Medium-chain triglycerides: an 2

Andr#{233}C Bach, ScD and Vigen K Babayan, PhD

ABSTRACT A review of the literature on the medical and nutritional use of medium-chain
triglycerides (MCTs) since 1970 is presented with additional discussions on the various modifica-
tions and applications of the MCTs in the synthesis of certain structured lipids. The metabolism of
MCTs in the liver and extrahepatic tissues is discussed along with further documentation of the use
of MCTs in malabsorption and hyperlipidemia cases. Recent applications of MCTs and modified
MCTs in hyperahimentation, deficiency in the carnitine system, epilepsy, obesity, and other special
areas of application are cited. The use of medium-chain monodiglycendes for dissolving cholesterol
gallstones is presented. The contraindications for the use of MCTs in ketosis, acidosis, and cirrhosis
are also discussed. Suggestions for use of MCTs in a variety of medical and nutritional applications
are presented. Am J Clin Nutr 1982;36:950-962.

KEY WORDS Medium-chain triglycerides, hong-chain triglycerides, medium-chain fatty acid

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(C6:0-Cl2:0), long-chain fatty acid (C 14:0 and longer), medium-chain monodiglycerides (mono-
diglycerides of caprylic and capric acids)

Introduction C8:0 versus 0.72 mg for C 16:0. The fact that

MCFAs are weak electrolytes and are highly
Medium-chain triglycerides (MCTs) were ionized at neutral pH, increases even more
first introduced in 1950 for the treatment of their solubility in biological fluids. As we
disorders of lipid absorption. Since then a shall see, the greater water solubility and the
great deal has been learned about the metab- smaller molecular size of the MCFAs have
olism and clinical use of MCTs and of their consequences in all levels of their metabo-
fatty acids. lism.
Herein, we have tried to evaluate the cur-
rent state of the art of MCTs emphasizing, Absorption and metabolism
particularly, what has been learned since
1970. References 1 to 4 supply earlier biblio- Absorption
graphical information.
The molecular weight of MCTs is smaller
than the molecular size of long-chain triglyc-
Physicochemical properties
erides (LCTs). This facilitates the action of
MCTs are made up of a mixture of C6:0 pancreatic lipase. Consequently, MCTs are
(1 to 2%), C8:0 (65 to 75%), ClO:0 (25 to hydrolyzed both faster and more completely
35%), and C12:0 (1 to 2%) medium-chain than LCTs. In the case of mixed triacylglyc-
fatty acids (MCFAs) obtained by the hydrol- erols the MCFAs are liberated preferentially.
ysis of coconut oil followed by the fractiona- Mott et a! (6) showed that in man, MCTs did
tion of the fatty acids. The MCFAs are ester- not produce any change in pancreatic secre-
ified with glycerol with or without a catalyst tion, whereas with LCTs, there was a signifi-
cant overall increase.
to form the triacylglycerols (5). The melting
point of the MCFAs is much lower (C8:0, I From the Laboratoire de Pathologic G#{233}n#{232}rahe,
5cr-
16.7#{176}C;C 10:0, 31.3#{176}C)than that of the long- vice de M#{233}decine Interne A, Clinique M#{233}dicale A, Hos-
chain fatty acids (LCFAs) (C 16:0, 63.1#{176}C). pices Civils, Strasbourg, France; and Nutritional Labo-
Thus MCFAs, but also medium-chain triac- ratories, Stokely-Van Camp, Inc, Indianapolis, IN.
2 Address reprint requests to: Vigen K Babayan, PhD
ylglycerols, are liquid at room temperature.
Stokehy-Van Camp, Inc, 941 N Meridian St, Indianap-
By virtue of their smaller molecular size olis, IN 46206.
MCFAs are relatively soluble in water: the Received December 4, 1981.
water solubility at 20#{176}C is 68 mg/lOO ml for Accepted for publication May 4, 1982.

950 The American Journal of Clinical Nutrition 36: NOVEMBER 1982, pp 950-962. Printed in USA
© 1982 American Society for Clinical Nutrition
 MEDIUM-CHAIN TRIGLYCERIDES: UPDATE 951

The products of MCTs hydrolysis are ab- LCFAs are easily bound to this protein and
sorbed faster than those of LCTs, and as fast incorporated abundantly into lipids.
as glucose (7). Since their intraluminal hy- MCFAs follow the portal venous system
drolysis is rapid and relatively complete, the (Fig 1), whereas LCFAs follow the lymphatic
MCTs-unlike LCTs- are absorbed mainly system. Thus, MCTs do not stimulate the
as free fatty acids, and only rarely as mono- flow of lymph, while LCTs stimulate it sig-
diacylglycerols (Fig 1). In cases where bile nificantly. The LCFAs are transported as
salts or pancreatic lipase deficiency or both chylomicrons, which are insoluble particles.
occur (8), a large fraction of MCTs can be The MCFAs, however, are transported in the
absorbed as triacylglycerols, whereas LCTs soluble form of fatty acids, bound to serum
cannot be absorbed. In enterocytes, these albumin. This bond between MCFAs and
MCTs are then hydrolyzed by an intestinal albumin, however, is not as easily formed as
lipase. that between LCFAs and albumin (1 1).
In the mucosa, LCFA are converted into Because MCFAs leave the intestinal mu-
acyl-CoAs in the presence of an acyl-CoA cosa by the portal venous system, they reach
synthetase. The acyl-CoAs are then incorpo- the liver more rapidly than the longer mole-
rated into triacylglycerols, which are a major cules. The latter move via the extrahepatic
component of chylomicrons. Since this en- tissues, where they may be partially retained.
zyme is specific for fatty acids with more than Thus, MCFAs reachthe liver in greater abun-

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12 carbon atoms, the MCFAs are not signifi- dance than do exogenous LCFAs. The ma-
cantly incorporated into chylomicrons; there- jority of the MCFAs is retained in the liver,
fore, MCFAs leave the intestine faster than and only a small amount appears in the pe-
the LCFAs. The tendency of fatty acids to be ripheral blood for a short period of time.
esterified is directly proportional to their abil- When LCTs and MCTs are ingested si-
ity to bind to fatty-acid-binding protein (9, multaneously, the latter partially inhibit the
10). MCFAs are not easily bound to this absorption of the former. Nevertheless, the
protein and are not easily esterified, while total number of calories absorbed in this sit-

FIG. 1. Digestion, absorption, and transport of fats. MG, monoacylglycerol: C/ni. chylomicrons: gp, ca-glycero-
phosphate; G’CIRC, general circulation.
952 BACH AND BABAYAN

uation is greater than the calories absorbed not bind easily to the fatty-acid-binding pro-
when either fat is ingested alone (12). tein (19), and the acyl-CoA synthetase spe-
The mode of transport of MCFAs results cific for these fatty acids is located in the
in reduced sterol absorption (13). To be ab- mitochondrial matrix, MCFAs are almost
sorbed, sterols must be incorporated into mi- never activated in the extramitochondrial
celles; and to be transported they must be space. Consequently, MCFAs are not signifi-
bound to LCFAs, and incorporated into chy- cantly incorporated into the lipids synthe-
lomicrons (14). These two processes do not sized by the hepatic tissue (20).
take place with MCFAs and consequently MCFAs cross the double mitochondrial
the absorption of sterols is diminished. membrane very rapidly and, unlike the
The absorption of calcium (15) and mag- LCFAs, they do not require the presence of
nesium appears to be enhanced when the diet carnitine (Fig 2) (21). In the mitochondrial
contains MCTs, particularly in infants (16). matrix MCFAs are acylated by means of
The absorption of amino acids also appears an octanoyl-CoA synthetase. In contrast,
to be improved (17, 18). LCFAs or their acyl-CoA derivatives cannot
cross the mitochondrial wall. In the presence
Hepatic metabolism of a carnitine palmityl transferase-I, LCFAs
In the endoplasmic reticulum of the hepa- are transformed into acyl-carnitines that cross
tocyte, the LCFAs are actively fixed on the the membrane and regenerate long-chain-

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fatty-acid-binding protein (9) and activated acyl-CoAs in the matrix, by the action of a
into acyl-CoAs under the influence of a long- carnitine palmityl transferase-Il.
chain-acyl-CoA synthetase (Fig 2). These The mitochondrial acyl-CoAs, of whatever
acyl-CoAs then preferentially esterify a-glyc- chain length, then undergo fl-oxidation, with
erophosphate to give triacylglycerols and production of acetyl-CoA. In a healthy, well-
phospholipids; and esterify cholesterol, to nourished organism, relatively few LCFAs
give cholesterol esters. Because MCFAs do reach this stage at the same time, since these

-
#{149}- #{149}-- :-

LONG CHAIN :-

I
hCVtCo SYNThITASE

#{149}
- ‘oAS

.LCIA
- - . - -s_’_ !_‘:

TelIL
.
2k

T
DENC

:
- ACETYLCoA
IIYNTHESISt’-

...y::;c;

#{163}
LYRJ
I
- HopatOcyte -. -

1-’ #{149}--#{149}#{149}.

- i___..=-- -

FIG. 2. Hepatic metabolism of fatty acids. TG, triacylglycerols; PL, phospholipids; CE, esterified cholesterol:
CPT, carnitine palmityl transferase.
 MEDIUM-CHAIN TRIGLYCERIDES: UPDATE 953

fatty acids tend to be incorporated into the By complicated transfer mechanisms in-
lipids synthesized by the liver. The carnitine volving citrate and acetylcarnitine, acetyl-
palmityl transferase complex is rather mac- CoA is transported to the cytosol and can be
tive under these conditions. The MCTs, how- used in the production of fatty acids and
ever, are available and are rapidly oxidized. cholesterol. A carbohydrate-rich diet in-
The result is an excess of acetyl-CoA (22), creases the de novo synthesis of fatty acids
which then follows various metabolic path- and cholesterol by the liver. The synthesis
ways, both in the mitochondria (Krebs cycle, decreases when some of the carbohydrate is
ketogenesis, elongation of fatty acids) and in replaced by fats. The decrease is even smaller
the cytosol (de novo synthesis of fatty acids when MCTs, rather than LCTs, are provided
and cholesterol). During this accelerated /9- in the diet (33-35). The slight cholesterol-
oxidation of MCFAs, many hydrogen atoms lowering effect of MCTs identified by many
are released, and thus the cell medium is investigators can be accounted for by a de-
noticeably reduced (22). Recently, it has been crease in the intestinal absorption of choles-
demonstrated that fatty acids can also un- terol and a slowing of its synthesis from ace-
dergo fl-oxidation in the peroxisomes. But tyl-CoA in the liver (34, 36). Less cholesterol
the amount of peroxisomal oxidation of is synthesized because the acetyl-CoA is used
MCFAs is negligible, because the key enzyme in the de novo synthesis of fatty acids (37);
in this metabolic pathway, acyl-CoA oxidase, and because the activity of fi-hydroxy-fi-

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is not very active with acyl-CoAs that have methylglutaryl-CoA reductase, the key en-
fewer than 12 carbon atoms (23). zyme in cholesterol synthesis, is reduced (34).
A fraction of the acetyl-CoA supplied en- After a single oral dose of MCTs a slight
ters into the Krebs cycle and is oxidized into hypoglycemia develops (27, 38). It is caused,
CO2. The liver produces about 10 times more apparently, by a decrease in the hepatic out-
CO2 from C8:0 than from Cl6:0 (24); but the put of glucose and not by an increase in the
capacity of the Krebs cycle is limited (25). peripheral utilization ofglucose. Interestingly
Furthermore, because of both the excess of enough, the concentration of insulin in the
acetyl-CoA produced from MCTs and the blood increases at the same time, because the
reduction in the cell medium, oxaloacetate islets of Langerhans are stimulated either by
will be in short supply (26) (Fig 2). A large the ketone bodies or by the MCFAs them-
part of the acetyl-CoA is then redirected to- selves or by both. But, in general, it appears
ward the synthesis of ketone bodies. that MCTs improve carbohydrate tolerance
MCTs are ketogenic (27, 28), much more (39, 40).
so than LCTs. Wieland and Matschinsky (29)
Extrahepatic metabolism
and McGarry and Foster (25, 30) found that
the classic antiketogenic substances-fruc- Given the magnitude ofthe hepatic uptake
tose, glucose plus insulin, glycerol, and lac- ofMCFAs, the role ofthe extrahepatic tissues
tate-had little effect on the ketogenesis in- in the metabolism of MCTs is small, except
duced in the rat by octanoic acid. Freund and for the utilization of ketone bodies. The
Weinsier (3 1 ), however, found that sucrose MCFAs, however, play an important role in
greatly decreased the amount of acetone in the human fetus. Pilz (41) reported that 15 to
the air exhaled by subjects who had ingested 20% of the fatty acids in cord blood have
MCTs. The simultaneous administration of eight or fewer carbon atoms.
MCTs and oxaloacetic acid donors noticeably As in the liver, the extrahepatic tissues do
reduces the production of ketone bodies from not incorporate much MCFAs in the lipids
MCTs in the rat (26). they synthesize (24). In addition, LCFAs di-
The mitochondria have a system that don- minish the capacity of fat cells to esterify
gates fatty acids that have 12 or more carbon C8:0 (42). As in the liver, it appears that
atoms. A small fraction of the acetyl-CoA MCFAs do not need carnitine to cross the
produced during the oxidation of MCFAs mitochondrial membrane of extrahepatic tis-
serves to lengthen endogenous fatty acids. sues. This, however, has been questioned by
The relative importance of this metabolic Groot and H#{252}lsmann (43). MCFAs are oxi-
pathway increases when LCTs are replaced dized into CO2 in the extrahepatic tissues
by MCTs in the diet (32). more rapidly than are LCFAs (24). Also, as
 954 BACH AND BABAYAN

in the liver, MCFAs inhibit, only slightly, the MCTs are a fat and thus can be used in
de novo synthesis of fatty acids in adipose cooking. In addition, MCTs are a concen-
tissue (35). trated source ofcalories (8.3 kcal/g compared
to 3 to 4 kcal/g for carbohydrates and pro-
Clinical use teins), and a good source of acetyl groups
which are useful in lipid synthesis.
Fat malabsorption The ingestion of labeled fats followed by
For 30 yr the special properties of MCTs the detection of the tracer in the expired CO2
have been applied in human therapy, partic- is a method often used to measure the amount
ularly in cases where the digestion, absorp- of fat absorbed. Since MCTs are oxidized
tion, or transport of usual dietary fats are much more rapidly than LCTs, labeled trioc-
disturbed. In such cases steatorrhea is present tanoylglycerol has been preferred to triolein
and is often followed by a progressive 5cc- by Schwabe et a! (56) (‘4C tracer) and by
ondary malnutrition caused by the loss of Watkins et a! (57) (‘3C tracer) to detect ma!-
nitrogen, water, and electrolytes in the feces. absorption of fats.
In general, the steatorrhea subsides when di-
Gallbladder disease
etary LCTs are replaced by MCTs, and the
number and weight of the stools are reduced. The medium-chain monodiglycerides of
The low concentration of lipids in the serum caprylic and capric acid can be solubilized in

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remains unchanged, but the dyspepsia and aqueous solutions, oils, and other organic
the nutritional state improves. Patients gain compounds. The medium-chain monodigly-
weight and children start to grow again. Thus cerides have been investigated in in vitro (58)
MCTs have been used successfully in adults, and in vivo studies for their use in dissolution
children, and newborns with the following of gallstones. A product containing these me-
disorders: dium-chain monodiglycerides is under an in-
1 ) In disorders of lipid digestion, as with vestigational new drug status in the USA
major or total resection of the esophagus or (Capmul 8210, Stokely-Van Camp, Inc, In-
of the stomach; biliary atresia, obstructive dianapolis, IN; US patent 4,205,086, May 27,
jaundice, primary biliary cirrhosis (44), and 1980). It has been used successfully in the
blind-loop syndrome; and pancreatitis (45), treatment of cholesterol-related choleithiasis
cystic fibrosis (46-48), and pancreatectomy. (59, 60) by perfusing it into the common bile
2) In disorders oflipid absorption, as when duct. Recently, further advances have been
there is massive resection of the small intes- reported in both percutaneous and endo-
tine (49, 50), ceiac disease, Whipple’s disease, scopic entry techniques confirming the safety,
Crohn’s disease, enteritis, gluten enteropathy, efficacy, and rapid dissolution of gallstones
tropical or idiopathic sprues, and malabsorp- with this product (61, 62).
tion in neonates (18, 51).
3) In disorders of lipid transport, as in Application of the energy-providing and
deficiency of chylomicron synthesis (eg, con- ketogenic properties of MCTs
genital /9-lipoprotein deficiency); and in lym- When MCTs are supplied in the diet, they
phatic disorder due to engorgement (eg, in- are rapidly oxidized, rendering many ketone
testinal lymphangiectasia) or leakage [eg, bodies and supplying a quick source of en-
chyluria (52, 53), chylous ascites, and chylo- ergy. The energy is delivered to the whole
thorax (54, 55)]. In the case of an abnormal body, both the liver (during the oxidation of
exchange between the lymphatic system and fatty acids), and the extrahepatic tissues
another system or a cavity, MCTs decreases (mainly during the utilization of ketone bod-
lipid and protein losses. Since MCTs, unlike ies). A modest elevation of the concentration
LCTs, do not stimulate the flow of lymph, of ketone bodies in the blood is known not to
they favor the healing of fistulas. be dangerous: all the extrahepatic tissues can
In cases of maldigestion and/or malab- use the ketone bodies supplied by the blood.
sorption where LCTs are not well tolerated, When the blood level of fi-hydroxybutyrate
MCT-containing diets have a great advantage and acetoacetate increases, the utilization of
over low-fat diets. The advantage is that ketone bodies is enhanced (63). These tissues
 MEDIUM-CHAIN TRIGLYCERIDES: UPDATE 955

are enzymatically equipped to produce ace- plete success by some authors (7 1-73). The
tyl-CoA from ketone bodies. The activated diet provides 70% of the calories from MCTs,
acetate is then used according to local needs, as compared to 87% calories from fat in the
either as a source of energy, or as a basic LCT-based ketogenic diet. However, some
ingredient in the de novo synthesis of lipids. setbacks in the treatment of epilepsy with
MCTs have recently been reported (74-77).
Sources of energy
Hyperalimentation
The MCTs are, therefore, a food of choice
for any organism that has increased energy MCTs arc a preferable food for any orga-
needs, as after major surgery (64), or during nism that has increased energy needs, such as
normal or retarded growth (16, 18, 65). It is undernourished patients after major surgery
generally believed that MCTs should be in- (64) or children during normal or retarded
cluded in the nutritional management of the growth (16, 18, 65).
severe undernourished patient. The metabolism of MCFAs by the extra-
Another major consumer of ketone bodies hepatic tissues is increased considerably when
is the fetus. Rubaltelli et al (66) have sug- MCTs are supplied intravenously. MCTs are,
gested that the perfusion of LCTs into cx- consequently, supplied in abundance to the
pectant mothers could help the treatment of various tissues where they are hydrolyzed. In
the fetus with slow intrauterine growth. From these tissues, part of the released fatty acids

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what is known about MCTs, it allows us to are incorporated into lipids (42), but most of
think that in this instance, it would be pref- them are oxidized. The resulting acetyl-CoA
erable to use MCTs rather than LCTs. generates energy in situ and contributes to
lipid synthesis. The caloric demands of the
Lipid precursors stressed patient are difficult to meet without
The acetyl-CoA produced in the peripheral incorporating fat into the parenteral regimen.
tissues from MCTs can also enter into ana- Lipid emulsions containing LCFAs, which
bolic pathways. In the brain, large synthesis for the most part are stored in the hepatic
of lipids-mainly phospholipids-from ke- and adipose tissues, are not capable of sup-
tone bodies have been demonstrated (67). plying quick energy in large quantities.
This synthesis appears to be very effective Therefore, replacement of LCTs with MCTs
during the period of myclinization of the could be valuable. Sailer and Berg (64)
brain. The use of MCTs as a source of energy showed that emulsions of LCTs containing
and lipid precursors in complicated pregnan- 25 or 50% MCTs were very useful in patients
cies should be further explored. requiring intensive nutritional therapy. The
MCTs were rapidly removed from the circu-
A nticonvulsive properties
lation, the increase in ketonemia was within
Ketone bodies also have a narcotic and acceptable levels, and the tolerance to these
anticonvulsive property that has not yet been fats was excellent, even in protracted therapy.
explained (68). This property has long been In chronically ill patients in critical condition,
used in the treatment of epilepsy. Although MCTs not only cover the energy needs, but
many drugs are now available, a ketogenic also contribute a sparing action for the low-
diet (69) remains a valuable alternative in ered muscular carnitine levels (78) and cor-
anticonvulsive therapy in at least two cases: rect the depression in ketonemia (79) related
when there is resistance to the usual drugs to septicemia or trauma.
(eg, epileptic myoclonia of childhood) and in In recent years with the introduction of
intolerance to the medication, or both. structured lipids based on the MCTs as the
In addition to providing an insufficient main backbone of the lipid, we are seeing
amount of carbohydrates, a ketogenic diet modifications of MCTs which improve their
has the disadvantages of being unpalatable utility and nutritional suitability in hyperali-
and difficult to prepare and administer. These mentation. Although physical mixtures of
disadvantages are partially overcome with the MCTs and LCTs have been tried in paren-
MCT-based ketogenic diet introduced by teral nutrition (64, 80, 81), such mixes dem-
Huttenlocher et al (70) and used with com- onstrate the dual pattern of clearance and
956 BACH AND BABAYAN

energy utilization of MCTs and LCTs. With genic. 4) The life span is longer when the
the advent of structured lipids of MCTs and diet is richer in MCTs than in LCTs (92).
LCTs at random distribution in the same
triglyceride molecule, there is now the poten- Deficiency of the carnitine system
tial for tailor-making of lipids to meet the In skeletal muscle, the transport of LCFAs
physical and nutritional needs of patients from the sarcoplasm into the mitochondria is
receiving parenteral or enteral nutrition. Ba- dependent on the carnitine system. Therefore,
bayan (82) has projected the types of struc- a deficiency of carnitine or carnitine palmityl
tured lipids that are available for clinical transferase (I or II, or both) results in a
investigations. Such structured lipids promise diminished capacity to oxidize LCFAs (93).
real progress in the hyperalimentation field The lowering of this energy catabolism,
where lipids and high-density calorie require- which is essential for the working muscle, is
ments are sought by the physician. manifested by various symptoms: muscular
weakness, pain after exertion, myoglobinuria,
Hyperhpidemias lipid-filled vacuoles within muscle fibers, and
Because MCFAs are incorporated into lip- episodes of metabolic encephalopathy. As the
ids only in small amounts, many studies have fatty acids continue to reach the muscle, they
been performed to find out whether MCTs are incorporated into triacylglycerols, which
can be useful in the treatment of hyperlipi- accumulate. In the myopathic form of carni-

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demias. tine deficiency, the pathology is limited to the
Although some authors (32, 34, 36, 83, 84) skeletal muscles, but in the systemic form the
have reported their observations on the de- heart, liver, and kidneys are affected.
crease in blood and liver cholesterol levels In view of the particular intramitochon-
with an MCT diet, we do not have a clear drial transfer of the MCFAs, patients suffer-
picture of the role MCT can play in the ing from a deficiency of muscular carnitine
treatment of hypercholesterolemia. This area have been treated rather successfully with an
deserves further study. MCT-based diet (93-97). In some instances,
In view of present knowledge of the causes carnitine was added. However, the disorders
ofhyperlipidemias, it is clear that MCTs have observed in patients with carnitine palmityl
no role in their treatment, except in type I transferase deficiency did not always regress
(lipoprotein lipase deficiency, mast-cell defi- when treated with a diet providing MCTs
ciency) and in type V (diminished activity of (98, 99). The more or less marked success of
lipoprotein lipase) hyperlipoproteinemias. treatment with MCTs is probably due to the
Since in these cases the clearing enzyme, or fact that only a small amount of MCFAs
its coenzyme are absent or insufficient, the reach the muscle. Undoubtedly, more studies
replacement ofdietary LCTs with MCTs (85) in this area are necessary. Studies on the
has been very useful in the treatment of these effect of intravenous MCT infusion would be
disorders. In studies done in rats, MCTs, of special interest in this regard.
unlike LCTs, slowed down the appearance of
alcoholic steatosis (86) and speeded up the Obesity
regression of established atherosclerotic le- Animal studies on the effect of the incor-
sions, when alcohol was withdrawn from the poration MCFAs into the adipose tissue have
diet (87). shown that MCTs can produce a slight re-
Malmros et a! (88) found that an MCT- duction (not always statistically significant)
based diet fed to rabbits induced atheroma- in body weight, and in the weight of the
tous changes in the aorta and coronary arter- adipose tissues (33, 35, 100- 105, Geliebter A,
ies. The diet, however, was probably deficient Torbay N, Bracco EF, Van Itallie TB,
in polyunsaturated fatty acids. In contrast, Hashim SA, unpublished data). The food
the following observations have been made efficiency ratio is diminished in rats fed
in the rat. 1) The aorta almost completely MCTs (104, 107): the animals need to con-
oxidizes MCFAs into Co2 (89). 2) MCTs sume 20.3 kcal/g of weight gain when fed
limit the deposition of cholesterol in all tissues MCTs as compared to 16.6 kcal/g of weight
(84, 90). 3) MCFAs are not thrombogenic, gain with LCTs. The reason for the lowered
while saturated LCFAs are (91) thrombo- food efficiency ratio seems to be an enhanced
 MEDIUM-CHAIN TRIGLYCERIDES: UPDATE 957

thermogenesis induced by MCTs (105). the capacity of the extrahepatic tissues to use
Kaunitz et al (108) found that the weight of ketone bodies is saturated. Therefore, the
normal and obese subjects diminished when additional supply of such substrates is not
LCTs were replaced with MCTs in their diet. only wasted as an energy source, but it also
The value of MCTs in obesity is not as yet aggravates the metabolic acidosis and accel-
well understood. The results of Rath et a! crates the breakdown of the homeostatic
(83) failed to provide any evidence in favor mechanisms. The solution to this problem
of MCTs. In their study, obese women given may be using MCTs with odd carbon chain
a 550 kcal diet containing 30 g of MCTs lost fatty acids instead of the even carbon chain
as much weight as when MCTs were replaced fatty acids. Indeed Guy and Tuley (118)
by sugars. Kaunitz et al (109) found that showed that tripelargonin is less ketogenic
obese subjects consuming a 1200 kcal diet than usual MCTs in rats.
lost the same amount of weight whether the
dietary fat was olive oil or MCTs. In the Cirrhosis
genetically obese Zucker rat (1 10) and the Since MCFAs are metabolized mostly in
BHE rat (1 1 1), an MCT diet did not reduce the liver, the intestinal perfusion of octanoate
body weight. in healthy subjects results in the appearance
Nevertheless, several reports indicate that of only small amounts of this fatty acid in the
MCTs may be a useful tool in the control of circulating blood (1 19). However, when the

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obesity. Lavau and Hashim (35), Schemmel functional cell mass of the liver is reduced, as
(104), Travis et a! (105), Turkenkopf et a! in cirrhosis, the C8:0 concentration in the
(1 12), Geliebter et al (106), Baba et a! (1 13), blood increases due to the reduced hepatic
Bray et a! ( 1 14), and Bach et a! ( 1 15) indicate clearance. In the case of a portacaval shunt,
a reduction of carcass mass with the use of for example, C8:0 reaches very high amounts
MCTs. In view of these conflicting results in (1 19). It is generally believed that fatty acids
the literature, additional studies are needed are somewhat toxic when given in large
to understand the role of MCTs in the treat- amounts. Intravenous infusion of C8:0, for
ment of obesity. One explanation for these example, results in a syndrome resembling
results could be that the nonincorporation of hepatic encephalopathy: hyperventilation,
MCFAs into the adipose tissue is more or less hyperammoniemia, hyperlactacidemia, and
compensated for by the weak inhibition of de disturbed electroencephalogram ( 120, 121).
novo synthesis of fatty acids by the liver and In healthy subjects, the binding of fatty acids
adipose tissue (35). to albumin in the serum relieves this toxicity.
The monoesters and diesters of polyglycer- But, in cirrhosis, the albuminemia drops. In
ols containing MCFAs can be considered as addition, the affinity of MCFAs for albumin
replacements for natural fats. These polygly- is weak, because LCFAs and MCFAs com-
cerol esters appear to have the ability to Pete for the albumin binding sites (122). Un-
impart a feeling of satiety while eliminating der these circumstances, free fatty acids, not
and/or reducing the lipid level in a food bound to protein, diffuse passively across the
product, while still maintaining the desired capillary membranes. Thus, free octanoic
appearance and physical form. Their energy acid has been found, not only in the blood,
value is only 6 to 8.5 kcal/g. The use of these but also in the ascitic fluid, and the cerebro-
esters in foods will be a convenient way to spinal fluid of persons with cirrhosis who
reduce calories, particularly fat calories (116). were given this fatty acid by intestinal per-
fusion (123). It appears that, in cirrhosis, there
Contraindications is the danger that the energy metabolism of
the brain may be altered.
Ketosis and acidosis
MCTs are ketogenic in the normal subject Availability and suggestions for use
and even more in the patient with hyperos-
molar diabetic syndrome (117). Hence, MCTs Initially, MCTs were available only in the
should not be given to patients with diabetes. form of oil or margarine. MCTs are now
They should also not be given to patients available in liquid or solid preparations and
with ketosis or acidosis. In these conditions, in simple or complex combinations with pro-
958 BACH AND BABAYAN

teins, sugars, vitamins, essential fatty acids, In total parenteral nutrition, the essential
and minerals. These various forms make it fatty acids should be included in the regimen.
possible to provide the infant or the adult While Kaunitz et a! (126) showed in the rat
with the amounts of MCTs needed for par- that MCTs lowered the need for linoleic acid
enteral, oral, or tube feeding (124). more than LCTs, Hirono et a! (127) reported
It is indispensable to determine for each that the need for this fatty acid was increased
patient the threshold dose that must not be in newborn babies given an MCT-based milk.
exceeded if problems are to be prevented Williams and Oski (128) found no change in
from arising, eg, osmotic diarrhea in ileitis the vitamin E status of newborn babies fed
and in extensive resection of the small intes- MCT-based milk. It is, therefore, important
tine, or in dumping syndrome in patients with that when MCTs are given intravenously or
gastrectomy. enterally as the sole source of fat, that the
In enteral feeding, MCTs should first be needs for essential fatty acids are met. There
introduced in small amounts and gradually are now available tailor-made MCTs with
increased to the prescribed dose. In general, varying amounts oflinoleic acid (Captex 810,
MCTs are well tolerated when the daily dose Stokely-Van Camp, Inc) These products are
is divided proportionally into meals of a well- facilitating the design of regimens that meet
balanced diet. MCTs diets seem to be better the essential fatty acid requirements of pa-
tolerated by children than by adults (90). A tients.

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nutritionally balanced diet is the best way of When MCTs are used for cooking or
avoiding ketosis. A daily supply of 50 or even frying, they should not be heated to temper-
100 g is easily tolerated. Obviously, when atures above 150 to 160#{176}C.Above this tem-
MCTs are given for their ketogenic properties perature, it will result in oxidation and ther-
the procedure will be different (68, 75). ma! breakdown which will affect the palata-
MCTs are not a panacea. Only rarely do bility and acceptability of the product.
MCTs alone provide the best therapeutic so-
lution. Very often, it is advisable to combine Conclusions
MCTs with the standard therapy of the par-
ticular illness: a reduction in the supply of The particular physicochemical properties
LCTs, or the provision of bile salts (in biliary of MCFAs make MCTs a valuable tool in the
deficiency), enzyme therapy (in pancreatic dietetic management ofa number of disorders
deficiency), a gluten-free diet (in celiac dis- of lipid metabolism. Most fat maldigestion
ease), antibiotics (in tropical sprue), or car- and malabsorption conditions, and some dis-
nitine (in carnitine deficiency). orders of the lymphatic fat transport and of
It must be remembered that when the the fat removal from the blood, can be com-
digestion or absorption of LCTs is perturbed, pletely or partially corrected by replacing
a smaller amount of MCTs is absorbed than dietary LCTs with MCTs. The crucial needs
in the healthy organism; but in any case more for energy or for acetyl-CoA as precursors of
MCTs are absorbed than LCTs. As discussed lipids, can be met by a supply of MCTs,
previously, the ingestion of large amounts of whether the need is transient or long lasting.
MCTs decreases the absorption of LCTs, and Although MCTs are fats, they tend some-
increases the losses of LCFAs in the feces. times, to behave like carbohydrates. Al-
Nevertheless, extrapolating the results ob- though MCTs are oxidized rapidly and have
tained in rats to patients with reduced lipid low tendency to be stored in the adipose
absorption, Clark and Holt (12) suggested tissue, MCTs are not hyperlipidemic, but they
that the amount of LCTs normally tolerated are ketogenic. Although MCTs are not hy-
could be doubled, by means of an MCT perglycemic, they slightly stimulate insulin
supplement, without inducing steatorrhea. production, but do not lower lipogenesis sig-
When MCTs are infused parenterally, the nificantly. MCTs are not drugs-they have
dose should be carefully calculated and the no pharmacological effect.
patient closely monitored. If the dose is in In summary, the beneficial effects of MCTs
excess, there is danger of acidosis due to are: 1) MCTs are digested, absorbed, and
hyperketonemia and hyperlacticacidemia transported easily and rapidly in disorders
(125). where the digestion, absorption, or transport
 MEDIUM-CHAIN TRIGLYCERIDES: UPDATE 959

of LCTs are not optimal. 2) MCTs are oxi- I Chin Invest 1969;48:2235-43.
13. Takahashi Yl, Underwood BA. Effect of long and
dized rapidly in the organism and they have
medium chain length lipids upon aqueous solubility
a very low tendency to deposit as body fat. 3) of a-tocopherol. Lipids l974;9:855-9.
MCTs are a source of abundant and rapidly 14. Roels OA, Hashim SA. Influence of fatty acids on
available energy. 4) MCTs are ketogenic. 5) serum cholesterol. Fed Proc 1962;21:71-6.
15. Agnew IE, Holdsworth CD. The effect of fat on
MCTs are donors of hydrogen ions and pre-
calcium absorption from a mixed meal in normal
cursors of acetyl-CoA. subjects, patients with malabsorptive disease,
MCTs do not behave as conventional fats. and patients with a partial gastrectomy. Gut
Thus, MCTs must be treated separately and 197 1; 12:973-7.
differently from our understanding of fats 16. Tantibhedhyangkul P, Hashim SA. Medium-chain
triglyceride feeding in premature infants: effects on
and oils. The unique physical, chemical, and
calcium and magnesium absorption. Pediatrics
structural characteristics of MCTs and their 1978;6 1:537-45.
modifications (structured lipids) makes such 17. Holtzapple P. Berman W, Segal S. Enhancement of
special lipids tools for solving certain medical non-electrolyte transport in jejunal mucosa by fatty
problems. a 18.
acids. Gastroenterology
Tantibhedhyangkul
1972;62:849.
P, Hashim SA. Medium-chain
The authors acknowledge the assistance and contri- triglyceride feeding in premature infants: effects of
bution of Margarita Nagy for editing the manuscript. fat and nitrogen absorption. Pediatrics 1975;
55:359-69.
19. Wu-Rideout MYC, Elson C, Shrago E. The role of

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References fatty acid binding protein on the metabolism of
fatty acids in isolated rat hepatocytes. Biochem
1. Senior IR, ed. Medium chain triglycerides. Phila- Biophys Res Commun 1976;71:809-16.
delphia, PA: University of Pennsylvania Press, 20. McGarry ID, Foster DW. Regulation of hepatic
1968. fatty acid oxidation and ketone body production.
2. Kalser MH. Medium chain triglycerides. Adv In- Ann Rev Biochem l980;49:395-420.
tern Med 197 1;17:301-32. 2 1. Bremer I. Carnitine and its role in fatty acid me-
3. Sickinger K. Clinical aspects and therapy of fat tabohism. Trends Biochem Sci 1980;2:207-9.
malassimilation with particular reference to the use 22. Bach A, Phan T, M#{233}taisP. Effect of the fatty acid
of medium-chain triglycerides. In: Vergroesen Al, composition of ingested fats on rat liver interme-
ed. The role of fats in human nutrition. London: diary metabolism. Horm Metab Res 1976;8:375-9.
Academic Press, 1975: 1 15-209. 23. Osumi T, Hashimoto T. Acyl-CoA oxidase of rat
4. Bach A, M#{233}taisP. Graisses a chalnes courtes et liver: a new enzyme for fatty acid oxidation. Bio-
moyennes. Aspects physiologiques, biochimiques, chem Biophys Res Commun 1978;83:479-85.
nutritionnels et therapeutiques. Ann Nutr Ahiment 24 Scheig R. Hepatic metabolism of medium chain
1970;24:74-144. fatty acids. In: Senior IR, ed. Medium chain tri-
5. Babayan VK. Medium-chain triglycerides-their glycerides. Philadelphia, PA: University of Penn-
composition, preparation, and application. I Am sylvania Press, 1968:39-49.
Oil Chem Soc l968;45:23-5. 25. McGarry ID, Foster DW. The regulation of keto-
6. Mott CB, Sarles H, Tiscornia 0. Action diff#{233}rente genesis from oleic acid and the influence of anti-
des triglycerides a chalnes courtes, moyennes ou ketogenic agents. I Biol Chem 197 l;246:6247-53.
longues, sur la s#{233}cr#{233}tion pancr#{233}atique exocrine de 26. Bach A. Oxahoacetate deficiency in MCT-induced
l’homme. Biol Gastro-ent#{233}rol 1972;5:79-84. ketogenesis. Arch Int Physiol Biochim 1978;
7. Iber F. Relative rates of metabolism MCT, LCT 86:1133-42.
and ethanol in man. In: Kaunitz H, Lang K, Fekl 27. Yeh YY, Zee P. Relation of ketosis to metabolic
W, eds. Mittelkettige Triglyceride in der Dint. Z changes induced by acute medium-chain triglycer-
Ern#{228}hrungswiss 1974; 17(suppl):9- 16. ide feeding in rats. I Nutr 1976; 106:58-67.
8. Valdivieso V. Absorption of medium-chain triglyc- 28. Bach A, Schirardin H, Bauer M, Weryha A. Keto-
erides in animals with pancreatic atrophy. Am I genie response to medium-chain triglyceride load
Dig Dis 1972;17:129-36. in the rat. I Nutr 1977;107:1863-70.
9. Mishkin S. Stein L, Gatmaitan Z, Arias IM. The 29. Wieland 0, Matschinsky F. Zur Natur der antike-
binding offatty acids to cytoplasmic proteins: bind- togenen Wirkung von Glycerin und Fruktose. Life
ing to Z protein in liver and other tissues of the rat. Sci 1962;2:49-54.
Biochem Biophys Res Commun l972;47:997-1003. 30. McGarry ID, Foster DW. The regulation of keto-
10. Ockner RK, Manning IA, Poppenhausen RB, Ho genesis from octanoic acid. The role of the tricar-
WKL. A binding protein for fatty acids in cytosol boxylic acid cycle and fatty acid synthesis. I Biol
of intestinal mucosa, liver, myocardium and other Chem 171246:1149-59.
tissues. Science 1972; 177:56-8. 31. Freund G, Weinsier RL. Standardized ketosis in
11. Spector AA. Fatty acid binding to plasma albumin. man following medium chain triglyceride ingestion.
I Lipid Res 1975;16:165-79. Metabolism 1966; 15:980-91.
12. Clark SB, Holt P. Inhibition of steady-state intes- 32. Leveille GA, Pardini RS, Tillotson IA. Influence
tinal absorption of long-chain triglyceride by me- of medium chain triglycerides on lipid metabolism
dium-chain triglyceride in the unanesthetized rat. in rat. Lipids 1967;2:287-94.
960 BACH AND BABAYAN

33. Alice GL, Romsos DR. Leveihle GA, Baker DH. rhea in patients with ileal resection. Gastroenter-
Metabolic consequences of dietary medium chain ology l972;62:918-34.
triglycerides in the pig. Proc Soc Exp Biol Med 50. Tandon RK, Rodgers JB, Bahint IA. The effects of
1972; 139:422-7. medium-chain triglycerides in the short bowel syn-
34. Takase 5, Morimoto A, Nakanishi M, Muto Y. drome. Increased glucose and water transport. Am
Long-term effect of medium-chain triglyceride in I Dig Dis 1972;17:233-8.
hepatic enzymes catalyzing hipogenesis and choles- 51. Roy CC, Ste-Marie M, Chartrand L, Weber A,
terogenesis in rats. I Nutr Sci Vitaminol 1977; Bard H, Doray B. Correction of the malabsorption
23:43-51. of the preterm infant with a medium-chain triglyc-
35. Lavau MM, Hashim SA. Effect of medium chain eride formula. I Pediatr 1975;86:446-50.
triglyceride on hipogenesis and body fat in the rat. 52. Van Devenne A, Brogard IM, Iahn H, Viville C.
I Nutr 1978;108:613-20. Communication lympho-py#{233}hique avec chylurie.
36. Kritchevsky D, Tepper SA. Influence of medium- Influence favorable du traitement di#{233}t#{233}tique. Ann
chain triglycerides on cholesterol metabolism in Med Intern l970;121:367-74.
rats. I Nutr 1965;86:67-72. 53. Warter I, M#{233}taisP, Berthier G, Bach A. Traitement
37. Kritchevsky D, Rabinowitz IL. lnfluence of dietary d’une chylurie par un r#{233}gimea base de triglycerides
fat on fatty acid biosynthesis in rat. Biochim Bio- a chalnes moyennes. Pathol Biol 1972;20:865-9.
phys Acta 1966;1 16:185-8. 54. Brenner WI, Boal BH, Reed GE. Chyhothorax as a
38. Bach A, Weryha A, Schirardin H. Influence of an manifestation of rheumatic mitral stenosis. Its post-
oral MCT or LCT load on glycemia in Wistar and operative management with a diet of medium-chain
Zucker rats and in guinea pigs. Ann Biol Anim triglyceride. Chest l978;73:672-3.
Biochim Biophys l979;l9:625-35. 55. Christophe A, Matthys F, Verdonk G. Chylous-
39. Tantibhedhyangkul P. Hashim SA, Van Itallie TB. fluid triglycerides and hipoproteins in a patient with

Downloaded from www.ajcn.org by on May 6, 2009

Effects of ingestion of long-chain and medium- chylothorax on a diet of butter or medium-chain
chain triglycerides on glucose tolerance in man. triglyceride. Arch Int Physiol Biochim 1980;
Diabetes 1967; 16:769-9. 88:B 17-8.
40. Lederer I, Lambert AE, Henquin IC, Pottier-Ar- 56. Schwabe AD, Cozzeto Fl, Bennett LR, Mellinkoff
nould AM, BettendorfB. Influence des triglycerides SM. Estimation of fat absorption by monitoring of
a chamnes moyennes sur la tolerance au glucose et expired radioactive carbon dioxide after feeding a
Ia production d’insuhine chez le rat. Diab#{233}te radioactive fat. Gastroenterology 1962;42:285-91.
1972;20:201-7. 57. Watkins lB. Schoeller DA, Klein P, Ott DG, New-
4 1. Pilz W. Untersuchungen #{252}berFermente des men- comer AD, Hofmann AF. ‘3C-Trioctanoin: a non-
schlichen Blutes. IX. Die Arylesterasen des men- radioactive breath test to detect fat mahabsorption.
schlichen Nabelschnurserums. Z Physiol Chem I Lab Clin Med 1977;90:422-30.
1964;338:238-50. 58. Thistle IL, Carlson GL, Hofmann AF, Babayan
42. Maragoudakis ME, Kalinsky HI, Lennane J. Me- VK. Medium chain glycerides rapidly dissolve cho-
tabohism of octanoate and its effect on glucose and lesterol gallstones in vitro, abstracted. Gastroenter-
palmitate utilization by isolated fat cells. Proc Soc ology 1977;72:A-1 18/1141.
Exp Biol Med 1975;148:606-l0. 59. Mack EA, Saito C, Goldfarb 5, et al. A new agent
43. Groot PHE, H#{252}lsmann WC. The activation and for gallstone dissolution: experimental and clinical
oxidation of octanoate and palmitate by rat skeletal evaluation. Surg Forum 1978;29:438-9.
muscle mitochondria. Biochim Biophys Acta 60. Thistle IL, Carlson GL, Hofmann AF, et al. Mono-
1973;3 16:124-35. octanoin a dissolution agent for retained cholesterol
44. Kehayoglou K, Hadziyannis 5, Kostamis P, Mala- bile duct stones: physical properties and clinical
mos B. The effect of medium-chain triglyceride on application. Gastroenterology 1980;78:1016-22.
47 calcium absorption in patients with primary 61. Witzel L, Wiederholt I, Wolbergs E. Dissolution of
biliary cirrhosis. Gut 1973;14:653-6. retained duct stones by perfusion with monooctan-
45. Harrison IE, McHattie JD, Ligon hR. Jeejeebhoy oin via a teflon catheter introduced endoscopically.
KN, Finlay IM. Effect of medium chain triglycer- Gastrointest Endosc 198 1;27:63-5.
ide on fecal calcium losses in pancreatic insuffi- 62. Mack E, Crummy AB, Babayan VK. Percutaneous
ciency. Clin. Biochem 1973;6: 136-40. transhepatic dissolution of common bile duct sto-
46. Galabert C, Filhiat M, Chazalette IP, Mendy F, nes. Surgery 198 l;90:584-8.
Delhaye N. Absorption intestinale des triglycerides 63. Robinson AM, Williamson DH. Physiological roles
a chamnes moyennes dans la fibrose kystique du of ketone bodies as substrates and signals in mam-
pancreas. Ann PCdiatr 1975;22:745-53. malian tissues. Physiol Rev 1980;60:l43-87.
47. Gracey M, Burke U, Anderson CM. Assessment of 64. Sailer D, Berg G. Stoffwechselwirkung handels#{252}b-
medium-chain triglyceride feeding in infants with licher und einer neuentwickelten MCT-haltigen
cystic fibrosis. Arch Dis Child 1969;44:401-3. Fettemulsion. Intensivmed 1978;15:96-8.
48. Dune PR, Newth CI, Forstner GG, Gall DO. 65. Graham GG, Baertl IM, Cordano A, Morales E.
Malabsorption of medium chain triglycerides in Lactose-free, medium-chain triglyceride formulas
infants with cystic fibrosis. Correction with pan- in severe malnutrition. Am I Dis Child
creatic enzyme supplements. I Pediatr 1980;96:862- 1973; 126:330-5.
4. 66. Rubaltelli FF, Enzi G, Debiasi F, Bondio M, Ron-
49. Hofmann AF, Poley IR. Role of bile acid malab- dinelhi M. Effect of lipid loading on fetal uptake of
sorption in pathogenesis of diarrhea and steator- free fatty acids, glycerol and $-hydroxybutyrate.
 MEDIUM-CHAIN TRIGLYCERIDES: UPDATE 961

Biol Neonate 1978;33:320-6. prevention of the fatty liver produced by prolonged

67. Yeh YY, Streuhi UL, Zee P. Ketone bodies serve as alcohol intake. Gastroenterohogy 1966:50:316-22.
important precursors of brain lipids in the devel- 87. Theuer RC, Martin WH, Friday TJ, Zoumas BL,
oping rat. Lipids 1977; 12:957-64. Sarett HP. Regression of alcoholic fatty liver in the
68. Withrow CD. The ketogenic diet: mechanism of rat by medium-chain triglycerides. Am I Clin Nutr
anticonvulsant action. In: Glaser GH, Penry 1K, 1972:25:175-81.
Woodbury DM, eds. Antiepileptic drugs: mecha- 88. Malmros H, Nilsson IM, Sternby NH, Arvidson 0,
nisms ofaction. New York: Raven Press, 1980:635- Kockum I. Coagulation defects and atherosclerosis
42. induced in rabbits by a diet containing medium
69. Wilder RM. Effect of ketonuria on course of epi- chain triglycerides. Acta Med Scand 1972;192:201-
hepsy. Mayo Chin Bull l92I;2:307-l0. 12.
70. Huttenlocher PR, Wilbourn Al, Signore IM. Me- 89. Hashimoto 5, Dayton S. Utilization of glucose,
dium chain triglycerides as a therapy for intractable octanoate and palmitate by normal rat aorta, and
childhood epilepsy. Neurology 197 I;2 1:1097-103. the effect of these acids and of albumin on glucose
7 1. Signore IM. Ketogenic diet containing medium- metabolism. Proc Soc Exp Biol Med 1968:129:35-
chain triglycerides. I Am Diet Assoc 1973;62:285- 41.
90. 90. Kaunitz H. Clinical uses of medium-chain triglyc-
72. Huttenhocher PR. Ketonemia and seizures: meta- erides. Drug Therapy l978;8:9I-9.
bohic and anticonvulsant effects of two ketogenic 91. Hornstra G, Lussenburg RN. Relationship between
diets in childhood epilepsy. Pediatr Res the type ofdietary fatty acid and arterial thrombosis
1976; 10:536-40. tendency in rats. Atherosclerosis 1975;22:499-516.
73. Gordon N. Medium-chain triglycerides in a keto- 92. Kaunitz H, Iohnson RE. Influence of dietary fats
genie diet. Dcv Med Child Neurol 1977;19:535-8. on disease and longevity. In: Chavez A, Bourges H,

Downloaded from www.ajcn.org by on May 6, 2009

74. Livingston 5, Pauhi LL, Pruce I. Ketogenic diet in Basta 5, eds. Proceedings of the 9th International
the treatment of epilepsy. Dcv Med Child Neurol Congress on Nutrition, Mexico, 1972. Basel: Kar-
l977;19:833-4. ger, 1975;l:362-73.
75. Clark BJ, House FM. Medium chain triglyceride 93. Mitchell ME. Carnitine metabolism in human sub-
oil ketogenic diets in the treatment of childhood jects. III. Metabolism in disease. Am I Clin Nutr
epilepsy. I Hum Nutr 1978;32:1 11-6. 1978:31:645-59.
76. Berman W. Medium-chain triglyceride diet in the 94. Angelini C, L#{252}cke5, Cantarutti F. Carnitine defi-
treatment of intractable childhood epilepsy. Dcv ciency of skeletal muscle: report of a treated case.
Med Child Neurol 1978;20:249-50. Neurology 1976;26:633-7.
77. Hahn TI, Halstead LR, Devivo DC. Disordered 95. Smyth D, Lake BD, Macdermot I, Wilson I. Inborn
mineral metabolism produced by ketogenic diet error of carnitine metabolism (carnitine deficiency)
therapy. Calcif Tissue Int 1979;28:17-22. in man. Lancet 1975;1:ll98-9.
78. Border JR. Burns GP, Rumph C, Schenk WG. 96. Hosking GP, Cavanagh NPC, Smith DPI, Wilson
Carnitine levels in severe infection and starvation: I. Oral treatment of carnitine myopathy. Lancet
a possible key to the prolonged catabolic state. 1977; 1:853.
Surgery 1970;68: 175-9. 97. Angehini C, Govoni E, Bragaglia MM, Vergani L.
79. Neufeld HA, Pace IA, White FE. The effect of Carnitine deficiency: acute postpartum crisis. Ann
bacterial infections on ketone concentrations in rat Neurol 1978;4:558-61.
blood. Metabolism 1976;25:877-84. 98. Carroll IE, Brooke MH, Devivo DC, Kaiser KK,
80. Sailer D, Muller M. Medium chain triglycerides in Hagberg IM. Biochemical and physiologic conse-
parenteral nutrition. IPEN 198l;5:1 15-9. quences ofcarnitine palmityl transferase deficiency.
81. Eckart I, Adolph M. van der Muhlen U, Naab V. Muscle Nerve 1978;1:103-10.
Fat emulsions containing medium chain triglycer- 99. Bertorini T, Yeh YY, Trevisan C, Stadlan E, Sa-
ides in parenteral nutrition of intensive care pa- besin 5, DiMauro S. Carnitine palmityl transferase
tients. IPEN 1980;4:360-6. deficiency: myoglobinuria and respiratory failure.
82. Babayan VK. Medium chain length fatty acid esters Neurology 1980;30:263-7 I.
and their medical and nutritional applications. I 100. Harkins RW, Sarett HP. Nutritional evaluation of
Am Oil Chem Soc 1981;58:49A-51A. medium-chain triglycerides in the rat. I Am Oil
83. Rath F, Sk#{225}laI, Nathov#{225} E. Metabolic aspects of Chem Soc 1968;45:26-30.
the use of medium chain triglycerides in the treat- 101. Stickney RR, Andrews 1W. Effects ofdietary lipids
ment of obesity. Z Ern#{228}hrungswiss 1972: on growth, food conversion, lipid and fatty acid
13(suppl):l 16-24. composition of channel catfish. I Nutr
84. Stewart JW, Wiggers KD, lacobson NL, Berger P1. 1972; 102:249-58.
Effect of various triglycerides on blood and tissue 102. Wiley IH, Leveihle GA. Metabolic consequences of
cholesterol ofcalves. I Nutr 1978;108:561-6. dietary medium-chain triglycerides in the rat. I
85. Furman RH, Howard RP, Brusco 01, Alaupovic P. Nutr 1973; 103:829-35.
Effects of medium chain length triglyceride (MCT) 103. Takase 5, Morimoto A, Muto Y, Hosoya N. Effect
on serum lipids and lipoproteins in familial hyper- of medium chain triglyceride (MCT) on lipid me-
chylomicronemia (dietary fat-induced lipemia) and tabohism in rats with respect to obesity. In: Pro-
dietary carbohydrate-accentuated lipemia. I Lab ceedings Subcommittee, eds. Tenth International
Clin Med 1965;66:912-26. Congress of Nutrition, Iapan, 1975. Kyoto: Pro-
86. Lieber CS, Decarhi LM. Study of agents for the ceedings of Subcommittee of XICN 1976:549
962 BACH AND BABAYAN

(abstr). Langue Fran#{231}aise, Paris, France, Dec 7, 1981.

104. Schemmel R. Physiological considerations of lipid 1 16. Babayan VK. Modification of food to control fat
storage and utilization. Am Zool 1976;16:661-70. intrke. I Am Oil Chem Soc 1974;51:260-4.
105. Travis D, Minenna A, Frier H. Effects of medium 1 17. Gordon EE, Duga I. Experimental hyperosmolar
chain triglyceride on energy metabolism and body diabetic syndrome. Ketogenic response to medium-
composition in the rat. Fed Proc 1979;38:561. chain triglycerides. Diabetes 1975;24:301-6.
106. Deleted in proof. 1 18. Guy DO, Tuley RI. Effects of diets high in carbo-
107. Fino JH, Schemmel R, Mickelsen 0. Effect of hydrate, soy oil, medium-chain triglycerides or tri-
dietary triglyceride chain length on energy utiliza- pelargonin on blood and liver lipid and glucose
tion and obesity in rats fed high fat diets. Fed Proc intermediates in meal-eating rats. I Nutr 1981;
1973;32:933 (abstr). 111:1437-45.
108. Kaunitz H, Slanetz CA, Johnson RE, Babayan VK, 1 19. Linscheer WG, Castell DO, Platt RR. A new
Barsky G. Relation of saturated, medium- and method for evaluation of portosystemic shunting.
long-chain triglycerides to growth, appetite, thirst The rectal octanoate tolerance test. Gastroenterol-
and weight maintenance requirements. I Nutr ogy 1969;57:415-23.
1958;64:5 13-24. 120. Trauner DA, Huttenlocher PR. Short chain fatty
109. Kaunitz H, Cotton RH, Johnson RE. Comparison acid-induced central hyperventilation in rabbits.
of medium-chain triglycerides and other fats in a Neurology 1978;28:940-4.
reducing diet. In: Proceedings Subcommittee, eds. 121. Rabinowitz IL, Staeffen I, Aumonier P. et al. The
Tenth International Congress in Nutrition, Japan effects of intravenous sodium octanoate on the
1975, Kyoto: Proceedings Subcommittee of XICN Rhesus Monkey. Am I Gastroenterol 1978;69:I87-
1976:63-4 (abstr). 90.
110. Bach A, Schirardin H, Chanussot F, Bauer M, 122. Ashbrook ID, Spector AA, Fletcher IE. Medium

Downloaded from www.ajcn.org by on May 6, 2009

Weryha A. Effects of medium- and long-chain chain fatty acid binding to human plasma albumin.
triglyceride diets in the genetically obese Zucker I Biol Chem 1972;247:7043-50.
rat. I Nutr 1980; 110:686-96. 123. Linscheer WG, Bhum AL, Platt RR. Transfer of
I 1 1. Lau HC, Flaim E, Ritchey SI. Body weight and medium chain fatty acids from blood to spinal fluid
depot fat changes as influenced by exercise and in patients with cirrhosis. Gastroenterology 1970;
dietary fat sources in adult BHE rats. I Nutr 58:509-15.
1979; 109:495-500. 124. Shils ME, Bloch AS, Chernoff R. Liquid formulas
1 12. Turkenkpof I, Maggio C, Greenwood MRC. Me- for oral and tube feeding. 2nd ed. New York:
dium chain triglyceridees reduce weight, but not Memorial Sloan-Kettering Cancer Center, 1979.
obesity in young (fafa) rats. Fed Proc 198 l;40:842. 125. Bach A, Guisard D, Debry 0, M#{233}taisP. Metabolic
1 13. Baba N, Bracco EF, Seylar 1, Hashim SA. En- effects following a medium chain triglycerides load
hanced thermogenesis and diminished deposition in dogs. V. Influence of the perfusion rate. Arch Int
of fat in response to overfeeding with diet contain- Physiol Biochim 1974;82:705-l9.
ing medium chain triglyceride. Am I Chin Nutr 126. Kaunitz H, Slanetz CA, Johnson RE, Babayan VK.
198 l;34:624 (abstr). Medium-chain and long-chain saturated triglycer-
114. Bray GA, Lee M, Bray TL. Weight gain of rats fed ides and linoleic acid requirements. I Nutr
medium-chain triglycerides is less than rats fed 1960;7 1:400-4.
long-chain triglycerides. lnt I Obesity 1980;4:27- 127. Hirono H, Suzuki H, Igarashi Y, Konno T. Essen-
32. tial fatty acid deficiency induced by total parenteral
115. Bach A, Chanez M, Bois-Joyeux B, Delhomme B, nutrition and by medium-chain triglyceride feed-
Schirardin H, Peret I. Regimes hyperprot#{233}iques et ing. Am I Chin Nutr 1977;30:1670-6.
hyperlipidiques (LCT ou MCT) chez le rat Zucker 128. Williams ML, Oski FA. Vitamin-E status of infants
genCtiquement obese. R#{233}sultats pruliminaires. Pre- fed formula containing medium-chain triglycerides.
sented at the Reunion Soci#{233}tC Nutrition DiCtCtique, I Pediatr 1980;96:70-2.