Introduction to Human Nutrition

140 Introduction to Human Nutrition

This is an invasive procedure that cannot be consid-
ered for routine investigations and population surveys.
Status can also be assessed by clinical and functional
tests, the plasma concentrations of retinol and RBP,
and the response to a test dose of vitamin A, the RDR
test.
In fi eld surveys, clinical signs of vitamin A defi -
ciency, including Bitot’s spots, corneal xerosis, corneal
ulceration, and keratomalacia, can be used to identify
those suffering from vitamin A defi ciency. The earliest
signs of corneal damage are detected by conjunctival
impression cytology (CIC); however, abnormalities
only develop when liver reserves are seriously
depleted.
The ability to adapt to dim light is impaired early
in defi ciency, and dark adaptation time is sometimes
used to assess vitamin A status. However, the test is
not suitable for use on children (the group most at
risk of defi ciency) and the apparatus is not suited to
use in the fi eld.
The fasting plasma concentration of retinol remains
constant over a wide range of intakes and only falls
signifi cantly when liver reserves are nearly depleted.
Therefore, although less sensitive to subtle changes
within the normal range than some methods of
assessing nutritional status, measurement of plasma
retinol provides a convenient and sensitive means of
detecting people whose intake of vitamin A is inade-
quate to maintain normal liver reserves.
The RDR test is a test of the ability of a dose of
retinol to raise the plasma concentration several hours
after chylomicrons have been cleared from the circu-
lation. It depends on the fact that apo-RBP accumu-
lates in the liver in vitamin A defi ciency. The RDR is
the ratio of the plasma concentration of retinol 5 h
after the dose to that immediately before it was given.
An RDR greater than 20% indicates depletion of liver
retinol to less than 70 μmol/kg.

Toxicity of vitamin A

There is only a limited capacity to metabolize vitamin
A. Excessively high intakes lead to accumulation in
the liver and other tissues, beyond the capacity of
normal binding proteins, so that free, unbound,
vitamin A is present. This leads to liver and bone
damage, hair loss, vomiting, and headaches. Single
doses of 60 mg of retinol are given to children in
developing countries as a prophylactic against vitamin
A defi ciency: an amount adequate to meet the child’s

needs for 4–6 months. About 1% of children so

treated show transient signs of toxicity, but this is

considered an acceptable risk in view of the high

prevalence and devastating effects of defi ciency.

The chronic toxicity of vitamin A is a more general

cause for concern; prolonged and regular intake of

more than about 7.5–9 mg/day by adults (and signifi -

cantly less for children) causes signs and symptoms

of toxicity affecting:

● the central nervous system: headache, nausea, ataxia

and anorexia, all associated with increased cerebro-

spinal fl uid pressure

● the liver: hepatomegaly with histological changes

in the liver, increased collagen formation and

hyperlipidemia

● bones: joint pains, thickening of the long bones,

hypercalcemia and calcifi cation of soft tissues

● the skin: excessive dryness, scaling and chapping of

the skin, desquamation and alopecia.

The recommended upper limits of habitual intake of

retinol, compared with reference intakes, are shown

in Table 8.2. As discussed above, habitual high intakes

of vitamin A, albeit below these prudent upper levels

of intake, may be associated with impaired respon-

siveness to vitamin D, poor mineralization of bone

and the early development of osteoporosis.

Teratogenicity of vitamin A

The synthetic retinoids (vitamin A analogues) used in

dermatology are highly teratogenic. After women

have been treated with them, it is recommended

that contraceptive precautions be continued for 12

months, because of their retention in the body. By

Table 8.2 Prudent upper levels of habitual vitamin A intake

Upper limit of intake Reference intakesa

Age group (μg/day) (μg/day)

Infants 900 350–375

1–3 years 1800 400

4–6 years 3000 400–500

6–12 years 4500 500–700

13–20 years 6000 600–700

Adult men 9000 600–1000

Adult women 7500 600–800

Pregnant women 3000–3300 700

a Reference intakes show range for various national and international

authorities.