The comparison of the digestion and absorption of trioctanoin (C8) and triheptanoin (C7) in patients with long-chain fatty acid oxidation disorders.

Gillingham MB1, Guillory KK1, Martin JM1, Matern, D2, Harding CO1, Vockley J3

1Oregon Health & Science University, Portland, OR, 2Mayo Clinic Biochemical Genetics Laboratory, Rochester, MN, 3University of Pittsburgh, Pittsburgh, PA, USA

Corresponding Author: Melanie Gillingham, PhD, RD, Oregon Health & Science University,

Portland, OR, USA email: gillingm@ohsu.edu phone: 503-494-1682

 

Objective: To determine if there is a difference in the appearance rates of triheptanoin or trioctanoin in peripheral circulation after a mixed meal or a single nutrient bolus.

Methods: This is a secondary analysis of Phase 2 Study of Triheptanoin to treat long-chain fatty acidoxidation disorders. Subjects with CPT2, VLCAD, or LCHAD/TFP were randomly assigned
to consume trioctanoin or triheptanoin in a mixed breakfast meal. Blood was drawn fasting and
at 1, 2, and4 hours after the meal. Separately, samples were drawn 20 minutes after an oral bolus of oil alone at 0.3mg/kg lean body mass and again after 45 minutes of exercise. Blood samples were analyzed for free fatty acids, quantitative total fatty acid profiles, triglycerides and Apolipoprotein B48 (apoB48, thelipoprotein found in chylomicrons).

Results: Blood samples were available for a total of 30 subjects, n=15 in each group. Serum total free fatty acid concentrations were higher at fasting due to fasting-induced mobilization
of endogenous fatty acid stores and then decreased after feeding and increased with exercise
as expected. After the trioctanoin or triheptanoin mixed meal, we observed a gradual rise in total C8 (in subjects receiving C8) and C7 (in subjects receiving C7) in the quantitative fatty acid profile (free and bound fatty acids) and both peaked at four hours. However, the total amount of C7 (104±25umol/L) measured in plasma at 4 hours after a mixed meal was less than that of C8 (177±88umol/L), after comparable intakes. The rises in plasma C8 and C7 corresponded with increased plasma total triglycerides and apoB48 suggesting that at least some of the C8 or C7
oil consumed as part of a mixed meal had been incorporated into chylomicrons. Total plasma
C7 (166±37umol/L) or C8 (343±191umol/L) concentrations were higher after the single nutrient oral bolus than after the mixed meal; total plasma triglycerides did not increase after the single nutrient bolus suggesting that C7 and C8 had been absorbed via the portal circulation rather than as chylomicrons.

Conclusions: We had expected C8 and C7 fatty acids to be rapidly absorbed through portal circulation and to peak in peripheral blood after 1 hour. However, levels of both C8 and C7 peaked only at 4 hours, suggesting that they may have been incorporated into chylomicrons after a mixed meal that also contained long-chain fat. The greater rise in C8 plasma levels was also unexpected which suggests there is a difference in the digestion, absorption or clearance of C8 and C7. Both fatty acids rose after the single nutrient oral bolus and peaked at the final blood sample following exercise suggesting a more rapid and dramatic rise in circulating C8 or C7 after a single nutrient bolus in comparison to a mixed meal. The appearance of medium chain fatty acids in peripheral circulation differs when the oil is fed as a mixed meal versus a single nutrient bolus.

This study was supported by a grant from the Office of Orphan Products Development of the Food and Drug administration (FD-03895).

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