their release into circulation (e.g., liver disease and severe protein malnutrition). The relative dose response (RDR) is a method that permits indirect assessment of the relative adequacy of hepatic vitamin A stores. The RDR test was first demonstrated in rats where the release of RBP from liver was shown to depend on the availability of retinol (Loerch et al., 1979). In experimental vitamin A deficiency in rats, RBP accumulated in liver but was rapidly released after vitamin A (retinol) was administered (Carney et al., 1976; Keilson et al., 1979). This observation led Loerch et al. (1979) to propose that a positive plasma retinol response to a small test dose of vitamin A could be used as an indicator of inadequate liver vitamin A reserves.
The test was subsequently validated against measured liver retinol stores in humans (Amedee-Manesme et al., 1984, 1987; Mobarhan et al., 1981). For the test, a blood sample is drawn before retinol administration (zero time), and then a small dose of vitamin A is administered; a second blood sample is taken after an interval, generally 5 hours. The concentration of retinol in each sample is determined and the difference (response) in plasma retinol concentration (5 hours minus zero hours) is calculated and expressed as a percentage of the 5-hour concentration.
Although various cutoff levels have been used, a plasma retinol response greater than or equal to 20 percent is generally considered to indicate that liver vitamin A is inadequate (Tanumihardjo, 1993). The synthesis of RBP depends on the adequacy of other nutrients, and other deficiencies, such as zinc deficiency and protein energy malnutrition, can confound the results of the RDR test, particularly when a repeat test is conducted within a week or less after the first or baseline test. With proper controls the RDR test is considered a valid test to determine inadequate vitamin A status. However, just as plasma retinol concentration is insensitive across a wide range of “adequate” liver vitamin A reserves, the RDR test does not distinguish among different levels of adequate vitamin A reserves (Solomons et al., 1990).
The modified relative dose response (MRDR) test is a variation of the RDR test (Tanumihardjo and Olson, 1991). The MRDR requires a single blood sample and uses as the test dose vitamin A2 (dehydroretinol), which combines with RBP in the same manner as retinol but is not found endogenously in human plasma (with the possible exception of populations consuming high levels of fresh water fish). The test is subject to the same limitations as the RDR test. Neither the RDR nor the MRDR was chosen for estimating an EAR because little data exist relating usual dietary intakes of individuals or populations to RDR or MRDR test value distributions.