Medium-Chain Triglycerides: An: Andr# (233) C Bach, SCD and Vigen K Babayan, PHD
Medium-Chain Triglycerides: An: Andr# (233) C Bach, SCD and Vigen K Babayan, PHD
Medium-Chain Triglycerides: An: 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.
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-
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-
-
#{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}.
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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-
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
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
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-
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
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.
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
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