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TY - JOUR

T1 - Exploring the metabolic fate of medium-chain triglycerides in healthy individuals using a stable isotope tracer

AU - Knottnerus, Suzan J. G.

AU - van Harskamp, Dewi

AU - Schierbeek, Henk

AU - Bleeker, Jeannette C.

AU - Crefcoeur, Loek L.

AU - Ferdinandusse, Sacha

AU - van Goudoever, Johannes B.

AU - Houtkooper, Riekelt H.

AU - IJlst, Lodewijk

AU - Langeveld, Mirjam

AU - Wanders, Ronald J. A.

AU - Vaz, Frédéric M.

AU - Wijburg, Frits A.

AU - Visser, Gepke

N1 - Funding Information: This study was supported by funding from Nutricia Advanced Medical Nutrition and Stichting Stofwisselkracht . Funding Information: This study was supported by funding from Nutricia Advanced Medical Nutrition and Stichting Stofwisselkracht.This study was financially supported by Nutricia Advanced Medical Nutrition and Stichting Stofwisselkracht. Publisher Copyright: © 2020

PY - 2021/3

Y1 - 2021/3

N2 - Background & aims: Medium chain triglyceride (MCT) supplementation is often recommended as treatment for patients with long-chain fatty acid β-oxidation (lcFAO) disorders, since they can be utilized as an energy source without the use of the defective enzyme. However, studies in mice and preterm infants suggest that not all medium-chain fatty acids (MCFA) are oxidized and may undergo elongation to long-chain fatty acids (LCFA). In this single blinded study, we explored the metabolic fates of MCT in healthy individuals using a 13C-labeled MCT tracer. Method: Three healthy males in rest received on two test days a primed continuous infusion of glyceryl tri[1,2,3,4–13C4]-octanoate with either an isocaloric supplementation of 1) exclusively MCT (MCT-only) or 2) a mixture of MCT, proteins and carbohydrates (MCT-mix). Gas chromatography - combustion - isotope ratio mass spectrometry (GC-C-IRMS) was used to determine 13C-enrichment of long-chain fatty acids in plasma and of 13CO2 in exhaled air. Results: When provided as single energy source, an estimated 42% of administered MCT was converted to CO2. In combination with carbohydrates and proteins in the diet, oxidation of MCT was higher (62%). In both diets <1% of 13C-label was incorporated in LCFA in plasma, indicating that administered MCT underwent chain-elongation to LCT. Conclusions: Although the relative MCT oxidation rate was higher when combined with carbohydrates and protein, quantitatively more MCT was oxidized when given an isocaloric meal with solely MCT. As these results were obtained in the resting state opposed to during exercise, it is too early to give a recommendation concerning the use of MCT in lcFAO disorders. The data show that in resting healthy individuals only a very small part of the MCT is traced back as LCFA in plasma, suggesting that MCT treatment does not result in a large LCFA burden, however further research on storage of MCT in tissues is warranted. Registration: The study was registered in the Nederlands Trialregister. Protocol ID: Trial NL7417 (NTR7650).

AB - Background & aims: Medium chain triglyceride (MCT) supplementation is often recommended as treatment for patients with long-chain fatty acid β-oxidation (lcFAO) disorders, since they can be utilized as an energy source without the use of the defective enzyme. However, studies in mice and preterm infants suggest that not all medium-chain fatty acids (MCFA) are oxidized and may undergo elongation to long-chain fatty acids (LCFA). In this single blinded study, we explored the metabolic fates of MCT in healthy individuals using a 13C-labeled MCT tracer. Method: Three healthy males in rest received on two test days a primed continuous infusion of glyceryl tri[1,2,3,4–13C4]-octanoate with either an isocaloric supplementation of 1) exclusively MCT (MCT-only) or 2) a mixture of MCT, proteins and carbohydrates (MCT-mix). Gas chromatography - combustion - isotope ratio mass spectrometry (GC-C-IRMS) was used to determine 13C-enrichment of long-chain fatty acids in plasma and of 13CO2 in exhaled air. Results: When provided as single energy source, an estimated 42% of administered MCT was converted to CO2. In combination with carbohydrates and proteins in the diet, oxidation of MCT was higher (62%). In both diets <1% of 13C-label was incorporated in LCFA in plasma, indicating that administered MCT underwent chain-elongation to LCT. Conclusions: Although the relative MCT oxidation rate was higher when combined with carbohydrates and protein, quantitatively more MCT was oxidized when given an isocaloric meal with solely MCT. As these results were obtained in the resting state opposed to during exercise, it is too early to give a recommendation concerning the use of MCT in lcFAO disorders. The data show that in resting healthy individuals only a very small part of the MCT is traced back as LCFA in plasma, suggesting that MCT treatment does not result in a large LCFA burden, however further research on storage of MCT in tissues is warranted. Registration: The study was registered in the Nederlands Trialregister. Protocol ID: Trial NL7417 (NTR7650).

KW - Fatty acid chain-elongation

KW - Isotope ratio mass spectrometry

KW - Lipid kinetics

KW - Medium-chain fatty acids

KW - Oxidation

UR - http://www.scopus.com/inward/record.url?scp=85092014481&partnerID=8YFLogxK

U2 - 10.1016/j.clnu.2020.08.032

DO - 10.1016/j.clnu.2020.08.032

M3 - Article

C2 - 32948349

VL - 40

SP - 1396

EP - 1404

JO - Clinical nutrition (Edinburgh, Scotland)

JF - Clinical nutrition (Edinburgh, Scotland)

SN - 0261-5614

IS - 3

ER -