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

Melanie B. Gillingham, Stephen B. Heitner, Julie Martin, Sarah Rose, Amy Goldstein, Areeg Hassan El-Gharbawy, Stephanie Deward, Michael R. Lasarev, Jim Pollaro, James P. DeLany, Luke J. Burchill, Bret Goodpaster, James Shoemaker, Dietrich Matern, Cary O. Harding, Jerry Vockley

Research output: Contribution to journalArticle

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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.govNCT01379625.

LanguageEnglish (US)
Pages1-13
Number of pages13
JournalJournal of Inherited Metabolic Disease
DOIs
StateAccepted/In press - Sep 4 2017

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Fatty Acids
Randomized Controlled Trials
Rhabdomyolysis
Triglycerides
Phosphocreatine
Body Composition
Exercise Test
Stroke Volume
Energy Metabolism
Oxidoreductases
Carbon
Heart Rate
Exercise
Carnitine O-Palmitoyltransferase
Exercise Tolerance
Citric Acid Cycle
Incidence
triheptanoin
tricaprylin
Biomarkers

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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Triheptanoin versus trioctanoin for long-chain fatty acid oxidation disorders : a double blinded, randomized controlled trial. / Gillingham, Melanie B.; Heitner, Stephen B.; Martin, Julie; Rose, Sarah; Goldstein, Amy; El-Gharbawy, Areeg Hassan; Deward, Stephanie; Lasarev, Michael R.; Pollaro, Jim; DeLany, James P.; Burchill, Luke J.; Goodpaster, Bret; Shoemaker, James; Matern, Dietrich; Harding, Cary O.; Vockley, Jerry.

In: Journal of Inherited Metabolic Disease, 04.09.2017, p. 1-13.

Research output: Contribution to journalArticle

Gillingham, MB, Heitner, SB, Martin, J, Rose, S, Goldstein, A, El-Gharbawy, AH, Deward, S, Lasarev, MR, Pollaro, J, DeLany, JP, Burchill, LJ, Goodpaster, B, Shoemaker, J, Matern, D, Harding, CO & Vockley, J 2017, 'Triheptanoin versus trioctanoin for long-chain fatty acid oxidation disorders: a double blinded, randomized controlled trial' Journal of Inherited Metabolic Disease, pp. 1-13. DOI: 10.1007/s10545-017-0085-8
Gillingham, Melanie B. ; Heitner, Stephen B. ; Martin, Julie ; Rose, Sarah ; Goldstein, Amy ; El-Gharbawy, Areeg Hassan ; Deward, Stephanie ; Lasarev, Michael R. ; Pollaro, Jim ; DeLany, James P. ; Burchill, Luke J. ; Goodpaster, Bret ; Shoemaker, James ; Matern, Dietrich ; Harding, Cary O. ; Vockley, Jerry. / Triheptanoin versus trioctanoin for long-chain fatty acid oxidation disorders : a double blinded, randomized controlled trial. In: Journal of Inherited Metabolic Disease. 2017 ; pp. 1-13
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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.govNCT01379625.",
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AU - Martin,Julie

AU - Rose,Sarah

AU - Goldstein,Amy

AU - El-Gharbawy,Areeg Hassan

AU - Deward,Stephanie

AU - Lasarev,Michael R.

AU - Pollaro,Jim

AU - DeLany,James P.

AU - Burchill,Luke J.

AU - Goodpaster,Bret

AU - Shoemaker,James

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