When does hyporetinolemia mean vitamin A deficiency?

Abstract

Serum retinol, which is bound to retinol binding protein (RBP), has at least 2 roles. One role (created by nutritionists) is to serve as an indicator of vitamin A status. Another role is to serve as the transport form of vitamin A from liver stores to peripheral tissues. Although most nutritionists would agree that the former role of serum retinol can be transiently compromised during the acute phase response, convincing evidence that the latter role is significantly compromised under the same circumstances is lacking. The authors of 2 studies—one involving women with night blindness (1) and the other involving children with night blindness or Bitot spots (2)—raise, but do not answer, the question of whether the low serum retinol concentrations seen during the acute phase response cause clinical manifestations of vitamin A deficiency (eg, night blindness). Serum retinol concentrations decrease transiently during the acute phase response to infection and trauma for several reasons, including decreased release of retinol-RBP from the liver (3). Thus, serum retinol concentrations typically rebound during resolution of the acute phase response as retinol is again released from the liver. This phenomenon can complicate the use of serum retinol as an indicator of vitamin A status because by status, nutritionists typically mean the amount of vitamin A stored in the liver (4). Whereas infection or trauma may lead to loss of vitamin A from body stores during severe infections (5), transient decreases in serum retinol occur during mild episodes of infection and trauma as well and thus are clearly not directly related to decreases in liver vitamin A stores in such cases. These transient decreases impair the assessment of nutritional status when they decrease serum retinol concentrations to the extent that subjects may be misclassified as having less than adequate liver vitamin A stores when, in fact, their stores are adequate. Persons with an active acute phase response may be identified by measuring serum concentrations of positive acute phase proteins, such as C-reactive protein (CRP) and a1-acid glycoprotein (AGP), which increase during the acute phase response (6). Such markers can be used to identify subjects with low serum retinol who may be misclassified as vitamin A deficient because of the acute phase response, a remedy that has been suggested to adjust measurements of other micronutrients as well (7). The concentrations of these acute phase proteins typically have a strong, negative correlation with serum retinol during the acute phase response. Semba et al (2) and Christian et al (1) found that such negative correlations are also found in subjects with clinical vitamin A deficiency, confirming that decreases in serum retinol induced by the acute phase response occur across a wide spectrum of vitamin A status. These findings are not unexpected.