The Vitamins 135vegetables, as well as in liver, margarine, and milk and
milk products. In addition to their role as precursors
of vitamin A, carotenoids have potentially useful anti-
oxidant action, and there is epidemiological evidence
that diets that are rich in carotenoids (both those that
are vitamin A active and those that are not) are associ-
ated with a lower incidence of cancer and cardio-
vascular disease. However, intervention studies with
β-carotene have been disappointing, and it is not pos-
sible to determine desirable intakes of carotene other
than as a precursor of vitamin A.
Retinoic acid is a metabolite of retinol; it has
important biological activities in its own right and
will support growth in vitamin A-defi cient animals.
The oxidation of retinaldehyde to retinoic acid is irre-
versible. Retinoic acid cannot be converted in vivo to
retinol, and does not support either vision or fertility
in defi cient animals.
Some 50 or more dietary carotenoids are potential
sources of vitamin A: α-, β-, and γ-carotenes and
cryptoxanthin are quantitatively the most important.
Although it would appear from its structure that one
molecule of β-carotene will yield two of retinol,
this is not so in practice. Nutritionally, 6–12 μg of β-
carotene is equivalent to 1 μg of preformed retinol.
For other carotenes with vitamin A activity, 12–24 μg
is equivalent to 1 μg of preformed retinol.
Conventionally, the total amount of vitamin A in
foods is expressed as μg retinol equivalents, calculated
from the sum of μg of preformed vitamin A + 1/6
× μg β-carotene + 1/12 × μg other provitamin A
carotenoids. Recent studies on the absorption of caro-
tenes and their bioeffi cacy as vitamin A precursors
have led to the defi nition of retinol activity equiva-
lents. 1 μg retinol activity equivalent = 1 μg preformed
retinol, 12 μg β-carotene or 24 μg other provitamin
A carotenoids.
Before pure vitamin A was available for chemical
analysis, the vitamin A content of foods was deter-
mined by biological assays and the results were
expressed in standardized international units (IU):
1 IU = 0.3 μg of retinol, or 1 μg of retinol = 3.33 IU.
Although obsolete, IU are sometimes still used in
food labeling.
Metabolism and storage of vitamin A and
pro-vitamin A carotenoids
Retinol is absorbed from the small intestine dissolved
in lipid. About 70–90% of dietary retinol is normally
absorbed, and even at high levels of intake this falls
only slightly. However, in people with a very low fat
intake (less than about 10% of energy from fat),
absorption of both retinol and carotene is impaired,
and low-fat diets are associated with vitamin A
defi ciency.
Dietary retinyl esters are hydrolyzed by lipases in
the intestinal lumen and mucosal brush border mem-
brane, then re-esterifi ed to form retinyl palmitate
before release into the circulation in chylomicrons.
Tissues can take up retinyl esters from chylomi-
crons, but most retinol is in the chylomicron rem-
nants that are taken up by the liver. Here retinyl esters
are hydrolyzed, and the vitamin may either be secreted
from the liver bound to retinol binding protein, or be
transferred to stellate cells in the liver, where it is
stored as retinyl esters in intracellular lipid droplets.
Some 50–80% of the total body content of retinol is
in the stellate cells of the liver, but a signifi cant amount
may also be stored in adipose tissue.
The main pathway for catabolism of retinol is
oxidation to retinoic acid (which, as discussed
below, has important biological activities in its
own right, distinct from the activities of retinol).
The main excretory product of both retinol and
retinoic acid is retinoyl glucuronide, which is secreted
in the bile.
As the intake of retinol increases, and the liver con-
centration rises above 70 μmol/kg, a different pathway
becomes increasingly important for the catabolism of
retinol in the liver. This is a microsomal cytochrome
P 450 -dependent oxidation, leading to a number of
polar metabolites that are excreted in the urine and
bile. At high intakes this pathway becomes saturated,
and excess retinol is toxic since there is no further
capacity for its catabolism and excretion.Carotene dioxygenase
Like retinol, carotenoids are absorbed dissolved in
lipid micelles. The biological availability and absorp-
tion of dietary carotene varies between 5% and 60%,
depending on the nature of the food, whether it is
cooked or raw, and the amount of fat in the meal.
As shown in Figure 8.2, β-carotene and other pro-
vitamin A carotenoids are cleaved in the intestinal
mucosa by carotene dioxygenase, yielding retinalde-
hyde, which is reduced to retinol, then esterifi ed and
secreted in chylomicrons together with retinyl esters
formed from dietary retinol.