cover story
(3) therefore utilisation of exogenous
status/flux is impractical on a routine (12). It follows then that downstream
nucleotides may be beneficial from
basis and the complexities are be- processes, which rely on nucleotides,
a bioenergetic point of view (12). yond the scope of this review but it such as glycogen synthesis, and
It appears that the intestinal mu- seems clear that understanding this protein and lipid metabolism may
cosa, bone marrow haematopoietic complex issue could hold the key to be disrupted. Indeed, many studies
cells and lymphoid tissue have a lim- how the body uses nucleotides and have demonstrated a reduction in
ited capacity for de novo synthesis whether exogenous nucleotides re- protein secretion including immuno-
and probably depend more heavily ally are essential. globulins (2) and this may partially
on the salvage pathways that supply Dietary nucleotides are not explain why dietary nucleotides are
nucleotides from the diet or from considered essential in the tradi-
closely associated with immune
the degradation of DNA and RNA
tional sense because they can be function.
(3,12). Thus if the exogenous supply
synthesised by the body (12). How- The supplementation of infant
of nucleotides is low these tissues
ever, a number of investigators have formula with nucleotides is consid-
may struggle to fulfil their need for
described dietary nucleotides as ered beneficial since it has been
nucleotides.
conditionally essential in a variety of found to influence lipid metabolism,
clinical situations and during devel- immunity and tissue growth, devel-
Dietary nucleotide metabolism
opment (12,14). opment and repair (16). The majority
Nucleotides are a normal com-
Dietary nucleotides could theoret- of standard infant formulas are now
ponent of the adult human diet and
ically become conditionally essential supplemented with nucleotides.
are ingested in the form of nucleo-
under three circumstances: Studies have demonstrated that
proteins (5). Proteases and nucleases
- during periods of insufficient babies fed nucleotide supplement-
degrade nucleoproteins and nucleic
intake; ed infant formula have increased
acids into nucleotides; phospha-
- where there is a high demand/ ‘friendly’ bifidobacteria counts in
high rate of growth or repair; and faeces compared to infants fed
tases and nucleotidases cleave the
- in the presence of disease (3). standard formula milk, but counts
phosphate group(s) to yield nucleo-
It has been demonstrated that were still lower than found in breast
sides. Whilst some report the body
enterocytes, whilst having a high fed babies (17). However in other
has mechanisms to digest, absorb
demand for nucleotides, have a studies, infants receiving a nucleo-
and incorporate nucleotides into
low capacity for de novo synthesis tide supplemented formula had
tissues (12) others suggest intestinal
(3). Thus it could be postulated that increased colonisation of Esch-
cells are a formidable barrier against
enterocytes rely more heavily on an erichia coli compared to infants fed
the transfer of dietary nucleotides
exogenous supply of nucleotides standard formula milk (7). Counts of
to peripheral tissues and absorbed
from the diet. Further, if the dietary bifidobacteria were also lower in the
nucleotides and derivatives are rap- intake of nucleotides is low, due to infants receiving the supplemented
idly degraded in the enterocyte and a restrictive diet, these compounds formula. These authors did not sup-
waste is eliminated in urine or faeces could be considered conditionally port the addition of nucleotides to
(4). Indeed (Yu, 2002) describes how
essential. infant formula milk.
absorbed nucleosides are mainly
In a study examining the effect of Nucleotide supplemented formu-
degraded to uric acid, but does
a nucleotide supplement on symp- las have also decreased the preva-
concede some are converted back
toms in Irritable Bowel Syndrome lence and duration of diarrhoeal
into nucleotides.
it was felt that dietary nucleotides disease in infants but this was not
Animal studies indicate that
were probably not essential in associated with changes in faecal
around 2-5% of dietary nucleotides
healthy people but under conditions microflora (18). Thus, mechanisms
are incorporated in the tissue pools
of stress, illness or a poor diet nucleo- other than the modification of fae-
primarily within the small intestine,
tides may well become semi-essen- cal microflora, for example, effects
liver and skeletal muscle (4) and
tial (15). on the immune system, might be
responsible for the reduction in diar-
dietary nucleotides are incorporated
The evidence for essentiality – do rhoeal disease.
into liver ATP in rats (13). It remains
diets devoid of nucleotides cause Infant studies also suggest those
to be established to what extent this
problems? receiving nucleotide supplemented
occurs in humans.
No particular disease or classical formula have an improved antibody
deficiency syndrome has been re- response following immunisation
Are dietary nucleotides essential?
lated to nucleotide deficiency (2,4). (19,20).
Research in infants and animal
But this may be because salvage Investigations in animals suggest
models clearly demonstrates that
pathways and de novo synthesis that dietary nucleotides influence
the body has a need for nucleotides
are up-regulated to compensate. several indices of immune function.
but whether a constant exogenous
Whilst this may be sufficient for most Restriction of dietary nucleotides
supply is needed or whether salvage
cells; for enterocytes and cells of in mice decreases cell mediated
from degradation of nuclear mate-
the immune system who’s synthetic immunity and decreases resistance
rial and de novo synthesis can be
capacity is lower, or in the presence when challenged with methicillin
completely relied upon to meet nu-
of tissue-specific injury or generalised resistant Staphylococcus aureus (21)
cleotide needs is poorly understood
illness, minor problems may result and Candida albicans (22). Further
and hotly debated. It has been which have not yet been detected. studies in mice have also demon-
estimated that human milk provides Studies in rats have demonstrated strated that a nucleotide-free diet
about one-third of the neonate’s that a diet devoid of nucleotides suppressed immune function and this
requirements (14). results in lower nucleotides levels was only restored when nucleotides
Measuring whole body nucleotide in the liver (13) and small intestine were re-introduced into the diet (23).
NHDmag.com Aug/Sep ‘08 - issue 37
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