Title: A Short Course of Supplementation with Vitamin E Isoform, Gamma Tocopherol (yT), Mitigates Endotoxin-Induced Inflammation in Humans Ex Vivo

Abstract Objectives The purpose of this study was to compare the effects of alpha tocopherol, gamma tocopherol, and the combination of alpha and gamma tocopherols on bone mineral density (BMD), bone mineral content (BMC), and bone metabolism in C57BL/6 J mice fed a high-fat diet. Methods A total of 75 male C57BL/6 mice were randomized to either a low fat diet (LFD) with 6% fat, a high fat diet (HFD) with 20% fat, HFD supplemented with alpha tocopherol (AT), gamma tocopherol (GT), or the combination of AT and GT. LFD and HFD were provided to corresponding groups of mice without vitamin E isoform supplements for 15 weeks to induce bone loss. At the end of the 15 weeks, AT, GT, and a combination of AT and GT were added to 3 of the HFD groups and fed for 10 weeks. LFD group and one of the HFD groups were continued on the same diet for another 10 weeks without additional supplements. All mice were euthanized at the end of the 25 weeks period. Left and right fibula bones were excised, cleaned, and scanned using the Lunar PIXImus dual-energy x-ray absorptiometry (DEXA) densitometer to assess BMD, BMC, lean tissue, and fat tissue content. Serum biomarkers of bone metabolism were evaluated post euthanization. Results HFD resulted in significantly lower fibular BMD and higher tibial bone fat content in comparison to LFD. Animals in the HFD supplemented with GT, but not AT, showed significantly reduced effect of HFD in lowering BMD. Additionally, in the group fed HFD supplemented with GT, a significantly higher concentration of alkaline phosphatase (ALP) and N-terminal propeptide of type I procollagen (PINP) were noted, compared to LFD. This may be indicative of increased bone formation resulting from GT incorporated into the HFD diet. Conclusions The findings of the study suggest that different isoforms of vitamin E affect bone density and bone metabolism differently. Within the different isoforms of vitamin E, gamma tocopherol may have protective effects in bone, especially in the situation of high fat diet induced bone loss. Further examination of the mechanistic action of vitamin E isoforms on skeletal health is warranted. Funding Sources Texas Woman's University.

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Relative Bioavailabilities of Natural and Synthetic Vitamin E Formulations Containing Mixed Tocopherols in Human Subjects

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831.69.2.92 ◽

1999 ◽

Vol 69 (2) ◽

pp. 92-95 ◽

Cited By ~ 16

Author(s):

Chopra ◽

Bhagavan

Keyword(s):

Vitamin E ◽

Animal Models ◽

Human Subjects ◽

Alpha Tocopherol ◽

Tocopheryl Acetate ◽

Normal Male ◽

Gamma Tocopherol ◽

Synthetic Vitamin ◽

Male Subjects ◽

Natural And Synthetic

There are several reports in the literature on the relative bioavailabilities of RRR (natural) vs. all-rac (synthetic) forms of vitamin E in humans and animal models but none on the bioavailability of alpha-tocopherol in mixed vitamin E formulations. In the present study we examined the bioavailability of alpha-tocopherol in a typical commercially available product containing mixed tocopherols. We also tested a formulation containing all-rac-alpha-tocopherol with mixed tocopherols for purposes of comparison along with straight RRR-and all-rac-alpha-tocopheryl acetate as reference products. Normal male subjects were given one of the four formulations of vitamin E (800 IU per day in softgel capsule form for 10 days): 1. All-rac-alpha-tocopheryl acetate, 2. RRR-alpha-tocopheryl acetate, 3. RRR-alpha-tocopherol with mixed tocopherols, and 4. all-rac-alpha-tocopherol with mixed tocopherols. Both serum alpha- and gamma-tocopherols were determined by HPLC at baseline, and at days 2, 4, 7 and 10. The values for alpha- at baseline and 10 days were 0.80, 0.80, 0.80 & 0.79 mg/dl and 1.67, 1.72, 1.76 & 1.62 mg/dl. The values for gamma- were 0.28, 0.29, 0.30 & 0.29 mg/dl and 0.11, 0.08, 0.10 & 0.10 mg/dl. Thus the data show that a) the bioavailability of RRR-and all-rac-alpha-tocopherols is not affected by other tocopherols, and b) both RRR-and all-rac-alpha-tocopherol (free or esterified) significantly suppress the serum gamma tocopherol to the same extent. Furthermore, since there was no difference in the serum values of alpha-tocopherol between RRR-and all-rac-vitamin E given the same dose as IUs, the data also support the currently accepted ratio of 1.36 for the biopotency of RRR- vs. all-rac-alpha-tocopheryl acetate.

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Gamma tocopherol: metabolism, biological activity and significance in human vitamin E nutrition1

American Journal of Clinical Nutrition ◽

10.1093/ajcn/27.8.980 ◽

1974 ◽

Vol 27 (9) ◽

pp. 980-986 ◽

Cited By ~ 8

Author(s):

John G. Bieri ◽

R. Poukka Evarts

Keyword(s):

Biological Activity ◽

Vitamin E ◽

Gamma Tocopherol

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Optimized vinpocetine-loaded vitamin E D-α-tocopherol polyethylene glycol 1000 succinate-alpha lipoic acid micelles as a potential transdermal drug delivery system: in vitro and ex vivo studies

International Journal of Nanomedicine ◽

10.2147/ijn.s187470 ◽

2018 ◽

Vol Volume 14 ◽

pp. 33-43 ◽

Cited By ~ 10

Author(s):

Osama A. A. Ahmed ◽

Khalid M. El-Say ◽

Bader M. Aljaeid ◽

Shaimaa M. Badr-Eldin ◽

Tarek A. Ahmed

Keyword(s):

Drug Delivery ◽

Polyethylene Glycol ◽

Vitamin E ◽

Transdermal Drug Delivery ◽

Ex Vivo ◽

Alpha Tocopherol ◽

Alpha Lipoic Acid ◽

Transdermal Drug Delivery System ◽

Polyethylene Glycol 1000

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Alpha-tocopherol, an effective inhibitor of platelet adhesion

Blood ◽

10.1182/blood.v73.1.141.141 ◽

1989 ◽

Vol 73 (1) ◽

pp. 141-149 ◽

Cited By ~ 65

Author(s):

J Jandak ◽

M Steiner ◽

PD Richardson

Keyword(s):

Vitamin E ◽

Platelet Adhesion ◽

Ex Vivo ◽

Platelet Rich Plasma ◽

Flow Chamber ◽

Alpha Tocopherol ◽

Tocopherol Concentration ◽

Average Decrease ◽

Platelet Adherence

Abstract Platelet adhesiveness was tested ex vivo in a group of six normal individuals receiving varying doses of alpha-tocopherol. Adhesion to glass slides coated with fibronectin, collagen, fibrinogen, or plasma proteins was studied by perfusing platelet-rich plasma through a flow chamber that allowed time- and space-resolved observations of platelet adhesion. Platelet adherence was measured in an area of parallel flow lines and low shear rate under standardized conditions before and after dietary supplementation with vitamin E at doses of 200 and 400 IU/d. Platelet adherence differed in magnitude depending on the adhesive surface. There was a distinct preference of platelets to adhere to sites that had been previously occupied. A remarkable decrease in platelet adherence was observed after vitamin E supplementation. The average decrease in adhesion after 2 weeks of 200 IU vitamin E was 75%. After 2 weeks of 400 IU vitamin E, platelet adhesion was reduced by 82%. The inhibitory activity of alpha-tocopherol was dose dependent and correlated well with the increase in alpha-tocopherol concentration in platelets after supplementation. Scanning electron microscopy revealed a striking decrease of pseudopodium formation in alpha-tocopherol- enriched platelets. Our results suggest that vitamin E may also be an effective antiadhesive agent in vivo.

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Vitamin E Supplementation Increases LDL Resistance to ex vivo Oxidation in Hemodialysis Patients

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831.73.4.290 ◽

2003 ◽

Vol 73 (4) ◽

pp. 290-296 ◽

Cited By ~ 10

Author(s):

Badiou ◽

Cristol ◽

Morena ◽

Bosc ◽

Carbonneau ◽

...

Keyword(s):

Oxidative Stress ◽

Vitamin E ◽

High Performance ◽

Ex Vivo ◽

Density Lipoprotein ◽

Thiobarbituric Acid ◽

Hemodialysis Patients ◽

Ldl Oxidation ◽

Oral Vitamin ◽

Vitamin E Supplementation

Background: Oxidative stress and alterations in lipid metabolism observed in hemodialysis patients potentiate the low-density lipoprotein (LDL) oxidability, recognized as a key event during early atherogenesis. Objective: To explore the effects of an oral vitamin E supplementation on oxidative stress markers and LDL oxidability in hemodialysis patients. Methods: Fourteen hemodialysis patients and six healthy volunteers were given oral vitamin E (500 mg/day) for six months. Oxidative stress was assessed using: plasma and lipoprotein vitamin E levels [high-performance liquid chromatography (HPLC) procedure]; thiobarbituric acid reactive substances (TBARS, Yaggi method); and copper-induced LDL oxidation. All parameters were evaluated before initiation of vitamin E supplementation, and at three and six months thereafter. Results: At baseline, a significantly higher TBARS concentration and a higher LDL oxidability were observed in hemodialysis patients when compared to controls. After six months of vitamin E supplementation, TBARS and LDL oxidability were normalized in hemodialysis patients. Conclusion: Our data confirm that hemodialysis patients are exposed to oxidative stress and increased susceptibility to ex vivo LDL oxidation. Since oral vitamin E supplementation prevents oxidative stress and significantly increases LDL resistance to ex vivo oxidation, supplementation by natural antioxidants such as vitamin E may be beneficial in hemodialysis patients.

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