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

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

Supplementation of iron alone and combined with vitamins improves haematological status, erythrocyte membrane fluidity and oxidative stress in anaemic pregnant women

Pregnancy is a condition exhibiting increased susceptibility to oxidative stress, and Fe plays a central role in generating harmful oxygen species. The objective of the present study is to investigate the changes in haematological status, oxidative stress and erythrocyte membrane fluidity in anaemic pregnant women after Fe supplementation with and without combined vitamins. The study was a 2 months double-blind, randomised trial. Pregnant women (n 164) were allocated to four groups: group C was the placebo control group; group I was supplemented daily with 60 mg Fe (ferrous sulphate) daily; group IF was supplemented daily with Fe plus 400 µg folic acid; group IM was supplemented daily with Fe plus 2 mg retinol and 1 mg riboflavin, respectively. After the 2-month trial, Hb significantly increased by 15·8, 17·3 and 21·8 g/l, and ferritin by 2·8, 3·6 and 11·0 µg/l, in the I, IF and IM groups compared with placebo. Polarisation (¿) and microviscosity (¿) decreased significantly in other groups compared with placebo, indicating an increase in membrane fluidity. Significant decreases of ¿ and ¿ values compared with group C were 0·033 and 0·959 for group I, 0·037 and 1·074 for group IF and 0·064 and 1·865 for group IM, respectively. In addition, significant increases of glutathione peroxidase activities and decreases of malondialdehyde were shown in all treated groups, as well as increases of plasma retinol and urine riboflavin in group IM. The findings show that supplementation with Fe and particularly in combination with vitamins could improve the haematological status as well as oxidative stress and erythrocyte membrane fluidit

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)

RPB4 and pathogenesis of diabetes

Obesity is an important risk factor for a number of chronic diseases that impose a huge burden on individuals and society. Recently it has become clear that adipose tissue-secreted products may play a significant role in mediating many obesity-related diseases including diabetes. Thus, in addition to being an energy depot, the adipocyte is a highly active cell, secreting a plethora of factors with profound effects on a number of organs and systems. The study of these factors and their endocrine effects has become a rapidly evolving and dynamic area of endocrinology. One paradigm for explaining the deleterious effects of adipokines is related to the sheer increase in adipose tissue mass in obesity. When preadipocytes differentiate to become mature adipocytes, they acquire the ability to synthesize numerous proteins, including cytokines, growth factors, and hormones that are involved in overall energy homeostasis and various paracrine effects. In health, these proteins do not spill over significantly into the circulation. In obesity, the massive increase in fat mass leads to a significant increase in circulation of many adipose tissue secreted factors that may have pathogenic effects. For example, the increase in circulating angiotensin II in obesity is related at least in part due to excess adiposity and may mediate hypertension (1). In recent years, adipose tissue has been found to be a major source of many proteins that may directly contribute to vascular injury, diabetes, and atherogenesis (2). These proinflammatory adipokines include TNF-α, IL-6, leptin, plasminogen activator inhibitor-1, angiotensinogen, and resistin, among many others. In contrast, the adipokine adiponectin confers protection against inflammation, atherogenesis, and obesity-linked insulin resistance