Glutamine and the gut

GAGTROENTEROLOGY 1994;107:l999-1901

Editorials Glutamine and the Gut compared See artlcle on page

1595.

with

showed that critically supplementation

G

lutamine

is one of the most abundant

acids in the body and central

ways of intermediary tionally

metabolism.

been thought

and

was considered

from all parenteral stored in liquid

dispensable,

solutions

glutamine

served as a precursor biosynthesis.

required

holme

showed similar

and, during

excluded

and tube feedings the first

studies showed that

for both purine

In addition,

that glutamine

energy

acid;

was essential for cell proliferation

systems,’ and subsequent

Glutamine

amino

while in solution

it has been

in culture rimidine

has tradi-

form. Eagle et al. were among

to show that glutamine

gested

to many of the path-

and cyclites

nutrient

free amino

Glutamine

of as a nonessential

because it slowly degrades

provided

by enterocytes,”

and py-

Windmueller

a major

sug-

portion

and Ardawi

of the

and News-

released from skeletal muscle,

serious illness, glutamine

from muscle are increased lease from the periphery

2-3-fold. is matched

synthesis

and efflux

This accelerated by increased

re-

uptake

by the intestinal tract, liver, lymphoid tissue, and kidneys. If the illness is prolonged, the tissue consumption of glutamine

typically

exceeds skeletal

tion, and plasma and intracellular amino

acid decrease.

under these conditions

Provision

muscle

concentrations of exogenous

improves

tissue structure

and function.

nitrogen

The paper by Tremel

of this

glutamine

balance, and enhances

As a result, glutamine

recently been thought of as a conditionally amino acid during critical illness associated flammation and injury.4 TEROLOGY

produc-

restores amino acid concentrations

toward normal,

similar cantly

Pharmacokinetic

ill patients

to normals,

whereas

below limits

accepted

has

essential with in-

et al.’ in this issue of GASTROENinformation to our under-

adds additional

for normal

D-Xylose is a rather nonspecific absorption;

rather heterogeneous

group

data should

be interpreted

glutamine

characteristics

the controls

uate gastrointestinal

evaluation

undergoing

had D-xylose absorption

were signifiabsorption.

substance therefore,

of critically cautiously.

used to evalin this small,

ill patients,

the

Assessment

using

an index of illness severity (such as an APACHE

II score)

would have been helpful to insure comparability

between

groups. However, when examining glutamine-supplemented patients

the available data, the appear to have more

organ dysfunction than the controls (creatinine clearance was lower and bilirubin levels were higher in the test group than controls). tion and excretion

This should favor enhanced of D-XyhSe in the control

not the glutamine-supplemented

effects in colonocytes3

is constantly

controls.

in patient

selection

mine. Additionally, entry would in absorption

but

group. Thus, the biases

do not favor the patients an initial

absorp-

group

given gluta-

test of all patients

at study

have ensured that the groups were similar characteristics. However, this is quite dif-

ficult to achieve in ventilated

patients

with ileus.

Despite these concerns, this paper brings important new information to the field when considered in the perspective of other human studies. First, two randomized prospective double-blinded trials in patients with bowel

injury

have observed

mine-supplemented length of hospital

beneficial

effects of gluta-

nutrition6” Infection rates and stay were reduced in patients given

glutamine compared with patients undergoing standard therapy in both studies. Second, patients with inflammatory bowel disease given glutamine-supplemented tion maintained mucosal cellularity and enhanced function

(as determined

by measurement

of the lactulose/

standing of the conditionally indispensable nature of glutamine and its role in maintaining gut function. Twelve critically ill patients given standard or glutamine-en-

mannitol

excretion

standard

parenteral

riched amino acid solutions in their total parenteral nutrition (TPN) were evaluated after 8-9 days ofparenteral feedings. D-Xylose absorption tests performed at the end of parenteral support showed that urinary excretion of

their remnant intestine. In some patients, the need for TPN has been eliminated.’ Fourth, premature infants

D-xylose over 5 hours after an oral load was about twice as great in the patients administered glutamine when

ratio) compared

nutribarrier

nutrition.’

with controls

Third,

short bowel syndrome given glutamine mone have shown enhanced nutrient

patients

given

with the

and growth horabsorption from

given glutamine-supplemented nutrition require less time on TPN and the ventilator and achieve full enteral feedings in fewer days than control infants given standard

1886

EDITORIALS

intravenous tients

GASTROENTEROLOGY Vol. 107, No. 6

nutrition.”

In this study,

given glutamine-supplemented

hanced given

absorption standard

these studies glutamine

of D-xylose parenteral

enhances

considered

compared

nutrition.

all indicate

gastrointestinal

normal

with

an essential

en-

controls

Taken

structure

ill pa-

showed

that parenterally

tract in humans.

is clearly beneficial

critically TPN

together,

administered

and function

of the

As such, it should

nutrient

in these situations

from the standpoint

be and

of cost-effective

therapy.” On a practical

note,

Tremel

et al. used glutamine

dipeptides in their study, and these substances will not be available for general use in the United States for several years. However, several hospitals and selective home care companies are supplementing commercially available formulas

with

mine.

Europe,

Unlike

the crystalline

allow daily or weekly mixing tions,

and,

when

glutamine

degradation

(amount) itation

at &‘C,

that should

studies performed

ing other

amino

Increased

with

benefits

in animals,

from increasing

acids to maintain

effects

approximately

Because

skeletal

acid nitrogen acid solution glutamine

the only lim-

over a wide

dose range,

when

glutamine

releases

25 % - 35%

of amino

we have found that an amino

provides

comparable

optimal

effects. If a patient

proportions

body wt, then 0.37-0.5

be glutamine.

com-

acids infused.

that

total should

test

and func-

provides

1.5 g protein/kg

dose

caused by reduc-

structural

achieved

as glutamine,

In

glutamine

33% of the amino

muscle

the dose

isonitrogenous

and sustained

were observed

maximal

prised

are minimal.12

be administered.

was related to the amino acid imbalance solutions.

solu-

the effects of

in such mixtures

we have observed

tional

regulations nutrient

should be made concerning

of glutamine

dose-response

acid, L-gluta-

pharmacy

of parenteral

refrigerated

A final comment

amino

the U.S.

In patients

of

requires

g/kg of this

who weigh

50-

70 kg, this would provide 19-35 g, a dose slightly greater than that proposed by the authors. This dose may not only insure the intestinal

more normal

structure

tract but also enhance

and function

function

of

of the im-

munologic tissue and achieve adequate synthesis of the hepatic antioxidant glutathione, another vital biochemi-

cal product

that is enhanced

during

glutamine

adminis-

tration. DOUGLAS W. WILMORE Department of Surgq Brigham and Women’s Hospital Boston, Massachusetts Referencers 1. Eagle H, Oyama VI, Levy M, Horton CL, Fleischman, R. The growth response of mammalian cells in tissue culture to Lglutamine and L-glutamic acid. J Biol Chem 1956;218:607-616. Windmueller GH. Glutamlne utilization by the small intestine. Adv Enzymol 1982;53:201-237. Ardawi MSM, Newsholme EA. Fuel utilization in colonocytes of the rat. Biochem J 1985;231:713-719. Lacey JM, Wilmore DW. Is glutamine a conditionally essential amino acid? Nutr Rev 1990;48:297-309. Tremel H, Kienle B, Weilemann LS, Stehle P, FUrst P. Glutamine dipeptide-supplemented parenteral nutrition maintains intestinal function in the critically ill. Gastroenterology 1994;107: 1595-1601. 6. Zielger TR, Young LS, Benfell K, Scheltinga M, Hortos K, Bye R, Morrow FD, Jacobs DO, Smith RJ, Antin JH, Wilmore DW. Clinical and metabolic efficacy of glutamine-supplemented parenteral nutrition after bone marrow transplantation. A randomized, double blind, controlled study. Ann Intern Med 1992;116:821-828. 7. Schloerb PR, Amare M. Total parenteral nutrition with glutamine in bone marrow transplantation and other clinical applications (a randomized, double-blind study). J Parenter General Nutr 1993; 17407-413. 8. Van der Hulst RRWJ, Van Kreel BK, Von Meyenfeldt MF, Brummer R-JM, Arends J-W, Deutz NEP, Soeters PB. Glutamine and the preservation of gut integrity. Lancet 1993;341:1363-1365. 9. Byrne TA, Morrissey TB, Ziegler TR, Gatzen C, Young LS, Wilmore DW. Growth hormone, glutamine, and fiber enhance adaptation of remnant bowel following massive intestinal resection. Surg Forum 1992;43:151-153. 10. Lacey J, Crouch J, Benfell K, Ringer S, Wilmore K, Maguire D, Wilmore D. The effects of glutamine-supplemented parenteral nutrition in premature infants. J Pediatr (submitted). 11. MacBurney M, Young L, Ziegler TR, Wilmore DW. A cost-evalua tion of glutaminesupplemented parenteral nutrition in adult bone marrow transplant patients. J Am Diet Assoc 1994;94:12631266. 12. Hardy G, Bevan SJ, McElroy B, Palmer TE, Griffiths RD, Braidwood C. Stability of glutamine in parenteral feeding solutions (letter). Lancet 1993;342:186. Address requests for reprints to: Douglas W. Wilmore, M.D., Department of Surgery, Brigham and Women’s Hospital, 75 Francis Street, Boston, Massachusetts. Fax: (617) 732-5506. 0 1994 by the American Gastroenterological Association 0016-5085/94/$3.00

Irritable Bowel Syndrome: Just a Pain in the Butt? See article

S

on page 1666.

ince the recognition of irritable bowel syndrome (IBS) as a distinct disease entity, considerable efforts have been made to understand its etiology and identify

objective criteria for its diagnosis. The generally agreed symptom cluster includes abdominal pain often relieved by defecation, distention of the abdomen, disordered bowel habit (diarrhea or constipation), a frequent feeling of incomplete evacuation, mucus in the stool, looser stools with pain onset, and more frequent stools with