Impact of medium and long chain triglycerides consumption on appetite and food intake in overweight men

Abstract

Background
Medium chain triglycerides (MCT) enhance thermogenesis and may reduce food intake relative to long chain triglycerides (LCT). The goal of this study was to establish the effects of MCT on appetite and food intake and determine whether differences were due to differences in hormone concentrations.

Methods
Two randomized, crossover studies were conducted in which overweight men consumed 20 g of MCT or corn oil (LCT) at breakfast. Blood samples were obtained over 3 h. In Study 1 (n=10), an ad lib lunch was served after 3 h. In Study 2 (n=7), a pre-load containing 10 g of test oil was given at 3 h and lunch was served 1 h later. Linear mixed model analyses were performed to determine the effects of MCT and LCT oil on change in hormones and metabolites from fasting, adjusting for body weight. Correlations were computed between differences in hormones just before the test meals and differences in intakes after the two oils for Study 1 only.

Results
Food intake at the lunch test meal after the MCT pre-load (Study 2) was (mean ± SEM) 532 ± 389 kcal vs. 804 ± 486 kcal after LCT (P < 0.05). MCT consumption resulted in a lower rise in triglycerides (P = 0.014) and glucose (P = 0.066) and a higher rise in peptide YY (P = 0.017) and leptin (P = 0.036) compared to LCT (combined data). Correlations between differences in hormone levels (GLP-1, PYY) and differences in food intake were in the opposite direction to expectations.

Conclusions
MCT consumption reduced food intake acutely but this does not seem to be mediated by changes in GLP-1, PYY, and insulin.

Full text

ORIGINAL ARTICLE
Impact of medium and long chain triglycerides consumption
on appetite and food intake in overweight men
M-P St-Onge
1,2
, B Mayrsohn
1
,MO’Keeffe
1,2
, HR Kissileff
1,2
, AR Choudhury
3
and B Laferrère
2
BACKGROUND: Medium chain triglycerides (MCT) enhance thermogenesis and may reduce food intake relative to long chain
triglycerides (LCT). The goal of this study was to establish the effects of MCT on appetite and food intake and determine whether
differences were due to differences in hormone concentrations.
METHODS: Two randomized, crossover studies were conducted in which overweight men consumed 20 g of MCT or corn oil (LCT)
at breakfast. Blood samples were obtained over 3 h. In Study 1 (n= 10), an ad lib lunch was served after 3 h. In Study 2 (n= 7),
a preload containing 10 g of test oil was given at 3 h and lunch was served 1 h later. Linear mixed model analyses were performed
to determine the effects of MCT and LCT oil on change in hormones and metabolites from fasting, adjusting for body weight.
Correlations were computed between differences in hormones just before the test meals and differences in intakes after the two
oils for Study 1 only.
RESULTS: Food intake at the lunch test meal after the MCT preload (Study 2) was (mean ± s.e.m.) 532 ± 389 kcal vs 804 ± 486 kcal
after LCT (Po0.05). MCT consumption resulted in a lower rise in triglycerides (P= 0.014) and glucose (P= 0.066) and a higher rise in
peptide YY (PYY, P= 0.017) and leptin (P= 0.036) compared with LCT (combined data). Correlations between differences in hormone
levels (glucagon-like peptide (GLP-1), PYY) and differences in food intake were in the opposite direction to expectations.
CONCLUSIONS: MCT consumption reduced food intake acutely but this does not seem to be mediated by changes in GLP-1,
PYY and insulin.
European Journal of Clinical Nutrition advance online publication, 30 July 2014; doi:10.1038/ejcn.2014.145
INTRODUCTION
Functional foods, 'those foods that encompass potentially
healthful products including any modified food or ingredient that
may provide a health benefit beyond the traditional nutrients it
contains',
1
have been suggested to provide benefits for weight
management
2
via decreased lipid storage and uptake, enhanced
rates of fat oxidation and increased satiety.
3–5
One functional food
that has been proposed to act on both energy expenditure and
energy intake is medium chain triglycerides (MCT). MCT bypass
chylomicron incorporation for lymphatic transportation, providing
the liver with a ready supply of energy and reducing peripheral fat
deposition into adipose tissue.
6,7
In humans, MCT consumption
enhances reductions in adiposity.
8,9
Ex vivo studies have shown that the rate of medium chain fatty
acid oxidation is 10-fold faster than that of long chain fatty acids.
10
Indeed, MCT consumption produces a greater thermic effect when
compared with long chain triglyceride (LCT)
11–16
and promotes
satiety in animal models
17,18
and humans.
19,20
Considering these
effects of MCT consumption, it has been hypothesized that
substituting MCT oil for LCT oils could potentially be used as an
adjunct in weight-loss programs.
21
Although an abundance of research on MCT’s effects on energy
expenditure and body composition is available,
16,21
their role in
modulating food intake has not been extensively studied
8,20,22
beyond their effect on cholecystokin (CCK). Studies have shown
that long chain fatty acids, but not medium chain fatty acids,
stimulate CCK release to reduce food intake.
23
However, a study by
Drewe et al.
24
does not support the role of endogenous CCK as
being responsible for the food intake reduction after LCT infusion.
One study showed that both MCT and LCT stimulated the release of
peptide YY (PYY), when infused intraduodenally, but that LCT did so
to a greater extent.
25
The authors suggested that the greater effect
of LCT may be because of its stimulation of CCK release, which then
stimulates PYY release. Of note is that those studies have used fat
duodenal infusions rather than oral intakes. In this study, we chose
to provide oils as would be consumed in a typical diet.
The main purpose of this study was to determine whether
(i) MCT consumption suppresses food intake relative to LCT; (ii)
MCT induces a profile of gut hormone responses indicating
increased satiety/reduced appetite signaling relative to LCT and
(iii) the hormonal response to MCT is related to the differences in
food intake after the consumption of MCT or LCT. We
hypothesized (i) lower food intake after a preload high in MCT
compared with LCT; (ii) lower circulating levels of ghrelin and higher
circulating levels of PYY and glucagon-like peptide 1 (GLP-1) after
MCT consumption relative to LCT and (iii) that the effect of MCT on
hormones would be related to the difference in food intake
observed after the consumption of either MCT or LCT. Gibbons
et al.
26
have reported that post-meal levels of ghrelin and GLP-1
were correlated with food intake at an ad libitum meal 3 h later.
PARTICIPANTS AND METHODS
Study participants
Adult men, age 19–50 years, with a body mass index of 25–29.9 kg/m
2
were
recruited to participate in two separate studies (Study 1, n= 10; Study 2, n=7)
1
College of Physicians and Surgeons, Columbia University, New York, NY, USA;
2
New York Obesity Nutrition Research Center, St. Luke’s/Roosevelt Hospital, New York, NY, USA and
3
Department of Biostatistics, Mailman School of Public Health, Columbia University, New York, NY, USA. Correspondence: Dr M-P St-Onge, 622 West 168th Street, PH9-105Q,
New York, NY 10032, USA.
E-mail ms2554@columbia.edu
Received 3 December 2013; revised 22 May 2014; accepted 27 May 2014
European Journal of Clinical Nutrition (2014), 1–7
© 2014 Macmillan Publishers Limited All rights reserved 0954-3007/14
www.nature.com/ejcn

during the summers of 2009 and 2010. Men were recruited from the
Columbia University/St. Luke’s-Roosevelt Hospital area (New York, NY, USA)
via flyers and online advertisements. Smokers and those with recent
weight change (410 lbs in the previous 3 months), excessive caffeine use
(46 caffeinated beverages per day), severe chronic health conditions,
allergies to any of the food products or ingredients provided in this study
or taking medications known to affect energy expenditure or gastro-
intestinal function were excluded from the study. These studies were
approved by the St Luke’s-Roosevelt Hospital Institutional Review Board
and all participants provided informed consent prior to the start of
the study.
Protocol details
Both studies employed a 2-arm, randomized, single-blind, cross-over
design with each arm consisting of one test day differing in the type of oil
incorporated in the breakfast: MCT oil (Neobee 1053, Stepan Company,
Northfield, IL, USA) or corn oil (LCT, Mazola, ACH Food Companies,
Cordova, TN, USA). A random digit table was used to determine test oil
sequence. The random allocation sequence and participant enrollment
were determined by a study investigator. Test days were held at least
3 days, but no more than 14 days, apart.
For 2 days prior to test day, participants were asked to refrain from
alcohol consumption. In addition, they were asked not to participate in any
structured exercise the day before each test day and to record their food
intake at dinner and consume the same meal on the night prior to their
second test day. They were also instructed to drink approximately 1.9l of
water the day before each test day to ensure proper hydration. These
precautions were implemented to ensure a greater degree of consistency
between test periods. Participants were asked to fast overnight for 12 h
prior to testing.
Each test day was performed at the St Luke’s/Roosevelt Hospital
Outpatient Clinical Research Resource of the Irving Center for Translational
Research (Columbia University, New York, NY, USA) in the morning. Upon
arrival, anthropometric measurements were taken and a catheter was
inserted in an antecubital vein for frequent blood sampling. Participants
then consumed the breakfast meal containing 20 g of oil over a 10-min
period. Immediately before and at fixed time points after breakfast, blood
samples were drawn from the catheter for hormone and metabolite
measurements. At the end of the 3- h blood sampling protocol,
participants from Study 1 were served an ad libitum single item lunch
test meal. Participants from Study 2 were given a preload containing 10 g
of the test oil, followed 1 h later by the ad libitum single item lunch. For the
ad libitum lunch test meal, men were instructed to eat as much as they
wanted until they were satisfied. Total food intake was measured by
weighing the food portion before and after lunch.
Test breakfast meals and preload
Breakfast meals differed in nutrient composition between Study 1 and
Study 2 (Table 1) but contained the same amount of test oil and were
consumed within 10 min in both studies. Participants in Study 1 received a
muffin (20 g of test oil) and 5 oz (148 ml) of orange juice. Muffins were
made from 71.5 g of fat-free muffin mix, either raisin bran or spice apple
bran (Bob’s Red Mill, Milwaukie, OR, USA). Participants in Study 2 received a
liquid meal replacement (14 oz of Boost, Nestle Healthcare Nutrition,
Fremont, MI, USA) to which 20 g of test oil was added. This dose of oil was
used because we have previously showed that consumption of 18–24 g/day
of MCT oil enhances weight loss relative to LCT
27
and Dulloo et al.
11
have
shown that 15–30 g/day of MCT raise 24-h energy expenditure relative to
LCT. The oils did not differ in taste. In Study 1, participants were not given
instructions on how to consume the breakfast and the order of intake of
the juice and muffin may have differed between participants and between
test days. This may have affected transit time and hormone release. The
breakfast meal for Study 2 was switched to a liquid meal to ensure greater
consistency in gastric emptying time and a more uniform consumption
and nutrient absorption pattern.
Participants in Study 2 were given a preload of yogurt (Dannon Light &
Fit yogurt, Dannon, Allentown, PA, USA; Table 1) containing 10 g of the test
oil 3 h after breakfast consumption. Provision of a preload is commonly
done to assess the satiating properties of a food. We chose to
provide 711.6 kJ as this is consistent with a snack, which typically provides
795.3–1172.1 kJ.
28
Blood sampling protocol
For both Study 1 and 2, blood samples were obtained in the fasted state
immediately before (−15 min) and after test breakfast consumption (0 min)
and at 30, 45, 60, 120, and 180 min. Study 2 participants provided
additional samples at 15, 75, 90 and 150 min. This 3-h sampling period has
been used by others to assess the impact of meal nutrient composition on
appetite-related hormones.
29–31
Samples were collected in EDTA-coated
chilled tubes for the measurement of gut hormones. Tubes were
pretreated with aprotinin (0.6 TIU per ml of blood) and dipeptidyl
peptidase 4 inhibitor (10 μl per ml of blood, for GLP-1 and total PYY
assays only) to prevent the degradation of gut hormones. Upon collection,
blood was immediately placed on ice. Plasma was separated within
60–180 min of collection via centrifugation for 20 min at 4 °C. Samples to
be analyzed for active ghrelin were acidified with 50 μl of 1N HCl and then
frozen at −80 °C until assayed.
All hormone analyses were performed in duplicate in the Hormone and
Metabolite Core Laboratory of the New York Obesity Nutrition Research
Center. Glucose measurements were performed with a glucose analyzer
(Analox Instruments USA Inc, Lunenburg, MA, USA). Insulin and total and
active ghrelin were assayed using RIA (EMD Millipore, Billerica, MA, USA).
Serum leptin was measured in duplicate aliquots using a double-antibody
RIA (Linco Research Products Inc., St Charles, MO, USA). Total PYY was
determined according to Millipore procedure using an antibody that
recognizes both 1–36 and 3–36 forms of human PYY. Total GLP-1 was
measured by RIA (Phoenix Pharmaceutical, Belmont, CA, USA) after plasma
extraction with 95% ethanol. This assay is 100% specific for GLP-1
7-36
,
GLP-1
9-36
and GLP-1
7-37
and does not cross-react with glucagon (0.2%),
GLP-2 (o0.001%) or exendin (o0.0.1%). Triglyceride (TG) levels were
assessed using an Ektachem DT II System (Johnson and Johnson Clinical
Diagnostics, Rochester, NY, USA) with appropriate standards and reagents
for Study 2 participants only. All other hormones and metabolites were
assessed in both studies.
Food intake measurement
At the end of the 3- h testing period, participants in Study 1 were served a
one item ad libitum lunch test meal (Stouffer’s macaroni and beef, Nestle
USA, Wilkes-Barre, PA, USA). In Study 2, a preload was served at 3h and the
single item ad libitum lunch (Penne Arrabiata, Trader Joe’s, Monrovia, CA,
USA) was provided 1 h later. One hour was noted as the time where the
difference in hunger ratings was seemingly greatest between MCT and LCT
and has been used by others previously.
32
In both studies, participants
were served in excess of their predicted energy intakes and instructed by
the investigator to eat ‘as much as you would like of this meal until you are
Table 1. Characteristics of study meals
Meal characteristics Study 1 Study 2
Breakfast meal Muffin with
orange juice
Boost shake
with test oil
Total energy (kJ) 2671 2510
Carbohydrate (g) 105 71.6
Protein (g) 9.6 17.5
Fat (g) 20 27
Test oil (g) 20 20
Preload n/a Yogurt with 10 g
test oil added
Total energy (kJ) 728
Carbohydrate (g) 16
Protein (g) 5
Fat (g) 10
Test oil (g) 10
Lunch meal Stouffer’s macaroni
and beef
Trader Joe’s Penne
Arrabiatta
Total energy (kJ) 5146 4971
Carbohydrate (g) 135 174
Protein (g) 66 42
Fat (g) 48 36
Abbreviation: n/a, not applicable.
Regulation of appetite by medium chain fatty acids
M-P St-Onge et al
2
European Journal of Clinical Nutrition (2014) 1 –7 © 2014 Macmillan Publishers Limited

satisfied’. Total food intake at the ad libitum lunch test meal was recorded
by weighing the food pre- and post-meal. Water was available to drink
with the meal but its intake was not recorded.
Anthropometric measurements
Body weight was measured on a standard balance beam scale to the
nearest 0.5 kg with the participant wearing light clothing and without
shoes on each test day, in the fasted state. Height was measured using a
wall-mounted stadiometer to the nearest 0.5 cm with the participants
shoeless. Waist circumference was measured halfway between the lowest
rib and the iliac crest using a non-stretchable measuring tape.
33
The
average of two measurements was used in the analyses. These
measurements were taken in the fasted state when the participant arrived
at the laboratory.
Statistical analyses
Appetite and hormone data were analyzed using a linear mixed model
analysis using R software (http://cran.r-project.org) and SAS (version 9.2,
SAS Institute, Cary, NC, USA). Each response measure was tested using a
likelihood ratio test to determine if log-transformation would significantly
improve the normal approximation of the measure. It was established
that the normal approximation would not improve because of
log-transformation for any of the measures. Normality of our test statistics
(t-test and F-test used in linear mixed model analyses) was ensured as 14
measures each taken from 17 (7 in some cases) participants gave us at
least 98, and at most 238, data points. Although we have performed
multiple tests in this study, an adjustment for multiple comparisons was
not required because it is only necessary when multiple tests are used for
testing a single hypothesis. In this study, each hypothesis was examined
using a single test.
Test oil (LCT vs MCT) was used as a fixed effect and time as a linear
variable in hormone data. However, when fasting values were used as
response measures, time was not used as an independent variable. Body
weight was used as a covariate and subject was treated as a random effect.
A test oil × time interaction was included in the models initially but was
removed if it was not significant. Data are reported with test oil and time as
fixed effects, subject as a random effect, and body weight as a covariate.
Statistical analyses were performed for both studies combined (n= 17)
and also for Study 2 (n= 7) separately because the composition of the
breakfast meals was too different between studies: liquid and solid in
Study 1 vs liquid only in Study 2. Hormone data from Study 2 are
presented in the figures. Food intake data are reported separately for each
study as the difference in protocol for this measurement precludes
combining data. In Study 1, there was a 3-h time gap between breakfast
and the lunch test meal, whereas in Study 2, a preload was served at 3 h
and the lunch test meal was administered 1 h later. Data are presented as
means ± s.e.m. Significance was considered as Po0.05.
Pearson correlations were performed to assess the relationship between
hormone concentration at 180 min after breakfast and food intake at the
ad libitum lunch test meal as well as change in hormone/metabolite
concentration at 180 min from fasting and food intake at the ad libitum
lunch in Study 1. Pearson correlations were also performed to assess the
relationship between the difference in hormone concentrations at 180 min
between MCT and LCT and the difference in food intake at the ad libitum
lunch in Study 1. Study 2 participants were not included in these analyses
because they received a preload after the 180 min blood draw. Correlations
were performed with both test oils combined and separately by test oil.
RESULTS
Twenty men were recruited (Study 1, n= 13; Study 2, n= 7) and 17
completed (Study 1, n= 10; Study 2, n= 7, Table 2) the study. Two
participants dropped out after screening because of scheduling
conflicts, another dropped out in the middle of the first test day
after feeling faint and nauseated following consumption of the
MCT-containing breakfast. Another participant (Study 2) reported
diarrhea following the MCT test day, but remained in the study. No
other side effects were noted.
Food intake
Food intake at the ad libitum test lunch did not differ by oil type in
Study 1 (MCT, 2548.0 ± 459.6 kJ vs LCT, 2773.2 ± 531.6 kJ, P= 0.41).
In Study 2, when participants received a 711.6-kJ preload 1 h
before lunch, food intake at lunch was significantly lower during
the MCT test day (MCT, 2227.0 ± 616.2 kJ vs LCT, 3369.3 ± 769.0 kJ,
Po0.050).
Hormones and metabolites: Absolute change
In the combined analyses, there was a significant effect of time on
change in glucose concentrations (P= 0.025) and a trend for an
effect of oil with a lower rise in glucose with MCT consumption
compared with LCT (P= 0.066) that was significant in Study 2
alone (P= 0.0017; Figure 1a). Concurrent with these results, the
change in insulin was not affected by oil in the combined analyses
(P= 0.99) but there was a trend for a lower rise in insulin (effect of
oil P= 0.13; time P= 0.017) when data from Study 2 were analyzed
separately (Figure 1b). There was a significant time × oil
interaction on TG concentrations (P= 0.0046) with a lower rise in
TG (Figure 1c) with MCT consumption compared with LCT
(Study 2).
In the combined analyses, leptin levels after the MCT-containing
breakfast increased to a greater extent compared with LCT
consumption (effect of oil P= 0.036; time P= 0.62). Active ghrelin
concentration after the MCT-containing breakfast was reduced to
a lesser extent compared with LCT (effect of oil P= 0.0031; time
P= 0.10), but the effect of oil type on the change in total ghrelin,
albeit in the same direction, was not significant (effect of oil
P= 0.21; time P= 0.20). When the analyses were restricted to Study 2,
the effect of oil type on changes in leptin was stronger (effect of
oil Po0.001; time P= 0.038; Figure 2a), that is, leptin remained
higher after MCT consumption relative to LCT, whereas the
change in active ghrelin was no longer significant (effect of oil
P= 0.28; time P= 0.95).
There was a significant effect of oil (P= 0.017) and time
(Po0.0001) on total PYY with a greater rise in total PYY post-
prandially with MCT oil than LCT (Study 2 alone: effect of oil
P= 0.030; time Po0.0001; Figure 2b). GLP-1 was not affected by
oil type in the combined analysis (P= 0.39) or in Study 2 alone
(P= 0.40; Figure 2c), although there was a significant effect of time
in the combined analysis (P= 0.0097) but not in Study 2 alone
(P= 0.071).
Online Supplementary material provides information on
percent change in hormone concentrations from baseline.
Correlation between hormones and food intake at the ad libitum
lunch
Food intake at the ad libitum lunch was negatively correlated with
leptin concentrations at time 180 min when both test oils were
combined (r=−0.46, P= 0.037). However, food intake at the ad
libitum lunch test meal was positively correlated with GLP-1
(r= 0.81, Po0.0001), PYY (r= 0.52, P= 0.018), and percent change
Table 2. Characteristics of study participants
Characteristics All participants Study 1 Study 2
Age (year) 39.4 ±1.8 39.2 ±2.7 39.6 ±2.1
Body weight (kg) 88.9 ±2.3 87.1 ±1.7 91.9 ±5.1
Body mass index (kg/m
2
)28.2±0.3 28.1±0.6 28.4±0.5
Height (m) 1.77 ±0.02 1.76 ±0.01 1.79 ±0.04
Systolic blood pressure (mm Hg) 122 ±2 117 ±2 127 ±3
Diastolic blood pressure (mm Hg) 80 ±179±282±2
Ethnicity (C, AA, H, O) 5, 8, 2, 2 3, 7, 0, 0 2, 1, 2, 2
Abbreviations: AA, African Americans; C, Caucasian; O, Other. Results are
means ±s.e.m., n=17 for all participants, 10 for Study 1, and 7 for Study 2.
Regulation of appetite by medium chain fatty acids
M-P St-Onge et al
3
© 2014 Macmillan Publishers Limited European Journal of Clinical Nutrition (2014) 1 –7

in PYY from fasting (r= 0.56, P= 0.010). There was a trend for food
intake to be correlated with percent change in insulin concentra-
tions (r= 0.44, P= 0.053). Those correlations indicate that those
with lower leptin and higher GLP-1, PYY and change in PYY and
insulin from fasting had greater intakes at the ad libitum meal.
When correlations were run separately by oil type, only GLP-1
concentrations were correlated with food intake after the MCT-
rich breakfast (r= 0.89, P= 0.0005), indicating that higher GLP-1
concentrations pre-meal were associated with greater food intake.
Intake at the ad libitum lunch following the LCT breakfast was
correlated with GLP-1 (r= 0.74, P= 0.037), percent change in
insulin (r= 0.66, P= 0.038) and percent change in PYY (r= 0.78,
P= 0.0073). Percent change in leptin tended to be inversely
correlated with food intake (r=−0.62, P= 0.058): a rise in leptin
was associated with lower intakes at the ad libitum lunch
test meal.
The difference in food intake between MCT and LCT was
negatively correlated with the difference in total ghrelin between
MCT and LCT immediately before lunch (r=−0.85, P= 0.0017).
There was also a trend for a positive correlation between the
difference in food intake and the difference in insulin concentra-
tions with MCT and LCT breakfast meals (r= 0.60, P= 0.069). Also,
the difference in food intake between MCT and LCT tended to be
correlated with the difference in the area under the curve for
glucose (r= 0.581, P= 0.078) and insulin (r= 0.59, P= 0.073). There
was no significant correlation for the difference in leptin, GLP-1,
PYY or ghrelin area under the curve.
DISCUSSION
This report provides results of studies examining the effects of
MCT vs LCT consumption on food intake and a wide range of
hormones involved in food intake control, and metabolic risk
factors. No previous study has examined the effects of MCT
consumption on leptin, ghrelin, PYY and GLP-1, specifically. We
show that food intake is lower after an MCT-rich preload
compared with an LCT-rich preload and that leptin and PYY
levels remained higher after MCT consumption compared with
LCT. These results suggest that MCT consumption may trigger the
release of satiety signals more effectively than LCT. However,
correlations between hormone levels and food intake were not in
the direction expected. Moreover, GLP-1 concentrations were not
affected by the type of oil consumed at breakfast and active
ghrelin was reduced to a lesser extent, in the combined analysis,
with MCT consumption. In line with these data, MCT is known to
be a good substrate for the conversion of ghrelin to active ghrelin,
without necessarily affecting total ghrelin concentrations.
34
However, why MCT, which trigger ghrelin acylation via ghrelin
O-acyltransferase, a seemingly orexigenic process,
35
would also be
associated with weight loss and increased reduction in adiposity
27
warrants further investigation. We also found that MCT consump-
tion leads to lower post-prandial glucose and TG than LCT
consumption.
That differences in appetite-regulating hormones were not
related to differences in food intake is puzzling. In fact, the
correlation between differences in ghrelin levels and differences in
food intake between MCT and LCT was in the opposite direction
than expected, as were correlations of food intake with GLP-1 and
PYY. Gibbons et al.
26
have assessed the effects of various
macronutrients on ghrelin, GLP-1 and PYY levels and reported
significant associations between changes in circulating levels of
GLP-1 and ghrelin and food intake at an ad libitum meal, despite
no difference in food intake between test diets. On the basis of
this, we would have expected the greater rise in PYY after MCT
consumption relative to LCT to be related to lower food intake at
the ad libitum meal. On the other hand, van der Klaauw et al.
36
also found significant differences in PYY and GLP-1 in response to
meals varying in protein content with no differences in food
intake at a test meal. Other studies examining the role of protein
on appetite-regulation have assessed hormone concentrations.
Leidy et al.
37
found lower ghrelin and higher leptin after
consumption of a high protein breakfast compared with skipping
breakfast but there was no difference when compared with the
-10
0
10
20
30
40
50
-15 0 15 30 45 60 75 90 120 150 180
Glucose, absolute change from baseline
(mg/dL)
Time relative to breakfast consumption (min)
0
20
40
60
80
100
120
-15 0 15 30 45 60 75 90 120 150 180
Insulin, absolute change from basleine
(µU/mL)
Time relative to breakfast consumption (min)
-10
0
10
20
30
40
50
60
70
80
90
-15 0 15 30 45 60 75 90 120 150 180
Triglycerides, absolute change from
baseline (mg/dL)
Time relative to breakfast consumption (min)
Figure 1. Absolute change from baseline in glucose (a), insulin (b)
and triglycerides (c) in response to a meal containing MCT oil (black
squares) and LCT oil (open squares) in Study 2. Blood samples were
obtained after consumption of a liquid meal containing 20 g of
either MCT oil or corn oil (LCT). Data were analyzed using linear
mixed model, controlling for body weight. The meal was provided
immediately before the time 0 blood draw. There was a significant
effect of oil type on glucose (P=0.0017) and a trend for insulin
(P=0.13). There was a significant effect of time on insulin (P=0.017)
and a time × oil interaction on triglycerides (P=0.0046). Data
represent means ±s.e.m., n=7.
Regulation of appetite by medium chain fatty acids
M-P St-Onge et al
4
European Journal of Clinical Nutrition (2014) 1 –7 © 2014 Macmillan Publishers Limited

normal protein breakfast; food intake was not assessed in that
study. Ratliff et al.
31
also found that an egg breakfast led to lower
glucose, insulin and ghrelin area under the curve over 3h post
consumption relative to a breakfast consisting of bagel and cream
cheese but found no effect of breakfast type on leptin, GLP-1 and
PYY. It is important to note, however, that our study was not
meant to establish a mechanism of action by which MCT
modulation of appetite-regulating hormones could affect satiety
and food intake. Prior to conducting this study, the effects of MCT
consumption on circulating levels of ghrelin, PYY and GLP-1 were
relatively unknown and this study provides some basic informa-
tion on the effects of MCTon those hormones. Future studies are
needed to determine whether changes in these hormones
mediate the effects of MCT consumption on food intake.
From the results obtained in this study, we posit that changes in
gut hormones might not be the primary modulators of food intake
control following MCT consumption. Thermal and oxidative
pathways may be a more likely mechanism. In fact, prior research
by our group and others has shown that MCT can enhance
thermogenesis relative to LCT
11–13,16,21,38
and increases in thermic
effect of food have been correlated with enhanced satiety.
39
Although the association between substrate oxidation rate and
energy intake has not been consistently observed,
40
others have
proposed that fatty acid oxidation rate could influence appetite
and subsequent food intake.
39,41
It is therefore plausible that the
thermogenic- and fat oxidation-enhancing effects of MCT could
be involved in appetite regulation, leading to lower energy
intakes. This remains to be addressed directly.
The effects of MCT on food intake may be acute, rather than
long-acting. In the present study, there was no effect of MCT vs
LCT at breakfast on food intake 3 h later (Study 1), whereas food
intake 1 h after a preload (Study 2) was reduced. It is unfortunate
that no blood samples were obtained after the preload and prior
to the ad libitum lunch test meal in Study 2 to assess correlations
between hormones and food intake. Follow-up studies would be
needed to perform this measurement and also to test the effects
of hormone antagonists on food intake after MCT- and LCT-rich
breakfasts. This would truly help uncover a mechanism linking
hormonal responses to MCT consumption and food intake. For
example, PYY, a hormone previously demonstrated to induce
satiation when infused, and described as being secreted in
proportion to macronutrient intake,
42
was higher after MCT than
LCT consumption. Further studies with blockers of PYY receptors
in conjunction with MCT consumption would be needed to test
whether an increase in PYY could be one mechanism by which
MCT induces satiation.
Data from Study 2 demonstrate a lower rise in TG with MCT
consumption relative to LCT after the test breakfast. This
corroborates data from Maki et al.
43
who found a lower TG
incremental area under the curve over 8 h after consumption of a
milkshake containing 30 g of MCT compared with LCT (mix of high
oleic safflower oil, canola oil, soy oil and safflower oil). However,
contrary to our results, that study reported higher median blood
glucose levels at 2 h after MCT compared with LCT consumption.
43
The difference in blood sampling protocol between our two
studies may explain the different results: Maki et al.
43
sampled
-1.2
-1
-0.8
-0.6
-0.4
-0.2
0
0.2
0.4
0.6
0.8
-15 0 15 30 45 60 75 90 120 150 180
Leptin, absolute changr from baseline
(ng/dL)
Time relative to breakfast consumption (min)
0
2
4
6
8
10
12
14
16
18
20
-15 0 15 30 45 60 75 90 120 150 180
GLP-1, absolute change from baseline
(pg/mL)
Time relative to breakfast consumption (min)
0
10
20
30
40
50
60
70
80
Total PYY, ansolute change from
baseline pg/mL
20
25
30
35
40
45
50
Active ghrelin, absolute change from
baseline (pg/mL)
Time (relative to breakfast consumption (min)
Time relative to breakfast consumption (min)
-15 0 15 30 45 60 75 90 120 150 180
-15 0 15 30 45 60 75 90 120 150 180
Figure 2. Absolute change from baseline for leptin (a), GLP-1 (b), total PYY (c) and active ghrelin (d) in response to a meal containing MCT oil
(black squares) and LCT oil (open squares) in Study 2. Data were analyzed using linear mixed model, controlling for body weight. The meal was
provided immediately before the time 0 blood draw. There was a significant effect of oil type and time on leptin (Po0.001 and 0.038,
respectively), PYY (P=0.030 and o0.0001, respectively) and active ghrelin (P=0.0031; trend for time P=0.10, respectively). There was no
effect of oil type on GLP-1 (P=0.40) but a trend for an effect of time (P=0.071). Data represent means ±s.e.m., n=7.
Regulation of appetite by medium chain fatty acids
M-P St-Onge et al
5
© 2014 Macmillan Publishers Limited European Journal of Clinical Nutrition (2014) 1 –7

blood every 2 h for 8 h following the breakfast meal, whereas we
had frequent samples starting immediately after the meal. By not
sampling blood before 2 h post-prandially, the glucose peak may
have been missed. This is evident from our 120 min data point,
which would have prompted different conclusions in the present
study as well. In addition, Broussolle et al.
44
noted more
pronounced reductions in plasma glucose with a 1:1 intravenous
infusion of coconut oil, a rich source of MCT, to soy oil compared
with saline or soy oil infusion alone in healthy normal weight men.
Future studies should examine the long-term effects of MCT
consumption on glucose and lipid profiles.
To date, only two studies have examined the effects of MCT on
satiety-modulating hormones such as CCK.
40,46
It has been well
established that the regulation of CCK release following con-
sumption of fat is chain length-dependent, with long chain fatty
acids exerting a greater effect than short and medium chain fatty
acids.
41,46
An analysis of CCK was not included in the present
study and this could be considered a weakness. However, on the
basis of prior knowledge of the regulation of CCK release, LCT
would have elicited a larger release of CCK than MCT. Measure-
ment of apolipoprotein A-IV, which is secreted in response to
dietary fats,
49
may have also been relevant.
Other weaknesses of the present study include its small sample
size, the difference in the format of the breakfast meals and lack of
provision of a preload before the ad libitum lunch test meal in
Study 1. Also, although we have exhaustive objective information
on food intake and its hormonal controls, we did not take
subjective measures of appetite and satiety, which would have
provided additional information. Our study may have been under-
powered to detect some differences between test oils but this was
a pilot study and the data provided can be used as the basis for a
larger study in the future. On the basis of the exploratory nature of
this study, a small sample size was warranted to avoid wasting
resources and unduly performing research on healthy participants.
None of the hypothesis tests should be taken as definitive but
rather as indicative of potential effects, subject to confirmation.
Our study has several strengths. We used a crossover design
and enrolled only overweight men, reducing the variability of our
results. On the other hand, this prevents extrapolation to women
or normal weight individuals. Our study included purified MCT oil
and provided identical breakfast test meals within each study.
Additionally, we obtained frequent blood samples over a 3-h post-
prandial period and analyzed a variety of hormones and
metabolites that could be involved in the appetite-regulating
effect of foods.
The results from the present study suggest that fats differing in
fatty acid chain length and saturation level differentially affect the
secretion of metabolites and hormones that regulate food intake.
However, those differences were not correlated with differences in
food intake. These results prompt further research in the
mechanism by which MCT consumption could modulate food
intake to lead to improved weight management. This report
further provides evidence that acute intakes of up to 20 g of MCT
do not adversely affect glucose and TG concentrations. The long-
term safety, and potentially beneficial, effects of MCT consump-
tion on metabolic risk factors should be examined further.
CONFLICT OF INTEREST
Dr St-Onge is on the Advisory Board of Freelife LLC. The remaining authors declare no
conflict of interest.
ACKNOWLEDGEMENTS
We would like to thank all participants for their involvement in this study and Xinyue
Tong and Lilly Nhan for their assistance in the conduct of the study for study 1
participants. MPSO, BM, HRK and BL designed the research; MPSO, BM and MO
conducted research; MPSO, BM and AR analyzed data; MPSO, BM, HRK, BL and AR
wrote the paper; MPSO had primary responsibility for final content. All authors read
and approved the final manuscript. This publication was supported by the National
Center for Advancing Translational Sciences, National Institutes of Health, through
Grant Number UL1 TR000040, formerly the National Center for Research Resources,
Grant Number UL1 RR024156, the New York Obesity Nutrition Research Center Grant
Number P30-DK26687. MCT oil was provided by Stepan Company. This trial was
registered on Clinicaltrials.gov, identifier NCT01952977.
REFERENCES
1 Institute of Medicine. Opportu nities in the nutrition and food sciences--a institute
of medicine report. Nutr Rev 1994; 52: 106–109.
2 St-Onge MP. Dietary fats, teas, dairy, and nuts: potential functional foods for
weight control? Am J Clin Nutr 2005; 81:7–15.
3 St-Onge MP, Jones PJ. Greater rise in fat oxidation with medium-chain triglyceride
consumption relative to long-chain triglyceride is associated with lower initial
body weight and greater loss of subcutaneous adipose tissue. Int J Obes Relat
Metab Disord 2003; 27: 1565–1571.
4 Schwartz MW, Woods SC, Porte Jr D, Seeley RJ, Baskin DG. Central nervous system
control of food intake. Nature 2000; 404:661–671.
5 Seimon RV, Wooster T, Otto B, Golding M, Day L, Little TJ et al. The droplet size of
intraduodenal fat emulsions influences antropyloroduodenal motility, hormone
release, and appetite in healthy males. Am J Clin Nutr 2009; 89:1729–1736.
6 Babayan VK. Medium chain triglyce rides and structured lipids. Lipids 1987; 22:
417–420.
7 Bach AC, Babayan VK. Medium-chain triglycerides: an update. Am J Clin Nutr 1982;
3: 950–962.
8 St-Onge M-P, Bosarge A. Weight-loss diet that includes consumption of medium-
chain triacylglycerol oil leads to a greater rate of weight and fat mass loss than
does olive oil. Am J Clin Nutr 2008; 87: 621–626.
9 Tsuji H, Kasai M, Takeuchi H, Nakamura M, Okazaki M, Kondo K. Dietary Medium-
Chain Triacylglycerols Suppress Accumulation of Body Fat in a Double-Blind,
Controlled Trial in Healthy Men and Women. J Nutr 2001; 131: 2853–2859.
10 Hill JO, Peters JC, Reed GW, Schlundt DG, Sharp T, Greene HL. Nutrient balance in
humans: effects of diet composition. Am J Clin Nutr 1991; 54:10–17.
11 Dulloo AG, Fathi M, Mensi N, Girardier L. Twenty-four-hour energy expenditur e
and urinary catecholamines of humans consuming low-to-moderate amounts of
medium-chain triglycerides: a dose-response study in a human respiratory
chamber. Eur J Clin Nutr 1996; 50: 152–158.
12 ScalfiL, Coltorti A, Contaldo F. Postprandial thermogenesis in lean and obese
subjects after meals supplemented with medium-chain and long-chain trigly-
cerides. Am J Clin Nutr 1991; 53: 1130–1133.
13 Seaton T, Welle S, Warenko M, Campbell R. Thermic effect of medium-chain and
long-chain triglycerides in man. Am J Clin Nutr 1986; 44: 630–634.
14 Hill JO, Peters JC, Yang D, Sharp T, Kaler M, Abumrad NN et al. Thermogenesis in
humans during overfeeding with medium-chain triglycerides. Metabolism 1989;
38:641–648.
15 White MD, Papamandjaris AA, Jones PJ. Enhanced postprandial energy expen-
diture with medium-chain fatty acid feeding is attenuated after 14 d in
premenopausal women. Am J Clin Nutr 1999; 69: 883–889.
16 St-Onge MP, Bourque C, Jones PJ, Ross R, Parsons WE. Medium- versus long-chain
triglycerides for 27 days increases fat oxidation and energy expenditure without
resulting in changes in body composition in overweight women. Int J Obes Relat
Metab Disord 2003; 27:95–102.
17 Bray GA, Lee M, Bray TL. Weight gain of rats fed medium-chain triglycerides is less
than rats fed long-chain triglycerides. Int J Obes 1980; 4:27–32.
18 Furuse M, Choi YH, Mabayo RT, Okumura J. Feeding behavior in rats fed diets
containing medium chain triglyceride. Physiol Behav 1992; 52:815–817.
19 Stubbs RJ, Harbron CG. Covert manipulation of the ratio of medium- to long-chain
triglycerides in isoenergetically dense diets: effect on food intake in ad libitum
feeding men. Int J Obes Relat Metab Disord 1996; 20:435–444.
20 Van Wymelbeke V, Himaya A, Louis-Sylvestre J, Fantino M. Influence of
medium-chain and long-chain triacylglycerols on the control of food intake in
men. Am J Clin Nutr 1998; 68:226–234.
21 St-Onge MP, Ross R, Parsons WD, Jones PJ. Medium-chain triglycerides increase
energy expenditure and decrease adiposity in overweight men. Obes Res 2003;
11:395–402.
22 Poppitt SD, Strik CM, MacGibbon AK, McArdle BH, Budgett SC, McGill AT.
Fatty acid chain length, postprandial satiety and food intake in lean men. Physiol
Behav 2010; 101: 161–167.
23 Matzinger D, Degen L, Drewe J, Meuli J, Duebendorfer R, Ruckstuhl N et al.
The role of long chain fatty acids in regulating food intake and cholecystokinin
release in humans. Gut 2000; 46:688
–693.
Regulation of appetite by medium chain fatty acids
M-P St-Onge et al
6
European Journal of Clinical Nutrition (2014) 1 –7 © 2014 Macmillan Publishers Limited

24 Drewe J, Gadient A, Rovati LC, Beglinger C. Role of circulating cholecystokinin in
control of fat-induced inhibition of food intake in humans. Gastroenterology 1992;
102: 1654–1659.
25 Maas MI, Hopman WP, Katan MB, Jansen JB. Release of peptide YY and inhibition
of gastric acid secretion by long-chain and medium-chain triglycerides but not by
sucrose polyester in men. Eur J Clin Invest 1998; 28:123–130.
26 Gibbons C, Caudwell P, Finlayson G, Webb DL, Hellstrom PM, Naslund E et al.
Comparison of postprandial profiles of ghrelin, active GLP-1, and total PYY to
meals varying in fat and carbohydrate and their association with hunger and the
phases of satiety. J Clin Endocrinol Metab 2013; 98:E847–E855.
27 St-Onge MP, Bosarge A. Weight-loss diet that includes consumption of medium-
chain triacylglycerol oil leads to a greater rate of weight and fat mass loss than
does olive oil. Am J Clin Nutr 2008; 87:621–626.
28 Kant AK, Graubard BI. Secular trends in patterns of self-reported food
consumption of adult Americans: NHANES 1971-1975 to NHANES 1999-2002.
Am J Clin Nutr 2006, 84: 1215–1223.
29 Batterham RL, Heffron H, Kapoor S, Chivers JE, Chandarana K, Herzog H et al.
Critical role for peptide YY in protein-mediated satiation and body-weight
regulation. Cell Metab 2006; 4:223–233.
30 Holt S, Brand J, Soveny C, Hansky J. Relationship of satiety to postprandial
glycaemic, insulin and cholecystokinin responses. Appetite 1992; 18:129–141.
31 Ratliff J, Leite JO. de Ogburn R, Puglisi MJ, VanHeest J, Fernandez ML. Consuming
eggs for breakfast influences plasma glucose and ghrelin, while reducing energy
intake during the next 24 h in adult men. Nutr Res 2010; 30:96–103.
32 Anderson GH, Tecimer SN, Shah D, Zafar TA. Protein source, quantity, and time of
consumption determine the effect of proteins on short-term food intake in
young men. J Nutr 2004; 134:3011–3015.
33 Wang J, Thornton JC, Bari S, Williamson B, Gallagher D, Heymsfield SB et al. Com-
parisons of waist circumferences measured at 4 sites. Am J Clin Nutr 2003; 77:379–384.
34 Nishi Y, Hiejima H, Hosoda H, Kaiya H, Mori K, Fukue Y et al. Ingested medium-
chain fatty acids are directly utilized for the acyl modification of ghrelin.
Endocrinology 2005; 146: 2255–2264.
35 Kirchner H, Gutierrez JA, Solenberg PJ, Pfluger PT, Czyzyk TA, Willency JA et al.
GOAT links dietary lipids with the endocrine control of energy balance. Nat Med
2009; 15: 741–745.
36 van der Klaauw AA, Keogh JM, Henning E, Trowse VM, Dhillo WS, Ghatei MA et al.
High protein intake stimulates postprandial GLP1 and PYY release. Obesity 2013;
21: 1602–1607.
37 Leidy HJ, Ortinau LC, Douglas SM, Hoertel HA. Beneficial effects of a higher-
protein breakfast on the appetitive, hormonal, and neural signals controlling
energy intake regulation in overweight/obese, ‘breakfast-skipping, late-
adolescent girls. Am J Clin Nutr 2013; 97: 677–688.
38 Astrup A. The relevance of increased fat oxidation for body-weight management:
metabolic inflexibility in the predisposition to weight gain. Obes Rev 2011; 12:
859–865.
39 Brondel L, Landais L, Romer MA, Holley A, Penicaud L. Substrate oxidation
influences liking, wanting, macronutrient selection, and consumption of food
in humans. Am J Clin Nutr 2011; 94:775–783.
40 Langhans W. The enterocyte as an energy flow sensor in the control of eating.
Forum Nutr 2010; 63:75–84.
41 Feinle-Bisset C, Patterson M, Ghatei MA, Bloom SR, Horowitz M. Fat digestion is
required for suppression of ghrelin and stimulation of peptide YY and pancreatic
polypeptide secretion by intraduodenal lipid. Am J Physiol Endocrinol Metab 2005;
289: E948–E953.
42 Feltrin KL, Little TJ, Meyer JH, Horowitz M, Smout AJ, Wishart J et al. Effects of
intraduodenal fatty acids on appetite, antropyloroduodenal motility, and plasma
CCK and GLP-1 in humans vary with their chain length. Am J Physiol Regul Integr
Comp Physiol 2004; 287: R524–R533.
43 Maggio CA, Koopmans HS. Satiety effects of intragastric meals containing
triglycerides with different chain lengths. Am J Physiol 1987; 252(6 Pt 2):
R1106–R1113.
44 Flatt JP, Ravussin E, Acheson KJ, Jequier E. Effects of dietary fat on postprandial
substrate oxidation and on carbohydrate and fat balances. J Clin Invest 1985; 76:
1019–1024.
45 Westerterp-Plantenga MS, Wijckmans-Du ijsens NE. Verboeket-van de Venne WP,
De Graaf K, Weststrate JA, Van Het Hof KH. Diet-induced thermogenesis and
satiety in humans after full-fat and reduced-fat meals. Physiol Behav 1997; 61:
343–349.
46 Maki KC, Mustad V, Dicklin MR, Geohas J. Postprandial metabolism with
1,3-diacylglycerol oil versus equivalent intakes of long-chain and medium-chain
triacylglycerol oils. Nutrition 2009; 25: 627–633.
47 Broussolle C, Beylot M, Chassard D, Beaufrere B. Effects of different lipid substrates
on glucose metabolism in normal postabsorptive humans. Metabolism 1992; 41:
1276–1283.
48 Vu MK, Verkijk M, Muller ESM, Biemond I, CBHW Lamers. Masclee AAM. Medium
chain triglycerides activate distal but not proximal gut hormones. Clin Nutr 1999;
18:359–363.
49 D'Alessio D. Intestinal hormones and regulation of satiety: the case for CCK, GLP-1,
PYY, and Apo A-IV. JPEN. J Parenter Enteral Nutr 2008; 32:567–568.
Supplementary Information accompanies this paper on European Journal of Clinical Nutrition website (http://www.nature.com/ejcn)
Regulation of appetite by medium chain fatty acids
M-P St-Onge et al
7
© 2014 Macmillan Publishers Limited European Journal of Clinical Nutrition (2014) 1 –7