Serum levels of retinol and other antioxidants for hearing impairment among Japanese older adults.

BACKGROUND: The objective of this study was to assess the relation between serum levels of retinol and other antioxidants and hearing impairment in Japanese older adults. METHODS: This is a community-based cross-sectional study comprising 762 residents aged 65 years or older in Kurabuchi, Gumma, Japan. We measured serum retinol and other antioxidants (alpha- and gamma-tocopherols, and carotenoids including beta-cryptoxanthin, alpha- and beta-carotenes, lycopene, and lutein plus zeaxanthin) by high-performance liquid chromatography and divided each measurement into quartiles. Hearing impairment was defined as a failure to hear a 30-dB hearing level (HL) signal at 1 kHz and a 40-dB HL signal at 4 kHz in the better ear in pure-tone audiometric tests. The odds ratios (OR) for hearing impairment were calculated for each of the upper three quartiles of retinol and other antioxidant levels relative to the lowest quartile. RESULTS: Crude analysis showed that serum levels of retinol and provitamin A carotenoids (beta-cryptoxanthin, and alpha- and beta-carotenes) were inversely related to the prevalence of hearing impairment. The multiadjusted ORs (95% confidence intervals) for the highest quartile of retinol and the provitamin A family (combinations of provitamin A carotenoids) compared with the lowest were 0.51 (0.26-1.00) and 0.53 (0.27-1.02), respectively. A dose-response relationship was observed for retinol (p = .03) and provitamin A (p = .09). CONCLUSION: Increased serum levels of retinol and provitamin A carotenoids were clearly associated with a decreased prevalence of hearing impairment

The retina visual cycle is driven by cis retinol oxidation in the outer segments of cones

Vertebrate rod and cone photoreceptors require continuous supply of chromophore for regenerating their visual pigments after photoactivation. Cones, which mediate our daytime vision, demand a particularly rapid supply of 11-cis retinal chromophore in order to maintain their function in bright light. An important contribution to this process is thought to be the chromophore precursor 11-cis retinol, which is supplied to cones from Müller cells in the retina and subsequently oxidized to 11-cis retinal as part of the retina visual cycle. However, the molecular identity of the cis retinol oxidase in cones remains unclear. Here, as a first step in characterizing this enzymatic reaction, we sought to determine the subcellular localization of this activity in salamander red cones. We found that the onset of dark adaptation of isolated salamander red cones was substantially faster when exposing directly their outer vs. their inner segment to 9-cis retinol, an analogue of 11-cis retinol. In contrast, this difference was not observed when treating the outer vs. inner segment with 9-cis retinal, a chromophore analogue which can directly support pigment regeneration. These results suggest, surprisingly, that the cis-retinol oxidation occurs in the outer segments of cone photoreceptors. Confirming this notion, pigment regeneration with exogenously added 9-cis retinol was directly observed in the truncated outer segments of cones, but not in rods. We conclude that the enzymatic machinery required for the oxidation of recycled cis retinol as part of the retina visual cycle is present in the outer segments of cones

Comparison of the Effects of Supplemental Red Palm Oil and Sunflower oil on Maternal Vitamin A Status.

Conflicting results have been reported on the ability of dietary carotenoids to improve vitamin A status in lactating women. Red palm oil is one of the richest dietary sources of beta-carotene. We aimed to determine the efficacy of red palm oil in increasing retinol and provitamin A status in pregnant and lactating women. Ninety rural, pregnant Tanzanian women from 3 randomly selected villages were recruited during their third trimester to participate in 3 dietary intervention groups: a control group, who were encouraged to maintain the traditional practice of eating staples with dark-green leafy vegetables, and 2 study groups, who were given either sunflower or red palm oil for use in household food preparations. The intervention lasted 6 mo. Plasma samples were collected at the third trimester and 1 and 3 mo postpartum, and breast-milk samples were collected 1 and 3 mo postpartum. Supplementation with red palm oil, which is rich in provitamin A, increased alpha- and beta-carotene concentrations significantly (P < 0.001) in both plasma and breast milk. Plasma retinol concentrations were similar in all dietary groups. Breast-milk retinol concentrations tended to decrease from 1 to 3 mo postpartum in the control group, but were maintained in both oil groups. The difference in change in breast-milk retinol concentration between the red palm oil group and the control group was significant (P = 0.041). Consumption of red palm oil increases concentrations of alpha- and beta-carotene in both breast milk and serum and maintains breast-milk retinol concentrations. Sunflower oil consumption seems to conserve breast-milk retinol similarly to consumption of red palm oil. Breast-milk retinol might be maintained through increased dietary intake of these vegetable oils and use of mild cooking preparation methods (such as the addition of oil at the end of cooking and avoidance of frying)

Vitamin A Metabolism by Dendritic Cells Triggers an Antimicrobial Response against Mycobacterium tuberculosis.

Epidemiological evidence correlates low serum vitamin A (retinol) levels with increased susceptibility to active tuberculosis (TB); however, retinol is biologically inactive and must be converted into its bioactive form, all-trans retinoic acid (ATRA). Given that ATRA triggers a Niemann-Pick type C2 (NPC2)-dependent antimicrobial response against Mycobacterium tuberculosis, we investigated the mechanism by which the immune system converts retinol into ATRA at the site of infection. We demonstrate that granulocyte-macrophage colony-stimulating factor (GM-CSF)-derived dendritic cells (DCs), but not macrophages, express enzymes in the vitamin A metabolic pathway, including aldehyde dehydrogenase 1 family, member a2 (ALDH1A2) and short-chain dehydrogenase/reductase family, member 9 (DHRS9), enzymes capable of the two-step conversion of retinol into ATRA, which is subsequently released from the cell. Additionally, mRNA and protein expression levels of ALDH1A2 and DC marker CD1B were lower in tuberculosis lung tissues than in normal lung. The conditioned medium from DCs cultured with retinol stimulated antimicrobial activity from M. tuberculosis-infected macrophages, as well as the expression of NPC2 in monocytes, which was blocked by specific inhibitors, including retinoic acid receptor inhibitor (RARi) or N,N-diethylaminobenzaldehyde (DEAB), an ALDH1A2 inhibitor. These results indicate that metabolism of vitamin A by DCs transactivates macrophage antimicrobial responses.IMPORTANCE Tuberculosis (TB) is the leading cause of death by a single infectious agent worldwide. One factor that contributes to the success of the microbe is the deficiency in immunomodulatory nutrients, such as vitamin A (retinol), which are prevalent in areas where TB is endemic. Clinical trials show that restoration of systemic retinol levels in active TB patients is ineffective in mitigating the disease; however, laboratory studies demonstrate that activation of the vitamin A pathway in Mycobacterium tuberculosis-infected macrophages triggers an antimicrobial response. Therefore, the goal of this study was to determine the link between host retinol levels and retinoic acid-mediated antimicrobial responses against M. tuberculosis By combining established in vitro models with in situ studies of lung tissue from TB patients, this study demonstrates that the innate immune system utilizes transcellular metabolism leading to activation between dendritic cells and macrophages as a means to combat the pathogen

Vitamin A and iron supplementation of Indonesian pregnant women benefits vitamin A status of their infants

Many Indonesian infants have an inadequate nutritional status, which may be due in part to inadequate maternal nutrition during pregnancy. This study was designed to investigate whether infant nutritional status could be improved by maternal vitamin A and Fe supplementation during gestation. Mothers of these infants from five villages had been randomly assigned on an individual basis, supervised and double-blind, to receive supplementation once weekly from approximately 18 weeks of pregnancy until delivery. Supplementation comprised 120 mg Fe and 500 μg folic acid with or without 4800 retinol equivalent vitamin A. Mothers of infants from four other villages who participated in the national Fe and folic acid supplementation programme were also recruited; intake of tablets was not supervised. Anthropometric and biochemical parameters of infants and their mothers were assessed approximately 4 months after delivery. Infants of mothers supplemented with vitamin A plus Fe had higher serum retinol concentrations than infants of mothers supplemented with Fe alone. However, the proportion of infants with serum retinol concentrations 70 n all groups. Maternal and infant serum retinol concentrations were correlated. Fe status, weight and length of infants were similar in all groups. Fe status of girls was better than that of boys, but boys were heavier and longer. We conclude that supplementation with vitamin A in conjunction with Fe supplementation of women during pregnancy benefits vitamin A status of their infants. However, considering the large proportion of infants with marginal serum retinol concentrations, it may still be necessary to increase their vitamin A intake

Metabolic interactions between vitamin A and conjugated linoleic acid

Lipid-soluble molecules share several aspects of their physiology due to their common adaptations to a hydrophilic environment, and may interact to regulate their action in a tissue-specific manner. Dietary conjugated linoleic acid (CLA) is a fatty acid with a conjugated diene structure that is found in low concentrations in ruminant products and available as a nutritional supplement. CLA has been shown to increase tissue levels of retinol (vitamin A alcohol) and its sole specific circulating carrier protein retinol-binding protein (RBP or RBP4). However, the precise mechanism of this action has not been elucidated yet. Here, we provide a summary of the current knowledge in this specific area of research and speculate that retinol and CLA may compete for catabolic pathways modulated by the activity of PPAR- and RXR heterodimer. We also present preliminary data that may position PPAR- at the crossroads between the metabolism of lipids and vitamin

Vitamin A Transport Mechanism of the Multitransmembrane Cell-Surface Receptor STRA6.

Vitamin A has biological functions as diverse as sensing light for vision, regulating stem cell differentiation, maintaining epithelial integrity, promoting immune competency, regulating learning and memory, and acting as a key developmental morphogen. Vitamin A derivatives have also been used in treating human diseases. If vitamin A is considered a drug that everyone needs to take to survive, evolution has come up with a natural drug delivery system that combines sustained release with precise and controlled delivery to the cells or tissues that depend on it. This "drug delivery system" is mediated by plasma retinol binding protein (RBP), the principle and specific vitamin A carrier protein in the blood, and STRA6, the cell-surface receptor for RBP that mediates cellular vitamin A uptake. The mechanism by which the RBP receptor absorbs vitamin A from the blood is distinct from other known cellular uptake mechanisms. This review summarizes recent progress in elucidating the fundamental molecular mechanism mediated by the RBP receptor and multiple newly discovered catalytic activities of this receptor, and compares this transport system with retinoid transport independent of RBP/STRA6. How to target this new type of transmembrane receptor using small molecules in treating diseases is also discussed