Efecto de la Vitamina E en Células Peritubulares de Testículos de Ratones Mus musculus Tratados con Ácido Valproico Durante el Estado Fetal y Pubertad / Effect of Vitamin E on Peritubular Cells from Testis of Mus musculus Mice Treated with Valproic Acid During the Fetal Stage and Puberty

El ácido valproico (VPA) es un fármaco antiepiléptico teratógenico que, al ser administrado durante etapas tempranas del embarazo, puede producir alteraciones en el desarrollo embriofetal, las que se manifiestan tanto a nivel del sistema nervioso como del testículo. No obstante, se ha reportado que la administración de vitamina E (VE) podría revertir dichas alteraciones. El objetivo del presente estudio fue determinar el efecto protector de la VE a nivel testicular en fetos y ratones púberes expuestos a VPA durante la fase embrionaria de su desarrollo. Se utilizó un total de 30 ratones hembra adultas gestantes (Mus musculus) cepa BALB/c, las cuales se dividieron en 6 grupos. El estudio contempló el análisis de fetos machos a los 17,5 días post-coital (dpc) y machos juveniles a las 6 semanas post-natal. A los grupos 1 y 4 se les administró 0,3 mL de solución fisiológica (grupos control para 17,5 dpc y 6 semanas postnatal, respectivamente). A los grupos 2 y 5 se les suministró la cantidad de 600 mg/kg de VPA (grupos VPA), en tanto que a los grupos 3 y 6 se les aplicó la misma dosis de VPA complementada con 200 UI de VE (grupos VPA+VE). Se describió la histología normal y patológica del compartimento peritubular del testículo. En los grupos VPA se evidenció una degeneración de la pared peritubular, y atrofia de túbulos seminíferos, así como exfoliación de las células germinales. Por el contrario, en los grupos VPA+VE tales signos no fueron observados y la morfología presentó aspecto normal solo con algunas alteraciones focales. Estos resultados corroboran el hecho que la administración de VE contrarresta en parte, los efectos deletéreos que ocasiona el VPA.

SUMMARY: Valproic acid (VPA) is a teratogenic antiepileptic drug that, when administered during the early stages of pregnancy, can produce alterations in embryo-fetal development, which manifest both at the level of the nervous system and the testicle. However, it has been reported that the administration of vitamin E (VE) could reverse these alterations. The study aimed to determine the protective effect of VE at the testicular level in fetuses and pubertal mice exposed to VPA during the embryonic phase of their development. 30 pregnant adult female mice (Mus musculus) BALB/c strain were used, which were divided into 6 groups. The study included the analysis of male fetuses at 17.5 days post-coital (dpc) and juvenile males at 6 weeks post-natal. Groups 1 and 4 were administered 0.3 mL of physiological solution. Groups 2 and 5 were given 600 mg/kg of VPA (VPA groups), while groups 3 and 6 were given the same dose of VPA supplemented with 200 IU of VE (VPA+VE). The normal and pathological histology of the peritubular compartment of the testis was described. In the VPA groups, degeneration of the peritubular wall, and atrophy of the seminiferous tubules, as well as exfoliation of the germ cells, were evident. On the contrary, in the VPA+VE groups such signs were not observed and the morphology presented a normal appearance with only some focal alterations. These results corroborate the fact that the administration of VE partially counteracts the deleterious effects caused by VPA.

Vitamins E and A increase the passing of the P-gp substrate ivermectin into the brain in mice.

This study aimed to determine the effect of administration of oral vitamins A and E at different doses on plasma and brain concentrations of ivermectin in mice. The study was carried out on 174 Swiss Albino male mice aged 8-10 weeks. After leaving six mice for method validation, the remaining mice were randomly divided into seven groups with equal numbers of animals. Mice received ivermectin (0.2 mg/kg, subcutaneous) alone and in combination with low (vitamin A: 4000 IU/kg; vitamin E: 35 mg/kg) and high (vitamin A: 30 000 IU/kg; vitamin E: 500 mg/kg) oral doses of vitamins A and E. The plasma and brain concentrations of ivermectin were measured using high-performance liquid chromatography-fluorescence detector. We determined that high doses of vitamins A and E and their combinations increased the passing ratio of ivermectin into the brain significantly. The high-dose vitamin E and the combination of high-concentration vitamins E and A significantly increased the plasma concentration of ivermectin (P < 0.05). The high-dose vitamins E and A and their high-dose combination increased the brain concentration of ivermectin by 3, 2, and 2.7 times, respectively. This research is the first in vivo study to determine the interaction between P-gp substrates and vitamins E and A.

The diabetogenic effects of chronic supplementation of vitamin C or E in rats: Interplay between liver and adipose tissues transcriptional machinery of lipid metabolism.

AIM: The chronic administration of vitamin C and E can differentially disrupt hepatic insulin molecular pathway in rats. Hence, this study evaluated their effects on lipogenesis in the liver and adipose tissue and investigated the possible involvement of microRNA (miR)-22/29a/27a in the induced impaired glucose tolerance. MAIN METHODS: Wistar rats were orally supplemented with vitamin C (100, 200, and 500 mg/kg) or vitamin E (50, 100, and 200 mg/kg) for eight months. KEY FINDINGS: Vitamin C or E at the highest doses significantly altered liver weight and index, serum and hepatic lipids, adiponectin, and liver enzymes; besides their reported unfavorable effect on glucose homeostasis. Vitamin C and E negatively affected peroxisome proliferator-activated receptor coactivator-1 (PGC-1α), sterol regulatory element-binding protein (SREBP)-1c/-2, miR-22/29a/27a expression, and adipose perilipin 1 to different extents, effects that were supported by the histopathological examination. SIGNIFICANCE: The current study provides a deeper insight into the findings of our previous study and highlights the detrimental effects of chronic vitamins supplementation on lipid metabolism. Overall, these findings emphasize the damage caused by the mindless use of supplements and reinforce the role of strict medical monitoring, particularly during the new COVID-19 era during which numerous commercial supplements are claiming to improve immunity.

Omega-3 fatty acid, carotenoid and vitamin E supplementation improves working memory in older adults: A randomised clinical trial.

BACKGROUND & AIMS: Accumulating evidence suggests that omega-3 fatty acids (ω-3FAs), carotenoids and vitamin E can improve cognitive performance. However, their collective impact on cognition has not yet been investigated in healthy individuals. This study investigated the combined effect of ω-3FA, carotenoid and vitamin E supplementation on the cognitive performance of older adults. METHODS: Cognitively healthy individuals aged ≥65 years consumed daily 1 g fish oil (of which 430 mg docosahexaenoic acid, 90 mg eicosapentaenoic acid), 22 mg carotenoids (10 mg lutein, 10 mg meso-zeaxanthin, 2 mg zeaxanthin) and 15 mg vitamin E or placebo for 24 months in a double-blind, placebo-controlled, randomised clinical trial. RESULTS: Following 24-month supplementation, individuals in the active group (n = 30; aged 69.03 ± 4.41 years; 56.7% female) recorded significantly fewer errors in working memory tasks than individuals receiving placebo (n = 30; aged 69.77 ± 3.74 years; 70% female) (point estimate effect sizes ranged 0.090-0.105). Interestingly, as the cognitive load of the working memory tasks increased, the active group outperformed the placebo group. Statistically significant improvements in tissue carotenoid concentrations, serum xanthophyll carotenoid concentrations and plasma ω-3FA concentrations were also observed in the active group versus placebo (point estimate effect sizes ranged 0.078-0.589). Moreover, the magnitude of change of carotenoid concentrations in tissue, and ω-3FA and carotenoid concentrations in blood were related to the magnitude of change in working memory performance. CONCLUSION: These results support a biologically plausible rationale whereby these nutrients work synergistically, and in a dose-dependent manner, to improve working memory in cognitively healthy older adults. Increasing nutritional intake of carotenoids and ω-3FAs may prove beneficial in reducing cognitive decline and dementia risk in later life. STUDY ID NUMBER: ISRCTN10431469; https://doi.org/10.1186/ISRCTN10431469.

Effects of grape pomace supplementation on the diet of lactating ewes as compared to vitamin E on the meat shelf life of suckling lambs.

Forty-eight Churra ewes and their suckling lambs were assigned to four dietary treatments: control (CTRL), VIT-E (500 mg kg-1 TMR vitamin E), GP-5 (5% grape pomace) and GP-10 (10% grape pomace). After slaughter (11.5 kg live weight), longissimus muscle of lambs was sliced, packaged under modified atmosphere (80,20%/O 2:CO 2) and stored in retail conditions. At each sampling point (0, 3, 7, 10, 14 days), microbiological, physicochemical and sensory characteristics were analysed. Vitamin E and GP-5 were found to be effective (p < 0.05) at preventing enterobacteria growth as of day 10. After day 10, vitamin E and grape pomace in the ewe's supplementation reduced metmyoglobin (p < 0.05) lipid oxidation (p < 0.05) and sensory spoilage throughout the storage period. An effect of the grape pomace dosage was observed, with the supplementation at 5% being more effective. Therefore, we can conclude that grape pomace was just as effective as vitamin E in preventing spoilage during retail storage.

Effect of Vitamin E Supplement on Bone Turnover Markers in Postmenopausal Osteopenic Women: A Double-Blind, Randomized, Placebo-Controlled Trial.

Vitamin E is a strong anti-oxidative stress agent that affects the bone remodeling process. This study evaluates the effect of mixed-tocopherol supplements on bone remodeling in postmenopausal osteopenic women. A double-blinded, randomized, placebo-controlled trial study was designed to measure the effect of mixed-tocopherol on the bone turnover marker after 12 weeks of supplementation. All 52 osteopenic postmenopausal women were enrolled and allocated into two groups. The intervention group received mixed-tocopherol 400 IU/day, while the control group received placebo tablets. Fifty-two participants completed 12 weeks of follow-up. Under an intention-to-treat analysis, vitamin E produced a significant difference in the mean bone resorption marker (serum C-terminal telopeptide of type I collagen (CTX)) compared with the placebo group (-0.003 ± 0.09 and 0.121 ± 0.15, respectively (p < 0.001)). In the placebo group, the CTX had increased by 35.3% at 12 weeks of supplementation versus baseline (p < 0.001), while, in the vitamin E group, there was no significant change of bone resorption marker (p < 0.898). In conclusion, vitamin E (mixed-tocopherol) supplementation in postmenopausal osteopenic women may have a preventive effect on bone loss through anti-resorptive activity.

Fat-Soluble Vitamin Supplementation Using Liposomes, Cyclodextrins, or Medium-Chain Triglycerides in Cystic Fibrosis: A Randomized Controlled Trial.

Fat-soluble vitamin deficiency remains a challenge in cystic fibrosis (CF), chronic pancreatitis, and biliary atresia. Liposomes and cyclodextrins can enhance their bioavailability, thus this multi-center randomized placebo-controlled trial compared three-month supplementation of fat-soluble vitamins in the form of liposomes or cyclodextrins to medium-chain triglycerides (MCT) in pancreatic-insufficient CF patients. The daily doses were as follows: 2000 IU of retinyl palmitate, 4000 IU of vitamin D3, 200 IU of RRR-α-tocopherol, and 200 µg of vitamin K2 as menaquinone-7, with vitamin E given in soybean oil instead of liposomes. All participants received 4 mg of ß-carotene and 1.07 mg of vitamin K1 to ensure compliance with the guidelines. The primary outcome was the change from the baseline of all-trans-retinol and 25-hydroxyvitamin D3 concentrations and the percentage of undercarboxylated osteocalcin. Out of 75 randomized patients (n = 28 liposomes, n = 22 cyclodextrins, and n = 25 MCT), 67 completed the trial (89%; n = 26 liposomes, n = 18 cyclodextrins, and n = 23 MCT) and had a median age of 22 years (IQR 19-28), body mass index of 20.6 kg/m2 [18.4-22.0], and forced expiratory volume in 1 s of 65% (44-84%). The liposomal formulation of vitamin A was associated with the improved evolution of serum all-trans-retinol compared to the control (median +1.7 ng/mL (IQR -44.3-86.1) vs. -38.8 ng/mL (-71.2-6.8), p = 0.028). Cyclodextrins enhanced the bioavailability of vitamin D3 (+9.0 ng/mL (1.0-17.0) vs. +3.0 ng/mL (-4.0-7.0), p = 0.012) and vitamin E (+4.34 µg/mL (0.33-6.52) vs. -0.34 µg/mL (-1.71-2.15), p = 0.010). Liposomes may augment the bioavailability of vitamin A and cyclodextrins may strengthen the supplementation of vitamins D3 and E relative to MCT in pancreatic-insufficient CF but further studies are required to assess liposomal vitamin E (German Clinical Trial Register number DRKS00014295, funded from EU and Norsa Pharma).

Beneficial Effects of Vitamin E Supplementation on Endothelial Dysfunction, Inflammation, and Oxidative Stress Biomarkers in Patients Receiving Hemodialysis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Inflammation and oxidative stress are closely related to cardiovascular complications and atherosclerosis, and have the potential to lead to an increase in death in patients receiving hemodialysis. Vitamin E has antioxidant and anti-inflammatory properties. We conducted a systematic review and meta-analysis to assess the effects of vitamin E supplementation on endothelial dysfunction, inflammation, and oxidative stress biomarkers in adult patients receiving hemodialysis. We searched the MEDLINE, EMBASE, Web of Science, and Cochrane Library databases and identified randomized controlled trials of adult patients receiving hemodialysis until 30 August 2021. A total of 11 trials with 491 randomized patients were included. The pooled data indicated that vitamin E supplementation significantly decreased intercellular adhesion molecule-1 [standardized mean difference (SMD): -1.35; 95% confidence interval (CI): -2.57, -0.13; p = 0.03, I2 = 89%], vascular cell adhesion molecule-1 (SMD: -1.08; 95% CI: -2.05, -0.11; p = 0.03, I2 = 81%), C-reactive protein (SMD: -0.41; 95% CI: -0.75, -0.07; p = 0.02, I2 = 64%), and malondialdehyde (SMD: -0.76; 95% CI: -1.26, -0.25; p = 0.003, I2 = 77%) levels, but not interleukin-6 levels compared to those in the control group. Our results suggest that vitamin E supplementation may help alleviate oxidative stress and both vascular and systemic inflammation in patients receiving hemodialysis.

Tocotrienol-Rich Vitamin E (Tocovid) Improved Nerve Conduction Velocity in Type 2 Diabetes Mellitus Patients in a Phase II Double-Blind, Randomized Controlled Clinical Trial.

Diabetic peripheral neuropathy (DPN) is the most common microvascular complication of diabetes that affects approximately half of the diabetic population. Up to 53% of DPN patients experience neuropathic pain, which leads to a reduction in the quality of life and work productivity. Tocotrienols have been shown to possess antioxidant, anti-inflammatory, and neuroprotective properties in preclinical and clinical studies. This study aimed to investigate the effects of tocotrienol-rich vitamin E (Tocovid SuprabioTM) on nerve conduction parameters and serum biomarkers among patients with type 2 diabetes mellitus (T2DM). A total of 88 patients were randomized to receive 200 mg of Tocovid twice daily, or a matching placebo for 12 months. Fasting blood samples were collected for measurements of HbA1c, renal profile, lipid profile, and biomarkers. A nerve conduction study (NCS) was performed on all patients at baseline and subsequently at 2, 6, 12 months. Patients were reassessed after 6 months of washout. After 12 months of supplementation, patients in the Tocovid group exhibited highly significant improvements in conduction velocity (CV) of both median and sural sensory nerves as compared to those in the placebo group. The between-intervention-group differences (treatment effects) in CV were 1.60 m/s (95% CI: 0.70, 2.40) for the median nerve and 2.10 m/s (95% CI: 1.50, 2.90) for the sural nerve. A significant difference in peak velocity (PV) was also observed in the sural nerve (2.10 m/s; 95% CI: 1.00, 3.20) after 12 months. Significant improvements in CV were only observed up to 6 months in the tibial motor nerve, 1.30 m/s (95% CI: 0.60, 2.20). There were no significant changes in serum biomarkers, transforming growth factor beta-1 (TGFß-1), or vascular endothelial growth factor A (VEGF-A). After 6 months of washout, there were no significant differences from baseline between groups in nerve conduction parameters of all three nerves. Tocovid at 400 mg/day significantly improve tibial motor nerve CV up to 6 months, but median and sural sensory nerve CV in up to 12 months of supplementation. All improvements diminished after 6 months of washout.

The Effect of Oral Vitamin E on Semen Parameters and IVF Outcome: A Double-Blinded Randomized Placebo-Controlled Clinical Trial.

BACKGROUND: Male infertility is a main clinical problem that affects about 7% of all men worldwide. Many patients with male infertility are caused by a reduced antioxidant capacity of semen. Several antioxidant supplements, especially vitamin E, are proposed to help male infertility treatment. This project was goaled to study the effects of oral synthetic vitamin E (400 IU/day) for eight weeks on betterment of semen parameters and pregnancy rate. METHODS: After dropping the cases, 124 infertile couples with a male factor who were admitted to the IVF program were included. The male patients with idiopathic abnormal motility and/or morphology were randomized into two groups: 61 receiving vitamin E and 63 as the control group receiving placebo for eight weeks. The pretreatment semen parameters of both groups were compared with those of posttreatment. The pregnancy outcomes were considered between the two groups. RESULTS: There were no significant differences statistically between before and after treatment in the term of sperm volume, count, motility, and morphology. Furthermore, the IVF outcomes of the two groups were not different significantly, either. Interestingly, the percent of normal sperm in the placebo group was significantly decreased after eight weeks. CONCLUSION: Vitamin E supplementation might neutralize free radical activity to keep sperm from more oxidative damages. Further studies regarding the influence of higher acceptable doses of vitamin E on semen characteristics and fertility rates are needed. This study was registered as a two-arm, blinded, randomized, placebo-controlled clinical trial (IRCTID: IRCT2014020616506N1, 2014-03-18).

Hepatoprotective, antioxidant and anti-inflammatory potentials of Vit-E/C@SeNPs in rats: Synthesis, characterization, biochemical, radio-biodistribution, molecular and histopathological studies.

This study aimed to synthesize a nano-structure between selenium, Vit. C, and Vit. E (Vit-E/C@SeNPs) as a promising protective and therapeutic agent for hepatocellular carcinoma. Vit-E/C@SeNPs were characterized using TEM and DLS and its zetapotential was measured to evaluate its stability. DPPH assay and SRB test were performed to estimate its antioxidant capacity and cytotoxicity, respectively. A radiosynthesis of 99mTc-Vit-E/C@SeNPs was done for further in-vivo pharmacokinetic studies on normal and solid tumor induced mice. Further, in-vivo studies were conducted to investigate Vit-E/C@SeNPs efficacy against hepatocellular damage in Wistar albino rats induced by diethylnitrosamine (DEN) / Carbon Tetra chloride (CCl4). The synthesis results showed spherical Vit-E/C@SeNPs with core size of 50 nm, radical scavenging activity (%RSC) of 75.9%, and IC50 of 27.9 µg/ml. The biochemical analysis results showed that the lower liver function biomarker values (ALT, AST, ALP, total bilirubin and GGT) has gone for the Vit-E/C@SeNPs prevention and treated group, which also showed significant depletion of liver tissue l-MDA, and obvious increase in GSH concentration and CAT activity and marked improvement in the histological feature of liver tissue. Additionally, a significant up-regulation of mRNA gene expression levels of inflammatory gene (TGFß1, NFκB, iNOS, PPAR-γ and TNFα) and Apoptotic gene (P53) were determined by using Quantitative real-time PCR (qPCR). The values down regulate and tend to normal in prevention and control group. All of these introduce Vit-E/C@SeNPs as a promising agent as protective and therapeutic agent against DEN/ CCl4-induced hepatocellular damage (Hepatocellular carcinoma).

Micronutrients and athletic performance: A review.

Optimising nutrition intake is a key component for supporting athletic performance and supporting adaption to training. Athletes often use micronutrient supplements in order to correct vitamin and mineral deficiencies, improve immune function, enhance recovery and or to optimise their performance. The aim of this review was to investigate the recent literature regarding micronutrients (specifically iron, vitamin C, vitamin E, vitamin D, calcium) and their effects on physical performance. Over the past ten years, several studies have investigated the impacts of these micronutrients on aspects of athletic performance, and several reviews have aimed to provide an overview of current use and effectiveness. Currently the balance of the literature suggests that micronutrient supplementation in well-nourished athletes does not enhance physical performance. Excessive intake of dietary supplements may impair the body's physiological responses to exercise that supports adaptation to training stress. In some cases, micronutrient supplementation is warranted, for example, with a diagnosed deficiency, when energy intake is compromised, or when training and competing at altitude, however these micronutrients should be prescribed by a medical professional. Athletes are encouraged to obtain adequate micronutrients from a wellbalanced and varied dietary intake.

Impact of acute antioxidant supplementation on vascular function and autonomic nervous system modulation in young adults with PTSD.

Posttraumatic stress disorder (PTSD) has been associated with an increase in risk of cardiovascular disease (CVD). The goal of this study was to determine if peripheral vascular dysfunction, a precursor to CVD, was present in young adults with PTSD, and if an acute antioxidant (AO) supplementation could modify this potential PTSD-induced vascular dysfunction. Thirteen individuals with PTSD were recruited for this investigation and were compared with 35 age- and sex-matched controls (CTRL). The PTSD group participated in two visits, consuming either a placebo (PTSD-PL) or antioxidants (PTSD-AO; vitamins C and E; α-lipoic acid) before their visits, whereas the CTRL subjects only participated in one visit. Upper and lower limb vascular functions were assessed via flow-mediated dilation and passive leg movement technique. Heart rate variability was utilized to assess autonomic nervous system modulation. The PTSD-PL condition, when compared with the CTRL group, reported lower arm and leg microvascular function as well as sympathetic nervous system (SNS) predominance. After acute AO supplementation, arm, but not leg, microvascular function was improved and SNS predominance was lowered to which the prior difference between PTSD group and CTRL was no longer significant. Young individuals with PTSD demonstrated lower arm and leg microvascular function as well as greater SNS predominance when compared with age- and sex-matched controls. Furthermore, this lower vascular/autonomic function was augmented by an acute AO supplementation to the level of the healthy controls, potentially implicating oxidative stress as a contributor to this blunted vascular/autonomic function.

Effect of dietary vitamins C and E on the risk of Parkinson's disease: A meta-analysis.

BACKGROUND & AIMS: A neuroprotective effect of dietary vitamins C and E on Parkinson's disease (PD) has been suggested, however, several human studies have reported controversial results. Therefore, we conducted a meta-analysis on the effect of vitamins C and E on the risk of Parkinson's disease. METHODS: A comprehensive literature search was conducted using the PubMed, EMBASE, Cochrane Library, and SCOPUS databases for studies published up to January 23, 2021. We included studies that reported (1) intake of vitamins C and E using validated methods; (2) assessment of odds ratio (OR), relative risk (RR), or hazard ratio (HR); and (3) patients with PD identified by a neurologist, hospital records, or death certificates. The Comprehensive Meta-Analysis Software 2 program was used for statistical analyses of the pooled data. RESULTS: A total of 12 studies (four prospective cohort and eight case-control studies) were included in our meta-analysis. No significant risk reduction was observed in the high vitamin C intake group compared to low intake group. On the other hand, the high vitamin E intake group showed a significantly lower risk of development of PD than the low intake group (pooled OR = 0.799. 95% CI = 0.721 to 0.885). CONCLUSIONS: We conclude that vitamin E might have a protective effect against PD, while vitamin C does not seem to have such an effect. However, the exact mechanism of the transport and regulation of vitamin E in the CNS remains elusive, and further studies would be necessary in this field.

Antioxidant Supplementation Does Not Affect Bone Turnover Markers During 60 Days of 6° Head-Down Tilt Bed Rest: Results from an Exploratory Randomized Controlled Trial.

BACKGROUND: Immobilization and related oxidative stress are associated with bone loss. Antioxidants like polyphenols, omega-3 fatty acids, vitamins, and micronutrients may mitigate these negative effects on bone metabolism through scavenging of free radicals. OBJECTIVES: We hypothesized that antioxidant supplementation during 60 days of 6° head-down tilt bed rest (HDBR) would reduce bone resorption and increase bone formation compared to nonsupplemented controls. METHODS: This exploratory randomized, controlled, single-blind intervention study conducted in a parallel design included 20 healthy male volunteers (age, 34 ± 8 years; weight, 74 ± 6 kg). The study consisted of a 14-day adaptation phase [baseline data collection (BDC)], followed by 60 days of HDBR and a 14-day recovery period (R). In the antioxidant group, volunteers received an antioxidant cocktail (741 mg/d polyphenols, 2.1 g/d omega-3 fatty acids, 168 mg/d vitamin E, and 80 µg/d selenium) with their daily meals. In the control group, volunteers received no supplement. Based on their body weight, all volunteers received an individually tailored and strictly controlled diet, consistent with DRIs. We analyzed biomarkers of calcium homeostasis, bone formation, and bone resorption during BDC, HDBR, and R, as well as for 30 days after the end of HDBR. Data were analyzed by linear mixed models. RESULTS: The antioxidant supplement did not affect serum calcium, parathyroid hormone, urinary C-telopeptide of type I collagen (CTX), urinary N-telopeptide of type I collagen, serum ß-C-telopeptide of type I collagen (ß-CTX), bone alkaline phosphatase, aminoterminal propeptide of type I collagen, osteocalcin, or urinary calcium excretion. In both groups, typical bed rest-related changes were observed. CONCLUSIONS: Supplementation of an antioxidant cocktail to a diet matching the DRIs did not affect bone resorption or formation during 60 days of HDBR in healthy young men. This trial was registered at clinicaltrials.gov as NCT03594799.

Dexamethasone reduces infectious bursal disease mortality in chickens.

Very virulent infectious bursal disease virus (vvIBDV) causes high mortality in chickens but measures to reduce the mortality have not been explored. Chickens (8-9 weeks) were treated with 3 agents before and during vvIBDV inoculation. Dexamethasone treatment reduced the mortality of infected chickens (40.7% vs. 3.7%; p < 0.001), but treatment with aspirin or vitamin E plus selenium did not affect the mortality. The bursa of Fabricius appeared to have shrunk in both dead and surviving chickens (p < 0.01). The results indicate that dexamethasone can reduce mortality in vvIBDV-infected chickens and may provide therapeutic clues for saving individual birds infected by the virus.

The role of biofactors in the prevention and treatment of age-related diseases.

The present demographic changes toward an aging society caused a rise in the number of senior citizens and the incidence and burden of age-related diseases (such as cardiovascular diseases [CVD], cancer, nonalcoholic fatty liver disease [NAFLD], diabetes mellitus, and dementia), of which nearly half is attributable to the population ≥60 years of age. Deficiencies in individual nutrients have been associated with increased risks for age-related diseases and high intakes and/or blood concentrations with risk reduction. Nutrition in general and the dietary intake of essential and nonessential biofactors is a major determinant of human health, the risk to develop age-related diseases, and ultimately of mortality in the older population. These biofactors can be a cost-effective strategy to prevent or, in some cases, even treat age-related diseases. Examples reviewed herein include omega-3 fatty acids and dietary fiber for the prevention of CVD, α-tocopherol (vitamin E) for the treatment of biopsy-proven nonalcoholic steatohepatitis, vitamin D for the prevention of neurodegenerative diseases, thiamine and α-lipoic acid for the treatment of diabetic neuropathy, and the role of folate in cancer epigenetics. This list of potentially helpful biofactors in the prevention and treatment of age-related diseases, however, is not exhaustive and many more examples exist. Furthermore, since there is currently no generally accepted definition of the term biofactors, we here propose a definition that, when adopted by scientists, will enable a harmonization and consistent use of the term in the scientific literature.

The Effect of Omega-3 Fatty Acid Supplementation on Serum Adipocytokines, Lipid Profile and Biochemical Markers of Inflammation in Recreational Runners.

BACKGROUND: The study aimed to evaluate the effects of a 3-week ω-3 PUFA supplementation on serum adipocytokines (i.e., adiponectin, leptin), neuregulin-4 (NRG4) and erythrocyte omega-3 (ω-3) fatty acid content, as well as the blood antioxidant defense capacity in non-elite endurance runners. METHODS: Twenty-four runners were randomized into two groups: the supplemented group, who received omega free fatty acids extract containing 142 mg of EPA, 267 mg of DHA, 12 mg of vitamin E and 5 µg of vitamin D, each administrated at a dose of six capsules twice a day for three weeks, or the placebo group. Venous blood samples were withdrawn at the start and at the end of the study protocols to estimate serum biochemical variables. RESULTS: A significantly higher ω-3 index and lower AA/EPA ratio was observed after ω-3 PUFA compared to pre-supplementation levels (p < 0.001 and p < 0.001, respectively). An increase in baseline adiponectin and NRG4 levels, as well as a decrease of leptin concentration and lipid profile improvement, were observed in subjects after a ω-3 PUFA diet. The increased ω-3 index had a significant effect on TNFα levels and a serum marker of antioxidant defense. CONCLUSIONS: The ω-3 PUFA extract with added vitamin E and D supplementation may have a positive effect on the function of the adipocyte tissue, as well as the ability to prevent cardiovascular complications in athletes.

Effects of colon-targeted vitamins on the composition and metabolic activity of the human gut microbiome- a pilot study.

An increasing body of evidence has shown that gut microbiota imbalances are linked to diseases. Currently, the possibility of regulating gut microbiota to reverse these perturbations by developing novel therapeutic and preventive strategies is being extensively investigated. The modulatory effect of vitamins on the gut microbiome and related host health benefits remain largely unclear. We investigated the effects of colon-delivered vitamins A, B2, C, D, and E on the gut microbiota using a human clinical study and batch fermentation experiments, in combination with cell models for the assessment of barrier and immune functions. Vitamins C, B2, and D may modulate the human gut microbiome in terms of metabolic activity and bacterial composition. The most distinct effect was that of vitamin C, which significantly increased microbial alpha diversity and fecal short-chain fatty acids compared to the placebo. The remaining vitamins tested showed similar effects on microbial diversity, composition, and/or metabolic activity in vitro, but in varying degrees. Here, we showed that vitamins may modulate the human gut microbiome. Follow-up studies investigating targeted delivery of vitamins to the colon may help clarify the clinical significance of this novel concept for treating and preventing dysbiotic microbiota-related human diseases. Trial registration: ClinicalTrials.gov, NCT03668964. Registered 13 September 2018 - Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03668964.