ArticlePDF AvailableLiterature Review

Medium chain fatty acid metabolism and energy expenditure: Obesity treatment implications

  • Nutritional Fundamentals for Health Inc

Abstract and Figures

Fatty acids undergo different metabolic fates depending on their chain length and degree of saturation. 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 directly 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.
Content may be subject to copyright.
Life Scieacea. Vol. 62, No. 14, pp. 1203-1215,1998
copyright 0 1998 Elseviex science Inc.
0024-3205i98 $19.00 + .OO
PII 80024-3205(97)01143-O
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:
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
Vol. 62, No. 14, 1998 Medium Chain Fats and Energy Metabolism 1205
Intestine Mucosal Cell Circulation
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
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
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.
. . .
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
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
. .
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
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.
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.
1. A.C. BACH and V.K. BABYAN. Am J Clin Nutr 36 950-962 (1982).
2. L. SCALFI, A. COLTORTI, F. CONTALDO. Am J Clin Nutr 53 1130-l 133 (1991).
3. A.C. BACH, Y. INGENBLEEK, A. FREY. I Lipid Res 37 708-726 (1996).
4. T.B. SEATON, S.L. WELLE, M.K. WARENKO, R. G. CAMPBELL. Am J Clin Nutr 44 630-634 (1986).
10-17 (1991).
6. A.G. DULLOO, M. FATHI, N. MENSI, L. GIRARDIER. Eur J Clin Nutr 50 52-158 (1996).
Metabolism 38 641-648 (1989).
8. J. CLEMENT. J Physio172 137-170 (1976).
22 668-674 (1981).
BABAYAN, B.R. BISTRIAN, G.L. BLACKBURN. Lipids 24 793-798 (1989).
Il. W.F. CASPARY. Am J Clin Nutr 55s 299S308S (1992).
12. B. BLOOM, I.L. CHAIKOFF, W.O. RElNHARDT, W.G. DAUBEN. J Biol Chem 189 261-268 (1950).
13. G.B. MCDONALD, D.R SAUNDERS, M. WEIDMAN, L. FISHER. Am J Physio1239 G 14 I-G 150 ( 1980).
14. A. VALLOT, A. BERNARD, H. CARLIER. Comp Biochem Physiol A 82 693-699 (1985).
15. B. BLOOM, I.L. CHAIKOFF, W.O. EINHARDT. Am J Phsiol 166 451-455.
16. A. BERNARD and H. CARLIER. Exp Physio176 445-455 (1991).
17. L.L.SWIFT, J.O.HILL,J.C.PETERS,H.L.GREENE.AmJClinNutr52834-836(1990).
1214 Medium Chain Fats and Energy Metabolism Vol. 62, No. 14, 1998
18. H. PAUST, T. KELES, W. PARK, G. KNOBLACH. Stable isotopes in Paediatric Nutritional and Metabolic
Research. Chapman et al (Eds), l-22, Intercept Ltd., Great Britain (1990).
19. E. CHRISTENSEN, M. GRONN, T.A. HAGVE, B.O. CHRISTOPHERSEN. Biochim Biophys Acta 1081
167-173 (1991).
20. R.C. JOHNSON, S.K. YOUNG, R. COTTER, L. LIN, W.B. ROWE. Am J Clin Nutr 52 502-508 (1990).
21. MI. FRIEDMAN, I. RAMIREZ, C.R. BOWDEN, M.G. TORDOFF. Am J Physiol258 R216-R221 (1990).
22. M.N. BERRY, D.G. CLARK, A.R. GRIVELL, P.G. WALLACE. Eur J Biochem 131205-214 (1983).
23. E. CHRISTENSEN, T.A. HAGVE, M. GRONN, B.O. CHRISTOPHERSEN. Biochim Biophys Acta 1004
187-195 (1989).
ELWYN. Am J PhysioI258 E944-E947 (1990).
25. J.A. HANDLER and R.G. THURMAN. Eur J Biochem 176 477-484 (1988).
26. A.E. GANNING, M.J. OLSSON, E. PATERSON, G. DALLNER. Pharmacol Toxicol 1989 65 265-268
27. P.S. BRADY, K.A. MARINE, L.J. BRADY, R.R. RAMSEY. Biochem J 260 93-100 (1989).
28. F.A. REUBSAET, J.H. VEERKAMP, J.M. TRIJBELS, L.A. MONNENS. Lipids 24 945-950 (1989).
29. R.K. BERGE, A. NILSSON, A.M. HUSOY. Biochim Biophys Acta 960 417-426 (1988).
Acta 958 434-442 (1988).
3 I. R.K. WHYTE, D. WHELAN, R. HILL, S. MCCLORRY. Pediatr Res 20 122-125 (1986).
32. H. BOHLES, Z. AKCETIN, W. LEHNERT. JPEN J Parenter Enteral Nutr 11 46-48 (1987).
33. K.Y. TSERNG, R.L. GRIFFIN, D.S. KERR. Metabolism 45 162-167 (1996).
10347-10350 (1989).
35. V.C. DIAS, E. FUNG, F.F. SNYDER, R.J. CARTER, H.G. PARSONS. Metabolism 39 887-891 (1990).
36. G. CROZIER, B. BOIS-JOYEUX, M. CHANEZ, J. GIRARD, J. PERET. Metabolism 36 807-814 (1987).
37. A. BACH, T. PHAN, P. METAIS. Harm Metab Res 8 375-379 (1976).
31 407-416 (1990).
39. J.H. WILEY and G.A. LEVEILLE. J Nutr 103 829-835 (1973).
40. M. CHANEZ, B. BOIS-JOYEUX, M.J. ARNAUD, J. PERET. J Nun 121 585-594 (1991).
4 1. T.J. YOST and R.H. ECKEL. Am J Clin Nutr 49 326-330 (1989).
42. M.M. LAVAU, and S.A. HASHIM. J Nutr 108 613-620 (1978).
43. M.J. GEELEN. Biochemical J 302 141-146 (1994).
44. M.J. GEELEN, W.J. SCHOOTS, C. BIJLEVELD, A.C. BEYNEN. J Nutr 125 2449-2456 (1995).
45. F. FOUFELLE, D. PERDEREAU, B. GOUHOT, P. FERRE, J. GIRARD. Em J Biochem 208 381-387
( 1992).
46. J.P. FLATT, E. RAVUSSIN, K.J. ACHESON, E. JEQUIER. J Clin Invest 76 1019-1024 (1985).
47. C. BENNETT, G.W. REED, J.C. PETERS, N.N. ABUMRAD. Am J Clin Nutr 55 1071-1077 (1992).
48. Y. SCHUTZ, J. P. FLATT, E. JEQUIER. Am J Clin Nutr 50 307-3 14 (1989).
49. K.J. ACHESON, A. THELM, E. RAVUSSIN, M.J. ARNAUD, E. JEQUIER. Am J Clin Nutr 41 881-890
50. N. SATO, Y. MATSUBARA, K. YOSHIKAWA, T. MUTO. JPEN J Parenter Enteral Nutr 16 451-454
5 1. R. COTTER, R.C. JOHNSON, S.K. YOUNG, L.I. LIN, W.B. ROWE. Am J Clin Nutr 50 794-800 (1989).
J 249 Sol-806 (1988).
53. G.L. CROZIER. J Nutr 118 297-304 (1988).
54. J. LEYTON, P. J. DRURY, M. A. CRAWFORD. Br J Nutr 57 383-393 (1987).
Gastroenterology 82 911-917 (1982).
BLACKBURN, B.R. BISTRIAN. JPEN J Parenter Enteral Nutr 15 27-3 1 (1991).
57. M.D. WHITE, A.A. PAPAMANDJARIS, P.J. JONES. Obesity Res 4s 17s (1996).
Vol. 62, No. 14, 1998 Medium Chain Fats and Energy Metabolism 1215
58. P. SATABIN, P. PORTERO, G. DEFER, J. BRICOUT, C.Y. GUEZENNEC. Med Sci Sports Exert 19 218-
223 (1987).
59. CC. METGES and G. WOLFRAM. J Nutr 1213 1-36 (1991).
60. A.D. SCHWABE, L.R. BENNETT, L.P. BOWMAN. J App Physiol 19 335-337 (1964).
1-4 (1983).
62. D.E. MACDOUGALL, P.J. JONES, J. VOGT, P.T. PHANG, D.D. KITTS. Eur J Clin Nutr 26 755-762
63. J.P. FLATT. Recent Advances in Obesity Research. II. G.S. Bray (Ed), 221-228, Newman, London (1978).
64. Y. SCHUTZ. Metabolism 44(S) 7-11 (1995).
65. P. R. PAYNE and A. E. DUGDALE. Lancet 1583-586 (1977).
66. B. SWINBURN and E. RAVUSSIN. Am J Clin Nutr 57 766%770s (1993).
67. J.B. LASEKAN, J. RIVERA, M.D. HIRVONEN, R.E. KEESEY, D.M. NEY. J Nutr 122 1488-1492 (1992).
68. A.G. DULL00 and L. GIRARDIER. Metabolism 41 1336-1342 (1992).
69. A.G. DULLOO, N. MENSI, J. SEDOUX, L. GIRARDIER. Metabolism 44 273-279 (1995).
70. P.J. JONES, J.E. RIDGEN, A.P. BENSON. Lipids 25 815-820 (1990).
71. N.B. CATER, H.J. HELLER, M.A. DENKE. Am J Clin Nutr 65 41-45 (1997).
... Reviewing the above two reports, it seems possible that MCTs have beneficial effects on body composition, body weight, and energy metabolism (174), but further examination is required. In particular, if an experiment will measure weight changes in the range of several 100 g per month, it will be necessary to measure body weight and fat mass in suitable facilities and under appropriate conditions, and it must be conducted under appropriate nutritional management for obese people. ...
Full-text available
In the 1950s, the production of processed fats and oils from coconut oil was popular in the United States. It became necessary to find uses for the medium-chain fatty acids (MCFAs) that were byproducts of the process, and a production method for medium-chain triglycerides (MCTs) was established. At the time of this development, its use as a non-fattening fat was being studied. In the early days MCFAs included fatty acids ranging from hexanoic acid (C6:0) to dodecanoic acid (C12:0), but today their compositions vary among manufacturers and there seems to be no clear definition. MCFAs are more polar than long-chain fatty acids (LCFAs) because of their shorter chain length, and their hydrolysis and absorption properties differ greatly. These differences in physical properties have led, since the 1960s, to the use of MCTs to improve various lipid absorption disorders and malnutrition. More than half a century has passed since MCTs were first used in the medical field. It has been reported that they not only have properties as an energy source, but also have various physiological effects, such as effects on fat and protein metabolism. The enhancement of fat oxidation through ingestion of MCTs has led to interest in the study of body fat reduction and improvement of endurance during exercise. Recently, MCTs have also been shown to promote protein anabolism and inhibit catabolism, and applied research has been conducted into the prevention of frailty in the elderly. In addition, a relatively large ingestion of MCTs can be partially converted into ketone bodies, which can be used as a component of “ketone diets” in the dietary treatment of patients with intractable epilepsy, or in the nutritional support of terminally ill cancer patients. The possibility of improving cognitive function in dementia patients and mild cognitive impairment is also being studied. Obesity due to over-nutrition and lack of exercise, and frailty due to under-nutrition and aging, are major health issues in today's society. MCTs have been studied in relation to these concerns. In this paper we will introduce the results of applied research into the use of MCTs by healthy subjects.
... MCFA has a specific pathway for the transportation of resulting acyl-CoA into the mitochondrial matrix, without depending on the carnitine transport system [85]. After transferring into mitochondria, medium-chain fatty acyl-CoA dehydrogenase enzyme can convert these medium-chain fatty acyl-CoA molecules into ketone bodies; most prominently acetoacetate and β-hydroxybutyrate. ...
Full-text available
The coconut tree (Cocos nucifera) which is also known as the “Tree of life” has its own values in each part of the tree and coconut oil is more prestigious among them. At present, the consumption of coconut oil is booming all around the world owing to its tremendous health benefits. The unique chemical composition of coconut oil enriched with medium chain fatty acids (MCFAs) has led to the exploration of these nutritional and therapeutic influences. Unlike the long chain fatty acids (LCFAs), the MCFAs generated from the digestion of medium chain triglycerides (MCTs) has a specific pathway for the metabolism, as it bypasses the lymphatic system and enter the liver directly through the portal vein. Due to such distinct attributes in absorption and metabolism, MCTs are readily capable of forming ketone bodies than other triglycerides. These ketone bodies are a competent energy source for the brains, especially those having cognitive impairments like Alzheimer's disease (AD). AD is a neurodegenerative disease characterized clinically by accelerating shortfalls in memory and behavioral changes. The principal biochemical hallmarks behind the pathogenesis of AD are the development of extracellular amyloid β plaques and the accumulation of intracellular neurofibrillary tangles. Occurrence of Cardiovascular diseases (CVD) with elevated LDL levels, hypertension, Type 2 diabetes, obesity, and insulin resistance are some key risk factors that are responsible for the increasing prevalence and incidence of AD. There is sufficient evidence to prove that MCTs in coconut oil are metabolized and absorbed in such a way that retards the severity of these physiological risk factors. Besides, coconut oil is endowed with many polyphenolic compounds that are serving as antioxidants by combating oxidative stress and inflammation, which in turn downregulates the etiology of AD. But depending on the different processing conditions applied in extraction techniques of coconut oil, variations in antioxidant capacity can take place. Even though there are inadequacies in peer-reviewed large cohort clinical data for the long run, this article reviews that coconut oil, its constituents, and metabolism have positive findings on the potentiality to treat AD as a nutritional supplement.
... The medium chain fatty acids (MCFAs) C8:0, C10:0 and C12:0 are versatile chemicals with potential application in food [1][2][3], feed [4], and the production of various compounds such as detergents [5], surfactants [6], antibiotics [7] and insect pheromones [8]. As part of the human diet, MCFAs are preferentially used for beta-oxidation in the liver as a source for quick energy, whereas long chain fatty acids (LCFAs) more readily trigger lipogenesis, making MCFAs a potential agent for treatment of obesity [1,9,10]. MCFAs further have potential for prevention of neurological disorders, such as Alzheimer's, due to their neuroprotective and cognition-enhancing properties, which may be linked to their hepatic metabolization and the production of ketone bodies, or to the stimulation of antioxidant activity [11][12][13]. ...
Full-text available
Medium chain fatty acids (MCFAs) are compounds of considerable commercial interest that have applications in food, feed, and the production of industrially relevant chemicals. Due to their antipathogenic and health-promoting effects, they are further discussed as potential therapeutic agents for disease treatment and infection prevention and control. Domesticated agricultural crops that can grow in temperate climates lack MCFAs, and increased cultivation of tropical MCFA-rich species such as oil palm is associated with deforestation and a decrease in biodiversity. Alternative sources for more sustainably produced MCFAs are non-domesticated plants such as Cuphea spp., as well as oil crops and oleaginous microalgae that can be genetically engineered to accumulate MCFAs by expression of acyl-acyl carrier protein thioesterases (TEs) from MCFA-producing plants. Here, we report the heterologous expression of a TE from Cuphea palustris in the industrially relevant microalga Nannochloropsis oceanica. Using a recently developed gene expression system, we engineered transformant strains that accumulated up to 2.84 and 4.15% of C8:0 and C10:0 in storage lipids, respectively, and we observed no effect on growth. We further show that MCFA accumulation was negatively correlated with total neutral lipid content, suggesting the presence of regulatory mechanisms that limit MCFA accumulation in Nannochloropsis.
... Medium-chain FAs containing 8-12 carbon atoms are subject to a rapid oxidative metabolism (3,4). Unlike long-chain FAs they may cross membranes in the non-esterified form (5)(6)(7). Medium-chain FAs are primarily catabolized in mitochondria, but like long-chain FAs may also undergo peroxisomal β-oxidation. Indeed, peroxisomes accommodate a related pathway that in mammals appears to be of greatest importance for the catabolism of very long-chain FAs and is independent of a carnitine-mediated transport (6)(7)(8)(9). ...
Full-text available
Fatty acid beta-oxidation is a key process in mammalian lipid catabolism. Disturbance of this process results in severe clinical symptoms, including dysfunction of the liver, a major beta-oxidizing tissue. For a thorough understanding of this process, a comprehensive analysis of involved fatty acid and acyl-carnitine intermediates is desired, but capable methods are lacking. Here, we introduce oxaalkyne and alkyne fatty acids as novel tracers to study the beta-oxidation of long- and medium-chain fatty acids in liver lysates and primary hepatocytes. Combining these new tracer tools with highly sensitive chromatography and mass spectrometry analyses, this study confirms differences in metabolic handling of fatty acids of different chain length. Unlike longer chains, we found that medium-chain fatty acids that were activated inside or outside of mitochondria by different acyl-CoA synthetases could enter mitochondria in the form of free fatty acids or as carnitine esters. Upon mitochondrial beta-oxidation, shortened acyl-carnitine metabolites were then produced and released from mitochondria. In addition, we show that hepatocytes ultimately also secreted these shortened acyl chains into their surroundings. Furthermore, when mitochondrial beta-oxidation was hindered, we show that peroxisomal beta-oxidation likely acts as a salvage pathway, thereby maintaining the levels of shortened fatty acid secretion. Taken together, we conclude that this new method based on oxaalkyne and alkyne fatty acids allows for metabolic tracing of the beta-oxidation pathway in tissue lysate and in living cells with unique coverage of metabolic intermediates and at unprecedented detail.
... Although a part of ingested MCFAs and MCTs are directly used for ghrelin acyl modification in X/A-like cells of the stomach (8), the fate of MCFAs in these cells is not clear. Most MCFAs entering the cells may be used for ATP production in mitochondria or synthesis of TG in cytosol (24,25). MCFAs stored as TG in cells and MCFAs directly entering from the circulation could also be used for acyl-ghrelin synthesis. ...
Objectives: Supplementation with 6 g/day of medium-chain triglycerides (MCTs) at dinnertime increases muscle function and cognition in frail elderly adults relative to supplementation with long-chain triglycerides. However, suitable timing of MCT supplementation during the day is unknown. Design: We enrolled 40 elderly nursing home residents (85.9 ± 7.7 years) in a 1.5-month randomized intervention trial. Participants were randomly allocated to two groups: one received 6 g/day of MCTs at breakfast (breakfast group) as a test group and the other at dinnertime (dinner group) as a positive control group. Measurements: Muscle mass, strength, function, and cognition were monitored at baseline and 1.5 months after initiation of intervention. Results: Thirty-seven participants completed the study and were included in the analysis. MCT supplementation in breakfast and dinner groups respectively increased right arm muscle area from baseline by 1.1 ± 0.8 cm2 (P<0.001) and 1.6 ± 2.5 cm2 (P<0.001), left arm muscle area by 1.1 ± 0.7 cm2 (P<0.001) and 0.9 ± 1.0 cm2 (P<0.01), right knee extension time by 39 ± 42 s (P<0.01) and 20 ± 32 s (P<0.05), leg open and close test time by 1.74 ± 2.00 n/10 s (P<0.01) and 1.67 ± 2.01 n/10 s (P<0.01), and Mini-Mental State Examination score by 1.5 ± 3.0 points (P=0.06) and 1.0 ± 2.1 points (P=0.06). These increases between two groups did not differ statistically significantly. Conclusion: Supplementation with 6 g MCTs/day for 1.5 months, irrespective of ingestion at breakfast or dinnertime, could increase muscle mass and function, and cognition in frail elderly adults.
Background Glycerol monolaurate (GML) is a fatty acid monoglyceride, which richly exists in coconut oil, palm oil, and human milk. Except for the recognized emulsifying properties, GML's good antibacterial ability and low energy density also make it an ideal functional additive and food quality improver. Scope and approach This review discusses GML synthesis, health benefits, positive effects on food storage and quality, and critically discusses its fate and safety in vivo. The routine emulsification of GML in foods is beyond the scope of this review. Key findings and conclusions GML is synthesized through direct esterification, methyl laurate glycerolysis or laurate glycerolysis. Although the in vivo fate of GML is assumed to be similar to that of glyceryl trilaurate, there is no direct experimental evidence for this inference. Previous studies proved that GML functions beyond an emulsifier. In food quality, GML inhibits the growth of harmful microorganisms and extends shelf life. It also improves the nutritional value and sensory properties of animal-derived food by regulating amino acid and fatty acid metabolism. In health efficacies, GML reduces lipid accumulation, rebuilds the intestinal barrier, modulates immune activity, and may have positive effects on the nervous system. These are associated with the direct intervention of GML on gut microbiota, immune cell activity and energy metabolism. However, developing more efficient GML synthesis schemes, enhancing the application of GML on food quality, and exploring the in vivo fate, health efficacy mechanism or safety of GML in different experimental models remain interesting topics in the future.
The targeted analysis of free fatty acids (FFAs) is attracting interest since several years with a plenty of studies. However, most of them are devoted to the solely determination of the short-chain fatty acids (SCFAs) arising from the symbiotic gut microbiota metabolism. Recently, the FFAs analysis highlighted changes in the plasma levels of octanoic and decanoic acids (medium-chain fatty acids or MCFAs) may be associated to gastrointestinal diseases, including colorectal cancer (CRC). Then, the simultaneous quantification of both SCFAs and MCFAs could be useful to put in evidence the interconnection between microbiota and metabolic alterations during hosts’ disease. To this aim, it was developed an isotopic dilution gas-chromatography coupled mass spectrometry (ID/GC-MS) method for the targeted analysis of both linear and branched FFAs (SCFAs, MCFAs, and LCFAs) in human plasma samples as specific markers for both microbiota and host metabolic alterations. In order to minimize sample manipulation procedures, an efficient, sensible and low time-consuming procedure is presented, which relies in a simple liquid-liquid extraction before the determination of underivatized free acids (FFAs) by Single Ion Monitoring (SIM) acquisition. The reached detection limits (LODs) were less than 100 μg L⁻¹ for most of analytes, except for acetic, hexadecanoic and octadecanoic acids that showed a LOD > 1 mg L⁻¹. Methods accuracy and precision, obtained by the analysis of the FFAs mixtures showed accuracy values between 84% and 100% and precision (RSD %) between 0.1% and 12.4% at the concentration levels tested. The proposed ID/GC-MS method was applied in a case study to evaluate the FFAs as specific markers for both microbiota and host alterations in CRC patients. Obtained results highlight the advantage of present method for its rapidity, simplicity, and robustness.
Oxidative stress is an important factor in the occurrence and development of liver disease. Medium‐chain fatty acids (MCFAs) have potential antioxidant function, whereas the exact underlying mechanism of MCFA in oxidative injury of hepatocytes remains unclear. In our present study, three different MCFAs, 8‐carbon octanoic acid (OA), 10‐carbon capric acid (CA), and 12‐carbon lauric acid (LA), have been performed to observe their protective action for hepatocyte under the H2O2 challenge. The result showed that MCFA treatment significantly increased the cell viability, T‐AOC, and expression of antioxidant‐related genes in AML12 cells under oxidative stress condition, and reduced reactive oxygen species (ROS) production. Moreover, MCFA treatment significantly increased the protein expression of Nrf2 and the phosphorylation level of ERK1/2; LA treatment significantly promoted the Nrf2 nuclear translocation. With a further test, the rescue ability of MCFA was blocked by treating with the ERK inhibitor U0126. Overall, our data suggested that MCFA treatment has positive impact on protecting AML12 cells against oxidative stress through ERK1/2/Nrf2 pathway.
Full-text available
To investigate the effects of dietary fat quality on synthesis and esterification of cholesterol, Syrian hamsters were fed diets containing corn, olive, coconut or menhaden oils (10% w/w) with added cholesterol (0.1% w/w). After 3 weeks, animals were sacrificed 90 min following IP injection of3H2O. Synthesis of free cholesterol and movement of free cholesterol into ester pools were measured from3H-uptade rate in liver and duodenum. Plasma total cholesterol and triglycerides levels were highest in coconut oil-fed animals, whereas hepatic total cholesterol and ester levels were elevated in olive oil-fed animals, as compared with all other groups. No diet-related differences were seen in duodenal cholesterol or total fatty acid content. In duodenum, uptake of3H per g tissue into cholesterol was greater compared with liver; however, within each tissue,3H-uptake into cholesterol was similar across groups. Notably,3H-uptake into cholesterol ester in liver was highest in menhaden oil-fed animals. These data suggest that menhaden fish oil consumption results in enhanced movement of newly synthesized cholesterol into ester as compared with other fat types.
The rates of O2 consumption during fatty acid oxidation to acetyl-CoA and to CO2 were determined for isolated liver cells from starved rats on the basis of measured rates of respiration and ketogenesis. About 60% of the endogenous O2 uptake was associated with acetyl-CoA formation. The remainder was assumed to represent total combustion of fatty acid to CO2 and H2O through the Krebs cycle. In the absence of added fatty acid, 1.90 μmol · min⁻¹· g⁻¹ of acetyl-CoA was generated, of which 1.40 μmol · min⁻¹· g⁻¹ gave rise to ketone bodies. O2 consumption was stimulated about 30% by the addition of 2 mM palmitate or 4 mM hexanoate. This increase was entirely due to stimulation of O2 consumption related to oxidation of fatty acid to acetyl-CoA. The extra acetyl-CoA produced was channelled into ketone body formation.
The serum fatty acid profiles of patients receiving either intravenous medium or long chain triglycerides were studied. Seventeen hospitalized patients, dependent on total parenteral nutrition, were randomly enrolled into a prospective study. The total parenteral nutrition (TPN) delivered amino acids and glucose and either a 75% medium chain triglyceride and 25% long chain triglyceride (MCT group) physical mixture or all long chain triglyceride (LCT group), as the respective fat sources. The amino acids and glucose were given continously, and the lipid was given for 10 hours each day over five days. Fatty acid profiles on serum triglycerides and free fatty acids were done in the morning before any lipid was given and also later in the afternoon, near the end of the lipid administration, on days 1, 3 and 5. Medium chain fatty acids rose quickly in the triglyceride fraction in patients given MCT. Rapid MCT hydrolysis occurred as evidenced by the appearance of medium chain fatty acids in the free fatty acid fraction in the afternoon sampling. Clearance of the hydrolyzed medium chain free fatty acids (MCFFA) occurred so that little, if any, were present in the morning sampling one day later. Long chain fatty acids, as either triglycerides or free fatty acids, showed expected increases during the daily infusion, but not of such relative magnitude as the medium chain fatty acids. Medium chain fatty acid incorporation into the phospholipid or cholesterol ester fractions by the end of the five-day feeding period was present but minimal. As opposed to conventional long chain triglycerides, intravenously administered medium chain triglycerides are hydrolyzed and cleared rapidly and do not accumulate in other lipid fractions, and are therefore a more readily available lipid fuel.
In recent years, the metabolism of triglycerides has attracted much attention. Oxidation of fatty acids is an essential energy supply, especially when glucose supply is limited. In the present study, the effect of a 3-day high medium-chain triglyceride (MCT; 51% of calories), low carbohydrate intake on plasma glucose and amino acid, and urinary organic acid levels, including dicarboxylic and tricarboxylic acid cycle intermediates, was determined in eight normal adult volunteer subjects. Urine was collected at baseline and at 48 to 72 hours for amino acid and organic acid levels, and plasma collected at 0 and 72 hours for glucose and amino acid concentration. The MCT diet increased urinary levels of dicarboxylic acids (adipic 8-, suberic 65-, sebacic 284-fold) and keto acids (acetoacetate and β-hydroxybutyrate, 67.5-fold); alanine and lactate were decreased 2.5- and 4-fold, respectively, while pyruvate, other amino acids and citric acid intermediates remained unchanged. Plasma amino acid levels were unchanged, while the plasma glucose levels decreased by 8% from baseline. The loss of calories as urinary dicarboxylic acids and keto acids, although increased during the MCT diet, was less than 1% of the daily caloric intake. The data suggest MCT sustain energy expenditure through medium-chain fatty acid (MCFA) oxidation with no decrease in citric acid cycle intermediates, while sparing protein oxidation.
Energy intake, weight gain, carcass composition, plasma hormones and fuels, hepatic metabolites and the activities of phosphoenolpyruvate carboxykinase (PEPCK), malic enzyme, and glucose 6-phosphate dehydrogenase (G6P-DH) were examined in adult rats during a 44-day period of low fat, high carbohydrate (LF) feeding or of consumption of one or two high (70% metabolizable energy) fat diets composed of 63% (metabolizable energy) long-chain (LCT) or medium-chain (MCT) triglycerides. Energy intake was similar in the LCT and MCT groups but was less than that of LF group. The weight gain of rats fed MCT diet was 30% less than that of rats fed LF or LCT diets. Energy retention was less when the diet provided MCT than LCT or LF, and that resulted in a 60% decrease in the daily lipids deposition. Plasma glucose, free fatty acids, glycerol, and insulin/glucagon ratio were similar in the three groups. Blood ketone body (KB) concentrations in rats fed the high fat diets were extremely elevated, particularly in the MCT group, but declined throughout the experiment and by the 44th day hyperketonemia decreased by 50% but remained higher than in the LF diet. The blood beta-hydroxybutyrate/acetoacetate (B/A) ratio remained slightly elevated in rats fed the high fat diets. Similar changes were observed in liver KB concentration and in the B/A ratio. Liver lactate/pyruvate ratio elevated in the LCT and MCT groups at the initiation of the diets decreased by 50% at the end of the experiment. The consumption of high fat diets led to a 1.5-fold increase in liver PEPCK activity.(ABSTRACT TRUNCATED AT 250 WORDS)
The energetics of body weight recovery after low food intake was examined in the rat during refeeding for 2 weeks with isocaloric amounts of high-fat (HF) diets providing 50% of energy as either lard, coconut oil, olive oil, safflower oil, menhaden fish oil, or a mixture of all these fat types. The results indicate that for both body fat and protein, the efficiency of deposition was dependent on the dietary fat type. The most striking differences were found (1) between diets rich in n-3 and n-6 polyunsaturated fatty acids (PUFA), with the diet high in fish oil resulting in a greater body fat deposition and lower protein gain than the diet high in safflower oil; and (2) between diets rich in long-chain (LCT) and medium-chain triglycerides (MCT), with the diet high in lard resulting in a greater gain in both body fat and protein than the diet high in coconut oil. Furthermore, the diet high in olive oil (a monounsaturated fat) and the mixed-fat diet (containing all fat types) were found to be similar to the fish oil diet in that the efficiency of fat deposition was greater (and that of protein gain lower) than with the diet high in safflower oil. Neither the efficiency of fat gain nor that of protein gain were found to correlate with fasting plasma insulin, the insulin to glucose ratio, or plasma lipids. The present studies, conducted specifically under conditions of isocaloric refeeding after low food intake, demonstrate that the fatty acid composition of HF diets influences the recovery of both lean and fat tissue compartments—apparently by mechanisms unrelated to plasma insulin and lipid status. The relevance of these findings is discussed in the context of nutritional rehabilitation after undernutrition, as well as in the context of dietary management of obesity relapse.
Body weight, epididymal and perirenal adipose tissue weights, plasma insulin, [1-¹⁴C]glucose incorporation into CO2 and lipid in epididymal and perirenal, and activity of lipogenesis-related enzymes in epididymal, perirenal and liver were measured in rats fed a low-fat diet (LF), a 55% (by energy) medium chain triglyceride diet (MCT), or a diet containing 60% corn oil, a long chain triglyceride (LCT). In rats fed the MCT diet for 8 weeks there was 10% decrease in body weight associated with 40% decrease in the combined epididymal and perirenal weights as compared to rats fed LF. After 4 weeks body weight and fat depots were significantly reduced with MCT feeding and significantly increased with LCT feeding, as compared to LF. In the four-week MCT fed rats, the capacity of the entire epididymal and perirenal adipose tissue to incorporate [1-¹⁴C]glucose into CO2 and lipids under both basal and insulin stimulated conditions was about ⅓ that of LF fed rats. LCT was more effective than MCT in reducing glucose utilization in perirenal adipose tissue. The activities of acetyl CoA carboxylase (AcCoAC), malic enzyme (ME), citrate cleavage enzyme (CCE), glucose-6-phosphate dehydrogenase (G6PDH) and 6-phosphogluconate dehydrogenase (6PGDH) in the two adipose tissue sites were strongly depressed by both LCT and MCT feeding, as compared to LF. In liver, MCT feeding decreased the activities of CCE, G6PDH and 6PGDH, by 50% but did not alter ME as compared to LF. All these enzyme activities were reduced by more than 70% by LCT feeding. Insulin levels did not differ significantly among the three groups of rats. The data show that, unlike LCT, MCT has a reductive effect on fat stores, and like LCT, has a depressive effect on lipogenesis, suggesting possible application of MCT in obesity control.
Various hypotheses for the mechanism of regulation of body-weight in human adults have been proposed in the light of the magnitude of the long-term changes in weight actually observed. One of these hypotheses has been represented in the form of a computer simulation model which has been used to demonstrate that (i) it is not necessary to postulate the existence of a set-point regulatory system, and (ii) in practice, several mechanisms, including hunger and satiety, the relative constancy of habits and customs of behaviour, and the existence of cognitive thresholds combined with a relatively simple physiological negative feedback system probably constitute the simplest hypothesis for the mechanism of weight stability.
The influence of a single load of medium chain triglycerides (MCT) or long chain triglycerides (LCT) on different intermediary metabolites of the rat liver was studied. Results showed that acetyl-CoA increased more after MCT than after LCT. MCT are more ketogenic than LCT. Mitochondrial and cytoplasmic redox state was greatly reduced after MCT. It is particularly interesting to note that MCT produced an increase in malate and citrate levels, whereas LCT had only a minor influence on these substances.