Article nutrition
Amino Acids for the Neonate:
Search for the Ideal Dietary Composition
H. Vlaardingerbroek, MD,*
C.H.P. van den Akker,
MD, PhD,* F. de Groof,
MD,* J.E. Hogewind-
Schoonenboom, MD,*
L. Huang, MD,*
M.A. Riedijk, MD, PhD,*
S.R.D. van der Schoor,
MD, PhD,† Y. Huang, MD,
PhD,§ J.B. van Goudoever,
MD, PhD*†‡
Disclosure
Drs Vlaardingerbroek,
van den Akker,
de Groof, Hogewind-
Schoonenboom,
Huang, Riedijk,
van der Schoor,
Huang, and
van Goudoever have
disclosed no financial
relationships relevant
to this article. This
commentary does not
contain a discussion
of an unapproved/
investigative use of a
commercial product/
device.
Abbreviations
BCAA: branched-chain amino acid
IAAO: indicator amino acid oxidation
LNAA: large neutral amino acids
NO: nitric oxide
PN: parenteral nutrition
e506 NeoReviews Vol.12 No.9 September 2011
Abstract
Amino acids play crucial roles as precursors for proteins and neurotransmitters, as
transport molecules, and in cell signaling. In this review, we describe the unique
functions of the individual amino acids and conclude that the amino acid requirements
of parenterally fed neonates are inadequately defined. Parenterally fed neonates are at
risk of amino acid deficiency or toxicity because the intestines serve as an important site
of metabolism, regulating systemic availability of individual amino acids.
Objectives After completing this article, readers should be able to:
1. Explain why certain amino acids are considered “conditionally essential” in infants.
2. Explain why the requirement for most amino acids is different for enteral and
parenteral nutrition.
3. Recognize the importance of individual amino acids and a balanced composition of
amino acids in the diet.
4. Realize the striking differences in the quality (ie, amino acid composition) of the
various enteral and parenteral protein and amino acid preparations.
Introduction
Amino acids can be divided into essential and nonessential, depending on whether they are
completely derived from the diet or they can be produced endogenously from other
substrates in sufficient amounts. Classically, isoleucine, leucine, valine, lysine, methionine,
phenylalanine, threonine, tryptophan, and histidine are considered essential amino acids
for adults. However, several metabolic processes are not fully developed in infants.
Therefore, the following amino acids are conditionally essential for the infant: arginine,
glutamine, glycine, proline, taurine, and tyrosine. Cysteine was historically defined as
conditionally essential, but recent studies have demonstrated that this is not the case for
enterally fed infants. Because all proteins have a fixed sequence of amino acid residues after
DNA translation, the rate of protein synthesis is determined by the first limiting amino acid
in the (cyto)plasma compartment.
An insufficient availability of certain (conditionally) essential amino acids may result in
increased protein breakdown to provide sufficient amounts for protein synthesis. An
overabundance of amino acids may also be detrimental to the infant. The capacity of infants
to regulate amino acid concentrations is limited because of
their immature kidney and liver functioning. Moreover, if
amino acids are supplemented intravenously, intestinal up-
take and metabolism are impaired. Therefore, not only the
quantity but also the quality (the composition) of the amino
acid supply is crucial for achieving optimal growth and
development.
Because of the higher amino acid requirements of preterm
infants, preterm formulas logically contain higher amounts
of protein. Term formulas, however, contain significantly
*Department of Pediatrics, Erasmus Medical Center–Sophia Children’s Hospital, Rotterdam, The Netherlands.
†
Department of Pediatrics, Vrije University Medical Center, Amsterdam, The Netherlands.
§
Gastroenterology, Pediatrics, Fudan Children’s Hospital, Shanghai, PR China.
‡
Department of Pediatrics, Academic Medical Center-Emma Children’s Hospital, Amsterdam, The Netherlands.
Downloaded from http://neoreviews.aappublications.org/ by guest on December 26, 2017
 nutrition amino acids

more protein than human milk. Whether the amino acid
composition of protein in formulas should be so different
from human milk protein composition is unknown. The
appropriate composition of parenteral amino acid solu-
tions is not known because the individual requirements
for parenterally fed preterm infants are not known, other
than requirements for tyrosine. (1) The lack of consensus
about and knowledge of the “optimal” amino acid pat-
tern in parenteral solutions is clearly demonstrated by the
diversity in the composition of current pediatric amino
acid solutions (Table 1).
Branched-chain Amino Acids:
Isoleucine, Leucine, and Valine
The essential branched-chain amino acids (BCAAs) dif-
fer from most other essential amino acids in that the
enzymes initially responsible for their catabolism are
found primarily in the extrahepatic tissue. BCAAs ac-
count for 35% to 40% of the dietary essential amino acids
found in body protein and 14% of the total amino acids
in skeletal muscle. Their primary metabolic fate is incor-
poration into body protein, although utilization by the
intestine and splanchnic tissues (first-pass utilization) is
also high. BCAAs are similar in structure and share
common enzymes for transamination and oxidative de-
carboxylation. The BCAAs compete with other large
neutral amino acids (LNAA), particularly tryptophan and
tyrosine, for membrane transport. Although BCAAs do
not act as direct precursors for neurotransmitters, they
can affect the transport of certain LNAAs across the
blood-brain barrier, thereby influencing central nervous
system concentrations of neurotransmitters. BCAAs are
both ketogenic and glucogenic, and their amino groups
are used for the synthesis of alanine and glutamine in
muscle, providing a shuttle for the transfer of BCAA
nitrogen from muscle to liver for urea formation. Among
the BCAAs, leucine can act independently as a nutrient
signal and stimulates protein synthesis via the activation
of translation initiation factors. Leucine may affect mus-
cle protein turnover and stimulates insulin release and

Amino Acid Concentrations of Commercially Available Parenteral

Table 1.

Amino Acid Solutions*

Product (% Amino Acids) (Manufacturer)
Primene Travasol FreAmine III TrophAmine Aminoven Vaminolact Aminosyn Aminosyn-PF Novamine
(10%) (10%) (10%) (10%) (10%) (6.5%) (10%) (10%) (10%)
(Baxter) (Baxter) (B. Braun) (B. Braun) (Fresenius Kabi) (Fresenius Kabi) (Hospira) (Hospira) (Hospira)
Essential
Isoleucine 6.7 6.0 6.9 8.2 5.0 5.5 7.3 7.6 5.0
Leucine 9.9 7.3 9.1 14.0 7.4 10.8 9.5 11.9 6.9
Valine 7.6 5.8 6.6 7.8 6.2 5.5 8.1 6.6 6.7
Lysine 10.9 5.8 7.3 8.2 9.3 8.6 7.3 6.8 7.9
Methionine 2.4 4.0 5.3 3.4 4.3 2.0 4.0 1.8 5.0
Phenylalanine 4.2 5.6 5.6 4.8 5.1 4.2 4.7 4.3 6.9
Threonine 3.7 4.2 4.0 4.2 4.4 5.5 5.2 5.1 5.0
Tryptophan 2.0 1.8 1.5 2.0 2.0 2.2 1.6 1.8 1.7
Histidine 3.8 4.8 2.8 4.8 3.0 3.2 3.0 3.1 6.0
Conditionally Essential
Cysteine 1.9 0 0 0.1 0 1.5 0 0 0
Tyrosine 0.9 0.4 0 2.3† 0.4 0.8 0.9 0.6 0.3
Arginine 8.4 11.2 9.5 12.2 12.0 6.3 9.9 12.3 9.8
Glutamine 9.9 0 0 5.0 0 10.9 0 8.2 5.0
Glycine 4.0 10.3 14.0 3.6 11.0 3.2 12.9 3.9 6.9
Proline 3.0 6.8 11.2 6.8 11.2 8.6 8.7 8.1 6.0
Taurine 0.6 0 0 0.2 1.0 0.5 0 0.7 0
Nonessential
Alanine 7.9 20.7 7.1 5.4 14.0 9.7 12.9 7.0 14.5
Aspartate 6.0 0 0 3.2 0 6.3 0 5.3 0
Serine 4.0 5.0 5.9 3.8 6.5 5.8 4.2 5.0 3.9
*g/100 g amino acids
†
Supplied as L-tyrosine (0.7 g/100 g amino acids) and N-acetyl-tyrosine (1.6 g/100 g amino acids)
Baxter, Deerfield, IL, B. Braun, Bethlehem, PA, Fresenius Kabi, Schaumburg, IL, Hospira, Lake Forest, IL

NeoReviews Vol.12 No.9 September 2011 e507

Downloaded from http://neoreviews.aappublications.org/ by guest on December 26, 2017
nutrition amino acids
tissue sensitivity. High intake of leucine by humans or
animals enhances the activity of the branched-chain keto
acid dehydrogenase in various tissues, (2)(3) thereby
decreasing valine and isoleucine concentrations in blood.
An excess of leucine increases the oxidation of isoleucine
and valine, thus limiting their availability as substrates for
protein synthesis. (2)(4)(5)
Considerable interaction has been reported in hu-
mans and animals in response to disproportional intakes
of BCAAs. In rats, imbalanced BCAA concentrations
result in impaired growth, and BCAA supplementation
has negative effects on fetal brain growth. (5) The iso-
leucine:leucine:valine ratio in human milk is 1:1.8:1.2.
Different formulas use BCAAs in different ratios, de-
pending on the casein-whey ratio (milk-based formula:
1:1.6:1.1, whey-adapted formula: 1:2.3:1.1). In paren-
teral feeding, the isoleucine:leucine:valine ratio varies
greatly, as shown in Table 1. During parenteral nutrition
(PN), isoleucine is believed to be the most limiting
BCAA of protein synthesis in piglets. A BCAA ratio of
1:1:1 is believed to optimize parenteral feeding because
this ratio reflects the metabolic activity of the intestines.
The gut has a high demand for leucine and a clear
preference for leucine compared with isoleucine or va-
line. An enterally fed diet deficient in leucine has been
shown to cause elevated plasma concentrations of valine
and isoleucine because protein synthesis is limited by
leucine intake. (6)(7) BCAA-enriched PN in preterm
neonates is associated with decreased apnea and im-
provement of the respiratory pattern and function, (4)
suggesting that current PN solutions might influence
functional outcome in the direct postnatal phase. To
optimize current parenteral and enteral feeding, the op-
timal BCAA ratio should be determined for both.
Lysine
Lysine is an essential amino acid that is the limiting
amino acid in cereal-based diets. Although the primary
use of dietary lysine is body protein synthesis, the meta-
bolic requirement for lysine also includes carnitine syn-
thesis and obligatory oxidation. In addition, lysine plays
a major role in calcium absorption and the formation of
collagen. Lysine released from digested protein under-
goes significant first-pass metabolism of approximately
30% to 42%, (8)(9) resulting in a lower lysine require-
ment in PN-fed neonates. (10) Current neonatal PN
amino acid solutions provide lysine intakes between
165 and 330 mg/kg per day (5.5 to 10.9 g/100 g)
(Table 1). These intakes are greater than an infant’s
enteral intake from human milk, which has been reported
to be 119 mg/kg per day. (11) An excess of lysine in
e508 NeoReviews Vol.12 No.9 September 2011
Downloaded from http://neoreviews.aappublications.org/ by guest on December 26, 2017
the current neonatal PN amino acid solutions might
result in nephrotoxicity in the neonate who receives PN
for a prolonged period of time. (12)
Recently, Chapman and associates (12) determined
by the indicator amino acid oxidation (IAAO) method
that the mean parenteral lysine requirement for post-
surgical neonates is 105 mg/kg per day, which is one
third of the lysine content of one of the commercially
prepared formulations and slightly lower than the recom-
mended enteral intake of 119 mg/kg per day.
Methionine and Cysteine
Sulfur is an essential element for cells that plays an
important role in membrane stabilization. The sulfur-
containing amino acids are methionine, homocysteine,
and cysteine. However, methionine and cysteine are the
only proteinogenic sulfur-containing amino acids. Homo-
cysteine is an intermediate in methionine metabolism
and is highly correlated with cardiovascular events in
neonates. (13) Methionine is the single essential sulfur-
containing amino acid. It plays a major role as a methyl
donor in several methylation processes, thereby affect-
ing DNA and RNA translation, proteins, phospholipids,
hormones, and neurotransmitters. Furthermore, it serves
as a precursor for cysteine synthesis through the trans-
sulfuration pathway. The splanchnic tissues play a major
role in the trans-sulfuration pathway and, thus, in cys-
teine production. The methionine requirement in PN-
fed neonates, determined by IAAO, is 49 mg/kg per day,
(14) close to what is provided in current commercial
available PN solutions. Studies in PN-fed neonates found
elevated plasma methionine concentrations that were
related to PN-associated cholestasis. (15)(16) Not much
is known about the enteral methionine requirement. In
1964, the enteral methionine requirement in infants was
determined by weight gain and nitrogen balance studies
to be 45 mg/kg per day. (17) In neonatal piglets, the
enteral requirement determined by IAAO is 420 mg/kg
per day, with one third of the amount used in first-pass
metabolism. (18)
Cysteine is involved in the production of gluta-
thione, taurine, coenzyme A, and inorganic sulfur.
Glutathione is the major intracellular antioxidant and is
crucial in preterm infants who are frequently exposed to
high inspired oxygen fractions and are at high risk of
developing sepsis and necrotizing enterocolitis. A higher
glutathione concentration was found in preterm infants
provided with parenteral amino acids compared with
infants receiving dextrose only. Increasing the cysteine
intake from 45 to 81 mg/kg per day did not have an
effect on glutathione metabolism. (19)

Although evidence is accumulating indicating that
preterm infants can synthesize cysteine, (20) demands
may still exceed synthetic capacity. The exact parenteral
cysteine requirement has not been investigated. Most
PN solutions lack cysteine because it is relatively unstable
in solution and oxidizes easily to cystine, which is insol-
uble. However, dietary cysteine can spare methionine.
(18)(21) The enteral cysteine requirement was first de-
termined by Snyderman, (22) based on nitrogen balance
and weight gain data. They recommended a minimal
intake of 85 mg/kg per day at term age in neonates who
were born preterm.
Phenylalanine and Tyrosine
The major routes of disposal of phenylalanine, an es-
sential aromatic amino acid, are protein synthesis and
hydroxylation to tyrosine. Tyrosine can be metabolized
into proteins; the monoamine neurotransmitters sero-
tonin, dopamine, norepinephrine, and epinephrine; and
the skin pigment melanin. The primary sites of hydroxy-
lation are the liver and kidneys. Hydroxylation of phe-
nylalanine to tyrosine disposes of excess phenylalanine,
preventing the accumulation of toxic concentrations,
and provides tyrosine when the diet is tyrosine-deficient,
such as due to poor tyrosine solubility in PN. (1) Sev-
eral studies have shown that neonates fed PN can hy-
droxylate phenylalanine to tyrosine and that the extent
of hydroxylation is related to the available phenylala-
nine. (23)(24)(25) However, the enzymatic activity
might be insufficient in preterm infants, making tyrosine
a conditionally essential amino acid. To improve stability,
some parenteral amino acid solutions contain acetylated
tyrosine. N-acetyl tyrosine might be only partially avail-
able because it has been reported that high amounts of
acetylated tyrosine were retrieved in the urine of pre-
term neonates. (26) The mean tyrosine requirement of
the PN-fed neonate is between 66 and 82 mg/kg per
day, representing 2.8 to 3.4 g/100 g amino acids. (1)
Snyderman and associates (27) determined the enteral
phenylalanine requirement in term infants at 1 to 9
months of age to be at least 90 mg/kg per day.
Threonine
The essential amino acid threonine is one of two pro-
teinogenic amino acids bearing an alcohol group (the
other is serine). Threonine is critical in the production of
mucins in the gut and contributes significantly to colla-
gen, elastin, and tooth enamel formation. A threonine-
deficient diet results in diarrhea and reduced mucin
production, indicating the important role of threonine
in the structure and function of the gastrointestinal tract.
Downloaded from http://neoreviews.aappublications.org/ by guest on December 26, 2017
nutrition amino acids
Chapman and colleagues (28) determined that the mean
parenteral threonine requirement for postsurgical neo-
nates is 32.8 mg/kg per day (upper and lower confi-
dence limits, respectively: 29.7 and 35.9 mg/kg per
day). They concluded that current parenteral solutions
should be revised to incorporate the population-safe
requirements of threonine to promote optimum meta-
bolic and neurologic growth in neonates. Recently, we
showed that the splanchnic tissues of preterm infants
retain dietary threonine to a substantial degree (⬎75%),
irrespective of the amount of enteral threonine delivery.
(29) The amount of threonine in three commonly used
commercial PN formulations is based on patterns of
amino acids in human milk, infant plasma, or human
cord blood. Currently, neonatal amino acid solutions
provide threonine intakes between 111 and 165 mg/kg
per day, which are greater than an infant’s enteral in-
take from human milk, which has been measured at
76 mg/kg per day. (11)
Tryptophan
Compared with the other essential amino acids, trypto-
phan concentrations are low in plasma and protein.
To regulate homeostasis, tryptophan degradation takes
place primarily in the liver. During inflammation, the
liver synthesizes acute-phase proteins such as C-reactive
protein, which contain large amounts of tryptophan.
Tryptophan degradation by immune cells into kynure-
nine may also be important for the immune response.
In addition, tryptophan is a precursor of melatonin and
the neurotransmitter serotonin. Melatonin and sero-
tonin regulate the sleep-wake rhythm and the response
to stress. The ratio of tryptophan to other large neutral
amino acids (leucine, isoleucine, valine, tyrosine, and
phenylalanine) influences the uptake of these amino acids
into the brain due to a single shared amino acid trans-
porter. Tryptophan supplementation studies in formula-
fed infants showed sleep patterns that were more similar
to breastfed infants than unsupplemented formula-fed
infants. (30)(31)
By studying weight gain and nitrogen balance,
Snyderman and associates (32) were the first to deter-
mine the enteral tryptophan requirement. They con-
cluded that approximately 22 mg/kg per day is sufficient
for normal growing infants. Because of the limitations
of the nitrogen balance method, current recommenda-
tions for infant formula are based on human milk, which
contains an average of 29 mg/kg per day of tryptophan
for infants during the first postnatal month. (11) Com-
mercially available formulas provide tryptophan ranging
from 25 to 30 mg/kg per day when infants receive
NeoReviews Vol.12 No.9 September 2011 e509
nutrition amino acids

150 mL/kg per day of milk. (33) Preterm formula
content ranges from 18 to 36 mg/kg per day per
160 mL/kg per day of milk. (33) No difference was
found in tryptophan requirements in neonatal piglets
when enteral and parenteral feeding were compared.
(34) Most PN solutions, therefore, contain similar con-
centrations of tryptophan compared with human milk
(Tables 1 and 2).
Histidine
Histidine is essential for growth and tissue repair. It
plays an important role in hemoglobin structure and
function as well as in the formation of antioxidative
peptides. It is metabolized into histamine, a substance
involved in allergic reactions, vasodilatation, neurotrans-
mitter action, and regulation of gut function.
In the 1960s, Snyderman and associates (36) deter-
mined the enteral histidine requirement to be 34 mg/kg
per day by means of the nitrogen balance method and
weight gain in eight infants who had an age range of
2 weeks to 7 months. In the first month after birth,
human milk contains an average histidine content of
36 mg/kg per day, decreasing to an average of 21 mg/kg
per day over the first 6 months. (11) Compared with
human milk, most parenteral amino acid solutions con-
tain similar or higher histidine concentrations (Tables
1 and 2). Current recommendations for the histidine
requirement for infant formulas are based on mean hu-
man milk content, despite the highly variable composi-
tion of human milk and the changing intake of each
infant. (37) The histidine content of formulas ranges
from 52.2 to 56.5 mg/kg per day for term infants and
66.6 to 87.3 mg/kg per day for preterm infants when fed
150 and 160 mL/kg per day, respectively. (33)
Arginine
Arginine is a precursor for the synthesis of important
molecules such as nitric oxide (NO), creatine, proline,
ornithine, agmatine, and polyamines. In addition, argi-
nine stimulates the secretion of growth hormone,
prolactin, insulin, and glucagon. Arginine turnover is
high in growing infants, and it plays a crucial role in
ammonia detoxification through the urea cycle. With
no or low nutritional arginine intake, hyperammonemia
is common. (38) Because it is a precursor for NO,
inadequate arginine availability has been associated with

Amino Acid Concentrations of Commercially Available Formulas

Table 2.

and Human Milk*

Human Standard Follow-up Preterm Soy-based Lactose-free Hypoallergenic
Milk (35) Formula Formula Formula Formula Formula Formula
Essential
Isoleucine 5.5 4.3 to 6.0 4.9 to 6.7 4.8 to 5.7 3.8 to 4.9 4.1 to 8.1 4.3 to 6.4
Leucine 10.5 7.8 to 10.5 9.2 to 10.1 8.4 to 9.6 6.4 to 7.3 8.4 to 10.5 7.2 to 10.5
Valine 5.5 4.6 to 6.5 5.6 to 7.9 5.9 to 6.2 3.9 to 5.3 5.0 to 7.3 5.0 to 7.2
Lysine 9.4 8.0 to 8.7 8.6 to 10.4 7.4 to 11.3 6.6 to 8.4 7.8 to 9.4 8.2 to 9.9
Methionine 1.6 1.9 to 2.3 2.1 to 3.2 2.2 to 2.9 1.9 to 2.4 2.8 to 3.3 2.3 to 3.0
Phenylalanine 5.1 3.3 to 6.2 3.6 to 5.0 3.5 to 3.8 3.7 to 9.4 3.5 to 4.4 3.1 to 4.0
Threonine 4.7 3.3 to 5.4 3.6 to 5.3 3.6 to 5.4 2.6 to 5.3 2.6 to 6.5 4.0 to 11.7
Tryptophan 1.9 0.9 to 1.0 0.3 to 0.8 0.6 to 1.0 0.7 to 0.8 0.6 to 1.1 0.7 to 1.0
Histidine 2.4 1.9 to 1.9 1.9 to 3.6 2.2 to 2.4 2.2 to 3.0 1.7 to 2.4 1.3 to 2.4
Conditionally Essential
Cysteine 2.4 1.7 to 2.8 1.5 to 3.3 1.9 to 4.1 1.4 to 1.9 0.8 to 2.6 2.9 to 4.8
Tyrosine 5.9 2.2 to 3.3 3.6 to 4.6 2.8 to 3.0 2.2 to 2.5 2.3 to 3.7 2.6 to 3.7
Arginine 4.9 3.4 to 8.0 3.5 to 3.6 2.9 to 6.2 5.9 to 6.8 2.6 to 3.1 2.1 to 3.3
Glutamine 16.9 12.7 to 18.8 12.4 to 17.0 15.1 to 18.2 12.1 to 14.0 12.4 to 17.1 13.5 to 19.6
Glycine 2.5 1.5 to 2.8 1.8 to 3.9 2.2 to 2.3 3.6 to 5.8 1.7 to 3.7 1.9 to 4.2
Proline 9.6 6.7 to 10.1 9.9 to 10.4 8.3 to 9.5 4.5 to 5.3 9.6 to 10.9 5.6 to 9.6
Taurine 0.3
Nonessential
Alanine 3.9 3.4 to 4.4 4.2 to 4.9 4.4 to 4.8 3.8 to 3.9 2.9 to 5.0 4.2 to 5.6
Aspartate 9.9 9.4 to 12.7 9.6 to 13.5 12.7 to 15.4 12.0 to 13.4 9.3 to 12.9 12.6 to 15.9
Serine 4.8 3.9 to 6.2 3.9 to 5.7 4.6 to 5.8 3.5 to 4.2 4.1 to 5.2 4.2 to 4.3
*g/100 g protein

e510 NeoReviews Vol.12 No.9 September 2011

Downloaded from http://neoreviews.aappublications.org/ by guest on December 26, 2017
 nutrition amino acids

many neonatal diseases, including

persistent pulmonary hypertension
(39)(40) and necrotizing entero-
colitis. (41) Arginine supplemen-
tation might prevent these morbid-
ities. (38)
In the neonate, the enterocytes
are the major cells responsible for
the net synthesis of arginine (Fig-
ure). (38)(42) Infants have very
high arginine requirements, pri-
marily because of the abundance
of arginine in tissue proteins and
the multiple pathways for arginine
utilization. Concentrations of argi-
nine in parenteral solutions vary
more than for other conditionally
essential and nonessential amino
acids (Table 1), ranging from 4.7
to 12.3 g/100 g amino acids.
However, even with 12.3 g/100 g
arginine in parenteral amino acid
solutions, plasma arginine concen-
trations are less than 50% of normal Figure. Interorgan arginine (ARG) synthesis in the neonate. In the small intestine, ARG is
plasma arginine concentrations in synthesized from proline (PRO) (but not from glutamine [GLN] and glutamate [GLU]) and
healthy breastfed term infants. (38) released to the portal vein. Arginine in the portal vein bypasses the liver and kidney and
Therefore, it is crucial to elucidate is used by the body. The crossed arrows indicate the absence of this pathway in neonates
arginine metabolism and dietary re- in contrast to adults. CITⴝcitrulline, ORNⴝornithine, P5Cⴝpyrolline-5-carboxylate,
TCAⴝtricarboxylic acid
quirements during PN and enteral
feeding in neonates.
critically ill adults have suggested that PN supplemented
Glutamine with glutamine may reduce sepsis and mortality. How-
Glutamine is not recognized as an essential amino acid, ever, beneficial effects of supplementation in preterm
but it may be conditionally essential in certain situations. infants have not been shown. (44) Any benefits of glu-
It is synthesized by the enzyme glutamine synthetase tamine supplementation may be confined to those in-
from glutamate and ammonia. The primary tissue that fants who are critically ill, such as with severe gastro-
synthesizes glutamine is muscle, accounting for about intestinal diseases related to necrotizing enterocolitis. To
90% of all glutamine synthesized. Glutamine plays a role date, glutamine supplementation is not a standard nutri-
in a variety of biochemical functions, including protein tional regimen in most neonatal intensive care units.
synthesis, the regulation of renal acid-base balance, cel-
lular energy, and nitrogen donation. Studies elucidating Glycine
mechanisms of glutamine action include tissue protec- Glycine is required for the synthesis of proteins, porphy-
tion, immune modulation, preservation of glutathione rins, nucleotides, creatine, and glutathione. Glycine is
and antioxidant capacity, preservation of metabolism, also required for conjugating bile acids, and it plays a role
decreased intestinal apoptosis, and enhancement of heat in cell signaling. Glycine and serine are readily trans-
shock proteins. The ability to decrease gastrointestinal- formed into one another. Glycine is extensively metabo-
derived systemic inflammation appears to have especially lized in the liver, where it serves as an ammonia donor.
significant implications for preterm infants. (43) The semi-essentiality of dietary glycine for the growth of
Free glutamine is abundant in human milk but is preterm infants who have low glycine intake was first
found in much lower concentrations in formula and is demonstrated by Jackson and associates (45) and was
not found in standard PN solutions. Previous studies in suggested to be due to the exceptionally high demands

NeoReviews Vol.12 No.9 September 2011 e511

Downloaded from http://neoreviews.aappublications.org/ by guest on December 26, 2017
nutrition amino acids
for growth, the relatively small amounts present in hu-
man milk, and the immaturity of the enzymes involved in
glycine synthesis. Because glycine is also essential for the
synthesis of glutathione (the major intracellular anti-
oxidant), glycine requirements might be increased in
infants during states of increased oxidative stress, such as
critical illness or when oxygen supplementation is being
administered. In addition, based on studies using [15N]-
glycine, in which almost no labeled urinary urea was
identified, infants (especially those who are small for
gestational age) might benefit from higher dietary gly-
cine intakes. (46)(47)
Proline
Proline is a key regulator of multiple biochemical and
physiologic processes in cells, such as cell differentiation
and free radical scavenging. It plays a role in wound
healing and the immune system and is a major pre-
cursor for the synthesis of polyamines in the intestine and
placenta. Proline comprises approximately one third of
all amino acids in collagen. On a per-gram basis, the
requirement of proline for whole-body protein synthesis
is the highest of all amino acids. Concentrations of
proline in tissue proteins increase markedly during pre-
and postnatal periods, indicating that proline require-
ments for protein accretion increase substantially. (48)
In neonates, proline is a dietary precursor for arginine
and is dependent on intact gut metabolism (Figure).
(42) This is in contrast to adults, in whom proline can
also be synthesized from glutamate. Generally, amino
acid solutions contain proline concentrations compara-
ble to that in human milk (Tables 1 and 2). Preterm
infants receiving PN are unable to synthesize sufficient
proline de novo. (49) In the mammary glands of lactat-
ing mothers, arginine is actively used to form proline,
resulting in an arginine deficiency and an abundance
of proline in milk protein relative to the needs of the
infant. (48)
Taurine
Taurine is a ␤-amino acid, which means that it is not
incorporated into proteins, in contrast to the 18 ␣-amino
acids. Taurine is the major intracellular free amino acid
in humans and may have important roles in intestinal
fat absorption, hepatic function, membrane stability, and
auditory and visual development in preterm infants.
Taurine is considered conditionally essential because
needs are not met when intake is low. Preterm infants are
especially dependent on an adequate dietary intake to
maintain plasma taurine concentrations because renal
immaturity limits tubular reabsorption and low hepatic
e512 NeoReviews Vol.12 No.9 September 2011
Downloaded from http://neoreviews.aappublications.org/ by guest on December 26, 2017
cystathionase activity might limit taurine biosynthesis
from cysteine. Taurine is abundant in human milk (about
3 to 8 mg/100 mL), but it is present in much lower
concentrations in cow milk and is removed during the
processing of infant formulas. Observational data sug-
gest that relative taurine deficiency during the neonatal
period is associated with adverse long-term neurodevel-
opmental outcomes in preterm infants. Given the po-
tential adverse effects of taurine deficiency, consensus
statements recommend that formula-fed preterm infants
receive about 4.5 to 9.0 mg/kg per day. Modern paren-
teral amino acid solutions also contain taurine concen-
trations that are more than sufficient to meet recommen-
dations and result in taurine concentrations as high as in
breastfed neonates. (50)
Alanine
Alanine is a nonessential amino acid. It can be metabo-
lized from pyruvate and from the BCAAs valine, leucine,
and isoleucine. In addition to its role in protein synthesis,
alanine is the second most important amino acid involved
in interorgan nitrogen transport, particularly from mus-
cles to the liver (glutamine is the first). In addition, it
plays a major role in glucose metabolism. Alanine inhibits
pyruvate kinase, thereby regulating gluconeogenesis and
glycolysis to ensure net glucose production by hepato-
cytes during periods of food deprivation (the glucose-
alanine cycle). The concentration of alanine in most
parenteral amino acid solutions is higher than in human
milk (Tables 1 and 2). However, no harmful effects of
these higher concentrations in PN have been described.
Glutamate and Aspartate
Glutamate and aspartate are both nonessential amino
acids. Glutamate provides a critical link between carbon
metabolism in carbohydrate and amino acid metabolism.
It plays a central role in all transamination reactions and
is the precursor of glutamine. Furthermore, glutamate
serves as a carbon and nitrogen donor in the synthesis of
proline, citrulline, arginine, and glutathione. Aspartate
plays a key function in transamination and in the urea
cycle and has a crucial role in purine and pyrimidine
synthesis, which depend on the donation of its amino
group. Moreover, aspartate is an excitatory neurotrans-
mitter and is involved in gluconeogenesis. More impor-
tantly, these two amino acids are the most important
oxidative substrates in the intestinal mucosa and are,
therefore, important energy sources for splanchnic tis-
sues. (51)(52) Furthermore, the splanchnic tissues pref-
erentially use dietary glutamate for glutathione synthesis.
(53) Clearly, in view of both energy supply and glutathi-

one synthesis, adequate dietary glutamate is crucial. Glu-
tamate and aspartate concentrations in formula and
breastfeeding should be adequate in healthy term neo-
nates. However, the minimal glutamate requirement for
neonates has not yet been investigated. The metabolic
rate and glutathione synthesis are increased in PN-fed
preterm infants when they are ill, suggesting that current
glutamate and aspartate concentrations in PN solutions
could be deficient for these infants.
Serine
Serine is a nonessential amino acid and can be formed
from intermediates of the glycolysis pathway as well as
bidirectionally metabolized from and into glycine. Serine
can also be converted to pyruvate, and the carbon skele-
ton of serine can be used together with the nitrogen
molecule of methionine to form cysteine. Serine is im-
portant in metabolism because in addition to being pro-
teogenic, it participates in the biosynthesis of purines and
pyrimidines.
Serine has not been studied intensively with regard to
its specific role in pediatric nutrition. It has been studied
extensively during fetal life in sheep. Together with glu-
tamate, serine is the only amino acid that has net pla-
cental uptake from the fetal circulation. All fetal serine
requirements, thus, are met by hepatic endogenous syn-
thesis. Placental serine metabolism releases glycine (avail-
able for placenta-fetal transport) and methylenetetra-
hydrofolate. The latter can be used in purine synthesis or
for homocysteine remethylation into methionine. (54)
Its applicability to human pregnancy has not been dem-
onstrated unequivocally.
Human milk does not differ much from the various
pediatric formulas and parenteral compositions in serine
content, which is approximately 4% to 5% by weight.
Summary
Amino acids play crucial roles during life as precursors
for proteins (and, thus, growth) and neurotransmitters,
as transport molecules, and in cell signaling. Each amino
acid has a unique function, but not much is known about
the amino acid requirements for infants. Recently, IAAO
studies have clarified the requirements for some amino
acids (eg, methionine). Generally, the amino acid con-
tent of human milk should be adequate for term infants.
Therefore, most infant formulas have a composition
comparable to human milk, although protein concen-
tration is higher on average. Preterm formulas contain
higher amounts of protein, but specific requirements
in this age group are lacking. Due to splanchnic extrac-
tion and metabolism, requirements during PN are differ-
Downloaded from http://neoreviews.aappublications.org/ by guest on December 26, 2017
nutrition amino acids
ent and most likely considerably lower than during en-
teral nutrition. The lack of consensus and knowledge
with regard to the “optimal” amino acid pattern in
parenteral amino acid solutions is clearly demonstrated
by the compositional diversity of current pediatric amino
acid solutions. Clearly, more studies of amino acid re-
quirements are needed, both in parenterally and enterally
fed infants, to optimize parenteral and enteral nutrition
for preterm infants.
American Board of Pediatrics Neonatal-Perinatal
Content Specifications
• Distinguish between indispensable,
essential, and non-essential amino acids.
• Know the protein requirements of preterm
and full-term infants.
• Know the consequences of feeding preterm
infants too little or too much protein.
• Know the physiology of protein/amino acid digestion
(absorption and metabolism) in newborn infants.
• Know the differences in the nutritional composition of
human milk and cow milk.
• Know how standard infant formulas are modified in order
to meet the needs of preterm infants.
• Know the nutritional composition of parenteral solutions.
• Know the importance of protein and non-protein nutrients
in achieving optimal utilization of energy and nitrogen.
References
1. Roberts SA, Ball RO, Moore AM, Filler RM, Pencharz PB. The
effect of graded intake of glycyl-L-tyrosine on phenylalanine and
tyrosine metabolism in parenterally fed neonates with an estimation
of tyrosine requirement. Pediatr Res. 2001;49:111–119
2. Block KP. Interactions among leucine, isoleucine, and valine
with special reference to the branched chain amino acid antago-
nism. In: Friedman M, ed. Absorption and Utilization of Amino
Acids. Boca Raton, FL: CRC Press; 1989;229 –244
3. Pelletier V, Marks L, Wagner DA, Hoerr RA, Young VR.
Branched-chain amino acid interactions with reference to amino
acid requirements in adult men: leucine metabolism at different
valine and isoleucine intakes. Am J Clin Nutr. 1991;54:402– 407
4. Blazer S, Reinersman GT, Askanazi J, Furst P, Katz DP, Fleisch-
man AR. Branched-chain amino acids and respiratory pattern and
function in the neonate. J Perinatol. 1994;14:290 –295
5. Harper AE, Miller RH, Block KP. Branched-chain amino acid
metabolism. Annu Rev Nutr. 1984;4:409 – 454
6. Elango R, Goonewardene LA, Pencharz PB, Ball RO. Parenteral
and enteral routes of feeding in neonatal piglets require different
ratios of branched-chain amino acids. J Nutr. 2004;134:72–78
7. Elango R, Pencharz PB, Ball RO. The branched-chain amino
acid requirement of parenterally fed neonatal piglets is less than the
enteral requirement. J Nutr. 2002;132:3123–3129
8. van der Schoor SR, Reeds PJ, Stellaard F, et al. Lysine kinetics in
preterm infants: the importance of enteral feeding. Gut. 2004;53:
38 – 43
NeoReviews Vol.12 No.9 September 2011 e513
nutrition amino acids
9. Van Der Schoor SR, Reeds PJ, Stoll B, et al. The high metabolic
cost of a functional gut. Gastroenterology. 2002;123:1931–1940
10. Snyderman SE, Norton PM, Fowler DI, Holt LE Jr. The
essential amino acid requirements of infants: lysine. AMA J Dis
Child. 1959;97:175– 85
11. Protein and amino acid requirements in human nutrition.
WHO Tech Rep Ser. 2007;935:1–265
12. Chapman KP, Courtney-Martin G, Moore AM, et al. Lysine
requirement in parenterally fed postsurgical human neonates. Am J
Clin Nutr. 2010;91:958 –965
13. Hogeveen M, Blom HJ, Van Amerongen M, Boogmans B,
Van Beynum IM, Van De Bor M. Hyperhomocysteinemia as risk
factor for ischemic and hemorrhagic stroke in newborn infants.
J Pediatr. 2002;141:429 – 431
14. Courtney-Martin G, Chapman KP, Moore AM, Kim JH, Ball
RO, Pencharz PB. Total sulfur amino acid requirement and metab-
olism in parenterally fed postsurgical human neonates. Am J Clin
Nutr. 2008;88:115–124
15. Brown MR, Putnam TC. Cholestasis associated with central
intravenous nutrition in infants. N Y State J Med. 1978;78:27–30
16. Coran AG, Drongowski RA. Studies on the toxicity and effi-
cacy of a new amino acid solution in pediatric parenteral nutrition.
JPEN J Parenter Enteral Nutr. 1987;11:368 –377
17. Snyderman SE, Boyer A, Norton PM, Roitman E, Holt LE Jr.
The essential amino acid requirements of infants. X. Methionine.
Am J Clin Nutr 1964;15:322–330
18. Shoveller AK, Brunton JA, Pencharz PB, Ball RO. The methi-
onine requirement is lower in neonatal piglets fed parenterally than
in those fed enterally. J Nutr. 2003;133:1390 –1397
19. te Braake FW, Schierbeek H, Vermes A, Huijmans JG, van
Goudoever JB. High-dose cysteine administration does not in-
crease synthesis of the antioxidant glutathione preterm infants.
Pediatrics. 2009;124:e978 – e984
20. Shew SB, Keshen TH, Jahoor F, Jaksic T. Assessment of
cysteine synthesis in very low-birth weight neonates using a
[13C6]glucose tracer. J Pediatr Surg. 2005;40:52–56
21. Di Buono M, Wykes LJ, Ball RO, Pencharz PB. Dietary
cysteine reduces the methionine requirement in men. Am J Clin
Nutr. 2001;74:761–766
22. Snyderman SE. The protein and amino acid requirements of
the premature infant. In: Jonxis JHP, Visser HKA, Troelstra JA,
eds. Nutricia Symposium. Metabolic Processes in the Foetus and
Newborn Infant. Leiden, Netherlands: Stenfert Kroese; 1971:
128 –143
23. Roberts SA, Ball RO, Filler RM, Moore AM, Pencharz PB.
Phenylalanine and tyrosine metabolism in neonates receiving par-
enteral nutrition differing in pattern of amino acids. Pediatr Res.
1998;44:907–914
24. Kilani RA, Cole FS, Bier DM. Phenylalanine hydroxylase ac-
tivity in preterm infants: is tyrosine a conditionally essential amino
acid? Am J Clin Nutr. 1995;61:1218 –1223
25. Denne SC, Karn CA, Ahlrichs JA, Dorotheo AR, Wang J,
Liechty EA. Proteolysis and phenylalanine hydroxylation in re-
sponse to parenteral nutrition in extremely premature and normal
newborns. J Clin Invest. 1996;97:746 –754
26. Van Goudoever JB, Sulkers EJ, Timmerman M, et al. Amino
acid solutions for premature neonates during the first week of life:
the role of N-acetyl-L-cysteine and N-acetyl-L-tyrosine. JPEN J
Parenter Enteral Nutr. 1994;18:404 – 408
27. Snyderman SE, Pratt EL, Cheung MW, et al. The phenylala-
nine requirement of the normal infant. J Nutr. 1955;56:253–263
e514 NeoReviews Vol.12 No.9 September 2011
Downloaded from http://neoreviews.aappublications.org/ by guest on December 26, 2017
28. Chapman KP, Courtney-Martin G, Moore AM, Ball RO,
Pencharz PB. Threonine requirement of parenterally fed post-
surgical human neonates. Am J Clin Nutr. 2009;89:134 –141
29. van der Schoor SR, Wattimena DL, Huijmans J, Vermes A,
van Goudoever JB. The gut takes nearly all: threonine kinetics in
infants. Am J Clin Nutr. 2007;86:1132–1138
30. Yogman MW, Zeisel SH, Roberts C. Assessing effects of
serotonin precursors on newborn behavior. J Psychiatr Res. 1982;
17:123–133
31. Steinberg LA, O’Connell NC, Hatch TF, Picciano MF, Birch
LL. Tryptophan intake influences infants’ sleep latency. J Nutr.
1992;122:1781–1791
32. Snyderman SE, Boyer A, Phansalkar SV, Holt LE Jr. Essential
amino acid requirements of infants: tryptophan. Am J Dis Child.
1961;102:157–162
33. Alegria A, Barbera R, Farre R, Lagarda MJ, Lopez JC. Amino
acid contents of infant formulas. J Food Composition Anal. 1999;
12:137–146
34. Cvitkovic S, Bertolo RF, Brunton JA, Pencharz PB, Ball RO.
Enteral tryptophan requirement determined by oxidation of gastri-
cally or intravenously infused phenylalanine is not different from the
parenteral requirement in neonatal piglets. Pediatr Res. 2004;55:
630 – 636
35. Rassin DK. Amino acid metabolism in total parenteral nutri-
tion during development. In: Friedman M, ed. Absorption and
Utilization of Amino Acids. Boca Raton, FL: CRC Press Inc;
1989:71– 85
36. Snyderman SE, Boyer A, Roitman E, Holt LE Jr, Prose PH.
The histidine requirement of the infant. Pediatrics. 1963;31:
786 – 801
37. Anderson DM, Williams FH, Merkatz RB, Schulman PK,
Kerr DS, Pittard WB 3rd. Length of gestation and nutritional
composition of human milk. Am J Clin Nutr 1983;37:810 – 814
38. Wu G, Jaeger LA, Bazer FW, Rhoads JM. Arginine deficiency
in preterm infants: biochemical mechanisms and nutritional impli-
cations. J Nutr Biochem. 2004;15:442– 451
39. Vosatka RJ, Kashyap S, Trifiletti RR. Arginine deficiency ac-
companies persistent pulmonary hypertension of the newborn. Biol
Neonate. 1994;66:65–70
40. Castillo L, DeRojas-Walker T, Yu YM, et al. Whole body
arginine metabolism and nitric oxide synthesis in newborns with
persistent pulmonary hypertension. Pediatr Res. 1995;38:17–24
41. Shah P, Shah V. Arginine supplementation for prevention of
necrotising enterocolitis in preterm infants. Cochrane Database Syst
Rev. 2007;3:CD004339
42. Tomlinson C, Rafii M, Sgro M, Ball RO, Pencharz P. Arginine
is synthesized from proline, not glutamate, in enterally fed human
preterm neonates. Pediatr Res. 2011;69:46 –50
43. Neu J, Li N. Pathophysiology of glutamine and glutamate
metabolism in premature infants. Curr Opin Clin Nutr Metab
Care. 2007;10:75–79
44. Tubman TR, Thompson SW, McGuire W. Glutamine supple-
mentation to prevent morbidity and mortality in preterm infants.
Cochrane Database Syst Rev. 2008;1:CD001457
45. Jackson AA, Shaw JC, Barber A, Golden MH. Nitrogen
metabolism in preterm infants fed human donor breast milk:
the possible essentiality of glycine. Pediatr Res. 1981;15:1454 –
1461
46. Van Goudoever JB, Sulkers EJ, Halliday D, et al. Whole-body
protein turnover in preterm appropriate for gestational age and
 nutrition amino acids

small for gestational age infants: comparison of [15N]glycine and
[1-(13)C]leucine administered simultaneously. Pediatr Res. 1995;
37:381–388
47. van Lingen RA, van Goudoever JB, Luijendijk IH, Wattimena
JL, Sauer PJ. Effects of early amino acid administration during total
parenteral nutrition on protein metabolism in pre-term infants.
Clin Sci (Lond). 1992;82:199 –203
48. Wu G, Bazer FW, Burghardt RC, et al. Proline and hydroxy-
proline metabolism: implications for animal and human nutrition.
Amino Acids. 2011;40:1053–1063
49. Miller RG, Jahoor F, Jaksic T. Decreased cysteine and proline
synthesis in parenterally fed, premature infants. J Pediatr Surg.
1995;30:953–958
50. Burger U, Gobel R. Taurine requirement of premature infants
in parenteral nutrition [in German]. Monatsschr Kinderheilkd.
1992;140:416 – 421
51. Corpeleijn WE, Riedijk MA, Zhou Y, et al. Almost all enteral
aspartate is taken up in first-pass metabolism in enterally fed preterm
infants. Clin Nutr. 2010;29:341–346
52. Riedijk MA, de Gast-Bakker DA, Wattimena JL, van Gou-
doever JB. Splanchnic oxidation is the major metabolic fate of
dietary glutamate in enterally fed preterm infants. Pediatr Res.
2007;62:468 – 473
53. Reeds PJ, Burrin DG, Stoll B, et al. Enteral glutamate is the
preferential source for mucosal glutathione synthesis in fed piglets.
Am J Physiol. 1997;273:E408 –E415
54. Regnault TR, de Vrijer B, Battaglia FC. Transport and metab-
olism of amino acids in placenta. Endocrine. 2002;19:23– 41

NeoReviews Quiz
3. An amino acid is considered essential when it must be derived completely from the diet and nonessential
when it can be produced endogenously from other substrates. An amino acid is considered conditionally
essential when its endogenous production is limited until further maturation of the metabolic pathways, as
in neonates. Of the following, the only conditionally essential amino acids in the neonate are:
A. Glutamine and glycine.
B. Leucine and lysine.
C. Methionine and phenylalanine.
D. Serine and alanine.
E. Threonine and tryptophan.

4. Branched-chain amino acids differ from other essential amino acids in that the enzymes initially responsible
for their catabolism are found primarily in the extrahepatic tissues. A balanced ratio of concentrations of
branched-chain amino acids (isoleucine, leucine, and valine) in the diet is important for optimal growth in
a neonate. Of the following, the optimal isoleucine:leucine:valine ratio in parenteral nutrition is believed to
be:
A. 1.0:0.7:1.2.
B. 1.0:1.0:1.0.
C. 1.0:1.6:1.1.
D. 1.0:1.8:1.2.
E. 1.0:2.3:1.1.

5. Sulfur is an essential element for cells that plays an important role in cell membrane stabilization. The
sulfur-containing amino acids are methionine, homocysteine, and cysteine. Of the following, methionine,
the single essential sulfur-containing amino acid, is critical for:
A. Calcium absorption.
B. Carnitine synthesis.
C. Collagen formation.
D. DNA translation.
E. Melanin production.

NeoReviews Vol.12 No.9 September 2011 e515

Downloaded from http://neoreviews.aappublications.org/ by guest on December 26, 2017
nutrition amino acids

6. The essential amino acid threonine is one of two proteinogenic amino acids bearing an alcohol group; the
other is serine. Of the following, threonine is critical for:
A. Coagulation promotion.
B. Hemoglobin function.
C. Immune response.
D. Melanin pigmentation.
E. Mucin production.

7. A 48-hour-old term neonate has clinical manifestations and echocardiographic evidence of persistent
pulmonary hypertension, which results in hypoxemic respiratory failure. Her plasma concentration of
ammonia is markedly elevated. Of the following, the amino acid most implicated in the pathogenesis of
this infant’s disorder is:
A. Arginine.
B. Glycine.
C. Proline.
D. Serine.
E. Taurine.

e516 NeoReviews Vol.12 No.9 September 2011

Downloaded from http://neoreviews.aappublications.org/ by guest on December 26, 2017
 Amino Acids for the Neonate: Search for the Ideal Dietary Composition
H. Vlaardingerbroek, C.H.P. van den Akker, F. de Groof, J.E.
Hogewind-Schoonenboom, L. Huang, M.A. Riedijk, S.R.D. van der Schoor, Y. Huang
and J.B. van Goudoever
NeoReviews 2011;12;e506
DOI: 10.1542/neo.12-9-e506

Updated Information & including high resolution figures, can be found at:
Services http://neoreviews.aappublications.org/content/12/9/e506
References This article cites 49 articles, 17 of which you can access for free at:
http://neoreviews.aappublications.org/content/12/9/e506#BIBL
Subspecialty Collections This article, along with others on similar topics, appears in the
following collection(s):
Fetus/Newborn Infant
http://classic.neoreviews.aappublications.org/cgi/collection/fetus:new
born_infant_sub
Nutrition
http://classic.neoreviews.aappublications.org/cgi/collection/nutrition
_sub
Permissions & Licensing Information about reproducing this article in parts (figures, tables) or
in its entirety can be found online at:
http://classic.neoreviews.aappublications.org/site/misc/Permissions.x
html
Reprints Information about ordering reprints can be found online:
http://classic.neoreviews.aappublications.org/site/misc/reprints.xhtml

Downloaded from http://neoreviews.aappublications.org/ by guest on December 26, 2017

 Amino Acids for the Neonate: Search for the Ideal Dietary Composition
H. Vlaardingerbroek, C.H.P. van den Akker, F. de Groof, J.E.
Hogewind-Schoonenboom, L. Huang, M.A. Riedijk, S.R.D. van der Schoor, Y. Huang
and J.B. van Goudoever
NeoReviews 2011;12;e506
DOI: 10.1542/neo.12-9-e506

The online version of this article, along with updated information and services, is
located on the World Wide Web at:
http://neoreviews.aappublications.org/content/12/9/e506

Neoreviews is the official journal of the American Academy of Pediatrics. A monthly publication,
it has been published continuously since . Neoreviews is owned, published, and trademarked by
the American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk Grove Village, Illinois,
60007. Copyright © 2011 by the American Academy of Pediatrics. All rights reserved. Online
ISSN: 1526-9906.

Downloaded from http://neoreviews.aappublications.org/ by guest on December 26, 2017