Plasma Retinol Concentrations Research Articles

Alterations in vitamin A/retinoic acid homeostasis in diet-induced obesity and insulin resistance.

Vitamin A is an essential micronutrient for life and the phytochemical β-carotene, also known as pro-vitamin A, is an important dietary source of this vitamin. Vitamin A (retinol) is the parent compound of all bioactive retinoids but it is retinoic acid (RA) that is the active metabolite of vitamin A. The plasma concentration of retinol is maintained in a narrow range and its normal biological activities strictly regulated since excessive intake can lead to toxicity and thus also be detrimental to life. The present review will give an overview of how vitamin A homeostasis is maintained and move on to focus on the link between circulating vitamin A and metabolic disease states. Finally, we will examine how pharmacological or genetic alterations in vitamin A homeostasis and RA-signalling can influence body fat and blood glucose levels including a novel link to the liver secreted hormone fibroblast growth factor 21, an important metabolic regulator.

Validation of blood vitamin A concentrations in cattle: comparison of a new cow-side test (iCheck\u2122 FLUORO) with high-performance liquid chromatography (HPLC)

BackgroundPlasma concentration of retinol is an accepted indicator to assess the vitamin A (retinol) status in cattle. However, the determination of vitamin A requires a time consuming multi-step procedure, which needs specific equipment to perform extraction, centrifugation or saponification prior to high-performance liquid chromatography (HPLC).MethodsThe concentrations of retinol in whole blood (n = 10), plasma (n = 132) and serum (n = 61) were measured by a new rapid cow-side test (iCheck™ FLUORO) and compared with those by HPLC in two independent laboratories in Germany (DE) and Japan (JP).ResultsRetinol concentrations in plasma ranged from 0.033 to 0.532 mg/L, and in serum from 0.043 to 0.360 mg/L (HPLC method). No significant differences in retinol levels were observed between the new rapid cow-side test and HPLC performed in different laboratories (HPLC vs. iCheck™ FLUORO: 0.320 ± 0.047 mg/L vs. 0.333 ± 0.044 mg/L, and 0.240 ± 0.096 mg/L vs. 0.241 ± 0.069 mg/L, lab DE and lab JP, respectively). A similar comparability was observed when whole blood was used (HPLC vs. iCheck™ FLUORO: 0.353 ± 0.084 mg/L vs. 0.341 ± 0.064 mg/L). Results showed a good agreement between both methods based on correlation coefficients of r2 = 0.87 (P < 0.001) and Bland-Altman blots revealed no significant bias for all comparison.ConclusionsWith the new rapid cow-side test (iCheck™ FLUORO) retinol concentrations in cattle can be reliably assessed within a few minutes and directly in the barn using even whole blood without the necessity of prior centrifugation. The ease of the application of the new rapid cow-side test and its portability can improve the diagnostic of vitamin A status and will help to control vitamin A supplementation in specific vitamin A feeding regimes such as used to optimize health status in calves or meat marbling in Japanese Black cattle.

Virgin olive oil enriched with its own phenolic compounds or complemented with thyme improves endothelial function: The potential role of plasmatic fat-soluble vitamins. A double blind, randomized, controlled, cross-over clinical trial

The aim of the present study was to assess whether different functional virgin olive oils (FVOOs) with varying phenolic compounds (PC) could protect the plasmatic fat-soluble vitamins, which in turn could improve the endothelial function. In order to select the optimal phenolic dose in the improvement of ischemic reactive hyperemia (IRH), a dose-response study (n=12, healthy subjects) was performed and the enrichment of 500mg PC/kg oil was selected. In a 3-week cross-over sustained study (n=33 hypercholesterolemic subjects), the consumption of 25mL/day of two phenol-enriched olive oils (one enriched with its own PC and another combined with thyme PC) increased IRH and plasma concentrations of retinol, β-cryptoxanthin and α-tocopherol, compared to a control virgin olive oil. A positive post-intervention correlation was observed for IRH values and HDL-c, β-cryptoxanthin, lutein and α-tocopherol. Results suggest that preservation of plasmatic fat-soluble vitamins by PC from FVOOS could partially explain the endothelial function benefits.

Short-Term Daily Consumption of Provitamin A Carotenoid–Biofortified Maize Has Limited Impact on Breast Milk Retinol Concentrations in Zambian Women Enrolled in a Randomized Controlled Feeding Trial

Background: Provitamin A carotenoid–biofortified maize is a conventionally bred staple crop designed to help prevent vitamin A deficiency. Lactating women are a potential target group, because regularly eating biofortified maize may increase vitamin A in breast milk—a critical source of vitamin A for breastfeeding infants.Objective: We assessed whether daily consumption of biofortified orange maize would increase the retinol concentration in the breast milk of Zambian women.Methods: Lactating women (n = 149) were randomly assigned to receive orange maize delivering 600 μg retinol equivalents (REs)/d as carotenoid plus placebo (OM), low-carotenoid white maize plus 600 μg REs/d as retinyl palmitate (VA), or white maize plus placebo (WM). Boiled maize (287 g dry weight/d) was served as 2 meals/d, 6 d/wk for 3 wk. We measured initial and final breast milk plasma retinol and β-carotene concentrations, and plasma inflammatory protein concentrations.Results: Groups were comparable at enrollment, with an overall geometric mean milk retinol concentration of 0.95 μmol/L (95% CI: 0.86, 1.05 μmol/L); 56% of samples had milk retinol <1.05 μmol/L. Median capsule and maize intake was 97% and 258 g dry weight/d, respectively. Final milk β-carotene did not vary across groups (P = 0.76). Geometric mean (95% CI) milk retinol concentration tended to be higher in the OM [1.15 μmol/L (0.96, 1.39 μmol/L)] and VA [1.17 μmol/L (0.99, 1.38 μmol/L)] groups than in the WM group [0.91 μmol/L (0.72, 1.14 μmol/L); P = 0.13], and the proportion of women with milk retinol <1.05 μmol/L was 52.1%, 42.9%, and 36.7% in the WM, OM, and VA groups, respectively (P-trend = 0.16).Conclusions: Daily biofortified maize consumption did not increase mean milk retinol concentration in lactating Zambian women; however, there was a plausible downward trend in the risk of low milk retinol across intervention groups. This trial was registered at clinicaltrials.gov as NCT01922713.

Mid-upper arm circumference is associated with biochemically determined nutritional status indicators among adolescent girls in Central Mozambique

Biochemically determined nutritional status measurements in low-income countries are often too expensive. Therefore, we hypothesized that some anthropometrical or functional measurements (handgrip) could reflect nutritional status measured by specific biochemical indicators. We did a population-based study from 1 urban area and 2 rural districts in Zambézia Province of Mozambique. The participants (n=386) were non-pregnant adolescent girls between 15 and 18 years of age. 96% had a normal BMI-for-age score. Weight and mid-upper arm circumference (MUAC) were highly correlated (r>0.8) with each other and with total body muscle mass, body mass index (BMI), and with waist circumference, as well as with skinfolds (r>0.6). Upper and total arm lengths were correlated (r>0.7) with height and with each other, and right and left handgrip were correlated only with each other, as were triceps and subscapular skinfolds (r>0.7). Serum albumin correlated negatively with waist circumference (P<.001) and positively with MUAC (P=.007). Stepwise regressions showed that waist circumference, MUAC, weight, and handgrip were important nutritional status indicators in the models using hemoglobin, serum albumin, ferritin, zinc, and plasma retinol concentrations as dependent variables. MUAC could be a valuable anthropometric marker of the overall nutritional status of adolescent girls in low-income countries. When nutrition transition proceeds, waist circumference together with MUAC could form tools for the prediction of worsening of nutritional status.

Contaminant concentrations and biomarkers in 21-day old Herring Gulls (Larus argentatus) and Double-crested Cormorants (Phalacrocorax auritus) from eastern Lake Ontario, and from Hamilton Harbour in western Lake Ontario in 1989 and 1990

This study measured concentrations of polychlorinated biphenyls, polycyclic aromatic hydrocarbons, organochlorine pesticides, trace metals and biochemical markers of contaminant exposure and potential toxicity (plasma and hepatic retinol, hepatic retinyl palmitate, ethoxyresorufin O-deethylase, hepatic porphyrins) in 21 day-old Herring Gull (Larus argentatus) and Double-crested Cormorant (Phalacrocorax auritus) chicks. The chicks were collected from breeding colonies at Hamilton Harbour, an industrialized site in western Lake Ontario, and at Snake and Pigeon Islands in eastern Lake Ontario in 1989 and 1990. The polycyclic aromatic hydrocarbons, benzo[a]pyrene and naphthalene, were detected in bile and concentrations were higher in both species, but particularly in Cormorants, at Hamilton Harbour in comparison to eastern Lake Ontario. Ethoxyresorufin O-deethylase activity correlated positively with polyaromatic hydrocarbon exposure in Cormorants. At Hamilton Harbour, Cormorants had significantly greater liver to body weight ratios, increased hepatic ethoxyresorufin O-deethylase activities and elevated plasma retinol concentrations compared to those from eastern Lake Ontario. Liver concentrations of selected polychlorinated biphenyl congeners were generally low (&amp;lt;2 ug g−1 w.wt) in birds from both areas but Hamilton Harbour Herring Gulls had mean concentrations that were significantly higher than eastern Lake Ontario Gulls, while Cormorants had low and similar polychlorinated biphenyl concentrations between sites. Trace metal levels did not vary substantially between sites for either species.

Interactions between retinol, α-tocopherol and cholecalciferol need consideration in diets for farmed mink (Mustela vison).

A sufficient but balanced vitamin supplementation is a prerequisite for a satisfactory growth pattern and an effective immune system in mink and all other species. The fat-soluble vitamins are very sensitive to over- or under-supply because they interact with each other with respect to dose-response and chemical form. The purpose of the present study was to investigate the effect of increasing the amount of retinol in combination with RRR-α-tocopherol or all-rac-α-tocopherol in the feed given to growing mink on their retinol, cholecalciferol and α-tocopherol concentrations in plasma and selected organs. The results showed that the mink met their retinol requirements from the basal diet, but there were no negative effects of supplying various amounts of retinol on their plasma α-tocopherol concentrations. On the other hand, the study showed that the cholecalciferol status in plasma, assessed as the 25-hydroxycholecalciferol concentration, was low when retinol was supplemented in the feed at high levels. In addition, supplementation with RRR-α-tocopherol in the feed negatively affected the plasma concentration of 25-hydroxycholecalciferol compared with supplementation with all-rac-α-tocopherol. In general, female mink had higher concentrations of fat-soluble vitamins in plasma than male mink.

Temporal plasma vitamin concentrations are altered by fat-soluble vitamin administration in suckling pigs.

Piglets are born with purportedly low plasma vitamin D levels. The objective of this study was to investigate the effect of fat-soluble vitamin administration, primarily vitamin D, by different administration routes on plasma vitamin concentrations in suckling pigs. A total of 45 pigs from 5 litters were allotted at birth to 3 treatments within each litter. Pigs were administered 400 IU of α-tocopherol, 40,000 IU of retinyl palmitate, and 40,000 IU of vitamin D at d 1 of age either orally or by i.m. injection and compared with control pigs with no supplemental vitamin administration. Blood samples were collected at d 0 (initial), 1, 2, 3, 4, 6, 9, 14, and 20 after administration. Plasma 25-hydroxycholecalciferol (25OHD), α-tocopherol, retinyl palmitate, and retinol concentrations were analyzed. Except for retinol, the effects of treatment, day, and day × treatment interaction ( < 0.01) were observed on plasma vitamin concentrations. Plasma concentrations of 25OHD and α-tocopherol increased immediately regardless of administration routes to peak at d 2 and 1 after administration, respectively. Plasma retinyl palmitate concentrations increased only with the injection treatment, with the peak at d 1 after administration. Plasma concentrations of 25OHD in both administration treatments and α-tocopherol in the injection treatment were maintained at greater levels than those in the control treatment until d 20 after administration. With regard to the pharmacokinetic parameters for plasma 25OHD concentrations, the injection treatment had greater elimination half-life ( < 0.01), maximum plasma concentrations ( < 0.05), and all area under the curve parameters ( < 0.01) but a lower elimination rate constant ( < 0.01) than the oral treatment. Relative bioavailability of oral administration compared with injection administration was 55.26%. These results indicate that plasma status of 25OHD,α-tocopherol, and retinyl palmitate are differentially changed between types of vitamins administered and between administration routes and that the injection route had a greater increase and slower disappearance of plasma vitamin levels than the oral route during the suckling period.

Concentrations of retinol and tocopherols in the milk of cows supplemented with conjugated linoleic acid.

This study was performed to investigate the hypothesis that supplementation of conjugated linoleic acid (CLA) changes the concentrations of retinol and tocopherols in the milk of cows. To investigate this hypothesis, Holstein cows received daily from 3 weeks ante-partum to 14 weeks post-partum either 172 g of a CLA-free rumen-protected control fat (control group, n = 20) or the same amount of a rumen-protected CLA fat, supplying 4.3 g of cis-9, trans-11 CLA and 3.8 g of trans-10, cis-12 CLA per d (CLA group, n = 20). Milk samples (collected at weeks 1, 3, 5, 8 and 11 of lactation) were analysed for retinol, α- and γ-tocopherol concentrations. Milk of cows supplemented with CLA had higher concentrations of retinol (+34%), α-tocopherol (+44%) and γ-tocopherol (+21%) than milk of control cows (p < 0.05). The daily output of these vitamins via milk was also greater in cows of the CLA group than in cows of the control group (+36, 50 and 24% for retinol, α-tocopherol and γ-tocopherol, respectively, p < 0.05). In agreement with higher concentrations of tocopherols, concentrations of thiobarbituric acid-reactive substances, determined in milk of week 5, were lower in cows of the CLA group than in control cows, indicative of a lower susceptibility of milk lipids to peroxidation. Plasma concentrations of retinol and α-tocopherol, determined at 1 and 5 weeks post-partum, were not different between the two groups of cows. In conclusion, this study shows that supplementing dairy cows with a moderate amount of CLA causes an increase of the concentrations of vitamins A and E in the milk and results in an increased output of those vitamins via milk. These effects might be beneficial with respect to the nutritional value of dairy products and the susceptibility of milk fat to oxidative deterioration.

Evaluation of supplemental vitamin A and E on 56-day growth performance, dietary net energy, and plasma retinol and tocopherol concentrations in Holstein steer calves

<h2>ABSTRACT</h2> Thirty Holsteins steers (initial weight 230±1kg) fed as calves were used in a 56-d experiment to evaluate the influence of vitamin A and E supplementation on growth performance, dietary energetics, and plasma retinol and tocopherol concentrations. Steers were fed a steam-flaked, corn-based diet. Three treatments (TMT) were evaluated: TMT1 had no supplemental vitamins, TMT2 supplemented 30,000IU/d of vitamin A as retinyl propionate plus 250IU/d of vitamin E as all-rac α-tocopheryl acetate, and TMT3 supplemented 30,000IU/d of vitamin A as retinyl palmitate plus 250IU/d of vitamin E as d-α-tocopherol (RRR α-tocopherol). Treatment supplements were freshly prepared and applied to feed once daily in the morning. Form of supplemental vitamins A and E did not affect cattle growth performance or dietary energetics. Vitamin supplementation increased final BW (3.7%, P=0.02), ADG (10.7%, P=0.02), and DMI (7.1%, P=0.05). There were no treatment effects (P>0.30) on gain efficiency or dietary net energy. There were no treatment effects on plasma retinol on d 28. However, by d 56, vitamin A supplementation increased (P=0.01) plasma retinol by 56%. Form of supplemental vitamin A did not influence (P>0.30) plasma retinol. Vitamin E supplementation increased (P<0.01) plasma tocopherol. On d 28, plasma tocopherol tended to be greater (P=0.12) with supplemental tocopheryl acetate than for supplemental tocopherol. By d 56 plasma tocopherol was 31% greater (P=0.03) for all-rac α-tocopheryl acetate than for RRR α-tocopherol supplemented steers. Vitamin supplementation may enhance DMI and corresponding ADG of Holstein steer calves fed a steam-flaked corn-based diet. Ester forms of vitamin A (retinyl propionate vs. retinyl palmitate) are comparable.

Effect of dietary carotenoids on vitamin A status and skin pigmentation in false tomato frogs (Dyscophus guineti)

Several species in captivity develop nutritional diseases including vitamin A deficiency; cases of this disease have been documented in amphibians, which may be linked to an insectivorous diet lacking in vitamin A or carotenoids. Adults and young of Dyscophus guineti were fed three diets over 9 weeks to evaluate effects on carotenoids and vitamin A status and skin pigmentation. Feeder crickets were either supplemented with soy oil (control, CON), soy oil enriched with β-carotene (BC) or mixed carotenoids (MIX) by direct injection of known dosages. Vitamin A from feeder crickets (measured as retinol) was higher in insects supplemented with both BC and MIX; (P=0.0001) and plasma retinol concentrations were significantly higher in frogs fed MIX (P<0.02). Results suggest that both false tomato frogs and feeder crickets could receive some provitamin A activity through consumption of diets supplemented with β-carotene, and xanthophylls like lutein and zeaxanthin. Pigmentation was evaluated weekly through the use of visual color charts, as well as quantitatively using a hand-held spectrophotometer. MIX diets had a significant effect on skin color values (P<0.0001), as well as on lightness (P=0.0005) and hue (P=0.0022). Results indicated that frogs fed with BC changed to yellower colors, and frogs fed with MIX changed to oranger colors. Visual color chart observations also scored significantly different between CON and MIX diets (P<0.05); the animals fed MIX also appeared oranger according to the qualitative observations. Dietary supplements with carotenoids resulted in color changes and higher circulating retinol concentrations in false tomato frogs. These pigments may provide provitamin A activity in diets, thus may support improved nutrition and health of captive-fed insectivorous amphibians.

Plasma and dietary carotenoids and vitamins A, C and E and risk of colon and rectal cancer in the European Prospective Investigation into Cancer and Nutrition.

Carotenoids and vitamins A, C and E are possibly associated with a reduced colorectal cancer (CRC) risk through antioxidative properties. The association of prediagnostic plasma concentrations and dietary consumption of carotenoids and vitamins A, C and E with the risk of colon and rectal cancer was examined in this case-control study, nested within the European Prospective Investigation into Cancer and Nutrition study. Plasma concentrations of carotenoids (α- and β-carotene, canthaxanthin, β-cryptoxanthin, lutein, lycopene, zeaxanthin) and vitamins A (retinol), C and E (α-, β- and γ- and δ-tocopherol) and dietary consumption of β-carotene and vitamins A, C and E were determined in 898 colon cancer cases, 501 rectal cancer cases and 1,399 matched controls. Multivariable conditional logistic regression models were performed to estimate incidence rate ratios (IRR) and corresponding 95% confidence intervals (CIs). An association was observed between higher prediagnostic plasma retinol concentration and a lower risk of colon cancer (IRR for highest quartile = 0.63, 95% CI: 0.46, 0.87, p for trend = 0.01), most notably proximal colon cancer (IRR for highest quartile = 0.46, 95% CI: 0.27, 0.77, p for trend = 0.01). Additionally, inverse associations for dietary β-carotene and dietary vitamins C and E with (distal) colon cancer were observed. Although other associations were suggested, there seems little evidence for a role of these selected compounds in preventing CRC through their antioxidative properties.

Plasma concentrations of retinol in obese children and adolescents: relationship to metabolic syndrome components

Objective: To evaluate obese children and adolescents' retinol plasma levels and to correlate them with metabolic syndrome components. Methods: Cross-sectional study with 61 obese children and adolescents (body mass index Z score - ZBMI>+2). Pubertal development, arterial blood pressure, body weight and height for nutritional classification and waist circumference were obtained. A 15mL blood sample was collected (after a 12-hour fasting in a low luminosity room) for retinol determination (cut-off inadequate if <30µg/dL), lipid profile (HDL-c, LDL-c, and triglycerides), oral glucose tolerance test (fasting and 120 minutes) and for high sensitivity C-reactive protein. Spearman correlation and multiple linear regression were used in the statistical analysis. Results: Mean age was 10.7±2.7 years. There was a predominance of male gender 38/61 (62%) and pre-pubertal 35/61 (57%) subjects. The average plasmatic retinol was 48.5±18.6ug/dL. Retinol deficiency and severe obesity were observed in 6/61 (10%) and 36/61 (59%), respectively. Glucose level at 120 minutes was the independent and predictive variable of plasma retinol levels [β=-0.286 (95%CI -0.013 - -0.001)]. Conclusions: An independent and inverse association between plasma retinol levels and glucose tolerance was observed, suggesting an important contribution of this vitamin in the morbidities associated to obesity in children and adolescents.

Serum retinol concentrations in mothers and newborns at delivery in a public maternity hospital in Recife, northeast Brazil.

Serum retinol concentrations were compared in a consecutive series of 65 mother-newborn pairs at delivery in a public maternity hospital in Recife, Brazil, from January to August 2008 and examined their association with biological, socioeconomic, environmental and obstetrical characteristics. Serum retinol concentrations of the newborns (umbilical cord) and mothers (brachial venipuncture) were analyzed by high-performance liquid chromatography. Prevalence of low (< 0.70 micromol/L) and inadequate (< 1.05 micromol/L) serum retinol concentrations were observed in 23.1% (95% CI 13.9-35.5) and 23.0% (95% CI 13.5-35.8) among newborns and mothers respectively. The serum retinol distribution was lower in male than female infants (-0.4 micromol/L, p = 0.01) and, across both sexes, concentrations in paired newborn and mother were correlated (r = 0.27, p = 0.04). Further, maternal status explains only 7% of the variance in retinol concentrations in newborn's cord plasma. Among mothers delivering in public facilities in Recife, hypovitaminosis may exist.

Interactions between nutrition and immune function: using inflammation biomarkers to interpret micronutrient status

The immune response promotes a complex series of reactions by the host in an effort to prevent ongoing tissue damage, isolate and destroy the infective organism and activate the repair processes that are necessary for restoring normal function. The homoeostatic process is known as inflammation and the early set of reactions that are induced are known as the acute phase response (APR). The APR has marked effects on the circulation, metabolism in the liver and the plasma concentration of many nutrients. The changes in nutrient concentrations follow a cyclic pattern; occurring before any clinical evidence of disease, being at their most pronounced during the disease and remaining in convalescence when all evidence of disease or trauma has disappeared. Therefore, where susceptibility to disease is high as in people who are HIV+ but still apparently healthy, obtaining an accurate measurement of nutritional status may not be possible. Accurate measurements of status are important for national statistics to plan for the proper utilisation of government resources and they are especially important to evaluate the effectiveness of nutritional interventions. Many acute phase proteins (APP) are synthesised during inflammation and they are used to monitor the progress of disease and recovery but, individually, none of their lifecycles compare well with those of the nutritional biomarkers. Nevertheless, recognising the presence of inflammation can help interpret data and, using two APP, this review paper will illustrate the methods we have developed to assist interpretation of plasma retinol, ferritin and zinc concentrations in apparently healthy, HIV+, Kenyan adults.

Plasma retinol and total carotenes and fracture risk after long-term supplementation with high doses of retinol

ObjectiveObservational studies suggest that moderate intakes of retinol and increased circulating retinol levels may increase fracture risk. Easy access to supplements, combined with an aging population, makes this a potentially important association. The aim of this study was to investigate plasma retinol and total carotene concentrations in relation to fracture risk after long-term supplementation with retinol and/or beta-carotene in 998 adults between 1990 and 2007. MethodsParticipants were 663 men and 335 women in a cancer prevention program who were initially randomized to a retinol (7.5 mg RE/d) or beta-carotene (30 mg/d) supplement between 1990 and 1996. After 1996, all participants received the retinol supplement only. Plasma retinol and total carotene, medication use and various lifestyle factors were measured at annual clinic visits. Fractures were identified by self-report in 2007. The risk for any fracture or osteoporotic fracture was modeled using Cox proportional hazard models. ResultsOver a median follow-up of 7.8 y, 123 participants with plasma samples reported an incident fracture. Although plasma retinol concentrations were markedly higher than those reported in observational studies, no association was observed between plasma retinol and risk for any fracture (hazard ratio [HR], 0.86 μmol/L; 95% confidence interval [CI], 0.65–1.14) or osteoporotic fracture (HR, 0.97 μmol/L; 95% CI, 0.66–1.43). A lower risk for any fracture was suggested with increasing plasma total carotenes (HR, 0.85 μmol/L; 95% CI, 0.71–1.01). ConclusionsThis study does not support earlier reports of an increased fracture risk associated with increased plasma retinol concentration. The potential for carotenes to prevent fractures deserves further investigation.

Alterations in the antioxidant defense system in prepubertal children with a history of extrauterine growth restriction

The role of oxidative stress is well known in the pathogenesis of acquired malnutrition. Intrauterine growth restriction has been associated with an imbalance in oxidative stress/antioxidant system. Therefore, early postnatal environment and, consequently, extrauterine growth restriction might be associated with alterations in the antioxidant defense system, even in the prepubertal stage. This is a descriptive, analytical, and observational case-control study. The study included two groups; 38 Caucasian prepubertal children born prematurely and with a history of extrauterine growth restriction as the case group, and 123 gender- and age-matched controls. Plasma exogenous antioxidant (retinol, β-carotene, and α-tocopherol) concentrations were measured by HPLC; antioxidant enzyme activities of catalase, glutathione reductase, glutathione peroxidase, and superoxide dismutase were determined in lysed erythrocytes by spectrophotometric techniques. Catalase and glutathione peroxidase concentrations were significantly lower in extrauterine growth restriction children than in controls (P < 0.001). Lower plasma retinol concentrations were found in the case group (P = 0.029), while concentrations of β-carotene and α-tocopherol were higher (P < 0.001) in extrauterine growth restriction prepubertal children as compared with controls. After correction by gestational age, birth weight, and length, statistically significant differences were also found, except for retinol. Prepubertal children with a history of extrauterine growth restriction present alterations in their antioxidant defense system. Knowing these alterations may be important in establishing pharmacological and nutritional treatments as this situation might be associated with higher metabolic disorders in adulthood.

Vitamin A regulates hypothalamic–pituitary–adrenal axis status in LOU/C rats

The aim of this study was to explore the involvement of retinoids in the hypoactivity and hyporeactivity to stress of the hypothalamic-pituitary-adrenal (HPA) axis in LOU/C rats. We measured the effects of vitamin A deficiency administered or not with retinoic acid (RA) on plasma corticosterone in standard conditions and in response to restraint stress and on hypothalamic and hippocampal expression of corticosteroid receptors, corticotropin-releasing hormone and 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) in LOU/C rats. Interestingly, under control conditions, we measured a higher plasma concentration of retinol in LOU/C than in Wistar rats, which could contribute to the lower basal activity of the HPA axis in LOU/C rats. Vitamin A deficiency induced an increased HPA axis activity in LOU/C rats, normalized by RA administration. Compared with LOU/C control rats, vitamin A-deficient rats showed a delayed and heightened corticosterone response to restraint stress. The expression of corticosteroid receptors was strongly decreased by vitamin A deficiency in the hippocampus, which could contribute to a less efficient feedback by corticosterone on HPA axis tone. The expression of 11β-HSD1 was increased by vitamin A deficiency in the hypothalamus (+62.5%) as in the hippocampus (+104.7%), which could lead to a higher production of corticosterone locally and contribute to alteration of the hippocampus. RA supplementation treatment restored corticosterone concentrations and 11β-HSD1 expression to control levels. The high vitamin A status of LOU/C rats could contribute to their low HPA axis activity/reactivity and to a protective effect against 11β-HSD1-mediated deleterious action on cognitive performances during ageing.

Selenium and Vitamin A and E in the Nutrition of Very Low-Birth Weight Preterm Infants

Deficient antioxidant defenses in preterm infants have been implicated in diseases such as bronchopulmonary dysplasia, retinopathy of prematurity, necrotizing enterocolitis, periventricular leukomalacia, and intraventricular hemorrhage. The antioxidant properties of selenium, vitamin A, and vitamin E make these elements important in the nutrition of Very Low-Birth Weight (VLBW) infants. Selenium is a component of glutathione peroxidase, an enzyme that prevents the production of free radicals. The decrease in plasma selenium in VLBW infants in the first month after birth makes evident that preterm infants have low selenium store and require supplementation by parenteral and enteral nutrition. A meta-analysis, with only three trials, showed that selenium supplementation did not affect mortality, and the incidence of neonatal chronic lung disease or retinopathy of prematurity, but was associated with a reduction in lateonset sepsis. Most VLBW infants and extremely Low-Birth Weight Infants (ELBW) are born with low vitamin A stores and need vitamin A supplementation by intramuscular or enteral route. Low plasma retinol concentrations increase the risk of chronic lung disease/bronchopulmonary dysplasia and long-term respiratory disabilities in preterm infants. There is evidence that vitamin A supplementation decreases the mortality or oxygen requirement at one month of age, and oxygen requirement at 36 weeks’ postmenstrual age. Vitamin E blocks natural peroxidation of polyunsaturated fatty acids from lipid layers of cell membranes. VLBW infants have a decrease in plasma concentrations in the first month after birth suggesting the need of vitamin E supplementation. A meta-analysis on vitamin E supplementation concluded that vitamin E did not affect mortality, risk of bronchopulmonary dysplasia, and necrotizing enterocolitis but reduced the risk of intraventricular hemorrhage and increased the risk of sepsis. Serum vitamin E concentrations higher than 3.5 mg/dL are associated with a decrease in the risk of severe retinopathy of prematurity, and blindness, but also with an increase in neonatal sepsis. Caution is recommended with the supplementation of high doses of parenteral vitamin E and supplementation that increases serum levels above 3.5 mg/dL. In conclusion: although it is known that preterm infants are deficient in selenium, vitamin A and E, more studies are required to determine the best way to supplement and the impact of supplementation on neonatal outcome

β-Carotene 15,15′-monooxygenase 1 single nucleotide polymorphisms in relation to plasma carotenoid and retinol concentrations in women of European descent

Carotenoids have been hypothesized to reduce the risk of many diseases, but associations with intakes or blood concentrations may arise from other constituents of fruit and vegetables. Use of genetic variation in β-carotene 15,15'-monooxygenase 1 (BCMO1), a key enzyme in provitamin A carotenoid metabolism, as a surrogate for carotenoid exposure may aid in determining the role of carotenoids unconfounded by other carotenoid-containing food constituents, but important variants must be identified. Our goal was to select BCMO1 single nucleotide polymorphisms (SNPs) that predict plasma carotenoid concentrations for use in future epidemiologic studies. We assessed the associations between 224 SNPs in BCMO1 ± 20 kb imputed from the 1000 Genomes Project EUR reference panel with plasma carotenoid and retinol concentrations by using 7 case-control data sets (n = 2344) within the Nurses' Health Study, randomly divided into training (n = 1563) and testing (n = 781) data sets. SNPs were chosen in the training data set through stepwise selection in multivariate linear regression models; β-coefficients were used as weights in weighted gene scores. Two or 3 SNPs were selected as predictors of β-carotene, α-carotene, β-cryptoxanthin, and lutein/zeaxanthin. In the testing data set, the weighted gene scores were significantly associated with plasma concentrations of the corresponding carotenoid (P = 6.4 × 10⁻¹², 3.3 × 10⁻³, 0.02, and 1.8 × 10⁻¹⁷, respectively), and concentrations differed by 48%, 15%, 15%, and 36%, respectively, across extreme score quintiles. SNPs in BCMO1 are associated with plasma carotenoid concentrations. Given adequate sample size, the gene scores may be useful surrogates for carotenoid exposure in future studies.