ABSTRACT
Background: Serum retinol decreases transiently during the
acute phase response and can thus result in misclassification of
vitamin A status.
Objective: Our objective was to determine the prevalence of
acute phase response activation in a representative sample of the
US population, identify the factors associated with this activa-
tion, and determine whether persons with an active acute phase
response have lower serum retinol concentrations.
Design: Data from the third National Health and Nutrition
Examination Survey (NHANES III) were analyzed. A serum
C-reactive protein (CRP) concentration 10 mg/L indicated an active acute phase response.
Results: Mean serum retinol was lowest in subjects aged < 10 y and increased with age. Concentrations were higher in males
than in females aged 2059 y. The prevalence of a CRP concen-
tration 10 mg/L was lowest in subjects aged <20 y (4%) and increased with age to a maximum of nearly 15%. An elevated
CRP concentration was 2.4-fold greater in females than in males
aged 2059 y. Serum retinol was lower in subjects with elevated
CRP concentrations.
Conclusions: Serum retinol increases with age and males have
higher mean values than do females aged 2059 y. The preva-
lence of a CRP concentration 10 mg/L also increases with age, is 2-fold greater in females than in males aged 2069 y, and is
associated with common inflammatory conditions. Thus, inflam-
mation appeared to contribute to the misclassification of vitamin
A status in the NHANES III population, and serum CRP is use-
ful in identifying subjects who may be misclassified. Am J Clin Nutr 2000;72:11708. KEY WORDS Retinol, vitamin A, acute phase response, C-reactive protein, CRP, third National Health and Nutrition
Examination Survey, NHANES III, infection, inflammation INTRODUCTION Serum retinol concentrations are normally maintained within a narrow range in individuals with adequate liver vitamin A stores.
When liver stores are depleted, serum retinol concentrations
decrease. Thus, serum retinol is a useful indicator of vitamin A
status and can be used to identify subjects with low or depleted
liver vitamin A stores (1, 2). However, serum retinol concentra- tions decrease transiently during the acute phase response to infec-
tion (37). Such decreases do not reect changes in liver vitamin A
stores and, thus, can interfere with the use of serum retinol as an
indicator of vitamin A status. Similar changes also occur with
other micronutrients, including iron and zinc (8). In populations in
whom infections are highly prevalent, such as young children liv-
ing in poor areas of developing countries, this phenomenon can be
a source of false-positive results in surveys designed to determine
the prevalence of micronutrient deciencies (9). The decrease in serum retinol seen during infection is an integral part of the acute phase response, which is induced not
only by infection but also by tissue-damaging trauma such as
surgery or by chronic inflammatory conditions such as arthritis
(1012). During the acute phase response the synthesis of neg-
ative acute phase proteins, such as retinol binding protein
(RBP), decreases (13). This contributes to the lower serum con-
centration of these proteins, although other factors also con-
tribute (4, 14). A hallmark of the acute phase response is the
rapid and substantial increase in synthesis of positive acute
phase proteins, which are involved in controlling infection and
resolving tissue damage caused by inflammation (11). For
example, serum C-reactive protein (CRP) concentrations
increase within a few hours (15) and reach peak concentrations
as much as 1000-fold above baseline within a few days (12).
The half-life of CRP in serum is 6 h; thus, serum CRP concen-
trations decrease to normal within days after the proinflamma-
tory stimulus has been eliminated (16). Serum retinol has been used to assess the vitamin A status of the US population in the National Health and Nutrition
Examination Surveys (NHANES) and the Hispanic HANES Am J Clin Nutr 2000;72:11708. Printed in USA.