Vitamin A requirements and reference intakes
There have been relatively few studies of vitamin A requirements in which subjects have been depleted of the vitamin for long enough to permit the development of clear deficiency signs. Current estimates of requirements are based on the intakes required to maintain a concentration in the liver of 70 μmol retinol/kg, as determined by measurement of the rate of metabolism of isotopically labeled vitamin A. This is adequate to maintain normal plasma concentra-tions of the vitamin, and people with this level of liver reserves can be maintained on a vitamin A-free diet for many months before they develop any detectable signs of deficiency.
The average requirement to maintain a concentra-tion of 70 μmol/kg of liver is 6.7 μg retinol equiva-lents/kg body weight, and this is the basis for calculation of reference intakes.
The only direct assessment of vitamin A status is by liver biopsy and measurement of retinyl ester reserves.
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 field 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 deficiency. 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 deficiency, 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 deficiency) and the apparatus is not suited to use in the field.
The fasting plasma concentration of retinol remains constant over a wide range of intakes and only falls significantly 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 deficiency. 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.