Melanie B. Gillingham, PhD, RD

Associate Professor, Department of Molecular and Medical Genetics Graduate Programs in Human Nutrition
Oregon Health & Science University, Portland, OR

image of Dr. Melanie Gillingham
Background: Unlike long-chain triglycerides (LCT), Medium-chain triglyceride (MCT) supplements are reported to be absorbed via the portal vein, preferentially oxidized in liver and peripheral tissues, and associated with increased energy expenditure. Clinically MCT has been used in patients with fat malabsorption syndromes and in patients with long-chain fatty acid oxidation disorders (LC-FAODs) to bypass the long-chain fatty acid oxidation pathway. Traditional MCT is typically composed of C8, C10 and some C12 fatty acids. Observational reports suggest that supplementation with odd chain MCT such as triglycerides composed of C7 fatty acids that increase citric acid cycle intermediates via anaplerosis may have therapeutic advantages over traditional MCT for the treatment of 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 thirty-two 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. Triheptanoin improved the cardiorespiratory fitness of patients over traditional MCT.