Nutritional factors that influence vitamin A status

Among various nutrients which infl uence vitamin
A nutritional status, fat and protein are the most
important.
7.5.1 Fat defi ciency
The presence of adequate amounts of dietary fat is
essential in forming micelles and providing a lipid vehicle
for vitamin A absorption and transport. The absorption
of retinol and carotenoids is markedly lower
than normal when diets contain very little fat (less
than 5 g per day). A study conducted in a Rwandan
village area in Africa showed that supplementation
of the carotenoid-suffi cient but low-fat diet with 18 g
per day of olive oil increased the absorption of vegetable
carotenoids from 5% to 25% in boys showing clear
signs of vitamin A defi ciency (Roels et al., 1958).
7.5.2 Protein defi ciency
In cases of severe protein–energy malnutrition, the
lack of dietary protein leads to an impairment of all
stages of vitamin A metabolism due to a depressed
synthesis of enzymes, retinoid-binding proteins and
receptors. Even where dietary carotenoids are abundant,
a reduced enzymatic cleavage of carotenoids
will result in vitamin A defi ciency. Furthermore,
liver stores of vitamin (even if plentiful) will not be
released into the bloodstream due to the depressed
synthesis of RBP.
7.5.3 Zinc defi ciency
Zinc is an essential cofactor for many enzymes, some
of which are directly critical to vitamin A metabolism;
for example, zinc defi ciency signifi cantly reduces the
enzymatic oxidation of retinol to retinaldehyde in the
retina (Huber & Gershoff, 1975). Other zinc-dependent
enzymes are involved in the synthesis of proteins,
including perhaps retinoid-binding proteins and receptors.
The synthesis of one particular protein, opsin
in the rod cells of the eye, is depressed in zinc-defi cient
rats (Dorea & Olson, 1986). The consequent depression
in rhodopsin levels, rather than a depressed
enzymatic oxidation of retinol, probably explains
the impaired dark adaptation found in zinc-defi cient
humans.
Zinc-defi cient animals exhibit low plasma vitamin
A levels even if large supplements of vitamin A are
given. Zinc defi ciency also reduces food intake, with
a consequent impairment of growth, and these parameters
confound experiments on zinc–vitamin A
interactions. Smith et al. (1976) showed that a severely
food-restricted group of rats fed a zinc-adequate diet
had plasma vitamin A levels similar to zinc-defi cient
rats. They concluded that either zinc defi ciency or
growth depression decreases plasma vitamin A levels,
and postulated that zinc defi ciency per se may impair
hepatic RBP synthesis. It was not possible from their
data to establish if the reduction in plasma vitamin
A in the zinc-defi cient animals was a result of zinc
defi ciency per se or a secondary effect of reduced food
intake accompanying zinc defi ciency.
7.5.4 Vitamin E
It is generally recognized that vitamin E is necessary
for optimal utilization of vitamin A. More vitamin A is
stored in the liver when the diet contains vitamin E than
when the diet is defi cient in vitamin E (Ames, 1969).
Vitamin A: retinoids and carotenoids 151
7.6 The role of vitamin A in vision
7.6.1 Overview
The function of vitamin A in vision is based upon the
binding of 11-cis retinaldehyde with the protein opsin
to form rhodopsin (visual purple) in the rod cells of
the retina. Light energy induces the decomposition
(bleaching) of rhodopsin through several unstable
intermediates. Rhodopsin must regenerate in the
dark to prepare for another response to light. This is
accomplished via isomerization reactions of retinoids
in the visual cycle.
7.6.2 Structure and function of the retina
The retina is composed of nervous tissue forming a
photosensitive inner lining within the posterior half
of the eyeball. The actual light receptor cells – the
rods and cones – are modifi ed neurons. The layers of
the retina are shown in Fig. 7.9. The retinal pigment
epithelium is a monolayer of cells interposed between
the rich choroidal blood supply and the neural retina.
This epithelial monolayer creates the blood–retina
barrier, which prevents blood proteins and many
other substances of lower molecular weight from
entering the retinal interstitial space. The human retina contains about 3 million cones
and 100 million rods. Rod cells make it possible to
form black-and-white images in dim light, while
cones are responsible for colour vision in bright
light. Both rods and cones are divided into inner and
outer segments situated outside the external limiting
membrane, and a conducting nucleated portion lying
within the outer nuclear layer. The rods and cones
make synaptic connections with dendrites of bipolar
neurons of the inner nuclear layer and with axons of
horizontal neurons. The inner plexiform layer marks
the junction between the bipolar neurons and the
ganglion cells. These cells give rise to the optic nerve
fi bres which run as the innermost layer of the retina
towards the optic nerve head.
The rod cell is a long, thin structure divided into
two parts – the outer segment and the inner segment
(Fig. 7.10). The outer segment consists of a narrow
tube fi lled with a stack of some 2000 tiny discs that
contain the light-absorbing pigment rhodopsin. The
discs originate near the bottom of the tube as invaginations
of the plasma membrane. They gradually migrate
toward the top, replacing those that are shed and
phagocytosed. The inner segment contains organelles
that generate energy and renew the molecules required
for light absorption.
7.6.3 Rhodopsin
Rhodopsin is a stereospecifi c combination of a
chromophore (11-cis retinaldehyde) and a protein
(opsin), joined covalently in a Schiff base linkage by
the condensation of the aldehyde group of retinaldehyde
with the ε-amino group of a lysine residue (Fig.
7.11). The bent shape of the 11-cis isomer of retinaldehyde
allows it to fi t snugly into the opsin molecule and
also holds the protein in the conformation specifi c to
rhodopsin. No other stereoisomer of retinaldehyde can combine with opsin in this manner. Whereas free
11-cis retinaldehyde in solution absorbs radiation in
the ultraviolet (UV) region of the spectrum (maximal
absorbance at a wavelength of 380 nm), the chromophore
in rhodopsin absorbs the much more plentiful
radiation in the visible (green) region (maximal absorbance,
498 nm).