The effect of oral medium chain triglycerides in healthy individuals

For patients with a disorder of the carnitine cycle or long-chain fatty acid
oxidation (lcFAO), a long-chain triglyceride (LCT) restricted diet, enriched
with medium-chain triglycerides (MCT), is currently one of the few therapeutic
options recommended by physicians. The effect of oral intake and utilization by
the body has been poorly understood and some studies even suggest that MCT is
elongated to LCT in the body. Since lcFAO patients are unable to oxidize LCT,
this could mean that the diet has no benefit compared to a regular diet. Our
study intends to test the uptake and metabolic route of oral MCT in healthy
subjects under different circumstances. We will first perform a small pilot
with one healthy subject to determine the optimal conditions for the actual
study. The results of the latter will help to determine the usefulness of MCT
in the diet of lcFAO patients.

Objective (pilot): to test if our research set-up allows us to accurately
measure uptake and metabolism of oral MCT.
Objective (actual study): to test if oral MCT is directly oxidized and/ or
elongated to LCT under the following conditions: fasted/fed/exercise.

Dietary intervention study

Medium-chain triglyceride emulsion (liquigen®), tracer:
glycerol-tri(octanoate-1,2,3,4-13C4)

Pilot (1 subject): After an inclusion and screening visit the subject will take
an adjusted fasting test, followed by the test day at least one week later. The
adjusted fasting test will be stopped if plasma glucose < 3.5 mmol/l, with a
maximum duration of 36 hours.
During the test day the subject will get constant oral infusion via nasogastric
tube of MCT-tracer for 6 hours, followed by a combination of MCT-tracer and
regular MCT for an additional 6 hours. The subject will be fasted from the
evening before the test, actual starting time depends on adjusted fasting test.
Blood and breath samples will be collected frequently throughout the test day.
In addition, the clearance of tracer from plasma will be tested, for which the
subject will have a vena puncture one week after the test day that will be
repeated weekly until there is no tracer left in his plasma. This will take
approximately 15 minutes each.
Total amount of time spent on the pilot study will be 48 * - 49 hours,
dependent on clearance of the tracer from plasma. Total amount of blood drawn
during the study will be 338 ml. The only risks are from placement of the
nasogastric tube: pharyngeal discomfort, nose bleed and placement of an
IV-cannula: phlebitis, hematoma. Gastrointestinal side-effects in the form of
diarrhoea may accompany the use of MCT. There is no risk associated with the
experimental use of stable isotopes in humans.

Actual study (6 subjects): Instead of 1 test day the subjects will undergo 2
test days with oral infusion via nasogastric tube of MCT-tracer and regular MCT
and the other in combination with a combination of oral MCT/ carbohydrates/
protein. Both test days will include 30 minutes of exercise on a bicycle
ergometer. The results of the pilot will help to determine the actual duration
of the two test days. It Is likely that the duration of these tests will be
shorter than the 12-hour period chosen for the pilot. Total amount of time
spent on the actual study will be a maximum of 25 hours (1-hour screening + 2 x
12 hours). In contrast to the pilot, the subjects do not need to undergo
additional vena punctures for tracer clearance . Total amount of blood drawn
during the study will be maximal 436 ml. The same risks are attributed to the
actual study as for the pilot.