Am J Clin Nutr-1982-Bach-950-62.pdf

8/19/2019 Am J Clin Nutr-1982-Bach-950-62.pdf

1/13

The m erican Jo urn a l o f lin ica l N u tr itio n

36 : N O VEM BER 1982 , p p 9 50 96 2

Prin te d in USA

© 1982 Am er ican So ciety fo r C lin ic al N u trit ion

M ed iu m ch a in trig lyce rid es : an

Andr {233}C Bach , ScD and V igen K Babayan , P hD

A BSTR AC T A rev iew of the l itera tu re on the m ed ica l an d nutritio na l u se o f m edium -cha in

tr ig lyce rid es (M CT s) sin ce 19 70 is p resen ted w ith additio nal d iscuss ion s o n the va rio us m odifica-

tion s and app lic atio ns o f th e M CT s in the syn thes is of cer ta in s tru ctu red lip ids . T he m etabo lism of

M CT s in the live r an d ex trahepat ic t issu es is d iscu ssed alo ng w ith fu rth er docum entatio n of the u se

o f M CT s in m alabsorp tio n and hyper lip idem ia cases. R ecen t app lica tion s of M CT s and m od ifie d

M CT s in h yp erah im entatio n , d efic ien cy in the carn it ine sys tem , ep i lep sy , ob es ity , an d o the r sp ec ial

a rea s of ap p lication are cite d . Th e use of m edium -ch ain m onod ig lycende s fo r d isso lv ing cho les tero l

g alls ton es is p resen ted . T he co ntrain d ica tio ns fo r th e use o f M C Ts in k eto sis , acidos is, an d cir rho sis

a re a lso d iscu ssed . S ugges tio ns for use of M C Ts in a va rie ty o f m edic al an d nu trit ion al ap p lications

a re p re se nt ed . Am J C lin N utr 1982;36 :950-962 .

K EY W OR DS M ed ium -chain trig lyc erid es, hon g-chain trig lyc erid es , m edium -cha in fatty a cid

(C6:0-C l2 :0), lo ng-cha in fa tty ac id (C 14 :0 and lo ng er), m edium -ch ain m onod ig lyce ride s (m ono -

d ig lyce ride s of capry lic and capric

acids

In troduct ion

M ed ium -cha in tr ig lyce rid es (M C T s) w ere

f irs t in tro duced in 1 950 fo r th e treatm en t o f

d iso rde rs o f lip id ab so rp tio n . S in ce then a

g rea t dea l has b een lea rned abou t th e m e tab -

o lism and clin ica l u se o f M C Ts and of the ir

fatty ac ids.

H e re in , w e h ave tried to eva lua te th e cu r-

ren t state o f the a rt o f M C T s em phasiz ing ,

p articu la rly , w ha t has b een learned s ince

19 70 . R e fe rences 1 to 4 su pp ly ea rlie r b ib lio -

g raph ica l in fo rm atio n .

P hy sicochem ical p ro pe rtie s

M C Ts a re m ade up o f a m ix tu re o f C 6 :0

(1 to 2% ), C 8 :0 (65 to 75% ), C lO :0 (2 5 to

35 ) , and C 12 :0 (1 to 2% ) m ed ium -cha in

fatty ac ids (M C FA s) ob tain ed by the hyd ro l-

y sis o f coconu t o il fo llow ed by the frac tiona -

tio n o f the fa tty ac ids. The M C FA s are es ter-

if ied w ith g lycero l w ith o r w itho u t a ca taly st

to fo rm the triacy lg ly ce ro ls

(5) .

The m elting

p o in t o f the M C FA s is m uch low er (C 8 :0 ,

16 .7 {176}C;C 10 :0 , 31 .3 { 176 }C )than th at o f the lo ng-

cha in fa tty ac ids (L C FA s) (C 16 :0 , 6 3 .1 { 17 6}C ).

T hus M C FA s, bu t a lso m ed ium -cha in triac -

y lg lyce ro ls , are liqu id at ro om tem pera tu re.

B y v ir tue o f the ir sm a lle r m olecu la r size

M C FA s a re rela tive ly so lu b le in w ate r : the

w a te r so lub ility a t 20 {1 76}Cs 68 m g/lO O m l fo r

95 0

C 8 :0 v ersus 0 .7 2 m g fo r C 16 :0 . T he fac t tha t

M C FA s are w eak e lec tro ly te s and a re h igh ly

ion ized a t neu tra l pH , in creases ev en m ore

the ir so lub ility in b io lo g ical f lu ids . A s w e

sh all see , the g rea te r w a ter so lub ility and the

sm alle r m o lecu la r size o f the M C FA s h ave

conseq uences in a ll lev els o f the ir m e tabo -

l ism.

A bsorp tio n an d m e tabo lism

Absorp tion

T he m olecu lar w e igh t o f M C T s is sm a ller

than th e m o lecu la r size o f long -cha in tr ig lyc -

e ride s (L C Ts). T h is fac ilita te s th e ac tion o f

panc rea tic lip a se. C onsequ en tly , M C T s are

hyd ro lyzed bo th fa ste r an d m o re com ple te ly

than LC T s. In the case o f m ixed triacy lg lyc -

e ro ls the M C FA s are libe rated p re feren tia lly .

M ott e t a (6 ) show ed tha t in m an , M C T s d id

n o t p rodu ce any ch an ge in panc rea tic sec re -

tio n , w he reas w ith L C Ts, th ere w as a sig n if i-

can t o ve ra ll inc rea se .

From the Laborato ire de Patho log ic G {233}n {23 2} rah e,cr -

v ice d e M {233}dec ine In tern e A , C lin iq ue M {233}dic ale A , H o s-

p ice s C iv ils, S trasbou rg , F ranc e; a nd N utri tio nal L abo -

rato ries , S tok ely -V an Cam p, In c, Ind ianapolis, IN .

2 Addres s rep rin t req ues ts to : V igen K Babay an , PhD

S tok ehy -V an C am p, Inc , 941 N M erid ian S t, In d ianap -

o lis , IN 46206 .

R eceiv ed D ecem ber 4 , 19 81 .

A ccep ted for pu blic ation M ay 4 , 198 2 .


2/13

M ED IU M -CH A I N T RIG L Y CER ID ES: U PD A T E

951

FIG. 1. D igesti on, absorption, and transport of f ats. MG monoacy lglycerol: C/n i chy lom ic rons: gp, ca-gly cero-

phosphate; G’ CIR C, general ci rculation.

T he products of M CTs hy drolysis are ab-

sorbed faster than those of L CT s, and as fast

as glucose (7). Since thei r intralum inal hy -

drolysis i s rapid and relati vely complete, the

M CT s-unl i ke L CTs- are absorbed mainly

as f ree f atty acids, and only rarely as m ono-

diacy lgl ycerols (Fig 1). I n cases w here bi le

sal ts or pancreati c l i pase def i ciency or both

occur (8), a large f raction of M CT s can be

absorbed as triacy lgl y cerols, w hereas L CT s

cannot be absorbed. In enterocytes, these

M CTs are then hy drolyzed by an intestinal

lipase.

In the m ucosa, L CFA are converted into

acy l -CoA s in the presence of an acy l -CoA

synthetase. The acy l -CoA s are then incorpo-

rated into triacy lgl ycerols, w hich are a m ajor

component of chy lomicrons. Since this en-

zy me is speci f i c for fatty acids w i th more than

12 carbon atom s, the M CFA s are not signi f i -

cantl y incorporated into chy lom icrons; there-

f ore, M CFA s leave the intestine f aster than

the L CFA s. The tendency of fatty acids to be

ester i f i ed is di rectl y proportional to thei r abi l -

i ty to bind to f atty -acid-binding protein (9,

10). M CFA s are not easi l y bound to this

protein and are not easi l y esteri f i ed, w hi le

L CFA s are easi l y bound to this protein and

incorporated abundantl y into l i pids.

M CFA s fol low the portal venous system

(Fig 1), w hereas L CFA s f ol low the lym phati c

sy stem. Thus, M CTs do not stimulate the

f low of l ymph, w hi le L CTs stim ulate i t sig-

ni f i cantl y . T he L CFA s are transported as

chy lomicrons, w hich are insoluble parti cles.

T he M CFA s, how ever, are transported in the

soluble f orm of f atty acids, bound to serum

album in. T his bond betw een M CFA s and

album in, how ev er, i s not as easi l y form ed as

that betw een L CFA s and album in (1 1).

B ecause M CFA s leave the intestinal mu-

cosa by the portal v enous system, they reach

the l i ver m ore rapidly than the longer mole-

cules. The latter m ove v ia the extrahepati c

ti ssues, w here they may be partial l y retained.

T hus, M CFA s reachthe l iv er in greater abun-

dance than do ex ogenous L CFA s. T he m a-

jor i ty of the M CFA s is retained in the l i v er,

and only a sm al l amount appears in the pe-

r ipheral blood for a short period of time.

W hen L CTs and M CTs are ingested si -

m ul taneously , the latter partial l y inhibi t the

absorption of the form er. N evertheless, the

total number of calor ies absorbed in this si t-


3/13

952 B A C H A N D B A B A Y A N

I

I

k

T

-

H o p a t O c y t e

-. -

1 #{ 149} - { 149} #{ 149}

-

i_ __..= -

-

T e l

I L

LYR J

FIG . 2. H epat i c m etabol i sm of fat ty ac ids. TG , t r iacy lglycerols ; PL , phospholip ids ; CE , ester if ied ch ol esterol :

C PT , carni t i ne palm i ty l transf erase.

uation is greater than the calories absorbed

w hen ei ther fat i s ingested alone (12).

The m ode of transport of M CFA s resul ts

in reduced sterol absorption (13). T o be ab-

sorbed, sterols m ust be incorporated into mi -

cel les; and to be transported they m ust be

bound to L CFA s, and incorporated into chy-

lomicrons (14). T hese tw o processes do not

take place w i th M CFA s and consequentl y

the absorption of sterols i s dim inished.

T he absorption of calcium (15) and mag-

nesium appears to be enhanced w hen the diet

contains M CTs, parti cular l y in infants (16).

The absorption of amino acids also appears

to be improv ed (17, 18).

H epati c metabol ism

In the endoplasmic reti culum of the hepa-

tocy te, the L CFA s are acti v ely f i xed on the

f atty -acid-binding protein (9) and acti vated

into acy l -CoA s under the inf luence of a long-

chain-acy l -CoA synthetase (Fig 2). These

acy l -CoA s then preferential l y ester i f y a-glyc-

erophosphate to give triacy lgl y cerols and

phosphol ipids; and ester i f y cholesterol , to

give cholesterol esters. B ecause M CFA s do

# { 1 4 9 } { 1 4 9 } -

-

L O N G

CHA IN

:-

-

h CVtCo SYNT h IT ASE

#{ 149} ‘ o A S

- - . -

-s_’_

_

LC IA

D E NC I Y N T H ESI St’ -

. .y::;c

- ACETYL oA

{163}

I

not bind easi l y to the fatty -acid-binding pro-

tein (19), and the acy l -CoA synthetase spe-

ci f i c f or these fatty acids is located in the

m i tochondrial matr i x , M CFA s are alm ost

nev er acti vated in the ex trami tochondrial

space. Consequentl y , M CFA s are not signi f i -

cantl y incorporated into the l ipids synthe-

sized by the hepati c ti ssue (20).

M CFA s cross the double m i tochondrial

membrane very rapidly and, unl i k e the

L CFA s, they do not requi re the presence of

carni ti ne (Fig 2) (21). In the m i tochondrial

matr i x M CFA s are acy lated by m eans of

an octanoy l -CoA sy nthetase. I n contrast,

L CFA s or thei r acy l -CoA deri v ati v es cannot

cross the mi tochondrial w al l . I n the presence

of a carni ti ne palm i ty l transferase-I , L CFA s

are transf orm ed into acy l -carni ti nes that cross

the mem brane and regenerate long-chain-

acy l -CoA s in the matri x , by the action of a

carni ti ne palm i ty l transferase-I l .

T he mi tochondrial acy l -CoA s, of w hatever

chain length, then undergo f l -ox idation, w i th

production of acety l -CoA . In a heal thy , w el l -

nouri shed organism , relati v ely f ew L CFA s

reach this stage at the sam e time, since these


4/13

M ED I U M -C H A IN T RI GL Y C ER ID ES: U PD A T E

953

fatty acids tend to be incorporated into the

l ipids synthesized by the l i ver. T he carni ti ne

palm i ty l transferase complex is rather mac-

ti ve under these condi ti ons. The M CTs, how -

ever, are av ai lable and are rapidly ox idi zed.

T he resul t i s an excess of acety l -CoA (22),

w hich then f ol low s various metabol i c path-

w ays, both in the mi tochondria (K rebs cy cle,

ketogenesis, elongation of f atty acids) and in

the cy tosol (de nov o synthesis of f atty acids

and cholesterol ) . D uring this accelerated /9-

ox idation of M CFA s, many hydrogen atoms

are released, and thus the cel l medium is

noti ceably reduced (22). Recentl y , i t has been

demonstrated that f atty acids can also un-

dergo f l -ox idation in the perox isomes. B ut

the am ount of perox isomal ox idation of

M CFA s is negl igible, because the key enzy me

in this metabol i c pathw ay , acy l -CoA ox idase,

i s not v ery acti ve w i th acy l -CoA s that have

few er than 12 carbon atoms (23).

A f raction of the acety l -CoA suppl ied en-

ters into the K rebs cy cle and is ox idi zed into

CO2. T he l i v er produces about 10 times more

CO2 f rom C8:0 than f rom Cl6:0 (24); but the

capaci ty of the K rebs cy cle is l im i ted (25).

Furthermore, because of both the ex cess of

acety l -CoA produced f rom M CTs and the

reduction in the cel l medium, ox aloacetate

w i l l be in short supply (26) (Fig 2). A large

part of the acety l -CoA is then redi rected to-

w ard the sy nthesis of ketone bodies.

M CT s are ketogenic (27, 28), much m ore

so than L CTs. W ieland and M atschinsky (29)

and M cGarry and Foster (25, 30) f ound that

the classic anti ketogenic substances-f ruc-

tose, glucose plus insul in, gl y cerol , and lac-

tate-had l i ttl e ef f ect on the k etogenesis in-

duced in the rat by octanoic acid. Freund and

W einsier (3 1 , how ever, found that sucrose

greatl y decreased the amount of acetone in

the ai r exhaled by subjects w ho had ingested

M CTs. T he simul taneous administration of

M CTs and ox aloaceti c acid donors noti ceably

reduces the production of ketone bodies f rom

M CT s in the rat (26).

The mi tochondria hav e a sy stem that don-

gates fatty acids that have 12 or more carbon

atoms. A smal l f raction of the acety l -CoA

produced during the ox idation of M CFA s

serves to lengthen endogenous fatty acids.

T he relati ve importance of thi s metabol i c

pathw ay increases w hen L CT s are replaced

by M CT s in the diet (32).

B y compl i cated transfer m echanisms in-

volv ing ci trate and acety l carni ti ne, acety l -

CoA is transported to the cytosol and can be

used in the production of f atty acids and

cholesterol . A carbohy drate-r i ch diet in-

creases the de nov o sy nthesis of fatty acids

and cholesterol by the l i ver. T he sy nthesis

decreases w hen some of the carbohydrate is

replaced by f ats. The decrease is even smal ler

w hen M CT s, rather than L CTs, are prov ided

in the diet (33-35). T he sl ight cholesterol -

l ow ering ef f ect of M CT s identi f i ed by many

investigators can be accounted for by a de-

crease in the intestinal absorption of choles-

terol and a slow ing of i ts synthesis f rom ace-

ty l -CoA in the l i ver (34, 36). L ess cholesterol

i s synthesized because the acety l -CoA is used

in the de novo synthesis of fatty acids (37);

and because the acti v i ty of f i -hy droxy -f i -

m ethy lglutary l -CoA reductase, the key en-

zy me in cholesterol synthesis, i s reduced (34).

A f ter a single oral dose of M CT s a sl ight

hy poglycemia dev elops (27, 38). I t i s caused,

apparentl y , by a decrease in the hepati c out-

put of glucose and not by an increase in the

peripheral uti l i zation ofglucose. I nterestingly

enough, the concentration of insul in in the

blood increases at the same tim e, because the

islets of L angerhans are stimulated ei ther by

the ketone bodies or by the M CFA s them-

selves or by both. B ut, i n general , i t appears

that M CT s improve carbohydrate tolerance

(39, 40).

Extr a hepa tic meta bo lism

Given the m agni tude of the hepati c uptake

of M CFA s, the role of the ex trahepati c ti ssues

in the metabol i sm of M CTs is smal l , except

f or the uti l i zation of ketone bodies. T he

M CFA s, how ev er, play an important role in

the hum an f etus. Pi l z (41) reported that 15 to

20% of the f atty acids in cord blood have

eight or f ew er carbon atoms.

A s in the l i ver, the extrahepati c ti ssues do

not incorporate much M CFA s in the l ipids

they sy nthesize (24). I n addi ti on, L CFA s di -

m inish the capaci ty of f at cel l s to ester i f y

C8:0 (42). A s in the l i ver, i t appears that

M CFA s do not need carni ti ne to cross the

mi tochondrial m em brane of extrahepati c ti s-

sues. This, how ever, has been questioned by

Groot and H #{ 252} l smann (43). M CFA s are ox i-

di zed into CO2 in the ex trahepati c ti ssues

more rapidly than are L CFA s (24). A lso, as


5/13

954

B A C H A N D B A B A Y A N

i n the l i v er, M CFA s inhibi t, only sl i ghtl y , the

de novo synthesis of fatty acids in adipose

ti ssue (35).

Cl ini cal use

F a t m ala bs or ptio n

For 30 yr the special properties of M CT s

have been appl ied in human therapy, parti c-

ularl y in cases w here the digestion, absorp-

ti on, or transport of usual dietary fats are

disturbed. I n such cases steatorrhea is present

and is of ten f ol l ow ed by a progressive 5cc-

ondary m alnutr i tion caused by the loss of

ni trogen, w ater, and electrol y tes in the feces.

I n general , the steatorrhea subsides w hen di -

etary L CT s are replaced by M CTs, and the

number and w eight of the stools are reduced.

T he low concentration of l i pids in the serum

rem ains unchanged, but the dyspepsia and

the nutri ti onal state improv es. Patients gain

w eight and chi ldren start to grow again. T hus

M CTs hav e been used successful l y in adul ts,

chi ldren, and new borns w i th the f ol low ing

disorders:

1

I n disorders of l i pid digestion, as w i th

major or total resection of the esophagus or

of the stomach; bi l i ary atresia, obstructi ve

jaundice, prim ary bi l i ary ci rrhosis (44), and

bl ind-loop syndrome; and pancreati ti s (45),

cy sti c f i brosis (46-48), and pancreatectomy .

2 In disorders of l i pid absorption, as w hen

there is massiv e resection of the smal l i ntes-

ti ne (49, 50), ceiac disease, W hipple’ s disease,

Crohn’ s disease, enter i ti s, gluten enteropathy ,

tropical or idiopathic sprues, and malabsorp-

ti on in neonates (18, 51).

3 I n disorders of l i pid transport, as in

def i ciency of chy lom icron synthesis (eg, con-

geni tal /9- l i poprotein def iciency); and in ly m-

phati c disorder due to engorgement (eg, in-

testinal l ymphangiectasia) or leakage [ eg,

chy luria (52, 53), chy lous asci tes, and chy lo-

thorax (54, 55 ] . I n the case of an abnorm al

exchange betw een the lymphati c system and

another system or a cav i ty , M CT s decreases

l ipid and protein losses. Since M CT s, unl i ke

L CT s, do not stimulate the f low of l y mph,

they f av or the heal ing of f i stulas.

In cases of m aldigestion and/or m alab-

sorption w here L CTs are not w el l tolerated,

M CT -containing diets have a great adv antage

over low -fat diets. The advantage is that

M CTs are a fat and thus can be used in

cook ing. I n addi ti on, M CT s are a concen-

trated source of calories (8.3 kcal /g compared

to 3 to 4 kcal /g for carbohydrates and pro-

teins), and a good source of acety l groups

w hich are usef ul in l i pid sy nthesis.

The ingestion of labeled fats f ol l ow ed by

the detection of the tracer in the ex pi red CO2

is a method of ten used to m easure the am ount

of fat absorbed. Since M CTs are ox idized

much more rapidly than L CTs, labeled trioc-

tanoy lgly cerol has been pref erred to triolein

by Schw abe et a (56) (‘ 4C tracer) and by

W atk ins et a (57) ( ‘ 3C tracer) to detect m a -

absorption of f ats.

G a llb la dde r d isea se

The m edium-chain monodiglycerides of

capry l i c and capri c acid can be solubi l i zed in

aqueous solutions, oi l s, and other organic

com pounds. T he medium -chain monodigly -

cerides have been inv estigated in in v i tro

5 8

and in v iv o studies for thei r use in dissolution

of gal l stones. A product containing these me-

dium-chain monodiglycerides is under an in-

vestigational new drug status in the U SA

(Capmul 8210, Stokely-V an Camp, Inc, I n-

dianapol i s, I N ; U S patent 4,205,086, M ay 27,

1980). I t has been used successf ul l y in the

treatm ent of cholesterol -related cholei thiasis

(59, 60) by perf using i t i nto the comm on bi le

duct. Recentl y , f urther adv ances have been

reported in both percutaneous and endo-

scopic entry techniques conf i rm ing the saf ety ,

ef f i cacy , and rapid dissolution of gal l stones

w i th this product (61, 62).

App lica tion of th e en er g y-p r ovid ing a nd

ke togen ic p r o pe r tie s o f MC Ts

W hen M CT s are suppl ied in the diet, they

are rapidly ox idi zed, rendering m any k etone

bodies and supply ing a quick source of en-

ergy. The energy is del i vered to the w hole

body, both the l i v er (during the ox idation of

f atty acids), and the ex trahepati c ti ssues

(mainly during the uti l i zation of ketone bod-

ies). A modest elev ation of the concentration

of k etone bodies in the blood is k now n not to

be dangerous: al l the extrahepati c ti ssues can

use the k etone bodies suppl ied by the blood.

W hen the blood lev el of f i -hy droxy buty rate

and acetoacetate increases, the uti l i zation of

ketone bodies is enhanced (63). These ti ssues


6/13

M ED IU M -CH A IN T R IG L Y CERI D ES: U PD A T E 955

are enzym ati cal l y equipped to produce ace-

ty l -CoA f rom k etone bodies. The acti v ated

acetate is then used according to local needs,

ei ther as a source of energy, or as a basic

ingredient in the de nov o synthesis of l i pids.

Sour ces o f en er g y

T he M CT s are, therefore, a f ood of choice

f or any organism that has increased energy

needs, as af ter m ajor surgery (64), or during

normal or retarded grow th (16, 18, 65). I t i s

general l y bel ieved that M CT s should be in-

cluded in the nutr i ti onal management of the

sev ere undernouri shed patient.

A nother m ajor consumer of k etone bodies

is the f etus. Rubal tel l i et al (66) have sug-

gested that the perf usion of L CTs into cx-

pectant mothers could help the treatment of

the f etus w i th slow intrauter ine grow th. From

w hat i s k now n about M CT s, i t al l ow s us to

think that in thi s instance, i t w ould be pref -

erable to use M CT s rather than L CT s.

Lip id p r ec ur so rs

The acety l -CoA produced in the peripheral

ti ssues f rom M CT s can also enter into ana-

bol i c pathw ays. I n the brain, large synthesis

of l i pids-mainly phosphol ipids-f rom k e-

tone bodies hav e been demonstrated (67).

T his synthesis appears to be very ef fecti v e

during the period of mycl ini zation of the

brain. The use of M CT s as a source of energy

and l ipid precursors in com pl i cated pregnan-

cies should be f urther explored.

A n tico nvu lsive p r op er ties

K etone bodies also hav e a narcoti c and

anti convulsi ve property that has not yet been

explained (68). This property has long been

used in the treatm ent of epi lepsy. A l though

many drugs are now av ai lable, a ketogenic

diet (69) remains a valuable al ternati v e in

anti convulsi ve therapy in at least tw o cases:

w hen there is resistance to the usual drugs

(eg, epi lepti c myoclonia of chi ldhood) and in

intolerance to the medication, or both.

I n addi ti on to prov iding an insuf f i cient

amount of carbohydrates, a ketogenic diet

has the disadvantages of being unpalatable

and di f f i cul t to prepare and administer. T hese

disadvantages are partial l y ov ercom e w i th the

M CT-based ketogenic diet introduced by

H uttenlocher et al (70) and used w i th com -

plete success by some authors (7 1-73). T he

diet prov ides 70% of the calor ies f rom M CTs,

as compared to 87% calories f rom fat in the

L CT-based ketogenic diet. H ow ever, som e

setbacks in the treatm ent of epi lepsy w i th

M CTs hav e recentl y been reported (74-77).

Hypera l imen t a t i o n

M CT s arc a pref erable food for any orga-

nism that has increased energy needs, such as

undernouri shed patients af ter major surgery

(64) or chi ldren during norm al or retarded

grow th (16, 18, 65).

The metabol i sm of M CFA s by the ex tra-

hepati c ti ssues is increased considerably w hen

M CTs are suppl ied intrav enously . M CTs are,

consequentl y , suppl ied in abundance to the

v arious ti ssues w here they are hydrolyzed. I n

these ti ssues, part of the released f atty acids

are incorporated into l i pids (42), but m ost of

them are ox idized. The resul ti ng acety l -CoA

generates energy in si tu and contr ibutes to

l i pid synthesis. T he calori c dem ands of the

stressed patient are di f f i cul t to m eet w i thout

incorporating fat into the parenteral regim en.

L ipid emulsions containing L CFA s, w hich

f or the most part are stored in the hepati c

and adipose ti ssues, are not capable of sup-

ply ing quick energy in large quanti ti es.

T heref ore, replacem ent of L CT s w i th M CT s

could be valuable. Sai ler and B erg (64)

show ed that emulsions of L CTs containing

25 or 50% M CT s w ere very usef ul in patients

requi r ing intensiv e nutri ti onal therapy. T he

M CTs w ere rapidly removed f rom the ci rcu-

lation, the increase in ketonem ia w as w i thin

acceptable levels, and the tolerance to these

f ats w as excel lent, even in protracted therapy.

I n chronical l y i l l patients in cr i ti cal condi ti on,

M CT s not only cov er the energy needs, but

also contribute a sparing action f or the low -

ered muscular carni ti ne lev els (78) and cor-

rect the depression in k etonemia (79) related

to septi cemia or trauma.

I n recent y ears w i th the introduction of

structured l ipids based on the M CTs as the

m ain backbone of the l ipid, w e are seeing

m odif i cations of M CT s w hich improve thei r

uti l i ty and nutr i ti onal sui tabi l i ty in hyperal i -

m entation. A l though physical m ix tures of

M CT s and L CT s hav e been tr ied in paren-

teral nutr i ti on (64, 80, 81), such m ixes dem -

onstrate the dual pattern of clearance and


7/13


genic. 4) T he l i fe span is longer w hen the

diet i s r i cher in M CT s than in L CT s (92).

956

energy uti l i zation of M CTs and L CTs. W i th

the adv ent of structured l ipids of M CT s and

L CT s at random distribution in the same

tr igl yceride m olecule, there is now the poten-

tial f or tai l or-mak ing of l i pids to meet the

physical and nutri ti onal needs of patients

receiv ing parenteral or enteral nutri ti on. B a-

bay an (82) has projected the types of struc-

tured l ipids that are avai lable for cl i ni cal

inv estigations. Such structured l ipids promise

real progress in the hyperal imentation f ield

w here l ipids and high-densi ty calor ie requi re-

ments are sought by the physician.

Hyperh p id em ias

B ecause M CFA s are incorporated into l i p-

ids only in sm al l amounts, many studies hav e

been perf ormed to f ind out w hether M CT s

can be useful in the treatm ent of hyperl i pi -

demias.

A l though som e authors (32, 34, 36, 83, 84)

hav e reported thei r observ ations on the de-

crease in blood and l i ver cholesterol lev els

w i th an M CT diet, w e do not have a clear

picture of the role M CT can play in the

treatm ent of hypercholesterolemia. T his area

deserves f urther study.

In v iew of present k now ledge of the causes

ofhyperl i pidemias, i t i s clear that M CT s hav e

no role in thei r treatment, except in ty pe I

( l i poprotein l i pase def i ciency, mast-cel l def i -

ciency) and in type V (dim inished acti v i ty of

l i poprotein l i pase) hyperl i poproteinem ias.

Since in these cases the clearing enzyme, or

i ts coenzyme are absent or insuf f i cient, the

replacement ofdietary L CTs w i th M CT s (85)

has been very usef ul in the treatment of these

disorders. I n studies done in rats, M CTs,

unl i ke L CTs, slow ed dow n the appearance of

alcohol i c steatosis (86) and speeded up the

regression of establ i shed atheroscleroti c le-

sions, w hen alcohol w as w i thdraw n f rom the

diet (87).

M almros et a (88) f ound that an M CT -

based diet fed to rabbi ts induced atheroma-

tous changes in the aorta and coronary arter-

ies. T he diet, how ever, w as probably def i cient

in polyunsaturated fatty acids. In contrast,

the fol l ow ing observ ations have been made

in the rat. 1 The aorta almost completely

ox idi zes M CFA s into Co2 (89). 2 M C T s

l im i t the deposi ti on of cholesterol in al l ti ssues

(84, 90).

3

M CFA s are not thrombogenic,

w hi le saturated L CFA s are (91) thrombo-

D efic iency of the ca r n itin e system

I n skeletal m uscle, the transport of L CFA s

f rom the sarcoplasm into the mi tochondria i s

dependent on the carni ti ne sy stem. T heref ore,

a def i ciency of carni ti ne or carni ti ne palm i ty l

transf erase (I or I I , or both) resul ts in a

dim inished capaci ty to ox idize L CFA s (93).

The low ering of thi s energy catabol i sm,

w hich is essential for the w ork ing muscle, i s

mani f ested by various sy mptoms: m uscular

w eakness, pain af ter exertion, my oglobinuria,

l i pid-f i l l ed v acuoles w i thin m uscle f ibers, and

episodes of metabol i c encephalopathy . A s the

f atty acids continue to reach the muscle, they

are incorporated into triacy lgly cerols, w hich

accumulate. I n the myopathic form of carni -

ti ne def i ciency, the pathology is l im i ted to the

skeletal m uscles, but in the systemic f orm the

heart, l i ver, and k idneys are af fected.

In v iew of the parti cular intrami tochon-

drial transf er of the M CFA s, patients suf fer-

ing f rom a def i ciency of muscular carni ti ne

hav e been treated rather successful l y w i th an

M CT-based diet (93-97). I n some instances,

carni ti ne w as added. H ow ever, the disorders

observ ed in patients w i th carni ti ne palm i ty l

transferase def i ciency did not alw ays regress

w hen treated w i th a diet prov iding M CTs

(98, 99). The more or less m arked success of

treatment w ith M CTs is probably due to the

fact that only a sm al l amount of M CFA s

reach the muscle. U ndoubtedly , more studies

in this area are necessary . Studies on the

ef f ect of intravenous M CT inf usion w ould be

of special i nterest in thi s regard.

Obesi ty

A nim al studies on the ef f ect of the incor-

poration M CFA s into the adipose ti ssue have

show n that M CT s can produce a sl ight re-

duction (not alw ay s stati sti cal l y signi f i cant)

in body w eight, and in the w eight of the

adipose ti ssues (33, 35, 100- 105, Gel iebter A ,

Torbay N , B racco EF, V an I tal l i e T B ,

H ashim SA , unpubl i shed data). The f ood

ef f i ciency ratio i s dim inished in rats fed

M CTs (104, 107): the anim als need to con-

sume 20.3 k cal /g of w eight gain w hen fed

M CTs as compared to 16.6 k cal /g of w eight

gain w i th L CTs. T he reason f or the low ered

f ood ef f i ciency ratio seems to be an enhanced


8/13

M ED IU M -C H A IN T R IG L Y CERID ES: U PD A T E

957

thermogenesis induced by M CT s (105).

K auni tz et al (108) f ound that the w eight of

normal and obese subjects dim inished w hen

L CT s w ere replaced w i th M CTs in thei r diet.

T he value of M CT s in obesi ty i s not as yet

w el l understood. T he resul ts of Rath et a

(83) fai l ed to prov ide any ev idence in favor

of M CT s. In thei r study, obese w om en given

a 550 kcal diet containing 30 g of M CTs lost

as m uch w eight as w hen M CT s w ere replaced

by sugars. K auni tz et al (109) f ound that

obese subjects consum ing a 1200 k cal diet

lost the same am ount of w eight w hether the

dietary fat w as ol i ve oi l or M CT s. In the

geneti cal l y obese Zuck er rat (1 10) and the

B H E rat (1 1 1), an M CT diet did not reduce

body w eight.

N evertheless, several reports indicate that

M CTs may be a useful tool in the control of

obesi ty . L av au and H ashim 3 5 , Schemmel

(104), T rav is et a 105 , T urkenk opf et a

(1 12), Gel iebter et al (106), B aba et a (1 13),

B ray et a 1 14), and B ach et a 1 1 5) indicate

a reduction of carcass mass w i th the use of

M CT s. I n v iew of these conf l i cti ng resul ts in

the l i terature, addi ti onal studies are needed

to understand the role of M CT s in the treat-

ment of obesi ty . One explanation f or these

resul ts could be that the nonincorporation of

M CFA s into the adipose tissue is more or less

compensated for by the w eak inhibi ti on of de

novo synthesis of fatty acids by the l i ver and

adipose ti ssue

3 5 .

T he monoesters and diesters of polyglycer-

ols containing M CFA s can be considered as

replacem ents for natural fats. T hese polygly -

cerol esters appear to have the abi l i ty to

im part a f eel ing of satiety w hi le el im inating

and/or reducing the l ipid level in a food

product, w hi le sti l l maintaining the desi red

appearance and physical form . Thei r energy

v alue is only 6 to 8.5 kcal /g. The use of these

esters in foods w i l l be a convenient w ay to

reduce calor ies, parti cularl y fat calor ies (116).

Contraindications

Keto sis a n d a cid osis

M CT s are ketogenic in the norm al subject

and even m ore in the patient w i th hyperos-

m olar diabeti c sy ndrom e (117). H ence, M CTs

should not be given to patients w i th diabetes.

T hey should also not be given to patients

w i th ketosis or acidosis. I n these condi ti ons,

the capaci ty of the extrahepati c ti ssues to use

ketone bodies is saturated. T heref ore, the

addi ti onal supply of such substrates is not

only w asted as an energy source, but i t al so

aggravates the metabol i c acidosis and accel -

crates the breakdow n of the homeostati c

mechanisms. T he solution to this problem

m ay be using M CTs w i th odd carbon chain

fatty acids instead of the even carbon chain

fatty acids. Indeed Guy and T uley (118)

show ed that tr i pelargonin is less ketogenic

than usual M CT s in rats.

C i r rh o s i s

Since M CFA s are metabol i zed mostl y in

the l i v er, the intestinal perf usion of octanoate

in heal thy subjects resul ts in the appearance

of only sm al l amounts of thi s fatty acid in the

ci rculating blood (1 19). H ow ev er, w hen the

functional cel l m ass of the l i ver i s reduced, as

in ci rrhosis, the C8:0 concentration in the

blood increases due to the reduced hepati c

clearance. In the case of a portacaval shunt,

for example, C8:0 reaches very high amounts

(1 19). I t i s general l y bel ieved that fatty acids

are somew hat tox ic w hen giv en in large

amounts. Intravenous infusion of C8:0, f or

example, resul ts in a syndrome resem bl ing

hepati c encephalopathy : hyperventi l ati on,

hy peramm oniemia, hyperlactacidemia, and

di st ur bed el ect roencephal og ram 1 20, 121).

I n heal thy subjects, the binding of f atty acids

to album in in the serum rel ieves this tox ici ty .

B ut, i n ci rrhosis, the album inemia drops. In

addi ti on, the af f i ni ty of M CFA s f or albumin

is w eak, because L CFA s and M CFA s com-

Pete for the albumin binding si tes (122). U n-

der these ci rcum stances, f ree fatty acids, not

bound to protein, di f fuse passiv ely across the

capi l l ary membranes. Thus, f ree octanoic

acid has been f ound, not only in the blood,

but also in the asci ti c f l uid, and the cerebro-

spinal f l uid of persons w i th ci rrhosis w ho

w ere giv en this fatty acid by intestinal per-

f usion (123). I t appears that, i n ci rrhosis, there

is the danger that the energy metabol i sm of

the brain may be al tered.

A vai labi l i ty and suggestions f or use

I ni ti al l y , M CTs w ere avai lable only in the

form of oi l or m argarine. M CT s are now

avai lable in l i quid or sol id preparations and

in simple or com plex com binations w i th pro-


9/13

958


teins, sugars, v i tam ins, essential f atty acids,

and m inerals. These various f orms m ak e i t

possible to prov ide the inf ant or the adul t

w i th the amounts of M CT s needed f or par-

enteral , oral , or tube f eeding (124).

I t i s indispensable to determ ine f or each

patient the threshold dose that must not be

exceeded i f problem s are to be prevented

f rom arising, eg, osmoti c diarrhea in i l ei ti s

and in ex tensive resection of the sm al l i ntes-

ti ne, or in dumping syndrome in patients w i th

gastrectomy.

In enteral feeding, M CT s should f i rst be

introduced in smal l am ounts and gradual l y

increased to the prescribed dose. I n general ,

M CTs are w el l tolerated w hen the dai l y dose

is div ided proportional l y into meals of a w el l -

balanced diet. M CT s diets seem to be better

tolerated by chi ldren than by adul ts (90). A

nutr i ti onal l y balanced diet i s the best w ay of

av oiding k etosis. A dai l y supply of 50 or even

100 g is easi l y tolerated. Obv iously , w hen

M CT s are given for thei r ketogenic properties

the procedure w i l l be di f f erent (68,

75 .

M CTs are not a panacea. Only rarely do

M CT s alone prov ide the best therapeuti c so-

lution. V ery of ten, i t i s adv isable to com bine

M CT s w i th the standard therapy of the par-

ti cular i l l ness: a reduction in the supply of

L CT s, or the prov ision of bi le sal ts ( in bi l i ary

def i ciency), enzym e therapy (in pancreati c

def i ciency), a gluten-f ree diet ( in cel iac dis-

ease), antibioti cs (in tropical sprue), or car-

ni ti ne (in carni ti ne def i ciency).

I t must be remembered that w hen the

digestion or absorption of L CT s is perturbed,

a smal ler am ount of M CT s is absorbed than

in the heal thy organism; but in any case more

M CT s are absorbed than L CT s. A s discussed

prev iously , the ingestion of large am ounts of

M CT s decreases the absorption of L CTs, and

increases the losses of L CFA s in the f eces.

N evertheless, extrapolating the resul ts ob-

tained in rats to patients w i th reduced l ipid

absorption, Clark and H ol t (12) suggested

that the amount of L CT s normal l y tolerated

could be doubled, by means of an M CT

supplement, w i thout inducing steatorrhea.

W hen M CTs are infused parenteral l y , the

dose should be caref ul l y calculated and the

patient closely moni tored. I f the dose is in

excess, there is danger of acidosis due to

hy perk etonemia and hyperlacticacidemia

(125).

I n total parenteral nutr i ti on, the essential

f atty acids should be included in the regimen.

W hi le K auni tz et a (126) show ed in the rat

that M CT s low ered the need for l i nolei c acid

m ore than L CTs, H i rono et a (127) reported

that the need f or thi s fatty acid w as increased

in new born babies given an M CT-based mi l k .

W i l l iam s and Oski (128) f ound no change in

the v i tamin E status of new born babies fed

M CT-based mi l k . I t i s, theref ore, important

that w hen M CT s are given intrav enously or

enteral l y as the sole source of fat, that the

needs for essential fatty acids are met. T here

are now av ai lable tai l or-made M CTs w i th

v ary ing amounts of l i nolei c acid (Captex 810,

Stokely-V an Cam p, I nc) T hese products are

f aci l i tati ng the design of regimens that meet

the essential f atty acid requi rements of pa-

tients.

W hen M CTs are used for cook ing or

f ry ing, they should not be heated to temper-

atures abov e 150 to 160#{ 176} C.A bov e this tem-

perature, i t w i l l resul t i n ox idation and ther-

m a breakdow n w hich w i l l af fect the palata-

bi l i ty and acceptabi l i ty of the product.

Conclusions

The parti cular phy sicochemical properties

of M CFA s make M CTs a valuable tool in the

dieteti c m anagem ent of a number of disorders

of l i pid metabol i sm. M ost fat maldigestion

and malabsorption condi ti ons, and some dis-

orders of the lym phati c f at transport and of

the f at rem oval f rom the blood, can be com-

pletely or partial l y corrected by replacing

dietary L CTs w i th M CT s. The crucial needs

for energy or for acety l -CoA as precursors of

l i pids, can be m et by a supply of M CT s,

w hether the need is transient or long lasting.

A l though M CTs are f ats, they tend som e-

times, to behave l i ke carbohy drates. A l -

though M CT s are ox idized rapidly and have

low tendency to be stored in the adipose

ti ssue, M CT s are not hyperl i pidem ic, but they

are ketogenic. A l though M CTs are not hy-

perglycemic, they sl ightl y stimulate insul in

production, but do not low er l i pogenesis sig-

ni f i cantl y . M CTs are not drugs-they hav e

no pharmacological ef f ect.

In summary, the benef i cial ef fects of M CTs

are: 1 M CTs are digested, absorbed, and

transported easi l y and rapidly in disorders

w here the digestion, absorption, or transport


10/13

M ED IU M -C H A IN T RIG L Y CER ID ES: U PD A T E

959

of L CT s are not optim al . 2 M CTs are ox i -

di zed rapidly in the organism and they have

a very low tendency to deposi t as body fat. 3

M CT s are a source of abundant and rapidly

av ai lable energy . 4) M CT s are ketogenic.

5

M CT s are donors of hydrogen ions and pre-

cursors of acety l -CoA .

M CT s do not behav e as conventional fats.

T hus, M CT s must be treated separately and

di f f erentl y f rom our understanding of fats

and oi l s. T he unique physical , chemical , and

structural character i sti cs of M CTs and thei r

modi f i cations (structured l ipids) makes such

special l i pids tools for solv ing certain medical

problems. a

T he authors ack now ledge the assi stance and contri -

bution of M argari ta N agy f or edi ting the manuscri pt.

References

1. Senior IR, ed. M edium chai n tri gl y cer ides. Phi la-

del phi a, PA : U niv ersi ty of Pennsy lv ani a Press,

1968.

2. K al ser M H . M edium chain trigl y cerides. A dv I n-

tern M ed 197 1;17:301-32.

3. Sick inger K . C l in i cal aspects and therapy of f at

m al assim i lati on w i th par ti cular reference to the use

of m edi um -chain trig l y cerides. I n: V ergroesen A l ,

ed. T he role of f ats in hum an nutri ti on. L ondon:

A cadem ic Press, 1975: 1 1 5-209.

4. B ach A , M #{ 233} tais P. Graisses

a

chal nes cour tes et

m oy ennes. A spects phy siol ogi ques, biochim iques,

nutri ti onnels et therapeutiques. A nn N utr A him ent

1970;24:74-144.

5. B abay an V K . M edium -chai n trig l y cerides- thei r

com posi ti on, preparation, and appl i cati on. I A m

O i l Chem Soc l 968;45:23-5.

6. M ott CB , Sar les H , T iscorni a 0. A ct ion di f f #{ 233} rente

d es t ri gl y cer id es a chalnes cour tes, m oy ennes ou

l ongues, sur l a s#{ 233} cr#{ 233} ti onancr#{ 233} ati que ex ocri ne de

l ’hom me. B iol Gastro-ent#{ 233} rol 1972;5:79-84.

7. I ber F. Relat i v e rates of metabol i sm M CT , L C T

and ethanol in m an. I n: K auni tz H , L ang K , Fek l

W , eds. M i ttelk ettige T r igly ceride i n der D int. Z

Ern#{ 228} hrungsw iss 1974; 17(suppl ) :9- 16.

8. V aldiv i eso V . A bsorpt ion of m edium -chai n trig l y c -

erides in ani mals w i th pancreati c atrophy . A m I

D ig D is 1972;17:129-36.

9. M ishk in S. Stein L , Gatmai tan Z , A r ias IM . T he

binding of f at ty ac ids to cy toplasm ic protei ns: bind-

ing to Z protein i n l i v er and other ti ssues of the rat .

B i ochem B i ophy s Res Com m un l 972;47:997-1003.

10. Ock ner RK , M anning IA , Poppenhausen RB , H o

W K L . A binding protein for f at ty acids in cy tosol

of intesti nal mucosa, l i v er, m y ocardium and other

ti ssues. Sc ience 1972; 177:56-8.

11. Spec tor A A . Fatty acid bi nding to plasma al bum in.

I L ipid R es 1975;16:165-79.

12. Cl ark SB , H ol t P. I nhibi ti on of steady -state intes-

tinal absorpti on of l ong-chain trigl y ceride by m e-

di um -chain tri gl y cer ide in the unanestheti zed rat.

I C hi n I nv est 1969;48:2235-43.

13. T ak ahashi Y l , U nderw ood B A . Ef f ect of long and

m edium chain length l ip ids upon aqueous solubi l i ty

of a-tocopherol . L ipi ds l974;9:855-9.

14. Roels OA , H ashim SA . Inf luence of f atty ac ids on

serum cholesterol . Fed Proc 1962;21:71-6.

15. A gnew IE, H ol dsw or th CD . T he ef f ect of f at on

calc ium absorption f rom a m ix ed m eal i n norm al

subjec ts, patients w i th malabsorpti v e disease,

and pat ients w i th a parti al gastrectomy . G ut

1 97 1 ; 1 2: 97 3- 7.

16. T antibhedhy angk ul P, H ashim SA . M edium-chain

trigl y ceride feeding in premature inf ants: ef f ects on

calc ium and m agnesium absorpt ion. Pedi atri cs

1 97 8; 6 1 :5 37 -4 5.

17. H ol tzapple P. B erman W , Segal S. Enhancem ent of

non-elec troly te transpor t i n jejunal m ucosa by fatty

ac ids. Gastroenterology 1972;62:849.

18. T antibhedhy angk ul P, H ashim SA . M edium-chain

tr igl y cer ide feeding in premature i nfants: ef f ec ts of

f at and ni trogen absorpt ion. Pediatri cs 1975;

55:359-69.

19. W u-R ideout M Y C, El son C , Shrago E. T he role of

f at ty acid binding protein on the metabol i sm of

fat ty ac ids in isolated rat hepatocy tes. B i ochem

B iophy s R es Comm un 1976;71:809-16.

20. M cGarry ID , Foster D W . Regul ation of hepati c

f at ty aci d ox idation and k etone body production.

A nn R ev B iochem l980;49:395-420.

2 1 . B remer I . Carni t i ne and i ts rol e in fat ty ac id m e-

tabohi sm . T rends B iochem Sci 1980;2:207-9.

22. B ach A , Phan T , M #{ 233} tai sP. E f f ect of the fatty acid

com posi t ion of ingested fats on rat l i v er i nterm e-

diary m etabol i sm . H orm M etab Res 1976;8:375-9.

23. Osum i T , H ashi moto T . A cy l -C oA ox idase of rat

l i v er: a new enzy me f or f atty ac id ox idation. B io-

chem B iophy s Res C om m un 1978;83:479-85.

24 Scheig R . H epat i c metabol i sm of medium chain

fatty acids. I n: Senior IR, ed. M edium chain tri -

gly ceri des. Phi ladelphia, PA : U ni v ersi ty of Penn-

sy lv ania Press, 1968:39-49.

25. M cGarry ID , Foster D W . T he regulation of k eto-

genesis f rom ol eic acid and the inf luence of anti -

k etogenic agents. I B iol Chem 197 l ;246:6247-53.

26. B ach A . O x ahoacetate def i c iency in M CT -i nduced

k etogenesis. A rch Int Phy siol B i ochim 1978;

86:1133-42.

27. Y eh Y Y , Z ee P. Rel ation of k etosis to metabol i c

changes i nduced by acute medium-chain trig l y cer-

ide f eeding in rats. I N utr 1976; 106:58-67.

28

B ach A , Schi rardi n H , B auer M , W ery ha A . K eto-

genie response to m edi um -chain trigl y ceride load

in the rat. I N utr 1977;107:1863-70.

29. W ieland 0, M atschinsk y F. Z ur N atur der ant i k e-

togenen W i rk ung v on Gly cer in und Fruk tose. L i f e

S ci 1 96 2; 2: 49 -5 4.

30. M cG arry ID , Foster D W . T he regulation of k eto-

genesis f rom octanoi c ac id. T he role of the tri car-

box y l i c ac id cy cl e and f atty acid sy nthesis. I B i ol

C hem 1 71 24 6: 11 49 -5 9.

31. Freund G , W ei nsier R L . Standardized k etosis in

m an f ol l ow ing m edi um chain tri gl y ceri de ingestion.

M etabol i sm 1966; 15:980-91.

32 L ev ei l l e G A , Pardini RS, T i l l otson IA . I nf luence

of m edium chai n tr igl y cerides on l i pid metabol i sm

i n rat . L ipi ds 1967;2:287-94.


11/13

960

33. A l i ce G L , Romsos D R. L ev ei hle GA , B ak er D H .

M etabol i c consequences of di etary medium chain

tri gl y cer ides in the pig. Proc Soc Ex p B iol M ed

1 97 2; 1 39 :4 22 -7 .

34. T ak ase 5, M or im oto A , N ak ani shi M , M uto Y .

L ong-term ef fect of m edi um -chain tr igl y ceride in

hepat i c enzy m es cataly zing hipogenesi s and choles-

terogenesis i n rats. I N utr Sc i V i tam inol 1977;

23:43-51.

35. L av au M M , H ashim SA . Ef f ect of medium chain

tri gl y cer ide on hipogenesi s and body fat in the rat.

I N utr 1 978 ;10 8:6 13 -20 .

36. K r i tchev sk y D , T epper SA . Inf luence of medium -

chain trig l y cerides on cholesterol m etabol i sm in

rats. I N utr 1965;86:67-72.

37. K r i tchev sk y D , R abinow i tz I L . lnf luence of di etary

fat on fatty acid bi osy nthesi s in rat. B iochim B io-

phy s A cta 1966;1 16:185-8.

38. B ach A , W ery ha A , Schi rardin H . Inf l uence of an

oral M C T or L C T load on gly cemia in W istar and

Z uck er rats and in guinea pigs. A nn B iol A nim

B iochim B iophy s l979;l9:625-35.

39.

T anti bhedhy angk ul P. H ashim SA , V an I tal l i e T B .

Ef f ec ts of ingesti on of long-chain and medium -

chai n tr igl y cerides on gl ucose tol erance in m an.

D iabetes 1967; 16:769-9.

40. L ederer I , L am bert A E, H enqui n IC , Pottier-A r-

nould A M, B ettendorf B . I nf luence des tri gl y cer ides

a chamnes m oy ennes sur la tolerance au glucose et

I a producti on d’ insuhi ne chez le rat . D iab#{ 233} te

1972;20:201-7.

4 1 . Pi lz W . U ntersuchungen #{ 252} berermente des men-

schl i chen B lutes. I X . D ie A ry lesterasen des m en-

schl i chen N abelschnurserums. Z Phy siol C hem

1964;338:238-50.

42. M aragoudak is M E, K al insk y H I , L ennane J. M e-

tabohism of oc tanoate and i ts ef f ect on gl ucose and

palm i tate uti l i zat ion by isolated fat cel l s. Proc Soc

Ex p B iol M ed 1975;148:606-l0.

43. G root PH E, H #{ 252} l sm ann W C . T he acti v ati on and

ox idation of oc tanoate and palm i tate by rat sk eletal

m usc le m i tochondria. B i ochim B iophy s A cta

1 97 3; 3 1 6: 12 4- 35 .

44. K ehay oglou K , H adz iy anni s 5, K ostam is P, M ala-

m os B . T he ef f ec t of medium-chai n tri gl y cer ide on

47 calci um absorpti on in patients w i th pr im ary

bi l i ary ci rrhosis. Gut 1973;14:653-6.

45. H arri son I E, M cH attie JD , L igon hR . Jeejeebhoy

K N , Finlay IM . Ef f ec t of medium chai n tr igl y cer -

i de on fecal cal cium losses in pancreat i c insuf f i -

c iency . C l in. B iochem 1973;6: 136-40.

46. G alaber t C , Fi l hiat M , C hazal ette IP, M endy F,

D elhay e N . A bsorpt ion intestinale des tr igl y cerides

a cham nes m oy ennes dans la f ibrose k y stique du

pancreas. A nn PCdiatr 1975;22:745-53.

47. Gracey M , B urk e U , A nderson C M . A ssessm ent of

m edium -chain trigl y ceride f eeding in inf ants w i th

cy sti c f ibrosis. A rch D i s C hi ld 1969;44:401-3.

48. D une PR,

N ew th CI , Forstner G G, Gal l D O.

M alabsorpt ion of m edium chain trig l y cerides i n

i nfants w i th cy st i c f i brosis. Correction w i th pan-

c reati c enzy m e suppl em ents. I Pediatr 1980;96:862-

4.

49. H of mann A F, Poley IR. R ole of bi l e ac id m alab-

sorption in pathogenesi s of diarrhea and steator-

B A CH A N D B A B A Y A N

rhea in patients w i th i leal resec tion. Gastroenter -

o lo gy l 97 2; 62 :9 18 -3 4.

50. T andon RK , Rodgers JB , B ahint I A . T he ef f ects of

m edium-chain tri gl y cer ides in the short bow el sy n-

drom e. I ncreased gl ucose and w ater transpor t. A m

I D ig D is 1972;17:233-8.

51. Roy C C , Ste-M arie M , C hartrand L , W eber A ,

B ard H , D oray B . C orrecti on of the m alabsorpt ion

of the preterm inf ant w i th a m edium -chai n tr igl y c-

er ide form ula. I Pediatr 1975;86:446-50.

52. V an D ev enne A , B rogard IM , Iahn H , V i v i l l e C .

Comm unication ly m pho-py #{ 233} hi que av ec chy l uri e.

I nf luence fav orabl e du trai tem ent di#{ 233} t#{ 233} ti que.nn

M ed I ntern l 970;121:367-74.

53. W arter I , M #{ 233} taisP, B erthi er G , B ach A . T rai tem ent

d’ une chy lurie par un r#{ 233} gim e

a

b ase d e t ri gl yc er id es

a chalnes m oy ennes. Pathol B iol 1972;20:865-9.

54. B renner W I , B oal B H , Reed G E. Chy hothorax as a

mani f estation of rheumatic m i tral stenosis. I ts post-

operati v e managem ent w i th a diet of m edium -chain

tri gl y cer ide. Chest l978;73:672-3.

55. Christophe A , M atthy s F, V erdonk G. C hy lous-

f lu id trig l y ceri des and hipoproteins i n a patient w i th

chy lothorax on a diet of but ter or m edium -chain

tri gl y cer ide. A rch Int Phy siol B iochi m 1980;

88:B 17-8.

56. Schw abe A D , Cozzeto Fl , B ennett L R , M el l i nk of f

SM . Estim at ion of f at absorption by moni toring of

ex pi red radioacti v e carbon diox ide af ter f eeding a

radioacti v e fat. G astroenterology 1962;42:285-91.

57. W atk i ns lB . Schoel ler D A , K lei n P, O tt D G , N ew -

comer A D , H ofm ann A F. ‘ 3C-T ri octanoin: a non-

radi oac ti v e breath test to detect f at mahabsorpti on.

I L ab Cl i n M ed 1977;90:422-30.

58. T hist le I L , C arl son G L , H ofm ann A F, B abay an

V K . M edium chain gly cerides rapidly dissolv e cho-

l esterol gal l stones in v i tro, abstrac ted. Gastroenter -

o l o gy 1 9 7 7 ; 72 : A 1 1 8 / 1 14 1

59. M ack EA , Sai to C, G oldfarb 5, et al . A new agent

f or gal l stone di ssoluti on: ex per im ental and cl i ni cal

ev aluation. Surg Forum 1978;29:438-9.

60. T histl e I L , Carlson G L , H ofm ann A F, et al . M ono-

octanoi n a dissol uti on agent f or retained chol esterol

bi le duct stones: phy sical properti es and cl in i cal

appl ication. Gastroenterology 1980;78:1016-22.

61. W i tzel L , W iederhol t I , W olbergs E. D issolut ion of

retai ned duc t stones by perf usi on w i th m onooctan-

oin v ia a tef lon catheter introduced endoscopi cal l y .

G astroi ntest Endosc 198 1;27:63-5.

62. M ack E, C rum m y A B , B abay an V K . Percutaneous

transhepati c dissolution of comm on bi le duct sto-

nes. Surgery 198 l ;90:584-8.

63. R obi nson A M , W i l l i amson D H . Phy siological roles

of k etone bodies as substrates and signals in m am -

m al i an ti ssues. Phy si ol R ev 1980;60: l43-87.

64. Sai ler D , B erg G. Stof f w echselw i rk ung handel s#{ 252} b-

l i cher und einer neuentw ick el ten M C T -hal tigen

Fettem ul sion. I ntensi v m ed 1978;15:96-8.

65. Graham G G, B aert l I M , C ordano A , M orales E .

L ac tose-f ree, m edi um -chain tri gl y ceri de form ul as

in sev ere m alnutri ti on. A m I D i s C hi ld

1 97 3; 1 26 :3 30 -5 .

66. Rubal tel l i FF, Enz i G, D ebi asi F, B ondi o M , R on-

di nel hi M . E f f ec t of l i pid l oading on fetal uptak e of

f ree fatty acids, gly cerol and $-hy drox y buty rate.


12/13

M ED IU M -C H A IN T R IG L Y CERI D ES: U PD A T E 961

B iol N eonate 1978;33:320-6.

67. Y eh Y Y , Streuhi U L , Z ee P. K etone bodies serv e as

impor tant precursors of brain l ip ids in the dev el -

oping rat . L ip ids 1977; 12:957-64.

68. W i throw C D . T he k etogenic diet : m echanism of

anti conv ul sant action. I n: G laser G H , Penry 1K ,

Woodbury

D M , eds. A nti epi lept i c drugs: mecha-

nisms ofaction. N ew Y ork : Rav en Press, 1980:635-

42.

69. W i lder RM . Ef f ec t of k etonur ia on course of epi -

hepsy . M ay o Chi n B ul l l 92I ;2:307- l0.

70. H uttenlocher PR , W i lbourn A l , Signore IM . M e-

dium chai n trigl y cerides as a therapy for intrac table

chi ldhood epi lepsy . N eurol ogy 197 I ;2 1:1097-103.

7 1 . Signore IM . K etogenic diet containing m edium -

chain tr igl y cerides. I A m D iet A ssoc 1973;62:285-

90.

72. H uttenhocher PR . K etonem ia and seizures: m eta-

bohic and ant i conv ulsant ef f ec ts of tw o k etogenic

diets in chi ldhood epi lepsy . Pediatr Res

1 97 6; 1 0: 53 6- 40 .

73. Gordon N . M edium-chain tr igl y cer ides in a k eto-

genie diet. D cv M ed C hi ld N eurol 1977;19:535-8.

74. L iv i ngston 5, Pauhi L L , Pruce I . K etogeni c diet in

the treatm ent of epi lepsy . D cv M ed Chi ld N eurol

l977;19:833-4.

75. Clark B J, H ouse FM . M edium chain trig l y ceride

oi l k etogenic diets in the treatm ent of chi ldhood

epi lepsy . I H um N utr 1978;32:1 11-6.

76. B erman W . M edium -chai n trigl y ceride diet in the

treatm ent of intrac table chi l dhood epi lepsy . D cv

M ed C hi ld N eurol 1978;20:249-50.

77. H ahn T I , H alstead L R, D ev iv o D C . D isordered

mineral m etabol i sm produced by k etogenic di et

therapy . Calci f T i ssue Int 1979;28:17-22.

78. B order JR . B urns G P, R um ph C , Schenk W G .

Carni ti ne l ev els in sev ere infecti on and starv ati on:

a possible k ey to the prolonged catabol i c state.

Surgery 1970;68: 175-9.

79. N eufel d H A , Pace IA , W hi te FE. T he ef f ect of

bac teri al inf ect ions on k etone concentrations i n rat

blood. M etabol ism 1976;25:877-84.

80. Sai ler D , M ul ler M . M edium chain tr igl y cerides in

parenteral nutri t i on. IPEN 198l ;5:1 15-9.

81. Eck art I , A dolph M . v an der M uhlen U , N aab V .

Fat em ul sions contai ning m edi um chain trig l y cer-

ides in parenteral nutri t i on of i ntensiv e care pa-

tients. IPEN 1980;4:360-6.

82. B abay an V K . M edium chain length fatty ac id esters

and thei r m edical and nutri ti onal appl i cations. I

A m O i l Chem Soc 1981;58:49A -51A .

83. R ath F, Sk #{ 225} la, N athov #{ 225} E . M etabol i c aspects of

the use of medium chai n trig l y cerides in the treat-

ment of obesi ty . Z Ern#{ 228} hrungsw iss 1972:

13(suppl ):l 16-24.

84. Stew art JW , W iggers K D , lacobson N L , B erger P1.

Ef f ect of v arious trig l y cerides on blood and ti ssue

chol esterol of calv es. I N utr 1978;108:561-6.

85. Furman RH , H ow ard RP, B rusco 01, A laupov i c P.

E f f ects of medium chain length tr igl y ceride (M C T )

on serum l i pids and l i poproteins in fam i l ial hy per-

chy l om icronem ia (dietary fat-induced l i pem ia) and

dietary carbohy drate-accentuated l ipem i a. I L ab

C li n M ed 1965;66:912-26.

86. L ieber C S, D ecarhi L M . Study of agents for the

prev ent ion of the fatty l i v er produced by prolonged

alcohol intak e. G astroenterohogy 1966:50:316-22.

87. T heuer R C, M art in W H , Friday T J, Z oum as B L ,

Sarett H P. Regressi on of alcohol i c f atty l i v er in the

rat by medium-chai n tr igl y cerides. A m I C l in N utr

1972:25:175-81.

88. M alm ros H , N i l sson IM , Sternby N H , A rv idson 0,

K ock um I . Coagulati on defec ts and atheroscl erosis

induced in rabbi ts by a diet containing medium

chai n trig l y ceri des. A cta M ed Scand 1972;192:201-

12.

89. H ashim oto 5, D ay ton S. U ti l i zat ion of gl ucose,

octanoate and palm i tate by normal rat aorta, and

the ef f ect of these ac ids and of albumi n on gl ucose

m etabol i sm . Proc Soc Ex p B i ol M ed 1968:129:35-

41.

90. K auni tz H . C l ini cal uses of medium -chai n tr igl y c-

erides. D rug T herapy l978;8:9I -9.

91. H ornstra G , L ussenburg R N . R elationship betw een

the ty pe of dietary fatty acid and arter ial throm bosis

tendency i n rats. A therosclerosis 1975;22:499-516.

92. K auni tz H , I ohnson R E. Inf l uence of dietary fats

on disease and l ongev i ty . I n: C hav ez A , B ourges H ,

B asta 5, eds. Proceedings of the 9th International

C ongress on N utri ti on, M ex i co, 1972. B asel : K ar-

g er , 1 97 5; l :3 62 -7 3.

93. M i tchel l M E. Carni t i ne m etabol i sm in hum an sub-

jects. I I I . M etabol i sm in disease. A m I C l in N utr

1978:31:645-59.

94. A ngel in i C, L #{ 252} ck e5, C antarutti F. Carni ti ne def i -

c iency of sk eletal muscle: report of a treated case.

N eurol ogy 1976;26:633-7.

95. Smy th D , L ak e B D , M acderm ot I , W i l son I . I nborn

error of carni ti ne m etabol i sm (carni ti ne def i ci ency )

in m an. L ancet 1975;1:l l 98-9.

96. H osk ing G P, Cav anagh N PC , Sm i th D PI , W i lson

I . O ral t reatment of carni t i ne my opathy . L ancet

1 97 7; 1 :8 53 .

97. A ngehi ni C , Gov oni E , B ragagl ia M M , V ergani L .

C arni ti ne def i ciency : acute postpar tum crisi s. A nn

N eur ol 19 78; 4:5 58- 61.

98. C arrol l IE , B rook e M H , D ev iv o D C , K aiser K K ,

H agberg IM . B iochem ical and phy siol ogi c conse-

quences of carni ti ne pal m i ty l transf erase def i c iency .

M uscl e N erv e 1978;1:103-10.

99. B ertorin i T , Y eh Y Y , T rev isan C , Stadl an E, Sa-

besin 5, D iM auro S. C arni ti ne palm i ty l transferase

def i c iency : my ogl obinuria and respi ratory fai lure.

N eurology 1980;30:263-7 I .

100. H ark ins RW , Saret t H P. N utri ti onal ev aluati on of

medium-chain trigl y cerides in the rat. I A m Oi l

C hem Soc 1968;45:26-30.

101. St i ck ney RR , A ndrew s 1W . Ef fec ts of dietary l ipi ds

on grow th, f ood conv ersi on, l i p id and fatty ac id

com posi tion of channel catf i sh. I N utr

1 97 2 ; 1 0 2 : 2 4 9 5 8

102. W i l ey IH , L ev ei hle G A . M etabol i c consequences of

dietary m edium -chain tri gl y cer ides i n the rat. I

N utr 1973; 103:829-35.

103. T ak ase 5, M ori moto A , M uto Y , H osoy a N . E f f ect

of m edi um chain trig l y ceride (M CT ) on l ipid me-

tabohism i n rats w i th respec t to obesi ty . I n: Pro-

ceedings Subcom m i ttee, eds. T enth I nternational

C ongress of N utr i ti on, I apan, 1975. K y oto: Pro-

ceedings of Subcomm i ttee of X I CN 1976:549


13/13

962

B A CH A N D B A B A Y A N

(abstr).

104. Schem mel R. Phy siol ogi cal considerat ions of l i p id

storage and ut i l i zation. A m Z ool 1976;16:661-70.

105. T rav is D , M inenna A , Fri er H . E f f ec ts of m edium

chain tr igl y ceride on energy m etabol i sm and body

com posi t ion in the rat . Fed Proc 1979;38:561.

106. D el eted i n proof .

107. F ino JH , Schem mel R, M i ck elsen 0. Ef f ect of

dietary tri gl y ceri de chain length on energy uti l i za-

t ion and obesi ty i n rats fed high f at diets. Fed Proc

1973;32:933 (abstr).

108. K auni tz H , Slanetz CA , Johnson R E, B abay an V K ,

B arsk y G . R elation of saturated, m edi um - and

long-chai n trig l y cerides to grow th, appeti te, thi rst

and w eight maintenance requi rem ents. I N utr

195 8;6 4:5 13 -24 .

109. K auni tz H , Cotton R H , Johnson RE. Comparison

of m edium-chain tri gl y cer ides and other f ats in a

reduc ing diet. I n: Proceedings Subcomm i ttee, eds.

T enth International C ongress i n N utri t i on, Japan

1975, K y oto: Proceedi ngs Subcom mi t tee of X ICN

1976:63-4 (abstr ).

110. B ach A , Schi rardin H , Chanussot F, B auer M ,

W ery ha A . Ef f ects of medium- and long-chain

trig l y ceri de di ets in the geneti cal l y obese Z uck er

rat. I N utr 1980; 110:686-96.

I 1 1. L au H C, Flaim E, Ri tchey SI . B ody w eight and

depot f at changes as inf luenced by ex erc ise and

dietary fat sources in adul t B H E rats. I N utr

1 97 9; 1 09 :4 95 -5 00 .

1 12. T urk enk pof I , M aggi o C, G reenw ood M R C. M e-

di um chai n trigl y ceridees reduce w eight, but not

obesi ty in y oung (fafa) rats. Fed Proc 198 l ;40:842.

1 13. B aba N , B racco EF, Sey lar 1, H ashim SA . En-

hanced therm ogenesis and dim inished deposi tion

of f at in response to ov erf eeding w i th diet contain-

ing medium chain tri gl y ceri de. A m I Chin N utr

198 l ;34:624 (abstr).

114. B ray G A , L ee M , B ray T L . W eight gain of rats fed

m edi um -chain tri gl y cer ides is l ess than rats fed

long-chain trig l y cerides. lnt I O besi ty 1980;4:27-

32.

115. B ach A , Chanez M , B ois-Joy eux B , D elhomm e B ,

Schi rardin H , Peret I . Regim es hy perprot#{ 233} iques et

hy perl i pid iques (L CT ou M CT ) chez l e rat Z uck er

genCti quement obese. R #{ 233} sul tats prul im inai res. Pre-

sented at the R euni on Soci #{ 2 33} t Cutri ti on D iCtCti que,

L angue Fran#{ 231} ai se, Paris, France, D ec 7, 1981.

1 16. B abay an V K . M odi f i cat ion of f ood to control f at

intrk e. I A m Oi l Chem Soc 1974;51:260-4.

1 17. G ordon EE, D uga I . Ex peri mental hy perosmolar

diabeti c sy ndrome. K etogenic response to medium -

chai n tri gl y ceri des. D iabetes 1975;24:301-6.

1 18. G uy D O , T uley RI . Ef f ec ts of diets high in carbo-

hy drate, soy oi l , medium -chai n trig l y cerides or tri -

pelargonin on bl ood and l i v er l i pid and gl ucose

interm ediates in m eal -eating rats. I N utr 1981;

111:1437-45.

1 19. L inscheer W G, C astel l D O , Pl att R R. A new

m ethod for ev al uat ion of portosy stem ic shunti ng.

T he rectal oc tanoate tolerance test. Gastroenterol -

o gy 1 96 9 ; 5 7 : 4 1 5 2 3

120. T rauner D A , H uttenlocher PR. Short chain fatty

ac id- induced central hy perv ent i l at ion i n rabbi ts.

N eurol ogy 1978;28:940-4.

121. R abi now i tz I L , Staef f en I , A umonier P. et al . T he

ef f ec ts of intrav enous sodi um octanoate on the

R hesus M onk ey . A m I Gastroenterol 1978;69:I 87-

90.

122. A shbrook ID , Spector A A , Fl etcher IE . M edium

chai n f atty aci d binding to hum an plasm a albumi n.

I B iol Chem 1972;247:7043-50.

123. L inscheer W G , B hum A L , Pl att R R. T ransf er of

m edi um chain fat ty ac ids f rom bl ood to spinal f l ui d

in pat ients w i th ci rrhosis. G astroenterology 1970;

5 8 : 5 0 9 1 5

124. Shi l s M E, B l och A S, C hernof f R . L iquid f orm ulas

for oral and tube feedi ng. 2nd ed. N ew Y ork :

M em ori al Sloan-K etteri ng Cancer Center, 1979.

125. B ach A , Guisard D , D ebry 0, M #{ 233} taisP. M etabol i c

ef f ec ts fol low ing a m edium chain trigl y cerides load

i n dogs. V . I nf l uence of the perfusion rate. A rch Int

Phy siol B iochim 1974;82:705-l 9.

126. K auni tz H , Slanetz CA , Johnson RE, B abay an V K .

M edium -chain and long-chain saturated trig l y cer-

ides and l inoleic aci d requi rem ents. I N utr

1 96 0; 7 1 :4 00 -4 .

127. H i rono H , Suzuk i H , I garashi Y , K onno T . Essen-

tial f atty acid def i ciency i nduced by total parenteral

nutri ti on and by medium -chai n trigl y ceride feed-

ing. A m I C hin N utr 1977;30:1670-6.

128. W i l l i am s M L , O sk i FA . V i tam in-E status of inf ants

fed formula containi ng medium-chain trigl y cerides.

I Pedi atr 1980;96:70-2.

Am J Clin Nutr-1982-Bach-950-62.pdf

Documents

Transcript of Am J Clin Nutr-1982-Bach-950-62.pdf