The Association Between Vitamin E Deficiency and Critically Ill Children With Sepsis and Septic Shock

Background: Literature is scarce on the assessment of vitamin E status in septic children. We aim to investigate the prevalence of vitamin E deficiency in critically ill children with sepsis and septic shock and its association with clinical features and outcomes.Methods: We compared serum vitamin E status between the confirmed or suspected infection and no infection groups, the sepsis shock and no sepsis shock groups upon pediatric intensive care unit admission. Clinical characteristics were compared in subgroup patients with and without vitamin E deficiency. The association between vitamin E deficiency and septic shock were evaluated using univariate and multivariable methods.Results: 182 critically ill children with confirmed or suspected infection and 114 without infection were enrolled. The incidence of vitamin E deficiency was 30.2% in the infection group and 61.9% in the septic shock subgroup (P < 0.001). Thirty-days mortality in critically ill children with vitamin E deficiency was significantly higher than that without vitamin E deficiency (27.3 vs. 14.2%, P < 0.05). Vitamin E levels were inversely associated with higher pediatric risk of mortality (r = − 0.238, P = 0.001) and cardiovascular sequential organ failure assessment (r = −0.249, p < 0.001) scores in critically ill children with infection. In multivariable logistic regression, vitamin E deficiency showed an independent effect on septic shock (adjusted OR: 6.749, 95%CI: 2.449–18.60, P < 0.001).Conclusion: Vitamin E deficiency is highly prevalent in critically ill children with sepsis and contributed to the septic shock.

Dietary omega-3 fatty acid supplementation does not impair vitamin E status or promote lipid peroxidation in growing horses

Omega-3 (n-3; ω-3) fatty acids (FA) are often included in the diet for their potential health benefits. However, because oxidative potential is increased with the degree of unsaturation in vitro, polyunsaturated FA such as eicosapentaenoic acid (EPA; 20:5n-3) and docosahexaenoic acid (DHA; 22:6n-3) may be at increased risk of lipid peroxidation. We aimed to determine the effects of dietary n-3 FA supplementation on antioxidant status and lipid peroxidation in yearling horses. Quarter Horses (mean ± SEM; 14.6 ± 0.2 mo) were randomly assigned to receive no n-3 FA supplementation (CON; n = 6) or 60 mg n-3/kg body weight from milled flaxseed (FLAX; n = 6) or encapsulated fish oil (FISH; n = 6). All horses received a basal diet of mixed grain concentrate fed individually at 1.5% body weight (dry matter basis) and ad libitum bahiagrass pasture forage. Blood samples were obtained before and after 70 d of supplementation to evaluate vitamin E, selenium, lipids, antioxidant status, and oxidative stress. Data were analyzed using a mixed model ANOVA with repeated measures. Supplementation with n-3 FA did not reduce serum vitamin E or Se and, in fact, elevated (P ≤ 0.0003) vitamin E status in FISH horses. At d 70, serum triglycerides were lower in FISH and FLAX horses than CON horses (P ≤ 0.02) and F2-isoprostanes were lower in FISH than CON horses (P = 0.0002). Dietary n-3 FA had no effect on cholesterol, reduced and oxidized glutathione, glutathione peroxidase, and thiobarbituric acid-reactive substances. In growing horses fed to meet their vitamin E requirements, supplementation with 60 mg n-3/kg body weight did not negatively affect vitamin E status or promote lipid peroxidation. Elevated vitamin E status in horses fed FISH, coupled with lower serum F2-isoprostanes, further suggest that the longer-chain, highly unsaturated n-3 FA, EPA and DHA, may actually attenuate lipid peroxidation.

Breeder Diet Strategies for Generating Ttpa-Null and Wild-Type Mice with Low Vitamin E Status to Assess Neurological Outcomes

ABSTRACT Studying vitamin E [α-tocopherol (α-T)] metabolism and function in the brain and other tissues requires an animal model with low α-T status, such as the transgenic α-T transfer protein (Ttpa)–null (Ttpa−/−) mouse model. Ttpa+/− dams can be used to produce Ttpa−/− and Ttpa+/+mice for these studies. However, the α-T content in Ttpa+/− dams’ diet requires optimization; diets must provide sufficient α-T for reproduction, while minimizing the transfer of α-T to the offspring destined for future studies that require low baseline α-T status. The goal of this work was to assess the effectiveness and feasibility of 2 breeding diet strategies on reproduction outcomes and offspring brain α-T concentrations. These findings will help standardize the breeding methodology used to generate the Ttpa−/− mice for neurological studies.

Plasma versus Erythrocyte Vitamin E in Renal Transplant Recipients, and Duality of Tocopherol Species

Redox imbalance is an adverse on-going phenomenon in renal transplant recipients (RTR). Vitamin E has important antioxidant properties that counterbalance its deleterious effects. However, plasma vitamin E affinity with lipids challenges interpretation of its levels. To test the hypothesis that erythrocyte membranes represent a lipids-independent specimen to estimate vitamin E status, we performed a cross-sectional study in a cohort of adult RTR (n = 113) recruited in a university setting (2015–2018). We compared crude and total lipids-standardized linear regression-derived coefficients of plasma and erythrocyte tocopherol species in relation to clinical and laboratory parameters. Strongly positive associations of fasting lipids with plasma tocopherol became inverse, rather than absent, in total lipids-standardized analyses, indicating potential overadjustment. Whilst, no variables from the lipids domain were associated with the tocopherol species measured from erythrocyte specimens. In relation to inflammatory status and clinical parameters with antioxidant activity, we found associations in directions that are consistent with either beneficial or adverse effects concerning α- or γ-tocopherol, respectively. In conclusion, erythrocytes offer a lipids-independent alternative to estimate vitamin E status and investigate its relationship with parameters over other biological domains. In RTR, α- and γ-tocopherol may serve as biomarkers of relatively lower or higher vulnerability to oxidative stress and inflammation, noticeably in opposite directions.

PSI-5 Effects of fat-soluble vitamin injection on plasma and tissue vitamin concentrations in nursery pigs

An experiment was conducted to investigate distribution of injected fat-soluble vitamins in plasma and tissue of nursery pigs. A total of 16 pigs were allotted to 2 treatments at d 7 post-weaning and fed a corn-soybean meal-based diet with no supplemental vitamin A. Treatments were control (no vitamins) and intramuscular injection with 3 mL VITAL E-A+D (STUARTPRODUCTS, Inc.) containing retinyl palmitate (RP; 300,000 IU), d-α-tocopherol (900 IU), and vitamin D3 (30,000 IU). All pigs were bled at d 0, 3, 7, and 14 post-injection and tissue samples were collected at d 7 and 14 post-injection (3 pigs/treatment). Data were analyzed by MIXED procedure of SAS. Plasma 25-hydroxycholecalciferol (3.44 vs. 71.00 ng/mL at d 3 post-injection) and retinol (0.09 vs. 0.18 µg/mL at d 3 post-injection) concentrations increased from d 3 to 14 post-injection (P < 0.05). Plasma RP was detected only in the vitamin treatment at d 3 and 7 post-injection (115.51 and 4.97 µg/mL, respectively). Liver retinol (0.63 vs. 19.10 µg/g at d 7 post-injection) and RP (43.33 vs. 199.13 µg/g at d 7 post-injection) concentrations increased at d 7 and 14 post-injection (P < 0.05) whereas those were not detected in the other tissues. The α-tocopherol concentrations increased in plasma (P < 0.05) at d 3 (0.99 vs. 17.14 µg/mL) and 7 post-injection and in liver (4.30 vs. 11.17 µg/g; P < 0.10), heart (4.60 vs. 24.80 µg/g; P < 0.10), and muscle (3.07 vs. 8.30 µg/g; P < 0.05) at d 7 post-injection. In conclusion, fat-soluble vitamin injection to nursery pigs increased plasma and liver status of α-tocopherol, retinol, and RP, and plasma 25-hydroxycholecalciferol concentrations. The α-tocopherol found in plasma post-injection was distributed to various tissues but RP only to the liver. Although plasma levels decreased post-injection, levels in liver increased for vitamins A and E, and vitamin E status was increased in all other tissues except brain.

α-Tocopherol Restriction Dysregulates Neurogenesis-Related Gene Expression in Brains of Weanling α-Tocopherol Transfer Protein Knockout Mice (P11-134-19)

Objectives Humans with vitamin E (α-tocopherol, αT) deficiency develop neurological disorders. Similarly, α-tocopherol transfer protein knockout (Ttpa−/−) mice have low vitamin E status and exhibit neurodegeneration with age. Shifts in the transcriptome may precede behavioral manifestations of vitamin E deficiency, but it is unknown how early abnormalities occur. Aberrations during brain development could have lifelong implications. The study objective was to determine how αT restriction during early-life affects the expression of pre-selected neurogenesis-related genes in the cerebellum (CB) and cerebral cortex (CC) of Ttpa−/− weanlings. Methods Female Ttpa+/+ (n = 9) and Ttpa−/− (n = 10) mice were nursed by Ttpa+/−dams until postnatal day 21. Dams were fed AIN-93G diet (75 mg αT/kg diet) during days 1–9 of gestation, and αT-stripped diet for the rest of the study. Homogenized brain tissues from 21 day old weanlings were used to measure αT concentrations via HPLC-PDA. The expression of genes critical for brain development (Rora, Shh), myelination (Plp1, Cntnap1, Mbp, Mobp, Nr1h3), synaptic function (Cplx1, Cplx2, Vamp2, Necab1, Prkcg), and αT cellular uptake (Scarb1) were measured in the CB and CC via real-time qPCR. Results αT levels were significantly decreased in brains of Ttpa−/− mice (0.1 ± 0.1 nmol/g) compared to Ttpa+/+ mice (9.8 ± 1.4 nmol/g) (P < 0.001), confirming their low αT status. Rora, Shh, Cntnap1, and Mbp were significantly upregulated (P < 0.05) in both the CB and CC of Ttpa−/− mice, while several genes were only upregulated in one brain region (Plp1 in the CB, Mobp in the CC). Necab1 and Scarb1 were significantly downregulated in the CB of Ttpa−/− mice (P < 0.05). Conclusions αT restriction during the fetal and postnatal periods alters the expression of neurogenesis-related genes. These findings support a role for αT in brain development. Funding Sources Abbott Nutrition through the Center for Nutrition, Learning and Memory, University of Illinois, Urbana-Champaign; USDA NIFA Hatch grant (ILLU-698-915); Division of Nutritional Sciences Vision 20/20 Grant Program; Division of Nutritional Sciences Margin of Excellence Research Program.