChildren were randomly assigned to receive the KD, MAD, or LGIT diet as additions to ongoing therapy with antiseizure drugs.Main outcomes and measuresPrimary outcome was percentage change in seizure frequency after 24 weeks of dietary therapy in the MAD cohort compared with the KD cohort and in the LGIT diet cohort compared with the KD cohort. The trial was powered to assess noninferiority of the MAD and LGIT diet compared with the KD with a predefined, noninferiority margin of -15 percentage points. Intention-to-treat analysis was used.ResultsOne hundred fifty-eight children completed the trial: KD (n = 52), MAD (n = 52), and LGIT diet (n = 54). Intention-to-treat analysis showed that, after 24 weeks of intervention, the median (interquartile range [IQR]) change in seizure frequency (KD: -66%; IQR, -85% to -38%; MAD: -45%; IQR, -91% to -7%; and LGIT diet: -54%; IQR, -92% to -19%) was similar among the 3 arms (P = .39). The median difference, per intention-to-treat analysis, in seizure reduction between the KD and MAD arms was -21 percentage points (95% CI, -29 to -3 percentage points) and between the KD and LGIT arms was -12 percentage points (95% CI, -21 to 7 percentage points), with both breaching the noninferiority margin of -15 percentage points. Treatment-related adverse events were similar between the KD (31 of 55 [56.4%]) and MAD (33 of 58 [56.9%]) arms but were significantly less in the LGIT diet arm (19 of 57 [33.3%]).Conclusions and relevanceNeither the MAD nor the LGIT diet met the noninferiority criteria. However, the results of this study for the LGIT diet showed a balance between seizure reduction and relatively fewer adverse events compared with the KD and MAD. These potential benefits suggest that the risk-benefit decision with regard to the 3 diet interventions needs to be individualized.Trial registrationClinicalTrials.gov Identifier: NCT02708030.

Project description:BackgroundAlzheimer's disease (AD) is increasing in prevalence, but effective treatments for its cognitive impairment remain severely limited. This study investigates the impact of ketone body production through dietary manipulation on memory in persons with mild cognitive impairment due to early AD and explores potential mechanisms of action.MethodsWe conducted a 12-week, parallel-group, controlled feasibility trial of a ketogenic diet, the modified Atkins diet (MAD), compared to a control diet in patients with cognitive impairments attributed to AD. We administered neuropsychological assessments, including memory tests, and collected blood samples at baseline and after 12 weeks of intervention. We performed untargeted lipidomic and targeted metabolomic analyses on plasma samples to detect changes over time.ResultsA total of 839 individuals were screened to yield 38 randomized participants, with 20 assigned to receive MAD and 18 assigned to receive a control diet. Due to attrition, only 13 in the MAD arm and nine in the control arm were assessed for the primary endpoint, with two participants meeting ketosis levels used to define MAD adherence criteria. The average change from baseline in the Memory Composite Score was 1.37 (95% CI: -0.87, 4.90) points higher in the MAD group compared to the control group. The effect size of the intervention on baseline MAD change was moderate (Cohen's D = 0.57, 95% CI: -0.67, 1.33). In the 15 participants (nine MAD, six control) assessed for lipidomic and metabolomic-lipidomics and metabolomics, 13 metabolites and 10 lipids showed significant changes from baseline to 12 weeks, including triacylglycerols (TAGs, 50:5, 52:5, and 52:6), sphingomyelins (SM, 44:3, 46:0, 46:3, and 48:1), acetoacetate, fatty acylcarnitines, glycerol-3-phosphate, and hydroxy fatty acids.ConclusionsAttrition was greatest between baseline and week 6. All participants retained at week 6 completed the study. Despite low rates of adherence by criteria defined a priori, lipidomic and metabolomic analyses indicate significant changes from baseline in circulating lipids and metabolites between MAD and control participants at 12-week postrandomization, and MAD participants showed greater, albeit nonsignificant, improvement in memory.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets