Evaluation of the safety of mixed tocopheryl phosphates (MTP)—A formulation of α-tocopheryl phosphate plus α-di-tocopheryl phosphate

Libinaki, Roksan; Ogru, Esra; Gianello, Robert; Bolton, L; Geytenbeek, Stephen Lindsay

doi:10.1016/j.fct.2005.10.013

Cited by 18 publications

(20 citation statements)

References 8 publications

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“…In animal tissues (including humans), the amount of aTP (0.1 mg/g) is about 100 times lower than that of aT (10 mg/g) [20]. Supplementation of the diet of rats with aTP results in an increased appearance of aTP and aT in liver and adipose tissue [19], and no significant toxicity is observed in several animal models [22,23]. aTP levels in plasma of un-supplemented rats, minipigs, and humans (Zingg et al, unpublished) are similar as measured in un-supplemented rabbits, having a basal plasma aTP level of 0.19 mM that increased to 29.4 mM after supplementation with 1.33 g/kg of body weight of aTP for 4 wk [24].…”

Section: Occurrence Of Atpmentioning

confidence: 99%

α‐Tocopheryl phosphate – An active lipid mediator?

Zingg

Meydani

Azzi

2010

Molecular Nutrition Food Res

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The vitamin E (alpha-tocopherol, alphaT) derivative, alpha-tocopheryl phosphate (alphaTP), is detectable in small amounts in plasma, tissues, and cultured cells. Studies done in vitro and in vivo suggest that alphaT can become phosphorylated and alphaTP dephosphorylated, suggesting the existence of enzyme(s) with alphaT kinase or alphaTP phosphatase activity, respectively. As a supplement in animal studies, alphaTP can reach plasma concentrations similar to alphaT and only a part is dephosphorylated; thus, alphaTP may act both as pro-vitamin E, but also as phosphorylated form of vitamin E with possibly novel regulatory activities. Many effects of alphaTP have been described: in the test tube alphaTP modulates the activity of several enzymes; in cell culture alphaTP affects proliferation, apoptosis, signal transduction, and gene expression; in animal studies alphaTP prevents atherosclerosis, ischemia/reperfusion injury, and induces hippocampal long-term potentiation. At the molecular level, alphaTP may act as a cofactor for enzymes, as an active lipid mediator similar to other phosphorylated lipids, or indirectly by altering membrane characteristics such as lipid rafts, fluidity, and curvature. In this review, the molecular and cellular activities of alphaTP are examined and the possible functions of alphaTP as a natural compound, cofactor and active lipid mediator involved in signal transduction and gene expression discussed.

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Section: Occurrence Of Atpmentioning

confidence: 99%

α‐Tocopheryl phosphate – An active lipid mediator?

Zingg

Meydani

Azzi

2010

Molecular Nutrition Food Res

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“…However, it is not known whether aTP would stimulate angiogenesis in tumor tissues, for example, in animals prone to develop tumors [82,83]. At high concentrations in vitro, aTP inhibits cell proliferation and cell migration.…”

Section: Introductionmentioning

confidence: 98%

“…Relative to aT, aTP's presence in food occurs in low amounts [80], its uptake as an intact molecule is much less efficient than that of aT even when given as supplement, and its tissue levels are low as most of it is hydrolyzed to aT, suggesting that it is not a transport or storage form of aT [70,[81][82][83][84]. A local synthesis of aTP in specific cells may thus be necessary to allow the position of aTP at specific subcellular sites relevant for signaling.…”

Section: Introductionmentioning

confidence: 99%

α‐Tocopheryl phosphate—An activated form of vitamin E important for angiogenesis and vasculogenesis?

2012

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Vitamin E was originally discovered as a dietary factor essential for reproduction in rats. Since then, vitamin E has revealed many important molecular properties such as the scavenging of reactive oxygen and nitrogen species or the modulation of signal transduction and gene expression in antioxidant and nonantioxidant manners. A congenital disease, ataxia with vitamin E deficiency, which is characterized by impaired enrichment of α-tocopherol (αT) in plasma due to mutations in the α-tocopherol transfer protein gene, has been discovered. An effect of vitamin E on angiogenesis and vasculogenesis has been observed in several studies, and recently, it has been demonstrated in the placenta of pregnant ewes, possibly involving the stimulation of vascular endothelial growth factor (VEGF) expression. We recently observed that the phosphorylated form of αT, α-tocopheryl phosphate (αTP), increases the expression of VEGF. We propose that the stimulatory effect of αT on angiogenesis and vasculogenesis is potentiated by phosphorylation to αTP, which may act as a cofactor or active lipid mediator increasing VEGF expression. Increased VEGF expression and consequent enhanced angiogenesis and vasculogenesis induced by αTP may explain not only the essential roles of vitamin E on reproduction, but also its beneficial effects against pre-eclampsia, ischemia/reperfusion injury, and during wound healing. It may also serve as a survival factor for brain and muscle cells. The finding that αTP may regulate vasculogenesis may indicate potential, important pathophysiological implications.

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“…In some cases, the amounts of -tocopheryl phosphate have been reported to be higher than free -tocopherol, e. g. in chocolate and certain cheeses [191]. Furthermore, supplementation of the diet of rats with -tocopheryl phosphate results in an increased deposition of -tocopheryl phosphate and -tocopherol in liver and adipose tissue [191] and no significant toxicity is observed in several animal models [192]. Furthermore, supplementation of the diet of rats with -tocopheryl phosphate results in an increased deposition of -tocopheryl phosphate and -tocopherol in liver and adipose tissue [191] and no significant toxicity is observed in several animal models [192].…”

Section: -Tocopheryl Phosphate (Tp)mentioning

confidence: 99%

Molecular and Cellular Activities of Vitamin E Analogues

Zingg

2007

MRMC

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Natural vitamin E comprises 8 different analogues, the alpha-, beta-, gamma-, and delta-tocopherols and the alpha-, beta-, gamma-, and delta-tocotrienols. However, only alpha-tocopherol is selectively enriched by the liver; the other vitamin E analogues and also excess alpha-tocopherol are converted to several metabolites and eliminated. Recently, a novel phosphorylated form of tocopherol, alpha-tocopheryl phosphate, was shown to occur naturally in animal and human tissues as well as in foods. Several synthetic vitamin E derivatives have been synthesized that are either converted by esterases to the natural form, or exert novel or vitamin E related biological activities. During the last years, specific cellular effects for each individual vitamin E analogue have been described that are the consequence of modulating signal transduction and gene expression. These effects possibly reflect specific interactions of each of the vitamin E analogues with enzymes, structural proteins, lipids and transcription factors. In this review, the different natural vitamin E analogues and synthetic derivatives are compiled in relation to their major molecular and cellular activities.

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Evaluation of the safety of mixed tocopheryl phosphates (MTP)—A formulation of α-tocopheryl phosphate plus α-di-tocopheryl phosphate

Cited by 18 publications

References 8 publications

α‐Tocopheryl phosphate – An active lipid mediator?

α‐Tocopheryl phosphate – An active lipid mediator?

α‐Tocopheryl phosphate—An activated form of vitamin E important for angiogenesis and vasculogenesis?

Molecular and Cellular Activities of Vitamin E Analogues

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