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ELSEVIER
Life Scieacea. Vol. 62, No. 14, pp. 1203-1215,1998
copyright 0 1998 Elseviex science Inc.
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MINIREVIEW
MEDIUM CHAIN FATTY ACID METABOLISM
AND ENERGY EXPENDITURE: OBESITY
TREATMENT IMPLICATIONS
Andrea A. Papamandjaris, Diane E. MacDougall, and
Peter J.H. Jones
School of Dietetics and Human Nutrition, Faculty of Agricultural and
Environmental Sciences, McGill University, Macdonald Campus,
Ste-Anne-de-Bellevue, Quebec
(Received in final form January 19,1998)
Fatty acids undergo different metabolic fates depending on their chain length and degree of
satumtion. The purpose of this review is to examine the metabolic handling of medium chain
fatty acids (MCFA) with specific reference to intermediary metabolism and postprandial and
total energy expenditure. The metabolic discrimination between varying fatty acids begins
in the GI tract, with MCFA being absorbed more efficiently than long chain fatty acids
(LFCA). Subsequently, MCFA are transported in the portal blood diily to the liver, unlike
LCFA which are incorporated into chylomicrons and transported through lymph. These
structure based differences continue through the processes of fat utilization; MCFA enter
the mitochondria independently of the carnitine transport system and undergo preferential
oxidation. Variations in ketogenic and lipogenic capacity also exist. Such metabolic
discrimination is supported by data in animals and humans showing increases in
postprandial energy expenditure after short term feeding with MCFA. In long term MCFA
feeding in animals, weight accretion has been attenuated. These differences in metabolic
handling of MCFA versus LCFA are considered with the conclusion that MCFA hold
potential as weight loss agents.
Key Wo4.s: medium chain fatty acids, energy expenditure, metabolism, obesity
Correspondmg author: Peter J. H. Jones, Ph.D., School of Dietetics and Human Nutrition, Faculty of Agricultural and
Environmental Sciences., 21,111 Lakeshore Road, McGill University, Macdonald Campus, Ste-Anne-de-Bellevue, Quebec
H9X 3V9 (514)398-7842 Fax:(514)398-7739 E-mail: Jonesp@gradm.lan.mcgill.ca
1204 Medium Chain Fats and Energy Metabolism Vol. 62, No. 14, 1998
Medium chain fatty acids (MCFA) containing 8- 12 carbons are saturated compared to long chain fatty
acids (LCFA) which contain 14 or more carbon atoms and can possess one or more double bonds.
These structural differences affect molecular size and water solubility and can lead to differentiation
between MCFA and LCFA during processes of digestion, absorption, and transport (1). In addition,
small chain length dependent differences in energy content of triglycerides and constituent fatty acids
(FA) exist (2,3). There has been growing evidence that in addition to the fate of nutrients as directed
by ATP requirements, chain length- and saturation-dependent differentiation in metabolic disposal
of dietary fatty acids occurs, potentially directing ingested fat toward oxidation versus storage and
thus influencing energy expenditure (2,4,5,6). Differences in MCFA versus LCFA energy content,
uptake, and transport as well as efficiency of energy transformation may therefore impact on long
term energy balance. Data suggest that such differences have implications in treatment strategies for
obesity. Dietary fat substitution of MCT for LCT has been shown to influence energy balance and
may therefore promote weight reduction (6,7). To address the question of the effect of MCFA on
energy balance, the purpose of this review is to examine MCFA intermediary metabolism and the
effect of MCFA administration on thermogenesis and total energy expenditure. The potential use of
MCT as weight loss agents is also explored.
Digestion and AbsorDtion of Medium Chain Trielvcerides
Metabolic discrimination between MCT and LCT commences in the gut. The smaller molecular
weight of MCT as compared to LCT facilitates the action of pancreatic lipase and therefore increases
the rate of digestion of MCT (1). Consequently, MCT undergo faster and more complete hydrolysis
to MCFA than LCT to LCFA (8,9,10) and MCFA are absorbed more quickly into the intestinal lumen
(1,ll). In addition, due to the longer chain length specificity of acyl-CoA synthetase, MCFA are not
significantly incorporated into triglycerides and the subsequent chylomicrons as are LCFA, and
therefore leave the intestine and enter the blood faster (1).
Internal Tranwort of Medium Chain Fattv Acids
Following digestion and absorption into the intestinal mucosa from the lumen, saturated LCFA are
incorporated into chylomicrons and transferred to the circulation primarily via the thoracic duct,
thereby initially bypassing the liver (Figure 1) (12,13,14). In contrast, higher concentrations of MCFA
and unsaturated LCFA, bound to albumin, travel directly to the liver in the portal blood (3,15). For
example, 49% of intraduodenally infused C1O:O was recovered from the rat mucosa in the portal
blood system compared to 7.8%, 6.4%, and 10.6% recovery of C 18: 1, C 18:2, and C20:4 respectively
(16). These results are consistent with the findings of McDonald et al. (13) who observed that 72%,
58%, 41%, 28%, 58%, and 68% of C12:0, Cl4:0, C16:0, C18:0, C18:2, and Cl&3 respectively,
bypassed the lymphatic pathway when individually infused in the rat duodenum.
The correlation between increasing FA chain length and incorporation into chylomicrons is also seen
in humans. Results of Swift et al (17) indicate that the mass of triglyceride transported in
chylomicrons from a formula-fed LCT diet was approximately five times greater than that from a
MCT diet. Chylomicron transport of triglycerides in the MCT diet, determined by chylomicron
triglyceride concentration, was found to be increased slightly from day 1 to day 6 of feeding, although
the reincorporation of MCFA as MCT in chylomicrons remained a quantitatively negligible pathway
of MCFA metabolism. MCFA are therefore transported directly to the liver via the portal circulation
unlike LCFA which are preferentially incorporated into chylomicrons as LCT and transported via
lymph.
Vol. 62, No. 14, 1998 Medium Chain Fats and Energy Metabolism 1205
Intestine Mucosal Cell Circulation
LCFA
MCFA
Lymphatic system
FIG. 1.
Differential MCFA and LCFA Transport. Following absorption from the intestine, MCFA pass directly
from the mucosai cell into the portal vein and am transported to the liver attached to albumin. Conversely,
LCFA are incorporated into chylomicrons which travel through the lymphatic system and exit at the left
subclavian vein, circulating peripherally en route to the liver.
Oxidative Pathwavs of Medium Chain Fattv Acids
Once transported to the liver, MCFA may follow various catabolic pathways incluclmg beta-oxidation,
omega-oxidation, and peroxisomal oxidation. Consequently, characteristic differences between
MCFA and LCFA metabolism also exist following uptake by hepatic tissues. The fatty acyl synthetase
responsible for TG re-esterification is most effective with FA of 14 or more carbons (18). As a result,
few MCFA are recovered in triglyceride (19) phospholipid or cholesterol ester fractions ( 10) and low
concentrations of MCFA are recovered in various tissues (20). The chain length preference of fatty
acyl synthetase exists therefore as a major point of partitioning differentiation between MCFA and
LCFA.
The majority of lipids are catabohzed by mitochondrial beta-oxidation. LCFA or their acybCoA
derivatives, once transformed into acylcamitine by camitine pahnityl transferase (CPT) I, cross the
mitochondrial membrane and are regenerated as long chain acyl-CoA in the mitochondrial matrix by
CPT II (1); the concentration of LCFA crossing the membrane is therefore limited. Conversely,
MCFA do not require a shuttle system to penetrate mitochondria (21). Mitochondrial acyl-CoA
derived from either MCFA or LCFA then undergo oxidation with production of acetyl-CoA. Berry
et al (22) noted that inhibition of FA entrance into the mitochondria caused a decrease in acetyl-CoA
production, a decrease in CO* production derived from the acetyl CoA precursor, and a decrease in
ketone production. Higher concentrations of acetyl-CoA were conducive to ketone body formation.
Inhibition of CPT I more effectively reduced ketone body levels associated with LCT consumption
compared to MCT consumption (2 1). Christensen et al (23) found that most C 12:0 gained access to
the mitochondria independently, however carnitine dependent mitochondrial oxidation may provide
a minor pathway of C12:O metabolism. Interestingly, Rossle et al (24) noted in healthy humans that
a MCFA infusion depressed free camitine levels and increased short chain acylcamitine levels,
relative to LCFA infusion. These results demonstrate the greater necessity of LCFA for a shuttle, CPT
I and II, to enter the mitochondria for oxidation.
An alternate route for cystolic fat utilization is peroxisomal oxidation. At high concentrations of FA
in the perfused rat liver, it is estimated that 25% of oxidation occurs in the peroxisome (25). Unlike
1206 Medium Chain Fats and Energy Metabolism Vol. 62, No. 14, 199%
mitochondrial beta-oxidation, peroxisomal beta-oxidation produces H,Oz and is not coupled to a
respiratory chain (26). Brady et al (27) found that the induction of peroxisomal and mitochondrial
beta-oxidation was coordinated. Regardless of FA substrate, mitochondrial bets-oxidation exceeded
(28) and preceded (29) that occurring in the peroxisome. The chain length specificity of acyl-CoA
oxidase, an enzyme which may be rate limiting for peroxisomal oxidation, is dependent on acyl-CoA
concentrations (1). Below 80 uM, pahnitoyl-CoA showed the highest activity in rat liver extract;
above that level, CoA derivatives of C8:O and Cl2:O produced the most activity, followed by C16:O
and C24:O (30). Similarly, Handler et al (25) found that peroxisomes preferentially oxidized Cl2:O
in rat homogenates and perhtsed rat livers. This rate decreased with increasing and decreasing chain
lengths (25,26). As peroxisomal beta-oxidation appears to be a significant pathway of fat catabolism
and MCFA may have a high affinity for peroxisomal oxidation, this energetically inefficient pathway
may contribute to enhanced thermogenesis.
Omega-oxidation of fat may also be structure specific. Omega-oxidation originates in the hepatocyte
microsome, producing water soluble dicarboxylic acid which can be excreted in the urine. Christensen
et al (19) found that Cl2:O and ClO:O have the greatest affmity for omega-oxidation. Administration
of MCT in children and animals has been associated with dicarboxylic aciduria (3 1,32,33), indicating
a possible preference of MCFA for this oxidative pathway. Christensen et al (19) suggested that
omega-hydroxy and dicarboxylic acids formed by FA omega-oxidation in the liver may be then
further metabolized in the liver, accounting for acetate release from peroxisomes (34). Normal adults
consuming a 3 day diet with MCT contributing 5 1% of energy, excreted less than 1% of the energy
intake in the form of urinary dicarboxylic and keto acids (35). Thus, reduced energy accumulation
associated with MCT ingestion does not appear to be the result of urinary excretion of omega
oxidation products.
That MCT ingestion can result in increased ketogenesis in both animals and humans has been well
documented (35,36,37). Several studies have indicated that MCT metabolism resulted in elevated B-
hydroxybutyrate (B-OH) compared to LCT metabolism (4,24,38,39). However, other researchers
have failed to notice similar effects of MCT metabolism (40,41).
Acetyl-CoA derived from MCFA and not directed toward ketone body formation or oxidation may
be resynthesized into longer chain FA and esterified (7,10). Thus, LCFA may result from MCFA
ingestion through de novo FA synthesis or through chain elongation. Christensen et al (23) noted that
a significant amount of Cl2:O was rapidly converted to Cl6:O and lesser amounts of C14:0, C16:1,
C 18:O and C 18: 1 in isolated hepatocytes derived from rats refed glucose.
Lipogenesis associated with LCT, MCT, and low fat (LF) consumption is frequently assessed by
measurement of lipogenic enzyme activity in the liver and adipose tissue. In rat adipose tissue, the
consumption of LCT was significantly more effective than MCT in inhibiting lipogenic enzyme
activities (39,42). Chanez et al (40) found in rats that hepatic glucose-6-phosphate dehydrogenase,
malic enzyme, ATP-citrate lyase, ace@-CoA carboxylase and fatty acid synthase activities were 1.7,
2.6, 1.4, 1.5, and 1.4 fold higher on the MCT diet and 40%, 30%, 55%, 50%, and 45% lower on the
LCT diet compared to the LF control diet, respectively. Gee\en (43) observed that short-term
exposure of isolated rat hepatocytes to MCFA stimulated fatty acid synthesis, as determined through
increased hepatocellular carboxylase activity. Further to this, in vivo, Geelen et al (44) determined
that in the rat model, a diet of MCT oil vs. corn oil increased hepatic acetyl-CoA carboxylase and
fatty acid synthase. Foufelle et al (45) examined the effect of MCT consumption on lipogenic enzyme
activity and gene expression during the suckling/weaning transition period in the rat. During
Vol. 62, No. 14, 1998 Medium Chain Fats and Energy Metabolism 1207
transition, lipogenic enzymes normally increase with the incorporation of a high carbohydrate rat
chow diet. This effect fails to occur with weaning to a high fat diet, unless the diet contains MCT.
It has been suggested that these discordant lipogenic effects noted with MCT consumption may be
due to carbohydrate content (36,40), polyunsaturated fat content (40,45) or the thyroid honnone
response (36) to dietary nutrients. Consequently, all aspects of the diet must be considered for
comparisons of dietary metabolic effects.
MCFA metabolism may be affected by the macronutrient composition of a mixed meal. Flatt et al
(46) found no significant difference in postprandial oxidation following consumption of test meals
containing similar amounts of carbohydrate and protein but differing across LCT, MCT or LF dietary
treatments. The authors suggested that although the metabolism of carbohydrate and protein are
highly regulated due to their limited storage ability, fat exhibits a greater degree of metabolic
flexibility since it can either be oxidized or readily stored. Flatt et al (46) proposed that the metabolic
pathway of dietary fat is not determined only by the composition or the amount of fat ingested, rather,
fat metabolism proceeds in a manner which ensures that carbohydrate, protein, and energy balance
are maintained. This theory is supported by Bennet at al (47) who added 50 g of dietary fat to a
standard breakfast and did not see an increase in fat oxidation or energy expenditure during the
following 24 h in humans. Schutz et al (48) observed a similar result when a fat supplement of 987
kcal/d did not alter 24 h energy expenditure and failed to promote the use of fat as a metabolic fuel.
Conversely, other workers noted a significant negative correlation between carbohydrate intake and
13C fatty acid oxidation rate to CO2 (18) or fat intake and carbohydrate oxidation (49). Sato et al (50)
found that total parenteral administration of an emulsion high in MCT resulted in increased glucose
oxidation, compared to an emulsion high in LCT. Compared to prediet levels, subjects consuming 800
kcal!day diets required significantly more glucose to maintain euglycemia during continuous similar
diets high in LCT (41). This result suggested MCT may stimulate insulin mediated carbohydrate
metabolism.
Medium chain triglyceride metabolism may also be influenced by corresponding consumption of
LCT. Johnson et al (20) found that the oxidation rate of 14C MCT lipid emulsion was not significantly
reduced when LCT were simultaneously administered, although there was a trend in this direction.
Paust et al ( 18) observed that some patients oxidized C 18: 1 in a pure LCT emulsion more rapidly than
in a mixed MCT/LCT emulsion. In other patients, no differences in the rate of FA oxidation were
detected. Cotter et al (5 1) also identified competitive interaction between intravenous MCT and LCT
emulsions in beagle dogs. These findings suggest that meal macronutrient composition must be taken
into account if specific alterations of metabolism attributable to MCT are to be exploited.
. . .
fsattv8EiQgvsOtber
Structure dependent differences in oxidation of fat as a function of structure have been shown to occur
using isotope tracer methodologies and respiratory gas exchange analysis. The utilization of [l-
“C]octanoate has been shown to exceed [ I-“Cloleate by at least five times in isolated hepatocytes
incubated with corresponding fatty acid (52,53). Similar findings were noted in whole body %tty acid
metabolism studies. Leyton et al (54), analyzing 14C0, evolution following oral dosing of various 14C
FAs to rats, reported that the oxidation decreased with increasing chain length. Faster oxidation
resulted in lower retention of these LCFA in the carcass and liver. A similar result was reported where
1208 Medium Chain Fats and Energy Metabolism Vol. 62, No. 14, 1998
lipid emulsions of ‘4c MCT or 14C LCT, when injected into rats, produced a more complete oxidation
of MCT (90%) compared to the oxidation of LCT (45%) after 24 hours (20).
Fatty acid chain length seems to affect not only the quantity of fat oxidized, but the sequence in which
oxidation takes place. In studies with normal children ranging from 3 months to 17 years who were
administered ‘3C-triolein, “C-pahnitic acid or ‘3C-trioctanoin, the appearance of “COz from 13C-
trioctanoin reached its maximum 2-4 hours after administration (55). ‘3C-triolein oxidation peaked
between 4-6 hours whereas labelled pahnitic acid appeared as 13C0, more slowly, gradually
increasing over a 6 h period. Cumulative excretion of 13C0, over 6 h was 27.6%, 11.3%, and 6.6%
for trioctanoin, triolein, and pahnitic acid respectively. Concurrent to these results, a single bolus
intravenous infusion of ‘3C-triolein or ‘3C-trioctanoin in newborn infants was shown to produce peak
13COz excretion levels 90 minutes and 45 minutes later respectively (18). Enrichment returned to
baseline levels 10 hours after triolein and 8 hours after trioctanoin administration.
In human studies using respiratory gas exchange analysis, intravenous administration of MCT or LCT
emulsions significantly increased the oxidation of MCFA over 10 hours, while the oxidation of LCFA
remained similar to basal levels (56). Here, the concurrent rise in energy expenditure due to MCT
administration could be entirely accounted for by energy expended for enhanced fat oxidation. White
et al (57) saw an increase in post prandial energy expenditure on an MCT vs. LCT supplemented diet
after 7 days of feeding, although the effect was attenuated after 14 days. Enhanced oxidation of MCT
compared to LCT has also been shown to occur during exercise (58).
The method of administration of lipids for the purpose of determining FA oxidation may have a large
bearing when comparing extent of oxidation. For example, the total oxidation of octanoate exceeds
oleate in humans (59); this result is similar whether administered orally or parenterally to humans
(59,60). In contrast, 13C0, breath enrichment of labelled oleate proceeds more rapidly when
administered parentemlly (59). Consequently, the length of feeding, the state of activity, and method
of administration must be considered in examining effects of MCT administration on fat oxidation.
Thermoeenesis and Medium Chain Fattv Acids
Increases occur in energy expenditure due to meal ingestion. This thermic effect of food (TEF) can
be determined from respiratory gas exchange analysis by comparing whole body total energy
expenditure (TEE) following consumption of a meal to resting metabolic rate (RMR). Flatt et al (46)
compared the effect of ingesting an 858 kcal test meal containing 40 g MCT versus 40 g LCT over
9 hours. Energy expenditure due to the consumption of the test meal was similar and equivalent to
11.2% and 12.5% of energy contained in the LCT and MCT meals, respectively. Conversely, Scalfi
et al (2) examined the TEF response to consumption of a 1300 kcal test meal containing 30 g of MCT
or LCT in lean subjects. Total energy expenditure of subjects increased and the respiratory quotient
decreased after the MCT test meal, resulting in a significantly elevated thermogenic response. Hill
et al (7) examined energy balance during 7 days of overfeeding diets containing 40% MCT or LCT
in healthy humans. Body weight, body composition and RMR did not change significantly during
either diet treatment; however, following ingestion of 1000 kcal test meal containing MCT, TEF was
significantly higher on both day 1 and day 6 compared to LCT. Seaton et al (4) compared the thermic
effect of meals consisting almost entirely of 48 g of MCT or 45 g of corn oil. The MCT meal
produced a significant increase in postprandial oxygen consumption compared to the LCT meal, thus
resulting in an increased energy expenditure over basal level of 53 kcal and 17 kcal/h. These changes
in energy expenditure were equivalent to 13% and 4% of energy contained in the MCT and LCT
meals, respectively. Dull00 et al (6) saw a 5% increase in 24 h energy expenditure when humans were
fed a diet containing 15-30 g MCT. Mascioli et al (56) noted that enhanced energy expenditure
Vol. 62, No. 14, 1998 Medium Chain Fats and Energy Metabolism 1209
associated with MCT ingestion occurred during intravenous administration of MCFA to hospitalized
patients. A summary of the studies reflecting the positive effect of MCFA vs LCFA on postprandial
energy expenditure can be found in Table 1.
Enerw Balance and Medium Chain Fattv Acids
Long term energy balance studies have examined the effect of MCFA administration on energy
balance, expressed as fluctuations in weight, fat deposition or energy deposition. In animals studies
with rats ingesting diets containing 63% of metabolizable energy as MCT or LCT, Crozier et al (36)
reported that the MCT treatment resulted in approximately 13% less energy intake and 30% less
weight gain than did the LCT diet. These fmdings are in agreement with other animal studies
conducted by Lavau and Hashim (42) and Geliebter et al (61) who observed reduced body weight and
smaller fat depots during MCT feeding. Conversely, Wiley and Leveille (39) found that rats fed an
MCT diet ad libitum did not gain less weight compared to rats on similar diets containing lard and
corn oil, but body composition measurements were not made, so that an effect of MCT in reducing
fat gain cannot be ruled out. Geliebter et al (61), however, stressed the importance of controlling
energy intake and physical activity to allow cross comparison among studies. Overfeeding rats with
an MCT diet (45% energy ) via gastronomy tube for 6 wk reduced weight gain by 20% and fat
deposition by 23% compared to a similar LCT diet (6 1). A more realistic level of fat consumption by
rats (32% metabolizable energy) showed that energy retention resulting from LF and MCT diet
treatments over 45 days was 26% less than that from a LCT diet (40). Similar long term studies in
humans are less common, although Yost and Eckel(41) found that obese women consuming 800
kcal/d liquid diets containing 24% of energy as MCT or LCT for up to 12 weeks did not differ in
either the rate or the amount of weight lost; however, body composition was not measured and
therefore any changes in total body fat could not be assessed.
The effect of MCT and LCT on long term energy balance needs to be considered in the context of
possible adaptation to the MCT diet. Crozier et al (36) examined progressive adaptation to extended
MCT consumption in rata. initially, elevated ketone body concentrations associated with consumption
of high fat diets were noted, particularly with the MCT diet. Ketone body concentrations continually
declined, and by day 44 were approximately 50% of the initial levels. In rats receiving 32%
metabolizable energy as MCT or LCT compared to LF controls, Chanez et al (40) observed that
plasma ketone body concentration was initially elevated with MCT consumption, but by day 45 this
effect was no longer significant. This adaptive response may involve decreased ketone production
and ior increased utilization.
In humans, Hill et al (7) found adaptive affects of MCT consumption to occur rapidly. Following
ingestion of 1000 kcal meals containing LCT, TEF did not change significantly during a 6 day LCT
feeding regime; TEF due to MCT feeding increased significantly over 6 days (7). Fasting TG levels,
which were not different between diet treatments on day 1 were nearly 3 fold higher on day 6 of the
MCT diet treatment versus the LCT diet treatment. Hill proposed that increased TEF on day 1 of the
MCT diet may be due to increase ketone body formation. The additional rise in TEF by day 6 of the
MCT diet may have been a result of a shift toward de novo fatty acid synthesis. This possible
explanation is supported by Hill et al (38) who found that, relative to the LCT diet treatment, the
composition of plasma TG on day 6 of the MCT diet contained twice as much C 16:O; however, the
C 160 content of the MCT diet was 5 fold less than that contained in the LCT diet. Increases in Cl 8:0
and C18:l levels associated with the MCT diet treatment suggested that chain elongation and
desaturation also occurred (38). White et al (57) observed an attenuation of the effect of MCT on
postprandial energy expenditure after 2 weeks of feeding, offering evidence that adaptive effects may
exist. This effect was also reported by MacDougall et al (62) who demonstrated that following an
TABLE 1
Summary of Studies IIIustrating the Positive Effect of Medium Chain Versus Long Chain
Triglyceride Consumption on Postprandial Thermogenesis in Humans
Subjects Energ content Macronutrient Treatment fat Difference in TFF Reference
(kcal) composition (medium vs long chain triglycerides)
7 lean males 400 100 % fat 48 g MC?: oil vs 53 vs 17 kcal* Seaton et al.
45 g corn oil 1986
10 lean males 1000 15 % protein MCT oil vs day 1: NH8 vs 58G kcaI* Hill et al.
45 % carbohydrate LCT oit day 6: 120+13 vs 66*10 kcal* 1989
40 % fat
6 lean males 1300 LCT meal 15 % protein 30 g MCT oiI vs Iean: 366-W-6 vs 246.U29.6 kcal* Scalfi et al.
6 obese males 1270 MCT meal 55 % carbohydrate 30 g corn oil obese: 367.1G2.4 vs 222 4k36.8 kcal* 1991
30 % fat
8 lean males weight maintenance 15 % protein 30 g MCT oil per day/ 93701490 vs 889W48 1 kJ* Dulloo et al.
45 % carbohydrate 10 g per meal 1996
40 % fat
Energy expenditure was measured for 6 hours with the exception of Dulloo et al. (6) where measurement was for 24 hours
indicates significant difference (p< 0 OS)
Vol. 62, No. 14, 1998 Medium Chain Fats and Energy Metabolism 1211
average of 8 and 11 days of feeding, no differences in postprandial energy expenditure existed
between a breakfast rich in MCT versus LCT.
Results of human feeding studies challenge, therefore, current notions concerning classical metabolic
pathways of ingested food as evidenced by differences in fat oxidation and TEF of MCFA and LCFA.
It has been generally assumed that 5-lo%, O-3%, and 20-30% of energy contained in carbohydrate,
fat and protein respectively will be expended during the process of thermogenesis (63). However, Hill
et al (7) estimated that obligatory costs of octanoate oxidation were 3.3% if directed toward oxidation,
compared to 6.7% if directed toward ketone formation and 32.3% if directed toward de novo FA
synthesis, Thus, the obligatory thermogenic costs of MCFA ingestion may be in excess of traditional
thermogenic costs of fat metabolism based on characteristic long chain metabolic pathways. This
difference bears importance for studying MCT metabolism in man using indirect calorimetry;
classical equations for calculating fat oxidation are based on values obtained using LCT, and may
require modificaGon for trials involving MCT feeding. With respect to weight control, this increase
in thermogenesis may affect energy balance by increasing energy expenditure without altering energy
intake and consequently may induce weight loss if energy intake is stabilized as expenditure
increases.
. .
Potential for Use of Medium Chain Trjgjveerides for Traeut m Obe&y
The previous discussion illustrates the concept that the metabolism and the thermogenic effects of
MCFA are different as compared to LCFA. The positive effect of MCFA on postprandial energy
expenditure and fat oxidation has a potential application in body weight regulation. When an
organism is in energy balance, the amount of energy entering the system equals that being expended.
Schutz (64) proposes the model that if the amount of energy entering the system increases, the amount
of energy expended will also increase as lean tissue mass grows to support the increase in fat tissue.
The result is an elevation in body weight to a level at which a new equilibrium of energy expenditure
and energy intake is achieved. This model expands upon the dynamic equilibrium hypothesis initially
described by Payne and Dugdale (65). A corollary to this is that if the amount of energy expended
increases and the amount of energy intake stays the same, the body compensates to reach a new
energy equilibrium. This is accomplished by decreasing body weight until a new energy equilibrium
is achieved. Such a scenario is represented in Figure 2. As presented, the source of this energy
expenditure increase is MCT feeding as a substitute for LCT in diet.
The postulated increase in energy expenditure is supported by the research presented in Table 1.
Differences in energy expenditure seen between MCT and LCT feeding may translate into weight
loss. For example, Dull00 et al (6) fed 30 g MCT in addition to a maintenance diet consisting of
approximately 15% of energy as protein, 40% as fat, and 45% as carbohydrate. The difference in
energy expenditure over 24 h as a result of 30 g MCT versus 30 g LCT was 9370 f 490 kJ compared
to 8899 f 48 1, a difference of 471 W, or 113 kcal. This difference can be translated into the
equivalent of approximately 12.6 g fat/day, or one pound of fat (0.45 kg) over approximately 36 days.
A greater rate of loss due to increased dietary substitution of MCT for LCT above 30 g and/or
continuing the dietary regimen over an extended period may be extremely clinically important in the
treatment of obesity. The relevance of such an increase is supported by the fat balance theory of
Swinburn and Ravussin (66) who state that the major influence on fat oxidation is energy expenditure,
with negative energy balance promoting fat oxidation. Consequently, a negative energy balance
created by MCT ingestion may promote fat oxidation and weight loss in the obese, recognizing that
energy intake must be actively maintained at a constant level.
1212 Medium Chain Fats and Energy Metabolism Vol. 62, No. 14, 1998
Energy Out
Energy In
Body Weight
MCT Feeding
Time
FIG. 2.
Energy Balance and Body Weight Before and After MCFA Feeding at Constant Energy intake. At weight
maintenance, energy intake equals energy expenditure. An increase in MCT ingestion at the expense of
LCT disturbs the equilibrium by increasing the energy expenditure. To achieve a new equilibrium, body
weight decreases.
In animal experiments, decreased weight gain during MCT feeding vs. LCT feeding has been
observed by several researchers. Lasekan et al (67) demonstrated that rats receiving an intragastric
or intravenous infusion over 24 h of a 3: 1 emulsion of MCT and LCT vs. an LCT emulsion had one
third the weight gain as well as a 13% increase in energy expenditure. During overfeeding for 6
weeks, Geliebter et al (61) observed that among rats fed 45% of calories either as MCT or LCT
through a gastrostomy tube, the MCT-fed rats gained 20% less weight and possessed fat depots
weighing 23% less than the LCT-fed rats. Similarly, Lavau and Hashim (42) saw a decrease in body
weight and fat depots in rats fed a 55% by energy MCT diet as compared to a low fat diet, whereas
a 55% LCT diet caused an increase in body weight and fat depots. Conversely, Dull00 and Girardier
(68) saw no effect of carbon-chain length on energy expenditure or on energy partitioning during two
weeks of calorie controlled refeeding in rats with 30% of energy as fat. However, in a subsequent
isocaloric refeeding trial with fat as 50% of energy (69), MCT fed as coconut oil resulted in higher
energy expenditure and less fat deposition as compared to LCT fed as lard. In general, these results
suggest that MCT feeding is less weight promoting than LCT in rats.
In humans, there is a relative lack of studies examining the longer term effect of MCT feeding on
weight gain and energy expenditure. Yost and Eckel(41) failed to see a difference in weight loss
between two groups of obese women being fed hypocaloric diets over 12 weeks containing either
30% of calories as LCT or 24% as MCT and 6% as LCT; neither energy expenditure nor body
composition was measured in this study. Hill et al (7) saw an increase in postprandial energy
expenditure over 6 days of MCT vs LCT over feeding in healthy young men. In the longest MCT
feeding trial to date that measured postprandial energy expenditure, White et al (57) saw an
attenuation of the positive effect of MCT on energy expenditure after 14 days of MCT vs. LCT
eucaloric feeding to non-obese college-age women. These findings suggest that the effect of increased
energy expenditure may be transient.
In addition, the extent of lipogenesis that results after MCT feeding will have to be determined over
the longer term. Hill et al (38) saw changes in triglycerides after 6 days of MCT vs. LCT feeding that
were consistent with the hypothesis that MCT overfeeding may result in de novo lipogenesis and
enhanced FA elongation by the liver. Potential lipogenesis as a result of MCT feeding is a concern
as this effect may negate the positive effect of MCT on energy expenditure. However, whether
significant lipogenesis will occur in eucaloric feeding remains to be determined.
Vol. 62, No. 14, 1998 Medium Chain Fats and Energy Metabolism 1213
Tbe effect of MCT feeding on blood lipids also warrants further examination. In rats fed MCT vs.
corn oil, MCT increased plasma triacylglycerols and decreased plasma cholesterol (44). Also in rats,
Jones et al (70) observed an increase in both triglycerides and plasma total cholesterol following a
coconut oil diet. In contrast, after 6 days of MCT vs. LCT feeding in humans, Hill et al (38) saw no
effect of MCT feeding on plasma cholesterol, but there was a significant threefold increase in
triglycerides. Cater et al (71) demonstrated that MCT oil, containing C8:O and ClO:O, had one-half
the potency of palmitic acid in raising serum total and LDL-cholesterol concentrations. Resultant
blood lipid profiles from MCT feeding need to be further elucidated to determine the potential of
MCT as hypercholesteremic agents.
conclusion
As presented, ample evidence exists that the pathways and energy costs of MCFA intermediary
metabolism result in a characteristic enhancement of post prandial energy expenditure. Within a wide
variety of circumstances, MCFA are consistently oxidized to a greater degree than LCFA. Ease of
absorption, hepatic portal transport, camitine independent mitochondrial metabolism and a low
affinity for esterification may facilitate the rapid and greater oxidation of MCFA, thus making it a
highly available energy substrate. Understanding the thermogenic effects of MCFA may provide
valuable insight into the suitability of MCFA use in various clinical and therapeutic situations.
The capacity of MCFA use as an agent in the treatment of obesity is still to be determined. Eucaloric
and hypocaloric mixed meal feeding paradigms that explore the long term effect of MCT on energy
expenditure and blood lipid profiles are required to determine whether dietary substitution of MCFA
for a proportion of LCFA can result in weight loss or in prevention of weight gain or regain following
slimming. At a constant level of energy intake, increased dietary MCFA has the potential to be an
effective tool in addressing the issue of obesity.
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