Tocopherols, tocotrienols and tocomonoenols: Many similar molecules but only one vitamin E.

The aim of this article is to correct a very general error in scientific articles, in textbooks and in the Internet that has become an accepted fact. In this literature, the term "vitamin E″ is used for several similar molecules (both tocopherols and tocotrienols) that have never been shown to have vitamin property, i.e. a protective effect against the human deficiency disease. In fact, the name "vitamin E″ should only be used to define molecules that prevent the human deficiency disease "Ataxia with Vitamin E Deficiency" (AVED). Only one such molecule is known, α-tocopherol. This error may confuse consumers as well as medical doctors, who prescribe vitamin E without realizing that the current use of the name includes molecules of unknown, if not unwanted functions.

Inhibition of Osteocyte Membrane Repair Activity via Dietary Vitamin E Deprivation Impairs Osteocyte Survival.

Osteocytes experience plasma membrane disruptions (PMD) that initiate mechanotransduction both in vitro and in vivo in response to mechanical loading, suggesting that osteocytes use PMD to sense and adapt to mechanical stimuli. PMD repair is crucial for cell survival; antioxidants (e.g., alpha-tocopherol, also known as Vitamin E) promote repair while reactive oxygen species (ROS), which can accumulate during exercise, inhibit repair. The goal of this study was to determine whether depleting Vitamin E in the diet would impact osteocyte survival and bone adaptation with loading. Male CD-1 mice (3 weeks old) were fed either a regular diet (RD) or Vitamin E-deficient diet (VEDD) for up to 11 weeks. Mice from each dietary group either served as sedentary controls with normal cage activity, or were subjected to treadmill exercise (one bout of exercise or daily exercise for 5 weeks). VEDD-fed mice showed more PMD-affected osteocytes (+ 50%) after a single exercise bout suggesting impaired PMD repair following Vitamin E deprivation. After 5 weeks of daily exercise, VEDD mice failed to show an exercise-induced increase in osteocyte PMD formation, and showed signs of increased osteocytic oxidative stress and impaired osteocyte survival. Surprisingly, exercise-induced increases in cortical bone formation rate were only significant for VEDD-fed mice. This result may be consistent with previous studies in skeletal muscle, where myocyte PMD repair failure (e.g., with muscular dystrophy) initially triggers hypertrophy but later leads to widespread degeneration. In vitro, mechanically wounded MLO-Y4 cells displayed increased post-wounding necrosis (+ 40-fold) in the presence of H2O2, which could be prevented by Vitamin E pre-treatment. Taken together, our data support the idea that antioxidant-influenced osteocyte membrane repair is a vital aspect of bone mechanosensation in the osteocytic control of PMD-driven bone adaptation.

Chronic vitamin E deficiency impairs cognitive function in adult zebrafish via dysregulation of brain lipids and energy metabolism.

Zebrafish (Danio rerio) are a recognized model for studying the pathogenesis of cognitive deficits and the mechanisms underlying behavioral impairments, including the consequences of increased oxidative stress within the brain. The lipophilic antioxidant vitamin E (α-tocopherol; VitE) has an established role in neurological health and cognitive function, but the biological rationale for this action remains unknown. In the present study, we investigated behavioral perturbations due to chronic VitE deficiency in adult zebrafish fed from 45 days to 18-months of age diets that were either VitE-deficient (E-) or VitE-sufficient (E+). We hypothesized that E- zebrafish would display cognitive impairments associated with elevated lipid peroxidation and metabolic disruptions in the brain. Quantified VitE levels at 18-months in E- brains (5.7 ± 0.1 nmol/g tissue) were ~20-times lower than in E+ (122.8 ± 1.1; n = 10/group). Using assays of both associative (avoidance conditioning) and non-associative (habituation) learning, we found E- vs E+ fish were learning impaired. These functional deficits occurred concomitantly with the following observations in adult E- brains: decreased concentrations of and increased peroxidation of polyunsaturated fatty acids (especially docosahexaenoic acid, DHA), altered brain phospholipid and lysophospholipid composition, as well as perturbed energy (glucose/ketone), phosphatidylcholine and choline/methyl-donor metabolism. Collectively, these data suggest that chronic VitE deficiency leads to neurological dysfunction through multiple mechanisms that become dysregulated secondary to VitE deficiency. Apparently, the E- animals alter their metabolism to compensate for the VitE deficiency, but these compensatory mechanisms are insufficient to maintain cognitive function.

Vitamin E deficiency during embryogenesis in zebrafish causes lasting metabolic and cognitive impairments despite refeeding adequate diets.

Vitamin E (α-tocopherol; VitE) is a lipophilic antioxidant required for normal embryonic development in vertebrates, but the long-term effects of embryonic VitE deficiency, and whether they are ameliorated by feeding VitE-adequate diets, remain unknown. We addressed these questions using a zebrafish (Danio rerio) model of developmental VitE deficiency followed by dietary remediation. Adult zebrafish maintained on VitE-deficient (E-) or sufficient (E+) diets were spawned to obtained E- and E+ embryos, respectively, which we evaluated up to 12 days post-fertilization (dpf). The E- group suffered significantly increased morbidity and mortality as well as altered DNA methylation status through 5 dpf when compared to E+ larvae, but upon feeding with a VitE-adequate diet from 5 to 12 dpf both the E- and E+ groups survived and grew normally; the DNA methylation profile also was similar between groups by 12 dpf. However, 12 dpf E- larvae still had behavioral defects. These observations coincided with sustained VitE deficiency in the E- vs. E+ larvae (p < 0.0001), despite adequate dietary supplementation. We also found in E- vs. E+ larvae continued docosahexaenoic acid (DHA) depletion (p < 0.0001) and significantly increased lipid peroxidation. Further, targeted metabolomics analyses revealed persistent dysregulation of the cellular antioxidant network, the CDP-choline pathway, and glucose metabolism. While anaerobic processes were increased, aerobic metabolism was decreased in the E- vs. E+ larvae, indicating mitochondrial damage. Taken together, these outcomes suggest embryonic VitE deficiency causes lasting behavioral impairments due to persistent lipid peroxidation and metabolic perturbations that are not resolved via later dietary VitE supplementation.

Vitamin E deficiency depressed fish growth, disease resistance, and the immunity and structural integrity of immune organs in grass carp (Ctenopharyngodon idella): Referring to NF-κB, TOR and Nrf2 signaling.

This study investigated the effects of dietary vitamin E on growth, disease resistance and the immunity and structural integrity of head kidney, spleen and skin in grass carp (Ctenopharyngodon idella). The fish were fed six diets containing graded levels of vitamin E (0, 45, 90, 135, 180 and 225 mg/kg diet) for 10 weeks. Subsequently, a challenge test was conducted by injection of Aeromonas hydrophila. The results showed that compared with optimal vitamin E supplementation, vitamin E deficiency caused depressed growth, poor survival rates and increased skin lesion morbidity in grass carp. Meanwhile, vitamin E deficiency decreased lysozyme and acid phosphatase activities, complement component 3 and complement component 4 contents in the head kidney, spleen and skin of grass carp (P < 0.05). Moreover, vitamin E deficiency down-regulated antimicrobial peptides (Hepcidin, liver-expressed antimicrobial peptide-2A, -2B, ß-defensin), IL-10, TGFß1, IκBα, TOR and S6K1 mRNA levels (P < 0.05) and up-regulated IL-1ß, IL-6, IL-8, IFN-γ2 and TNFα, NF-κB p65, IKKα, IKKß and 4EBP1 (not in the head kidney) mRNA levels (P < 0.05). In addition, vitamin E deficiency caused oxidative damage, decreased superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT) and glutathione reductase (GR) activities, and down-regulated the mRNA levels of antioxidant enzymes and signaling molecules Nrf2 (P < 0.05). Vitamin E deficiency also induced apoptosis by up-regulating capase-2, -3, -7, and -8 mRNA levels in the head kidney, spleen and skin of grass carp. In conclusion, this study indicated that dietary vitamin E deficiency depressed fish growth, impaired the immune function and disturbed the structural integrity of the head kidney, spleen and skin in grass carp, but optimal vitamin E supplementation can reverse those negative effects in fish. The optimal vitamin E requirements for young grass carp (266.39-1026.63 g) to achieve optimal growth performance and disease resistance based on the percent weight gain (PWG) and skin lesion morbidity were estimated to be 116.2 and 130.9 mg/kg diet, respectively. Meanwhile, based on immune indicator (LA activity in the head kidney) and antioxidant indicator (protection of spleen against MDA), the optimal vitamin E requirements for young grass carp were estimated to be 123.8 and 136.4 mg/kg diet, respectively.

Sheep deficient in vitamin E preferentially select for a feed with a higher concentration of vitamin E.

Given the capacity of ruminants to modify diet selection based on metabolic needs, we hypothesised that, when given a choice, lambs experiencing a vitamin E deficiency would consume more of a vitamin E-enriched feed than lambs not deficient in vitamin E. Fifty-six Dohne Merino lambs were divided into two groups and fed either a vitamin E-deficient diet over 40 days to induce low plasma vitamin E or a vitamin E-enriched diet to induce high plasma vitamin E. The lambs were then offered a choice of vitamin E-enriched and vitamin E-deficient pellets. For half of the animals, the enriched diet was paired with strawberry flavour and the deficient diet was paired with orange flavour, while the reverse pairings were offered to the others. Lamb preference for the diets was measured daily for the following 15 days. There was a three-way interaction between the high and low vitamin E treatment groups×vitamin E content and type of flavour in the feed×time (days). The lambs preferred pellets flavoured with strawberry but this preference changed to orange flavour in vitamin E-deficient lambs if the orange flavour was paired with high vitamin E. Lambs without a deficiency continued to prefer strawberry-flavoured pellets, regardless of the vitamin E concentrations in the pellets. It is possible that self-learning contributed to the low vitamin E group of lambs changing preference to orange flavour in order to consume more vitamin E, presumably to remediate the deficiency.

A novel animal model of impaired glucose tolerance induced by the interaction of vitamin E deficiency and (60)Co radiation.

Impaired glucose tolerance (IGT), known as the prediabetes stage, is usually induced by habits of life or environmental factors. Established IGT animal models are mostly conducted with chemical compounds such as streptozocin or genetic modification. However, the occasion of exposure to these factors in daily life is seldom. The objective of this study was to establish a new animal model of IGT induced by VE deficiency in diet and exposure to radiation. SD rats were treated individually or in combination of these two factors. In the combination group, the calculated insulin sensitivity index decreased; then HOMA-ß value increased. Oxidative damage and IGT were observed. Insulin secretion level in perfusate from pancreas response to glucose was characterized by a rapid but reduced first phase and an obviously defective second phase upon pancreas perfusion. Histopathological images demonstrated the pathological changes. Western blotting analysis showed that the insulin signaling pathway was downregulated. The interaction of VE deficiency in diet and exposure to radiation could break the equilibrium of oxidation and antioxidation and result in IGT. More importantly, a new IGT model was successfully established which may be conducive to further research into development of drugs against human IGT.

Serum α-Tocopherol Has a Nonlinear Inverse Association with Periodontitis among US Adults.

BACKGROUND: Previous experimental models suggest that vitamin E may ameliorate periodontitis. However, epidemiologic studies show inconsistent evidence in supporting this plausible association. OBJECTIVE: We investigated the association between serum α-tocopherol (αT) and γ-tocopherol (γT) and periodontitis in a large cross-sectional US population. METHODS: This study included 4708 participants in the 1999-2001 NHANES. Serum tocopherols were measured by HPLC and values were adjusted by total cholesterol (TC). Periodontal status was assessed by mean clinical attachment loss (CAL) and probing pocket depth (PPD). Total periodontitis (TPD) was defined as the sum of mild, moderate, and severe periodontitis. All measurements were performed by NHANES. RESULTS: Means ± SDs of serum αT:TC ratio from low to high quartiles were 4.0 ± 0.4, 4.8 ± 0.2, 5.7 ± 0.4, and 9.1 ± 2.7 µmol/mmol. In multivariate regression models, αT:TC quartiles were inversely associated with mean CAL (P-trend = 0.06), mean PPD (P-trend < 0.001), and TPD (P-trend < 0.001) overall. Adjusted mean differences (95% CIs) between the first and fourth quartile of αT:TC were 0.12 mm (0.03, 0.20; P-difference = 0.005) for mean CAL and 0.12 mm (0.06, 0.17; P-difference < 0.001) for mean PPD, whereas the corresponding OR for TPD was 1.65 (95% CI: 1.26, 2.16; P-difference = 0.001). In a dose-response analysis, a clear inverse association between αT:TC and mean CAL, mean PPD, and TPD was observed among participants with relatively low αT:TC. No differences were seen in participants with higher αT:TC ratios. Participants with γT:TC ratio in the interquartile range showed a significantly lower mean PPD than those in the highest quartile. CONCLUSIONS: A nonlinear inverse association was observed between serum αT and severity of periodontitis, which was restricted to adults with normal but relatively low αT status. These findings warrant further confirmation in longitudinal or intervention studies.

Patterns of dietary intake and serum carotenoid and tocopherol status are associated with biomarkers of chronic low-grade systemic inflammation and cardiovascular risk.

Dietary modification may affect inflammatory processes and protect against chronic disease. In the present study, we examined the relationship between dietary patterns, circulating carotenoid and tocopherol concentrations, and biomarkers of chronic low-grade systemic inflammation in a 10-year longitudinal study of Scottish postmenopausal women. Diet was assessed by FFQ during 1997-2000 (n 3237, mean age 54·8 (SD 2·2) years). Participants (n 2130, mean age 66·0 (SD 2·2) years) returned during 2007-11 for follow-up. Diet was assessed by FFQ (n 1682) and blood was collected for the analysis of serum high-sensitivity C-reactive protein (hs-CRP), IL-6, serum amyloid A, E-selectin, lipid profile and dietary biomarkers (carotenoids, tocopherols and retinol). Dietary pattern and dietary biomarker (serum carotenoid) components were generated by principal components analysis. A past 'prudent' dietary pattern predicted serum concentrations of hs-CRP and IL-6 (which decreased across the quintiles of the dietary pattern; P= 0·002 and P= 0·001, respectively; ANCOVA). Contemporary dietary patterns were also associated with inflammatory biomarkers. The concentrations of hs-CRP and IL-6 decreased across the quintiles of the 'prudent' dietary pattern (P= 0·030 and P= 0·006, respectively). hs-CRP concentration increased across the quintiles of a 'meat-dominated' dietary pattern (P= 0·001). Inflammatory biomarker concentrations decreased markedly across the quintiles of carotenoid component score (P< 0·001 for hs-CRP and IL-6, and P= 0·016 for E-selectin; ANCOVA). Prudent dietary pattern and carotenoid component scores were negatively associated with serum hs-CRP concentration (unstandardised ß for prudent component: -0·053, 95% CI -0·102, -0·003; carotenoid component: -0·183, 95% CI -0·233, -0·134) independent of study covariates. A prudent dietary pattern (which reflects a diet high in the intakes of fish, yogurt, pulses, rice, pasta and wine, in addition to fruit and vegetable consumption) and a serum carotenoid profile characteristic of a fruit and vegetable-rich diet are associated with lower concentrations of intermediary markers that are indicative of CVD risk reduction.

Vitamin E is essential for Purkinje neuron integrity.

α-Tocopherol (vitamin E) is an essential dietary antioxidant with important neuroprotective functions. α-Tocopherol deficiency manifests primarily in neurological pathologies, notably cerebellar dysfunctions such as spinocerebellar ataxia. To study the roles of α-tocopherol in the cerebellum, we used the α-tocopherol transfer protein for the murine version (Ttpa(-/)(-)) mice which lack the α-tocopherol transfer protein (TTP) and are a faithful model of vitamin E deficiency and oxidative stress. When fed vitamin E-deficient diet, Ttpa(-/)(-) mice had un-detectable levels of α-tocopherol in plasma and several brain regions. Dietary supplementation with α-tocopherol normalized plasma levels of the vitamin, but only modestly increased its levels in the cerebellum and prefrontal cortex, indicating a critical function of brain TTP. Vitamin E deficiency caused an increase in cerebellar oxidative stress evidenced by increased protein nitrosylation, which was prevented by dietary supplementation with the vitamin. Concomitantly, vitamin E deficiency precipitated cellular atrophy and diminished dendritic branching of Purkinje neurons, the predominant output regulator of the cerebellar cortex. The anatomic decline induced by vitamin E deficiency was paralleled by behavioral deficits in motor coordination and cognitive functions that were normalized upon vitamin E supplementation. These observations underscore the essential role of vitamin E and TTP in maintaining CNS function, and support the notion that α-tocopherol supplementation may comprise an effective intervention in oxidative stress-related neurological disorders.

Combined deficiency in glutathione peroxidase 4 and vitamin E causes multiorgan thrombus formation and early death in mice.

RATIONALE: Growing evidence indicates that oxidative stress contributes markedly to endothelial dysfunction. The selenoenzyme glutathione peroxidase 4 (Gpx4) is an intracellular antioxidant enzyme important for the protection of membranes by its unique activity to reduce complex hydroperoxides in membrane bilayers and lipoprotein particles. Yet a role of Gpx4 in endothelial cell function has remained enigmatic. OBJECTIVE: To investigate the role of Gpx4 ablation and subsequent lipid peroxidation in the vascular compartment in vivo. METHODS AND RESULTS: Endothelium-specific deletion of Gpx4 had no obvious impact on normal vascular homeostasis, nor did it impair tumor-derived angiogenesis in mice maintained on a normal diet. In stark contrast, aortic explants from endothelium-specific Gpx4 knockout mice showed a markedly reduced number of endothelial branches in sprouting assays. To shed light onto this apparent discrepancy between the in vivo and ex vivo results, we depleted mice of a second antioxidant, vitamin E, which is normally absent under ex vivo conditions. Therefore, mice were fed a vitamin E-depleted diet for 6 weeks before endothelial deletion of Gpx4 was induced by 4-hydroxytamoxifen. Surprisingly, ≈80% of the knockout mice died. Histopathological analysis revealed detachment of endothelial cells from the basement membrane and endothelial cell death in multiple organs, which triggered thrombus formation. Thromboembolic events were the likely cause of various clinical pathologies, including heart failure, renal and splenic microinfarctions, and paraplegia. CONCLUSIONS: Here, we show for the first time that in the absence of Gpx4, sufficient vitamin E supplementation is crucial for endothelial viability.

Vitamin E trafficking in neurologic health and disease.

Vitamin E was identified almost a century ago as a botanical compound necessary for rodent reproduction. Decades of research since then established that of all members of the vitamin E family, α-tocopherol is selectively enriched in human tissues, and it is essential for human health. The major function of α-tocopherol is thought to be that of a lipid-soluble antioxidant that prevents oxidative damage to biological components. As such, α-tocopherol is necessary for numerous physiological processes such as permeability of lipid bilayers, cell adhesion, and gene expression. Inadequate levels of α-tocopherol interfere with cellular function and precipitate diseases, notably ones that affect the central nervous system. The extreme hydrophobicity of α-tocopherol poses a serious thermodynamic barrier for proper distribution of the vitamin to target tissues and cells. Although transport of the vitamin shares some steps with that of other lipids, selected tissues evolved dedicated transport mechanisms involving the α-tocopherol transfer protein (αTTP). The critical roles of this protein and its ligand are underscored by the debilitating pathologies that characterize human carriers of mutations in the TTPA gene.

Recent applications of engineered animal antioxidant deficiency models in human nutrition and chronic disease.

Dietary antioxidants are essential nutrients that inhibit the oxidation of biologically important molecules and suppress the toxicity of reactive oxygen or nitrogen species. When the total antioxidant capacity is insufficient to quench these reactive species, oxidative damage occurs and contributes to the onset and progression of chronic diseases, such as neurodegenerative diseases, cardiovascular diseases, and cancer. However, epidemiological studies that examine the relationship between antioxidants and disease outcome can only identify correlative associations. Additionally, many antioxidants also have prooxidant effects. Thus, clinically relevant animal models of antioxidant function are essential for improving our understanding of the role of antioxidants in the pathogenesis of complex diseases as well as evaluating the therapeutic potential and risks of their supplementation. Recent progress in gene knockout mice and virus-based gene expression has potentiated these areas of study. Here, we review the current genetically modified animal models of dietary antioxidant function and their clinical relevance in chronic diseases. This review focuses on the 3 major antioxidants in the human body: vitamin C, vitamin E, and uric acid. We examine genetic models of vitamin C synthesis (guinea pig, Osteogenic Disorder Shionogi rat, Gulo(-/-) and SMP30(-/-) mouse mutants) and transport (Slc23a1(-/-) and Slc23a2(-/-) mouse mutants), vitamin E transport (Ttpa(-/-) mouse mutant), and uric acid synthesis (Uox(-/-) mouse mutant). The application of these models to current research goals is also discussed.

Alperujo extract, hydroxytyrosol, and 3,4-dihydroxyphenylglycol are bioavailable and have antioxidant properties in vitamin E-deficient rats--a proteomics and network analysis approach.

SCOPE: Olive products are rich in phenolic compounds, which are natural antioxidants in vitro. We tested the in vivo effects of alperujo, an olive production by-product, as well as hydroxytyrosol and 3,4-dihydroxyphenylglycol (DHPG) isolated from alperujo, on indices and pathways of oxidative and metabolic stress in a vitamin E-deficient rat model. METHODS AND RESULTS: Rats were fed a vitamin E-deficient diet for 10 weeks, followed by this diet supplemented with either 100 mg/kg diet dα-tocopherol, alperujo extract, hydroxytyrosol, or 10 mg/kg diet DHPG, for a further 2 weeks. We detected alperujo phenolics in tissues and blood, indicating they are bioavailable. Alperujo extract partially ameliorated elevated plasma levels of thiobarbituric acid reactive substances and also lowered plasma cholesterol levels, whereas hydroxytyrosol increased plasma triglyceride levels. Proteomics and subsequent network analysis revealed that hepatic mitochondrial aldehyde dehydrogenase (ALDH2), of which protein and activity levels were regulated by dα-tocopherol and olive phenolics, represents a novel central regulatory protein hub affected by the dietary interventions. CONCLUSION: The in vivo free radical scavenging properties of olive phenolics appear relatively modest in our model. But alternative mechanisms, including regulation of ALDH2, may represent relevant antioxidant mechanisms by which dietary olive phenolics could have beneficial impact on cardiovascular health.

Vitamin E and immunity.

Vitamin E is the most important chain-breaking, lipid-soluble antioxidant present in body tissues of all cells and is considered the first line of defense against lipid peroxidation and it is important for normal function of the immune cells. However, vitamin E deficiency is rare in well-nourished healthy subjects and is not a problem, even among people living on relatively poor diets, both T- and B-cell functions are impaired by vitamin E deficiency. While immune cells are particularly enriched in vitamin E because of their high polyunsaturated fatty acid content, this point puts them at especially high risk for oxidative damage. Besides its immunomodulatory effects, vitamin E also plays an important role in carcinogenesis with its antioxidant properties against cancer, and ischemic heart disease with limiting the progression of atherosclerosis. Supplementation of vitamin E significantly enhances both cell mediated and humoral immune functions in humans, especially in the elderly and animals.

Vitamin E-deficiency did not exacerbate partial skin reactions in mice locally irradiated with X-rays.

We previously showed that free radicals and oxidative stress are involved in radiation-induced skin reactions. Since vitamin E (VE) is a particularly important lipophilic antioxidant, VE-deficient mice were used to examine its effects on radiation-induced skin damage. The VE content of the skin was reduced to one fourth of levels of normal mice. Neither the time of onset nor the extent of the reactions quantified with a scoring system differed between normal and VE-deficient mice after local X-irradiation (50 Gy). Similarly, there was no difference in the levels of the ascorbyl radical between the groups, although they were higher in irradiated skin than non-irradiated skin. X-irradiation increased the amount of Bax protein in the skin of normal mice both in the latent and acute inflammatory stages, time- and dose-dependently. The increase was associated with an increase in cytochrome c in the cytosolic fraction, indicating that apoptosis was also promoted by the irradiation. The increase in Bax protein correlated well with the thickness of the skin. Although a deficiency in VE should lower resistance to free radicals in the mitochondrial membrane and thus enhance radiation-induced Bax expression and apoptosis, it actually attenuated the increase in Bax protein caused by irradiation.

The role of alpha-tocopherol in motor hypofunction with aging in alpha-tocopherol transfer protein knockout mice as assessed by oxidative stress biomarkers.

It has been hypothesized that oxidative stress plays a key role in aging. In order to elucidate the role of the antioxidant network - including alpha-tocopherol (alphaT) and alphaT transfer protein - in aging in vivo, alpha-tocopherol transfer protein knockout (alphaTTP(-/-)) mice were fed a vitamin-E-depleted diet, and wild-type (WT) mice were fed a diet containing 0.002 wt.% alphaT from the age of 3 months to 1 1/2 years. The lipid oxidation markers total hydroxyoctadecadienoic acid (tHODE) and 8-iso-prostaglandin F(2)alpha, and antioxidant levels in the blood, liver and brain were measured at 3, 6, 12 and 18 months. tHODE levels in the plasma of alphaTTP(-/-) mice were elevated at 6 months compared to 3 months, and were significantly higher those in WT mice, although they decreased thereafter. On the other hand, tHODE levels in the liver and brain were constantly higher in alphaTTP(-/-) mice than in WT mice. Motor activities decreased with aging in both mouse types; however, those in the alphaTTP(-/-) mice were lower than those in the WT mice. It is intriguing to note that motor activities were significantly correlated with the stereoisomer ratio (Z,E/E,E) of HODE, which is a measure of antioxidant capacity in vivo, in the plasma, in the liver and even in the brain, but not with other factors such as antioxidant levels. In summary, using the biomarker tHODE and its stereoisomer ratio, we demonstrated that alphaT depletion was associated with a decrease in motor function, and that this may be primarily attributable to a decrease in the total antioxidant capacity in vivo.

Correlation between neurological dysfunction with vitamin E deficiency and gastrectomy.

OBJECTIVE: We previously reported on vitamin E malabsorption after gastrectomy. In this study, we focused on neurological dysfunction due to serum vitamin E decrease during the postgastrectomy period in lager number of patients. METHODS: We examined the type of gastrectomy, type of reconstruction, serum vitamin E level, and neurological status for 96 gastrectomy patients. RESULTS: Low serum vitamin E levels were observed in 20 patients, and 10 of those patients suffered some neurological symptoms, i.e., peripheral neuropathy, limb or truncal ataxia. Vitamin E levels tended to decrease with time after gastrectomy, and the number of patients with low serum vitamin E levels increased at about 50 months after gastrectomy. This relationship was stronger in total gastrectomy patients than in subtotal gastrectomy patients. Ten patients were given oral vitamin E, and serum vitamin E levels normalized in 9 of the patients and neurological abnormalities improved in 8 patients. An oral intake of 300 mg or more of vitamin E was necessary for normalization of vitamin E levels. CONCLUSIONS: Gastrectomy should be considered a risk for vitamin E deficiency and neurological disturbance over the long-term clinical course. An oral vitamin E supply can improve serum vitamin E levels and neurological symptoms.

Dietary vitamin E deficiency increases anxiety-related behavior in rats under stress of social isolation.

It has been demonstrated that vitamin E deficiency from birth increases anxiety-related behavior using knockout animals with no vitamin E transfer proteins. The current study was undertaken to elucidate the effect of dietary vitamin E deficiency on anxiety-related behavior of rats in different housing conditions. Male Wistar strain rats were divided into two groups during the weaning period and fed a control or vitamin E-deficient diet. All rats were housed in groups (three rats per cage) for 3 weeks. In the fourth week, half of the rats in each dietary treatment were kept in social housing and the other half were kept in individual housing. Before sacrifice, rota-rod and elevated plus-maze (EPM) tests were performed to measure motor coordination and anxiety, respectively. The EPM test revealed that vitamin E-deficient rats spent less time in the open arms and showed more stretch-out posture than the control rats, showing that anxiety increased with dietary vitamin E deficiency. Furthermore, vitamin E deficiency-induced anxiety behavior was observed more prominent in individual housed rats than in social housed rats. On the basis of these results, we conclude that dietary vitamin E deficiency induces anxiety in rats especially under stress of social isolation.