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Acute Nutritional Ketosis in VLCAD Deficiency

Primary Purpose

VLCAD Deficiency, Fatty Acid Oxidation Defects

Status
Completed
Phase
Not Applicable
Locations
Netherlands
Study Type
Interventional
Intervention
ketone ester drink
exercise
muscle biopsy
Magnetic Resonance Imaging
Sponsored by
University Medical Center Groningen
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for VLCAD Deficiency focused on measuring Fatty acid Oxidation Disorders, ketone ester, VLCAD deficiency

Eligibility Criteria

16 Years - 65 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

- Confirmed VLCADD by genetic profiling

Exclusion Criteria:

  • contraindications for MRI studies (assessed by standardised questionnaire as previously used in METC 08-267/K; see UMCG section F METC documents)
  • inability to perform bicycle exercise.
  • recent episode of rhabdomyolysis, or treatment for acute renal failure in the past 2 months.
  • intercurrent illness which may influence exercise tolerance (anaemia, musculoskeletal injury, or other undiagnosed illness under investigation).
  • known coronary artery disease, positive history for angina, or changes on ECG suggestive of previous ischaemia without a negative stress test.
  • insulin-dependent diabetes mellitus.
  • loss of, or an inability to give informed consent.
  • pregnancy or current breastfeeding, or females not taking the oral contraceptive pill (this is due to the variability in hormonal patterns and substrate levels with different parts of the menstrual cycle).
  • any other cause which in the opinion of the investigators, may affect the volunteers ability to participate in the study.

Sites / Locations

  • Academic Medical Center
  • Dept of Neuroscience/ Neuroimaging Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

ketone ester drink

carbohydrate drink

Arm Description

Oral intake of ketone ester drink muscle biopsy exercise muscle biopsy Magnetic Resonance imaging

Oral intake of isocaloric carbohydrate drinkmuscle biopsy exercise muscle biopsy Magnetic Resonance imaging

Outcomes

Primary Outcome Measures

Change of ATP concentration in millimolar
steady-state in vivo intramuscular concentration of ATP metabolites during rest and exercise.
Change of PCr concentration in millimolar
steady-state in vivo intramuscular concentration of ATP metabolites during rest and exercise.
Change of Pi concentration in millimolar
steady-state in vivo intramuscular concentration of ATP metabolites during rest and exercise.

Secondary Outcome Measures

kinetic rate constant of ATP synthesis in Hertz
rate constant of Pi and PCr recovery post-exercise
intramuscular concentration of H+ in millimolar
steady-state in vivo intramuscular concentration of H+ during rest and exercise
completion of 35 minute upright bicycling bout at FATMAX
(yes/no; if no, #minutes)
completion of 10 minute supine bicycling bout at FATMAX in scanner
(yes/no; if no, #minutes)
HR in beats per minute
heart rate, VO2 and VCO2 dynamics. During session 2+3 breath sampling will be done for 2 minutes per timepoint, simultaneously with blood sampling.
VO2 in milliliter per minute per kilogram
heart rate, VO2 and VCO2 dynamics. During session 2+3 breath sampling will be done for 2 minutes per timepoint, simultaneously with blood sampling.
VCO2 in milliliter per minute per kilogram
VCO2 dynamics during session 2+3 breath sampling for 2 minutes per timepoint, simultaneously with blood sampling.
Changes in blood metabolites: D-betahydroxybutyrate in millimol per liter
Samples are taken at baseline, 30 minutes, 40 minutes, 50 minutes, 60 minutes, 75 minutes, 85 minutes and 265 minutes after ingestion of the testdrink
Changes in blood metabolites: glucose in millimol per liter
Samples are taken at baseline, 30 minutes, 40 minutes, 50 minutes, 60 minutes, 75 minutes, 85 minutes and 265 min after ingestion of the testdrink
Changes in blood metabolites: lactate in millimol per liter
Samples are taken at baseline, 30 minutes, 60 minutes, 85 minutes and 265 min after ingestion of the testdrink
Changes in blood metabolites: insulin in picomol per liter
Samples are taken at baseline, 30 minutes, 60 minutes, 85 minutes and 265 min after ingestion of the testdrink
Changes in blood metabolites: creatine kinase in units per liter
Samples are taken at baseline, 30 minutes, 60 minutes, 85 minutes and 265 min after ingestion of the testdrink
Changes in blood metabolites: triglycerides in millimol per liter
Samples are taken at baseline, 30 minutes, 60 minutes, 85 minutes and 265 min after ingestion of the testdrink
Changes in blood metabolites: LDL cholesterol in millimol per liter
Samples are taken at baseline, 30 minutes, 60 minutes, 85 minutes and 265 min after ingestion of the testdrink
Changes in blood metabolites: free fatty acids in millimol per liter
Samples are taken at baseline, 30 minutes, 40 minutes, 50 minutes, 60 minutes, 75 minutes, 85 minutes and 265 min after ingestion of the test drink
Changes in blood metabolites: total cholesterol in millimol per liter
Samples are taken at baseline, 30 minutes, 60 minutes, 85 minutes and 265 min after ingestion of the testdrink
Changes in blood metabolites: HDL cholesterol in millimol per liter
Samples are taken at baseline, 30 minutes, 60 minutes, 85 minutes and 265 min after ingestion of the testdrink
Changes in blood metabolites: acylcarnitines in micromol per liter
Samples are taken at baseline, 30 minutes, 40 minutes, 50 minutes, 60 minutes, 75 minutes, 85 minutes and 265 min after ingestion of the test drink
Subjective exertion
Measured with Borg score (range from 6 (rest) to 20 (extreme exertion)).
height in meters
height of patient
weight in kilogram
weight of patient to dose intervention and normalize outcome parameters
BMI in kg/m^2
weight and height will be combined to report BMI in kg/m^2
optional: TCA intermediates in muscle tissue (units is ratio of metabolite peak/ internal standard) and will be expressed as fold change from baseline
metabolomics (mass spectrometry) of muscle tissue on a voluntary basis
optional: glycolysis intermediates in muscle tissue (units is ratio of metabolite peak/ internal standard) and will be expressed as fold change from baseline
metabolomics (mass spectrometry) of muscle tissue on a voluntary basis
optional: acylcarnitines in muscle tissue (units is ratio of metabolite peak/ internal standard) and will be expressed as fold change from baseline
metabolomics (mass spectrometry) of muscle tissue on a voluntary basis
optional: D-betahydroxybutyrate in muscle tissue (units is ratio of metabolite peak/ internal standard) and will be expressed as fold change from baseline
metabolomics (mass spectrometry) of muscle tissue on a voluntary basis
optional: capillary density in muscle tissue based on CD31 staining (capillaries per millimeter^2)
individual phenotypic muscle properties on a voluntary basis. Immunohistochemistry.
optional: mitochondrial density based on ATPase, COX-SDH, SDH and NADH staining (intensity per microgram per minute).
individual phenotypic muscle properties on a voluntary basis. Immunohistochemistry.
optional: mitochondrial density based on as citrate synthase activity expressed as absorbance/s/mg.
individual phenotypic muscle properties on a voluntary basis.
optional: parameters for metabolism and mitochondrial function in muscle (AMPK, PPAR gamma, PGC1a, and GLUT4). All expressed as protein content as % of control.
individual phenotypic muscle properties on a voluntary basis. Westernblots.
optional: lipid accumulation based on Oil-Red-O staining (intensity of staining, and percentage positive-stained cells).
individual phenotypic muscle properties on a voluntary basis. Immunohistochemistry.
optional: muscle fiber type composition based on myosin heavy chain profiling. Type I, IIa, IIx fibres will be expressed as % of total fibres.
individual phenotypic muscle properties on a voluntary basis.
optional: muscle fiber type composition based on ATPase staining (intensity/ug/min). Type I, IIa, IIx fibres will be expressed as % of total fibres.
individual phenotypic muscle properties on a voluntary basis. Immunohistochemistry.
optional: glycogen content of muscle based on Periodic acid-Schiff (PAS) staining (intensity per millimeter^2)
individual phenotypic muscle properties on a voluntary basis. Immunohistochemistry.
optional: glycogen content of muscle measured as glucose released after enzymatic digestion with amyloglucosidase expressed as micromol per gram wet muscle weight.
individual phenotypic muscle properties on a voluntary basis.

Full Information

First Posted
October 17, 2017
Last Updated
May 8, 2018
Sponsor
University Medical Center Groningen
Collaborators
UMC Utrecht, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA), University of Oxford, ESN (Erfelijke Stofwisselingsziekten Nederland)
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1. Study Identification

Unique Protocol Identification Number
NCT03531554
Brief Title
Acute Nutritional Ketosis in VLCAD Deficiency
Official Title
Acute Nutritional Ketosis in VLCAD Deficiency: Testing the Metabolic Base for Therapeutic Use
Study Type
Interventional

2. Study Status

Record Verification Date
May 2018
Overall Recruitment Status
Completed
Study Start Date
April 1, 2016 (Actual)
Primary Completion Date
March 31, 2017 (Actual)
Study Completion Date
April 1, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University Medical Center Groningen
Collaborators
UMC Utrecht, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA), University of Oxford, ESN (Erfelijke Stofwisselingsziekten Nederland)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
To test if a ketone-ester based drink can boost muscle mitochondrial function in vivo in patients with VLCADD in order to establish a rational basis for therapeutic use in this disorder.
Detailed Description
Exertional rhabdomyolysis is a common symptom in very long-chain acylCoA dehydrogenase deficient (VLCADD) patients. Failing muscle ATP homeostasis, due to impaired fatty acid oxidation, is the most likely cause. Therefore, supplementation with an alternative energy substrate to boost ATP homeostasis, such as an exogenous ketone ester (KE) drink, could be a therapeutic option. Previous results suggest that KE is preferentially oxidized in the tricyclic acid (TCA) cycle and improves physical endurance in athletes. Our primary objective is to test if KE boosts muscular ATP homeostasis in VLCADD patients to establish a rational basis for therapeutic use. VLCADD patients will be included in a randomized, blinded, placebo controlled, 2-way cross-over trial. Prior to each test, patients receive a KE drink or an isocaloric carbohydrate equivalent, and completed a 35 min cycling test on an upright bicycle, followed by 10 minutes of supine cycling inside a MR scanner. The protocol will be repeated after at least one week with the opposite drink.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
VLCAD Deficiency, Fatty Acid Oxidation Defects
Keywords
Fatty acid Oxidation Disorders, ketone ester, VLCAD deficiency

7. Study Design

Primary Purpose
Other
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Model Description
randomized, blinded, placebo controlled, 2-way cross-over trial
Masking
ParticipantOutcomes Assessor
Masking Description
Double (Participant, Outcomes Assessor)
Allocation
Randomized
Enrollment
5 (Actual)

8. Arms, Groups, and Interventions

Arm Title
ketone ester drink
Arm Type
Experimental
Arm Description
Oral intake of ketone ester drink muscle biopsy exercise muscle biopsy Magnetic Resonance imaging
Arm Title
carbohydrate drink
Arm Type
Placebo Comparator
Arm Description
Oral intake of isocaloric carbohydrate drinkmuscle biopsy exercise muscle biopsy Magnetic Resonance imaging
Intervention Type
Dietary Supplement
Intervention Name(s)
ketone ester drink
Other Intervention Name(s)
deltaG (R)
Intervention Description
395 mg of ketone ester/kg
Intervention Type
Behavioral
Intervention Name(s)
exercise
Intervention Description
35 min cycling test on an upright bicycle, followed by 10 minutes of supine cycling inside a MR scanner.
Intervention Type
Procedure
Intervention Name(s)
muscle biopsy
Intervention Description
biopsy from the quadriceps muscle prior to and immediately after upright bicycling
Intervention Type
Diagnostic Test
Intervention Name(s)
Magnetic Resonance Imaging
Other Intervention Name(s)
Magnetic Resonance Spectroscopy
Intervention Description
1H MR images and 31P MR spectra were acquired from the upper leg prior to-, during and after exercise
Primary Outcome Measure Information:
Title
Change of ATP concentration in millimolar
Description
steady-state in vivo intramuscular concentration of ATP metabolites during rest and exercise.
Time Frame
During session 2 and 3: continuous measurements from t=75 minutes until t=85 minutes
Title
Change of PCr concentration in millimolar
Description
steady-state in vivo intramuscular concentration of ATP metabolites during rest and exercise.
Time Frame
During session 2 and 3: continuous measurements from t=75 minutes until t=85 minutes
Title
Change of Pi concentration in millimolar
Description
steady-state in vivo intramuscular concentration of ATP metabolites during rest and exercise.
Time Frame
During session 2 and 3: continuous measurements from t=75 minutes until t=85 minutes
Secondary Outcome Measure Information:
Title
kinetic rate constant of ATP synthesis in Hertz
Description
rate constant of Pi and PCr recovery post-exercise
Time Frame
session 2 and 3, 10 minutes each time
Title
intramuscular concentration of H+ in millimolar
Description
steady-state in vivo intramuscular concentration of H+ during rest and exercise
Time Frame
session 2 and 3, 10 minutes each time
Title
completion of 35 minute upright bicycling bout at FATMAX
Description
(yes/no; if no, #minutes)
Time Frame
Session 2 and 3, 35 minutes
Title
completion of 10 minute supine bicycling bout at FATMAX in scanner
Description
(yes/no; if no, #minutes)
Time Frame
Session 2 and 3, 10 minutes
Title
HR in beats per minute
Description
heart rate, VO2 and VCO2 dynamics. During session 2+3 breath sampling will be done for 2 minutes per timepoint, simultaneously with blood sampling.
Time Frame
During session 1, 15 minutes During Session 2 + 3: 35 minutes
Title
VO2 in milliliter per minute per kilogram
Description
heart rate, VO2 and VCO2 dynamics. During session 2+3 breath sampling will be done for 2 minutes per timepoint, simultaneously with blood sampling.
Time Frame
During session 1, 15 minutes During Session 2 + 3: 35 minutes
Title
VCO2 in milliliter per minute per kilogram
Description
VCO2 dynamics during session 2+3 breath sampling for 2 minutes per timepoint, simultaneously with blood sampling.
Time Frame
During session 1, 15 minutes During Session 2 + 3: 35 minutes
Title
Changes in blood metabolites: D-betahydroxybutyrate in millimol per liter
Description
Samples are taken at baseline, 30 minutes, 40 minutes, 50 minutes, 60 minutes, 75 minutes, 85 minutes and 265 minutes after ingestion of the testdrink
Time Frame
Session 2 and 3, 265 minutes per session
Title
Changes in blood metabolites: glucose in millimol per liter
Description
Samples are taken at baseline, 30 minutes, 40 minutes, 50 minutes, 60 minutes, 75 minutes, 85 minutes and 265 min after ingestion of the testdrink
Time Frame
Session 2 and 3, 265 minutes per session
Title
Changes in blood metabolites: lactate in millimol per liter
Description
Samples are taken at baseline, 30 minutes, 60 minutes, 85 minutes and 265 min after ingestion of the testdrink
Time Frame
Session 2 and 3, 265 minutes per session
Title
Changes in blood metabolites: insulin in picomol per liter
Description
Samples are taken at baseline, 30 minutes, 60 minutes, 85 minutes and 265 min after ingestion of the testdrink
Time Frame
Session 2 and 3, 265 minutes per session
Title
Changes in blood metabolites: creatine kinase in units per liter
Description
Samples are taken at baseline, 30 minutes, 60 minutes, 85 minutes and 265 min after ingestion of the testdrink
Time Frame
Session 2 and 3, 265 minutes per session
Title
Changes in blood metabolites: triglycerides in millimol per liter
Description
Samples are taken at baseline, 30 minutes, 60 minutes, 85 minutes and 265 min after ingestion of the testdrink
Time Frame
Session 2 and 3, 265 minutes per session
Title
Changes in blood metabolites: LDL cholesterol in millimol per liter
Description
Samples are taken at baseline, 30 minutes, 60 minutes, 85 minutes and 265 min after ingestion of the testdrink
Time Frame
Session 2 and 3, 265 minutes per session
Title
Changes in blood metabolites: free fatty acids in millimol per liter
Description
Samples are taken at baseline, 30 minutes, 40 minutes, 50 minutes, 60 minutes, 75 minutes, 85 minutes and 265 min after ingestion of the test drink
Time Frame
Session 2 and 3, 265 minutes per session
Title
Changes in blood metabolites: total cholesterol in millimol per liter
Description
Samples are taken at baseline, 30 minutes, 60 minutes, 85 minutes and 265 min after ingestion of the testdrink
Time Frame
Session 2 and 3, 265 minutes per session
Title
Changes in blood metabolites: HDL cholesterol in millimol per liter
Description
Samples are taken at baseline, 30 minutes, 60 minutes, 85 minutes and 265 min after ingestion of the testdrink
Time Frame
Session 2 and 3, 265 minutes per session
Title
Changes in blood metabolites: acylcarnitines in micromol per liter
Description
Samples are taken at baseline, 30 minutes, 40 minutes, 50 minutes, 60 minutes, 75 minutes, 85 minutes and 265 min after ingestion of the test drink
Time Frame
Session 2 and 3, 265 minutes per session
Title
Subjective exertion
Description
Measured with Borg score (range from 6 (rest) to 20 (extreme exertion)).
Time Frame
During Session 2 + 3, assessed during blood sampling, 265 minutes per session
Title
height in meters
Description
height of patient
Time Frame
1 minute during screening visit
Title
weight in kilogram
Description
weight of patient to dose intervention and normalize outcome parameters
Time Frame
1 minute during screening visit
Title
BMI in kg/m^2
Description
weight and height will be combined to report BMI in kg/m^2
Time Frame
1 minute during screening visit
Title
optional: TCA intermediates in muscle tissue (units is ratio of metabolite peak/ internal standard) and will be expressed as fold change from baseline
Description
metabolomics (mass spectrometry) of muscle tissue on a voluntary basis
Time Frame
Session 2+3: before and after exercise, 20 minutes per session
Title
optional: glycolysis intermediates in muscle tissue (units is ratio of metabolite peak/ internal standard) and will be expressed as fold change from baseline
Description
metabolomics (mass spectrometry) of muscle tissue on a voluntary basis
Time Frame
Session 2+3: before and after exercise, 20 minutes per session
Title
optional: acylcarnitines in muscle tissue (units is ratio of metabolite peak/ internal standard) and will be expressed as fold change from baseline
Description
metabolomics (mass spectrometry) of muscle tissue on a voluntary basis
Time Frame
Session 2+3: before and after exercise, 20 minutes per session
Title
optional: D-betahydroxybutyrate in muscle tissue (units is ratio of metabolite peak/ internal standard) and will be expressed as fold change from baseline
Description
metabolomics (mass spectrometry) of muscle tissue on a voluntary basis
Time Frame
Session 2+3: before and after exercise, 20 minutes per session
Title
optional: capillary density in muscle tissue based on CD31 staining (capillaries per millimeter^2)
Description
individual phenotypic muscle properties on a voluntary basis. Immunohistochemistry.
Time Frame
Session 2+3: before and after exercise, 20 minutes per session
Title
optional: mitochondrial density based on ATPase, COX-SDH, SDH and NADH staining (intensity per microgram per minute).
Description
individual phenotypic muscle properties on a voluntary basis. Immunohistochemistry.
Time Frame
Session 2+3: before and after exercise, 20 minutes per session
Title
optional: mitochondrial density based on as citrate synthase activity expressed as absorbance/s/mg.
Description
individual phenotypic muscle properties on a voluntary basis.
Time Frame
Session 2+3: before and after exercise, 20 minutes per session
Title
optional: parameters for metabolism and mitochondrial function in muscle (AMPK, PPAR gamma, PGC1a, and GLUT4). All expressed as protein content as % of control.
Description
individual phenotypic muscle properties on a voluntary basis. Westernblots.
Time Frame
Session 2+3: before and after exercise, 20 minutes per session
Title
optional: lipid accumulation based on Oil-Red-O staining (intensity of staining, and percentage positive-stained cells).
Description
individual phenotypic muscle properties on a voluntary basis. Immunohistochemistry.
Time Frame
Session 2+3: before and after exercise, 20 minutes per session
Title
optional: muscle fiber type composition based on myosin heavy chain profiling. Type I, IIa, IIx fibres will be expressed as % of total fibres.
Description
individual phenotypic muscle properties on a voluntary basis.
Time Frame
Session 2+3: before and after exercise, 20 minutes per session
Title
optional: muscle fiber type composition based on ATPase staining (intensity/ug/min). Type I, IIa, IIx fibres will be expressed as % of total fibres.
Description
individual phenotypic muscle properties on a voluntary basis. Immunohistochemistry.
Time Frame
Session 2+3: before and after exercise, 20 minutes per session
Title
optional: glycogen content of muscle based on Periodic acid-Schiff (PAS) staining (intensity per millimeter^2)
Description
individual phenotypic muscle properties on a voluntary basis. Immunohistochemistry.
Time Frame
Session 2+3: before and after exercise, 20 minutes per session
Title
optional: glycogen content of muscle measured as glucose released after enzymatic digestion with amyloglucosidase expressed as micromol per gram wet muscle weight.
Description
individual phenotypic muscle properties on a voluntary basis.
Time Frame
Session 2+3: before and after exercise, 20 minutes per session

10. Eligibility

Sex
All
Minimum Age & Unit of Time
16 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: - Confirmed VLCADD by genetic profiling Exclusion Criteria: contraindications for MRI studies (assessed by standardised questionnaire as previously used in METC 08-267/K; see UMCG section F METC documents) inability to perform bicycle exercise. recent episode of rhabdomyolysis, or treatment for acute renal failure in the past 2 months. intercurrent illness which may influence exercise tolerance (anaemia, musculoskeletal injury, or other undiagnosed illness under investigation). known coronary artery disease, positive history for angina, or changes on ECG suggestive of previous ischaemia without a negative stress test. insulin-dependent diabetes mellitus. loss of, or an inability to give informed consent. pregnancy or current breastfeeding, or females not taking the oral contraceptive pill (this is due to the variability in hormonal patterns and substrate levels with different parts of the menstrual cycle). any other cause which in the opinion of the investigators, may affect the volunteers ability to participate in the study.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jeroen AL Jeneson, PhD
Organizational Affiliation
Dept of Neuroscience/ Neuroimaging Center Groningen
Official's Role
Principal Investigator
Facility Information:
Facility Name
Academic Medical Center
City
Amsterdam
State/Province
Noord-Holland
ZIP/Postal Code
1105 AZ
Country
Netherlands
Facility Name
Dept of Neuroscience/ Neuroimaging Center
City
Groningen
ZIP/Postal Code
9700RB
Country
Netherlands

12. IPD Sharing Statement

Plan to Share IPD
Undecided
Citations:
PubMed Identifier
27475046
Citation
Cox PJ, Kirk T, Ashmore T, Willerton K, Evans R, Smith A, Murray AJ, Stubbs B, West J, McLure SW, King MT, Dodd MS, Holloway C, Neubauer S, Drawer S, Veech RL, Griffin JL, Clarke K. Nutritional Ketosis Alters Fuel Preference and Thereby Endurance Performance in Athletes. Cell Metab. 2016 Aug 9;24(2):256-68. doi: 10.1016/j.cmet.2016.07.010. Epub 2016 Jul 27.
Results Reference
background
PubMed Identifier
26881790
Citation
Diekman EF, Visser G, Schmitz JP, Nievelstein RA, de Sain-van der Velden M, Wardrop M, Van der Pol WL, Houten SM, van Riel NA, Takken T, Jeneson JA. Altered Energetics of Exercise Explain Risk of Rhabdomyolysis in Very Long-Chain Acyl-CoA Dehydrogenase Deficiency. PLoS One. 2016 Feb 16;11(2):e0147818. doi: 10.1371/journal.pone.0147818. eCollection 2016.
Results Reference
background
PubMed Identifier
31955429
Citation
Bleeker JC, Visser G, Clarke K, Ferdinandusse S, de Haan FH, Houtkooper RH, IJlst L, Kok IL, Langeveld M, van der Pol WL, de Sain-van der Velden MGM, Sibeijn-Kuiper A, Takken T, Wanders RJA, van Weeghel M, Wijburg FA, van der Woude LH, Wust RCI, Cox PJ, Jeneson JAL. Nutritional ketosis improves exercise metabolism in patients with very long-chain acyl-CoA dehydrogenase deficiency. J Inherit Metab Dis. 2020 Jul;43(4):787-799. doi: 10.1002/jimd.12217. Epub 2020 Feb 5.
Results Reference
derived

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Acute Nutritional Ketosis in VLCAD Deficiency

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