Using the best form of Vitamin E: synthetic vitamin E vs natural succinate

Vitamin E naturally occurs in the form of D-α-tocopherol, and synthetic vitamin E, or DL-α-tocopherol acetate, is derived from fossil fuels, which makes it similar to gasoline and plastic. While there is no significant basis for the belief that synthetic vitamin E is harmful, there are reasons to suspect that alpha-tocopherol in its natural form is better for the body and more effective at treating oxidative stress and other conditions.

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Comparative study on the plasma lipid oxidation induced by peroxynitrite and peroxyl radicals and its inhibition by antioxidants

Morita M, Naito Y, Itoh Y, Niki E

Free Radic Res. 2019 Nov 14:1-13. doi: 10.1080/10715762.2019.1688799.

Abstract

The unregulated oxidative modification of biological molecules has been implicated in the pathogenesis of various diseases, and the beneficial effects of antioxidants against detrimental oxidation have received much attention. Among the multiple oxidants, peroxyl radical and peroxynitrite play an important role as chain-carrying species in lipid peroxidation and one of the major oxidants produced in vivo, respectively. This study was performed to elucidate the prominent features of these two oxidants by comparing their reactivity and selectivity and also the effects of antioxidants against plasma lipid oxidation induced by the two oxidants. It was shown that despite peroxyl radical and peroxynitrite gave similar pattern of lipid peroxidation products of plasma, and these two oxidants exert different selectivity and reactivity towards probes and antioxidants. The capacity of antioxidants to scavenge peroxynitrite and peroxyl radical decreased in the order BSA > glutathione > α-tocopherol ∼ bilirubin ∼ α – tocotrienol > γ-tocotrienol ∼ γ – tocopherol > uric acid and α-tocopherol ∼ α – tocotrienol > bilirubin > γ-tocotrienol ∼ γ – tocopherol > BSA > glutathione > uric acid, respectively. α-Tocopherol localised within plasma lipoproteins was six times less effective than trolox in aqueous phase for scavenging peroxynitrite and the derived oxidants, despite the same chemical reactivity of the two chromanols. BSA was relatively more effective as antioxidant against peroxynitrite than peroxyl radical, whereas TEMPO did not act as efficient antioxidant against both oxidants. It was suggested that thiols act as more potent antioxidant against peroxynitrite than phenolic antioxidants, while phenolic antioxidants are potent inhibitor of lipid peroxidation induced by free radicals including those derived from peroxynitrite. Abbreviations: AAPH: 2,2′-azobis(2-amidinopropane) dihydrochloride; C11-BODIPY: 4,4-difluoro-5-(4-phenyl-1,3-butadienyl)-4-bora-3a,4a-diaza-s-indacene-3-undecanoic acid; BSA: bovine serum albumin; DPPP: diphenyl-1-pyrenylphosphine; H(p)ODE: hydro(pero)xyoctadecadienoates; PGR: pyrogallol red; PUFA: polyunsaturated fatty acid; SIN-1: 3-morpholinosydnonimine; TEMPO: 2,2-6,6 tetramethylpiperidine-1-oxyl; Trolox: 2-carboxy-2,5,7,8-tetramethyl-6-hydroxychroman.

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Investigation of the curative effects of palm vitamin E tocotrienols on autoimmune arthritis disease in vivo

Zainal Z, Rahim AA, Radhakrishnan AK, Chang SK, Khaza'ai H

Sci Rep. 2019 Nov 14;9(1):16793. doi: 10.1038/s41598-019-53424-7.

Abstract

The tocotrienol-rich fraction (TRF) from palm oil contains vitamin E, which possesses potent antioxidant and anti-inflammatory activities. Rheumatoid arthritis (RA) is a chronic joint inflammatory disease characterised by severe joint pain, cartilage destruction, and bone erosion owing to the effects of various pro-inflammatory mediators and cytokines. Here, we investigated the therapeutic effects of TRF in a rat model of collagen-induced arthritis (CIA). Arthritis was induced by a single intradermal injection of collagen type II in Dark Agouti (DA) rats. Rats were then treated with or without TRF by oral gavage from day 28 after the first collagen injection. Arthritic rats supplemented with TRF showed decreased articular index scores, ankle circumferences, paw volumes, and radiographic scores when compared with untreated rats. The untreated arthritic rats showed higher plasma C-reactive protein levels (p < 0.05) and production of pro-inflammatory cytokines than arthritic rats fed TRF. Moreover, there was a marked reduction in the severity of histopathological changes observed in arthritic rats treated with TRF compared with that in untreated arthritic rats. Overall, the results show that TRF had beneficial effects in this rat model of RA.

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Effect of maternal omega-3 fatty acids and vitamin E supplementation on placental apoptotic markers in rat model of early and late onset preeclampsia

Kasture V, Kale A, Randhir K, Sundrani D, Joshi S

Life Sci. 2019 Nov 12;239:117038. doi: 10.1016/j.lfs.2019.117038

Abstract

AIM:

Disturbed placentation results in pregnancy complications like preeclampsia. Placental development is influenced by apoptosis during trophoblast differentiation and proliferation. Increased oxidative stress upregulates placental apoptosis. We have earlier reported increased oxidative stress, lower omega-3 fatty acids and vitamin E levels in women with preeclampsia. Current study examines effect of maternal omega-3 fatty acids and vitamin E supplementation on apoptotic markers across gestation in a rat model of preeclampsia.

MAIN METHODS:

Pregnant Wistar rats were randomly assigned to control; early onset preeclampsia (EOP); late onset preeclampsia (LOP); early onset preeclampsia + omega-3 fatty acid + vitamin E supplementation (EOP + O + E) and late onset preeclampsia + omega-3 fatty acid + vitamin E supplementation (LOP + O + E) groups. Animals (Control, EOP, EOP + O + E) were sacrificed at d14 and d20 of gestation while animals (LOP, LOP + O + E) were sacrificed at d20 to collect blood and placentae. Protein and mRNA levels of apoptotic markers were analyzed by ELISA and RT-PCR respectively.

KEY FINDINGS:

Protein levels of proapoptotic markers like Bcl-2 associated X-protein (BAX) (p < 0.05), caspase-8 and 3 (p < 0.01 for both) and malondialdehyde (p < 0.01) were higher only in the EOP group as compared to control. However, the antiapoptotic marker, B cell lymphoma 2 (Bcl-2) protein levels were lower in both the subtypes of preeclampsia (p < 0.01 for both).

SIGNIFICANCE:

Our findings suggest that supplementation was beneficial in reducing the caspase-8 and 3 in early onset preeclampsia but did not normalize BAX and Bcl-2 levels. This has implications for reducing placental apoptosis in preeclampsia.

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Postoperative Administration of Alpha-tocopherol Enhances Osseointegration of Stainless Steel Implants: An In Vivo Rat Model

Savvidis M, Papavasiliou K, Taitzoglou I, Giannakopoulou A, Kitridis D, Galanis N, Vrabas I, Tsiridis E.

Clin Orthop Relat Res. 2019 Nov 6. doi: 10.1097/CORR.0000000000001037.

Abstract

BACKGROUND:

Alpha-tocopherol, a well-known antioxidative agent, may have a positive effect on bone formation during the remodeling phase of secondary fracture healing. Fracture healing and osseointegration of implants share common biological pathways; hence, alpha-tocopherol may enhance implant osseointegration.

QUESTIONS/PURPOSES:

This experimental study in rats assessed the ability of alpha-tocopherol to enhance osseointegration of orthopaedic implants as determined by (1) pull-out strength and removal torque and (2) a histomorphological assessment of bone formation. In addition, we asked, (3) is there a correlation between the administration of alpha-tocopherol and a reduction in postoperative oxidative stress (as determined by malondialdehyde, protein carbonyls, reduced and oxidized glutathione and their ratio, catalase activity and total antioxidant capacity) that develops after implantation of an orthopaedic implant?

METHODS:

This blinded study was performed in study and control groups, each consisting of 15 young adult male Wistar rats. On Day 0, a custom-designed stainless-steel screw was implanted in the proximal metaphysis of both tibias of all rats. On Day 1, animals were randomized to receive either alpha-tocopherol (40 mg/kg once per day intraperitoneally) or saline (controls). Animals were treated according to identical perioperative and postoperative protocols and were euthanized on Day 29. All animals completed the study and all tibias were suitable for evaluation. Implant pullout strength was assessed in the right tibias, and removal torque and histomorphometric evaluations (that is, volume of newly formed bone surrounding the implant in mm, percentage of newly formed bone, percentage of bone marrow surrounding the implant per optical field, thickness of newly formed bone in μm, percentage of mineralized bone in newly formed bone, volume of mature newly formed bone surrounding the implant in mm and percentage of mineralized newly formed bone per tissue area) were performed in the left tibias. The plasma levels of alpha-tocopherol, malondialdehyde, protein carbonyls, glutathione, glutathione disulfide, catalase, and the total antioxidant capacity were evaluated, and the ratio of glutathione to oxidized glutathione was calculated.

RESULTS:

All parameters were different between the alpha-tocopherol-treated and control rats, favoring those in the alpha-tocopherol group. The pullout strength for the alpha-tocopherol group (mean ± SD) was 124.9 ± 20.7 newtons (N) versus 88.1 ± 12.7 N in the control group (mean difference -36.7 [95% CI -49.6 to -23.9]; p < 0.001). The torque median value was 7 (range 5.4 to 8.3) versus 5.2 (range 3.6 to 6 ) N/cm (p < 0.001). The newly formed bone volume was 29.8 ± 5.7 X 10 versus 25.2 ± 7.8 X 10 mm (mean difference -4.6 [95% CI -8.3 to -0.8]; p = 0.018), the percentage of mineralized bone in newly formed bone was 74.6% ± 8.7% versus 62.1% ± 9.8% (mean difference -12.5 [95% CI -20.2 to -4.8]; p = 0.003), the percentage of mineralized newly formed bone per tissue area was 40.3 ± 8.6% versus 34.8 ± 9% (mean difference -5.5 [95% CI -10.4 to -0.6]; p = 0.028), the glutathione level was 2 ± 0.4 versus 1.3 ± 0.3 μmol/g of hemoglobin (mean difference -0.6 [95% CI -0.9 to -0.4]; p < 0.001), the median glutathione/oxidized glutathione ratio was 438.8 (range 298 to 553) versus 340.1 (range 212 to 454; p = 0.002), the catalase activity was 155.6 ± 44.6 versus 87.3 ± 25.2 U/mg Hb (mean difference -68.3 [95% CI -95.4 to -41.2]; p < 0.001), the malondialdehyde level was 0.07 ± 0.02 versus 0.14 ± 0.03 μmol/g protein (mean difference 0.07 [95% CI 0.05 to 0.09]; p < 0.001), the protein carbonyl level was 0.16 ± 0.04 versus 0.27 ± 0.08 nmol/mg of protein (mean difference -0.1 [95% CI 0.05 to 0.15]; p = 0.002), the alpha-tocopherol level was 3.9 ± 4.1 versus 0.9 ± 0.2 mg/dL (mean difference -3 [95% CI -5.2 to -0.7]; p = 0.011), and the total antioxidant capacity was 15.9 ± 3.2 versus 13.7 ± 1.7 nmol 2,2-diphenyl-1-picrylhydrazyl radical/g of protein (mean difference -2.1 [95% CI -4.1 to -0.18]; p = 0.008).

CONCLUSIONS:

These results using an in vivo rat model support that postoperatively administered alpha-tocopherol can enhance the osseointegration of an orthopaedic implant, although a cause and effect relationship between the administration of alpha-tocopherol and a reduction in postoperative stress cannot be securely established.

CLINICAL RELEVANCE:

These findings suggest that postoperative administration of alpha-tocopherol is a promising approach to enhance osseointegration of orthopaedic implants in patients. Further studies with different animal models and/or different implants and those evaluating the alpha-tocopherol dose response are needed before performing clinical trials that will examine whether these promising, preliminary results can be extrapolated to the clinical setting as well.

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Metabolic dysregulation in vitamin E and carnitine shuttle energy mechanisms associate with human frailty

Rattray NJW, Trivedi DK, Xu Y, Chandola T, Johnson CH, Marshall AD, Mekli K, Rattray Z, Tampubolon G, Vanhoutte B, White IR, Wu FCW, Pendleton N, Nazroo J, Goodacre R

Nat Commun. 2019 Nov 5;10(1):5027. doi: 10.1038/s41467-019-12716-2.

Abstract

Global ageing poses a substantial economic burden on health and social care costs. Enabling a greater proportion of older people to stay healthy for longer is key to the future sustainability of health, social and economic policy. Frailty and associated decrease in resilience plays a central role in poor health in later life. In this study, we present a population level assessment of the metabolic phenotype associated with frailty. Analysis of serum from 1191 older individuals (aged between 56 and 84 years old) and subsequent longitudinal validation (on 786 subjects) was carried out using liquid and gas chromatography-mass spectrometry metabolomics and stratified across a frailty index designed to quantitatively summarize vulnerability. Through multivariate regression and network modelling and mROC modeling we identified 12 significant metabolites (including three tocotrienols and six carnitines) that differentiate frail and non-frail phenotypes. Our study provides evidence that the dysregulation of carnitine shuttle and vitamin E pathways play a role in the risk of frailty.

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Therapeutic effect of Vitamin E in preventing bone loss: An evidence-based review

Nazrun Shuid A, Das S, Mohamed IN

Int J Vitam Nutr Res. 2019 Nov;89(5-6):357-370. doi: 10.1024/0300-9831/a000566.

Abstract

The present review explored the anti-inflammatory and immunomodulatory properties of vitamin E, which has protective action against osteoporosis. A systematic review of the literature was conducted to identify the published bone studies on vitamin E. The studies included inflammatory or immunology-related parameters. Medline and Scopus databases were searched for relevant studies published from 2005 till 2015. Research articles published in English and confined to the effect of vitamin E on bone were included. It is pertinent to mention that these studies took into consideration inflammatory or immunology parameters including interleukin (IL)-1, IL-6, receptor activator of nuclear factor kappa-B ligand (RANKL), inducible nitric oxide synthases (iNOS), serum amyloid A (SAA), e-selection and high-sensitivity C-reactive protein (hs-CRP). An extended literature search yielded 127 potentially relevant articles with seven articles meeting the inclusion and exclusion criteria. Another recent article was added with the total number accounting to eight. All these included literature comprised five animal studies, one in-vitro study and two human studies. These studies demonstrated that vitamin E, especially tocotrienol, was able to alleviate IL-1, IL-6, RANKL, iNOS and hs-CRP levels in relation to bone metabolism. In conclusion, vitamin E exerts its anti-osteoporotic actions via its anti-inflammatory and immunomodulatory effects.

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