Serum human

myoinositol concentrations milk, formula for infants,

Gilberto

R Pereira,

ABSTRACT rum

Lester

Myoinositol

of 65 neonates

and

of various

types

samples serum

Baker,

samples

Joseph

Egler,

concentration their

was

mothers

at the

of feedings

of 1 S premature

for

infants

in premature and parenteral

Linda

Corcoran,

studied

time

infants,

and

receiving

in se-

of birth,

in

in serial

human

and

Rosetta

glucuronic

Chiavacci

acid

pathway

(9) by its conversion

D-glucuronolactone. counts

milk,

infants fed nutrition13

Urinary

for only

by the kidney

a small

excretion

fraction

ofthe

to D-glucose of

total

and

myoinositol

disposal

ac-

of inositol

(1 1).

period. was greater in

Although myoinositol

neonates than in their mothers (108 ± 10 vs 52 ± 6 tmol/L, respectively, j; SEM, p < 0.01). In feedings for infants, the concentrations of myoinositol were significantly greater in hu-

ofmyoinositol

man

oflife, decreasing to adult concentrations by age 3-6 mo Additionally, the concentration of myoinositol in human

formulas

for infants,

At birth

or parenteral

the serum

milk

than

nutrition

concentration

over

a 3-wk

ofmyoinositol

in formulas

or parenteral

nutrition

solutions

( 1840 ± 45 1 vs 420 ± 1 10 vs 100 ± 8 zmol/L, respectively, p < 0.001). Over a 3-wk period the serum concentration of myoinositol not in those

increased receiving

concentrations adults

in infants receiving formulas or parenteral

of myoinositol

and

are

directly

Am J Clin Nutr KEY

WORDS

milk,

infant

in neonates influenced

1990;5

are

by

milk but Serum

greater

myoinositol

than

in

intake.

1:S89-93.

feedings

parenteral

of newborn,

human

Introduction alcohol,

is widely

distributed

in na-

in the body, where of phosphoinosi-

tides in cell membranes. It was shown that myoinositol essential growth factor for human cells in tissue culture well as a lipotropic factor for many animal species (2, humans have

alterations been

in serum

linked

to the

concentrations

pathogenesis

myoinositol is known variety of foodstuffs.

In mammals intestinal energy is taken kidney,

brush

as a component

dietary

myoinositol

border

membrane

ofthis

study

concerning

serum

concentrations

6-phosphate

(10).

total body poo1 not completely

Am

neuropathy

synthesis in newborn (6, 7). In addition, of human

is transported by a mechanism

milk

and

through that

from ingested understood,

of myoinositol

J C/in Nuir

l990;S1:S89-93.

the

relative

contributions

a

the

primarily Printed

in the kidney

in USA.

macroelements those ofvitamins

serum

and full-term concentrations

Subjects

milk,

and

normative

data in moth-

infants at the of myoinositol

or parenteral

time in

milk, formulas and 3) to study

of myoinositol

formula,

(12). milk

such as soand trace

of myoinositol

concentrations

human

of myomonths

for se-

in neonates

re-

nutrition.

methods

Myoinositol was measured in the cord sera of 65 neonates admitted to the Infant Intensive Care Unit at the Children’s

Hospital 1986.

of Philadelphia Thirty-nine

from

ofthese

July

infants

20 delivered

at term

Additionally,

through

December

premature

with

a birth

and gestational infants with

age a birth

of 33.5 weight

samples were obtained from of delivery; of the 3 1 mothers

and

serial

1984

were

1 1 delivered

concentrations

3 1 of the studied,

prematurely.

of myoinositol

were

de-

is both

are ca-

via the

© 1990 American

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I From the Divisions ofNeonatology and Endocrinology and Diabetes, Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, and the Children’s Hospital of Philadelphia. 2 Supported in part by a grant from the National Institutes of Health

(RR-00240).

to the

and synthesized myoinositol particularly in newborns. The

occurs

the

underestimated.

1) to acquire

were

in their premature 2) to measure the

of 3.2 ± 0.3 kg. Serum 65 mothers at the time

in most organs, such as brain, tract, by conversion of glucose-

However,

the

weight of 1.8 ± 0. 1 kg (1 ± SEM) ± 3 wk. Twenty-six were full-term

and sodium dependent (8). The absorbed myoinositol up by several organs, including the brain, liver, spleen, thyroid, and reproductive system (9). Myoinositol is

also synthesized endogenously liver, kidney and reproductive

tabolism

is an ( 1) as 3). In

of myoinositol

of diabetic

(4, 5) and to the regulation of surfactant infants with respiratory distress syndrome

has been

the serum concentration high through the early

elements. The purposes

rially

a C6 sugar

nutrition

is comparable with those of some dium and chloride and higher than

ceiving

Myoinositol,

in neonatal

Council does not recognize it may be that the role

commonly used feedings for infants (human infants, and parenteral nutrition solutions),

nutrition

ture. It is one of the most abundant sugars it occurs in its free form and as a component

Research requirement,

Preliminary data showed that inositol in newborns remains

ers and of birth,

Myoinositol, formula,

human nutrition.

the National as a dietary

Society

3 Address reprint requests to GR Pereira, Division The Children’s Hospital of Philadelphia, 34th Street Boulevard, Philadelphia, PA 19104.

ReceivedDecember

Accepted for Clinical

15, 1988.

for publication Nutrition

of Neonatology, and Civic Center

May 3, 1989.

589

590 termined

with ±

over

a birth

a 3-wk

weight

0.3 wk. These

infants

=

oflife

lection

ofinfant

feeding

milk

mothers the

in the study

were

to supply

study

was

not

breast.

Infants

Parenteral

tal tories,

with

Irvine,

by the

physicians

caring

willingness

based

own

milk

on the

for their

infants

were were

received

OH), 1 ; Mead

acid

the (n

Care

= 1; Ross Evansville,

in the

(Kendall-McGaw

amino

via a

from

(n

prepared

Myoinositol and

milk

Special

and

Necrotizing enterocolitis was feeding intolerance, abdominal

bloody stools pneumatosis

and was intestinalis.

for

tional

medical

man

the

milk

confirmed None

treatment

hospi-

included

suspected distension,

in infants

apnea

in human

sured

obtained

from

18 mothers,

and

8 of whom

mothers

who supplied

minimum

week

ofone

required

pies were

collected collected

tainers

and

The

surgical

human

and

milk

ofcolostrum

kept

frozen

±

0.00

1 ). The

All pump

until

was

birth

mea-

at term.

infants

types

a

the first

of three

human-milk into sterile

sam-

samples glass con-

analysis.

in formula

and

(including fat emulsions) a total of 1 S samples being

except

the

for a slow

inositol

of myoinositol of feedings data

(Clinfo Products

Data Management Corporation,

were

bound

in human

is not

tol(13). The

the

the

infant’s

infant’s

serum

concentra-

gestational

age,

birth

feedings

reaction

paren-

were deteranalyzed.

with

affected

analyzed

by

milk by

the

samples

System, MA) using

of myoinositol

to 6 wk (r

measurements

in preterm

so-

p cobs-

in mature

milk

As shown

in Figure

(2240 3,

decrease in the concentration of myoas the time oflactation increased from

p

-0.65,

=

greater than p < 0.05).

zmol/L,

nutrition 10 mol/L,

0.05).




formulas

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INFANT

MILK SEM).

FORMULA Mean

and parenteral

concentration

nutrition

PARENTERAL NUTRITION ofmyoinositol

solutions

(p

in preterm
-

U

I 000

Colostrum

I

2

3

WEEKS FIG

3. Myoinositol

Inverse

term sitol

infants

and

correlation

that

are influenced

after

concentration

between

birth

by nutritional

in preterm

myoinositol

and

observed

that

the serum concentrations of myoinositol in breast-fed infants were twofold higher than in infants fed formula or nourished parenterally after a period as short as 1 wk. It remains to be determined whether the serum concentrations

of myoinositol

300

in neonates

receiving

formula

or paren-

(U)

7JLi

milk

during

the

first

6-wk

(r

-0.65).

=

of lactation.

teral nutrition for periods exceeding 3 wk stay constant or decrease further. It is also unknown whether a state of myoinositol deficiency can be induced in humans by long-term administration of a myoinositol-deficient diet as Burton and Wells (1 5) demonstrated in rats. Rats submitted to a myoinositol deficient diet during pregnancy and lactation developed fatty

tion 200-

(20),

liver

but

no

adverse

effects

were

noted

in the

lactating

to glucuronic control

the

acid serum

(18,

19),

and

excretion

concentrations

by the

of myoinositol

kidney in the

neonate. Previous studies showed that either active synthesis or slow catabolism or excretion maintain high serum concentrations of myoinositol in fetuses (2 1, 22). The occurrence of necrotizing enterocolitis in the group of

-J

U)

0

z

infants

100-

who

received

parenteral

nutrition

could

have

been

causally related to the lower serum concentrations of myoinositol observed in those infants. This issue, however, could not be evaluated within the scope of human studies because it would be unethical to administer parenteral nutrition over a period of

Ui U)

3 wk to a control

0

FIG SEM.

tion

4. Myoinositol human fed

OF

concentration milk

Significant

in infants

3

2

WEEKS

receiving

group

ofinfants

with

tion. Nevertheless, it was interesting who were fed formula and who were

0’

±

human

milk and time oflactation

pups. Although the serum concentrations of myoinositol in premature infants receiving formula or parenteral nutrition were lower than those of infants receiving human milk, they were still higher than concentrations observed in maternal sera. This suggests that myoinositol nutrition might have been adequate for all types of nutrition provided and that factors other than diet, for example, endogenous synthesis ( 1 6, 1 7), oxida-

-

-J

term

in human

of myoino-

We also

6

5

OF LACTATION

concentrations

the concentrations intake.

(A)

4

(A),

differences

from

(#{149}), or parenteral

between

premature

infants

nutrition

serum myoinositol

milk and 1) prestudy milk and 2) concentrations nutrition (p < 0.05).

human

fants receiving human formula or parenteral

in sera

formula

colitis

STUDY

concentrations ofinfants

(Lx). I

concentraof inreceiving

Downloaded from https://academic.oup.com/ajcn/article-abstract/51/4/589/4695099 by Washington University in St. Louis user on 11 June 2018

had

serum

concentrations

intestinal

func-

to observe that free ofnecrotizing

normal

infants entero-

of myoinositol

comparable

with those of infants with necrotizing enterocolitis who received parenteral nutrition. This observation strongly suggests that the serum concentrations of myoinositol in premature infants are more dependent on myoinositol intake than on the occurrence of necrotizing enterocolitis. In summary, we observed that the amount of myoinositol contained

in the

different

types

of feeding

contributes

signifi-

MYOINOSITOL cantly

to the serum

concentrations

Further studies are tol has a nutritional

as a constituent

necessary role and

ofinfant

ofmyoinositol

to determine should therefore

AND

INFANT

FEEDINGS

10. Eisenberg F Jr. D-myoinositol-l-phosphate tion ofglucose 6-phosphate and substrate

in neonates.

whether myoinosibe recommended

in the

B

feedings.

rat testis.

1 1. Clements

H,

Oyama

VI,

Levy

M,

et a1. Myoinositol

growth factor for normal and malignant ture. J Biol Chem 1957:266:191-205. 2. Hayashi E, Maeda T, Tomita T. The on lipid

metabolism

accumulation

Biophys

in the

Acta

3. Anderson

in rats.

liver

tance inositol

human

essential

cells in tissue

cub-

The

of myoinositol

mechanism

defi-

of triaglycerol rats.

Biochim

Holub

BJ. The

relative

Al,

Greene

of insulin

DA.

Diabetes

deficiency,

metabolism

response

myoinositol

ofhepatic

and other

polyneuropathy:

hyperglycemia

the

and alterations

in its pathogenesis.

N Engl

lipids

J Med

in

lipotropes. impor-

in myo1976;295:

1416-21. 5. Greene DA, Lattimer SA, Sima AAF. Sorbitol, phosphoinositides and sodium-potassium-ATPase in the pathogenesis of diabetic complications. N Engi J Med l987;3 16:599-606. 6. Saugstad OD. Pathogenetic aspects of respiratory distress syndrome in adults and newborns. Eur Surg Res 1984; 16:1 13-9. 7. Hailman M, Jarvenpaa AL, Pahjavuori M. Double-blind randomized trial of myoinositol supplementation in respiratory distress syndrome. Pediatr Res 1986;20:41 lA(abstr). 8. Caspari

relation Biochim 9.

Lewin

l967;242: AG.

The

I 375-82. metabolism

ofmyoinositol

WF,

Crane

RK.

to the sugar Biophys LM,

Yannai

role ofmyoinositol.

Active

transport

Acta

transport

system

1970;203:308-

Y, Sulimovici

Biochem

13. McGregor LC, Matschinsky FM. An enzymatic for myoinositol. Anal Biochem 1984; 14 1:382-9. 14.

effect

1974; 360:146-55.

DB,

Winegrad

as an

of myoinositol-deficient

the rat to graded levels ofdietary J Nutr 1980; 1 10:496-504. 4.

Chem

by

Res 1987;2l:435A(abstr).

Pediatr

ciency

J Biol

RS Jr. Diethelm

as product of cyclizafora specific phosphatase

the human kidney. J Lab Clin Med 1979;93:2 10-9. 12. Pereira GR, Baker L, Egler J, et al. The effect of gestational age and types of feedings on serum levels of myoinositol in neonates.

References 1. Eagle

593

of myoinositol

in hamster

small

and

its

on the

metabolic

J 1976; 156:375-80.

Downloaded from https://academic.oup.com/ajcn/article-abstract/51/4/589/4695099 by Washington University in St. Louis user on 11 June 2018

P, Hallman

between

troenterol

Nutr

M.

intake 1986;

Myoinositol

and serum

in preterm

assay

infants:

concentration.

rela-

J Pediatr

Gas-

5:455-8.

15. Burton LE, Wells WW. Myoinositol metabolism during lactation and development in the rat. The prevention of lactation-induced fatty liver by dietary myoinositol. J Nutr 1976; 106: 16 17-28. 16. Quirk JG, Bleasdale JE. Myo-inositol homeostasis in the human fetus. Obstet Gynecol 1983;62:41-4. 17. Burton LE, Wells WW. Studies on the development pattern of the enzymes converting glucose 6-phosphate to myoinositol in the rat. Dev Biol 1974;37:35-42. 18. Howard CF Jr, Anderson L. Metabolism of myo-inositol in animals. II Complete catabolism of myo-inositol-’4C by rat kidney slices.

Arch

19. Hallman KO, 20.

Biochem

Biophys

M. Development

Hallman

1967;

1 18:332-9.

of pulmonary

N, Kouvalainen

surfactant.

K, Valimaki

L eds.

In: Raivio

Respiratory

tress syndrome. New York: Academic Press, 1984:33-50. Lewin LM, Melmed 5, Passwell JH, et al. Myoinositol neonates:

serum

concentrations

and

renal

handling.

dis-

in human Pediatr

Res

1978; 12:3-6. 21.

Campling

22.

Physiol (Lond) 1954; 126:191-205. Hallman M, Saugstad OD, Porreco

intestine.

16. 5, et al. Studies

Bromberger

tionship

fluorimetric

JD,

in regulation

Hum

Nixon

DA.

of surfactant

Dev 1985;

10:245-54.

The

inositol

contents

of foetal

fluids.

RP, et al. Role of myoinositol

phospholipids

in the

newborn.

Early

J