Vitamin A is the name given to a group of
biologically active, fat-soluble molecules that includes retinol,
retinal and retinoic acid.1,2 These retinoid compounds are
derived from the plant precursor molecule, ß-carotene. ß-carotene (also
referred to as provitamin A) has a structure that consists of two
molecules of retinal linked at their aldehyde ends.1 ß-carotene is converted to vitamin A by intestinal absorptive cells and hepatocytes.1,2 Vitamin A is stored in the liver and transported to extrahepatic tissues bound to retinol binding protein and albumin.1 Both retinol and ß-carotene levels are measured in plasma for assessing vitamin A inadequacy and/or toxicity.
Vitamin
A exists in humans in several forms and is tightly controlled.
Naturally occurring forms of vitamin A include retinol, retinol esters,
retinal and retinoic acid. The alcohol form, retinol, predominates in
the circulation, but it is too toxic for storage. Instead, the liver
stores as retinyl esters - principally palmitate. The active form of
vitamin A in the visual cycle is the aldehyde form, retinal. Retinoic
acid is the form in tissues responsible for the biological actions of
vitamin A in cellular division and differentiation.11
The
most important measurand for the estimation of vitamin A status is
circulating vitamin A as retinol. Serum retinol levels do not accurately
reflect liver retinyl ester levels. Despite this limitation, serum
retinol is still useful because the levels will diminish once the supply
from the liver is diminished. The serum retinol level at which vitamin A
deficiency occurs will coincide with the manifestation of night
blindness, due to the interruption of the visual cycle by lack of
retinal. Other more serious symptoms will occur later when retinoic acid
is depleted by even less available hepatic retinyl esters.12
The body must acquire vitamin A from the diet in order to sustain a number of essential physiological processes.3 These
include vision, organogenesis, tissue differentiation, immune function,
reproduction, embryonic development and maintenance of healthy skin and
barrier functions.3-7 More than five hundred genes are thought to be regulated by vitamin A.3
Vitamin A deficiency only manifests when liver stores are depleted by prolonged reduction of dietary intake.1,10
In healthy individuals, serum retinol concentrations are
homeostatically controlled and do not begin to decline until liver
reserves of vitamin A are dangerously low.2,4,10 The initial symptom of vitamin A deficiency is an inability to adapt vision to darkness (ie, night blindness).1 Vitamin A is an essential component of rhodopsin, a protein that absorbs light in the retinal receptors.2 Vitamin A also supports the normal differentiation and functioning of the conjunctival membranes and cornea.2
Protracted vitamin A deficiency causes degenerative changes in the
retina due to progressive keratinization of the cornea, a condition
referred to as xerophthalmia.2 In developing countries, vitamin A deficiency is the most common cause of preventable blindness.
Additional
symptoms of vitamin A deficiency include follicular hyperkeratosis,
increased susceptibility to infection and an anemia similar to iron
deficient anemia.1 ß-carotene is an important, but
insufficient, source of vitamin A among poor populations due to the
inefficiency of the conversion to retinol.5 Vitamin A
deficiency in poor countries is also a significant cause of infection
and death, particularly from diarrhea and measles.6
Excessive
levels of vitamin A can lead to toxicity. Vitamin A intoxication is a
concern in normal adults who ingest more than 15 mg per day and children
who ingest more than 6 mg per day of vitamin A for a period of several
months. The symptoms of acute vitamin A toxicity include dizziness,
nausea, vomiting, headaches, blurred vision, vertigo, reduced muscle
coordination, skin exfoliation.13,14 More chronic vitamin A
toxicity symptoms include weight loss, fatigue cheilosis, glossitis,
alopecia, bone demineralization, hypercalcemia, lymph node enlargement,
hyperlipidemia and amenorrhea. Excess accumulation of vitamin A in the
liver can also lead to hepatosplenomegaly, liver fibrosis with portal
hypertension.1,13 Congenital malformations, including
craniofacial abnormalities and valvular heart disease as well as
spontaneous abortions have been reported in children born to pregnant
women taking vitamin A in excess. A number of studies have reported an
increased risk of lung cancer among high-risk individuals (smokers and
asbestos workers) who were given high doses of ß-carotene alone or in
combination with other antioxidants.5
Toxicity
generally results from excessive ingestion of vitamin A supplements but
regular intake of large amounts of liver, although usually not a problem
in vitamin A-deficient areas, may also result in toxicity due to its
high content of vitamin A.15
The World Health Organization recommendations supplementation when vitamin A levels fall below 20.0 ug/dL.16 Severe deficiency is indicated at levels <10.0 ug/dL. 2,9,10
