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J Inherit Metab Dis. 2017 Nov;40(6):831-843. doi: 10.1007/s10545-017-0085-8. Epub 2017 Sep 4.

Triheptanoin versus trioctanoin for long-chain fatty acid oxidation disorders: a double blinded, randomized controlled trial.

Author information

1
Department of Molecular and Medical Genetics, Graduate Programs in Human Nutrition, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd, Portland, OR, 97239, USA. gillingm@ohsu.edu.
2
Knight Cardiovascular Institute, Oregon Health & Science University, Portland, OR, USA.
3
Department of Molecular and Medical Genetics, Graduate Programs in Human Nutrition, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd, Portland, OR, 97239, USA.
4
PRA Health Sciences, Raleigh, NC, USA.
5
Neurogenetics and Metabolism, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA, USA.
6
Division of Medical Genetics, University of Pittsburgh School of Medicine, Children's Hospital of Pittsburgh, Pittsburgh, PA, USA.
7
GeneDx, Gaithersburg, MD, USA.
8
Center for Research on Occupational and Environmental Toxicology, Oregon Health & Science University, Portland, OR, USA.
9
Advanced Imaging Research Center, Oregon Health & Science University, Portland, OR, USA.
10
Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
11
The Florida Hospital Translational Research Institute, and the Sanford Burnham Institute, Orlando, FL, USA.
12
Department of Biochemistry and Molecular Biology, Saint Louis University, Saint Louis, MO, USA.
13
Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.

Abstract

BACKGROUND:

Observational reports suggest that supplementation that increases citric acid cycle intermediates via anaplerosis may have therapeutic advantages over traditional medium-chain triglyceride (MCT) treatment of long-chain fatty acid oxidation disorders (LC-FAODs) but controlled trials have not been reported. The goal of our study was to compare the effects of triheptanoin (C7), an anaplerotic seven-carbon fatty acid triglyceride, to trioctanoin (C8), an eight-carbon fatty acid triglyceride, in patients with LC-FAODs.

METHODS:

A double blinded, randomized controlled trial of 32 subjects with LC-FAODs (carnitine palmitoyltransferase-2, very long-chain acylCoA dehydrogenase, trifunctional protein or long-chain 3-hydroxy acylCoA dehydrogenase deficiencies) who were randomly assigned a diet containing 20% of their total daily energy from either C7 or C8 for 4 months was conducted. Primary outcomes included changes in total energy expenditure (TEE), cardiac function by echocardiogram, exercise tolerance, and phosphocreatine recovery following acute exercise. Secondary outcomes included body composition, blood biomarkers, and adverse events, including incidence of rhabdomyolysis.

RESULTS:

Patients in the C7 group increased left ventricular (LV) ejection fraction by 7.4% (p = 0.046) while experiencing a 20% (p = 0.041) decrease in LV wall mass on their resting echocardiogram. They also required a lower heart rate for the same amount of work during a moderate-intensity exercise stress test when compared to patients taking C8. There was no difference in TEE, phosphocreatine recovery, body composition, incidence of rhabdomyolysis, or any secondary outcome measures between the groups.

CONCLUSIONS:

C7 improved LV ejection fraction and reduced LV mass at rest, as well as lowering heart rate during exercise among patients with LC-FAODs.

CLINICAL TRIAL REGISTRATION:

Clinicaltrials.gov NCT01379625.

PMID:
28871440
PMCID:
PMC6545116
DOI:
10.1007/s10545-017-0085-8
[Indexed for MEDLINE]
Free PMC Article

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